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Sample records for modulates inflammatory processes

  1. Chlorinated Flavonoids Modulate the Inflammatory Process in Human Blood.

    Science.gov (United States)

    Proença, Carina; Ribeiro, Daniela; Soares, Tânia; Tomé, Sara M; Silva, Artur M S; Lima, José L F C; Fernandes, Eduarda; Freitas, Marisa

    2017-08-01

    Flavonoids are known to react with neutrophil-generated hypochlorous acid (HOCl) at inflammation loci to form stable mono- and dichlorinated products. Some of these products have been shown to retain or even enhance their inflammatory potential, but further information is required in a broader approach to inflammatory mechanisms. In that sense, we performed an integrated evaluation on the anti-inflammatory potential of a panel of novel chlorinated flavonoids and their parent compounds, in several steps of the complex inflammatory cascade, namely, in the activity of cyclooxygenase (COX)-1 and COX-2, and in the production of cytokines [interleukin (IL)-6, IL-1β, tumor necrosis factor (TNF)], and the chemokine, IL-8, as well as in the production of reactive species, using human whole blood as a representative in vitro model, establishing, whenever possible, a structure-activity relationship. Although luteolin was the most active compound, chlorinated flavonoids demonstrated a remarkable pattern of activity for the resolution of the inflammatory processes. Our results demonstrated that 6-chloro-3',4',5,7-tetrahydroxyflavone deserves scientific attention due to its ability to modulate the reactive species and cytokines/chemokine production. In this regard, the therapeutic potential of flavonoids' metabolites, and in this particular case the chlorinated flavonoids, should not be neglected.

  2. Prevention of human cancer by modulation of chronic inflammatory processes

    Energy Technology Data Exchange (ETDEWEB)

    Ohshima, Hiroshi [International Agency for Research on Cancer, 150 Cours Albert Thomas, 69372 Lyon Cedex 08 (France)]. E-mail: ohshima@iarc.fr; Tazawa, Hiroshi [International Agency for Research on Cancer, 150 Cours Albert Thomas, 69372 Lyon Cedex 08 (France); Sylla, Bakary S. [International Agency for Research on Cancer, 150 Cours Albert Thomas, 69372 Lyon Cedex 08 (France); Sawa, Tomohiro [International Agency for Research on Cancer, 150 Cours Albert Thomas, 69372 Lyon Cedex 08 (France)

    2005-12-11

    Chronic inflammation induced by biological, chemical and physical factors has been associated with increased risk of human cancer at various sites. Inflammation facilitates the initiation of normal cells and their growth and progression to malignancy through production of pro-inflammatory cytokines and diverse reactive oxygen and nitrogen species. These also activate signaling molecules involved in inflammation and carcinogenesis such as nuclear transcription factor (NF-{kappa}B), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Several chemopreventive agents act through inhibition of signaling pathways (e.g. NF-{kappa}B), inhibition of oxidant-generating enzymes (e.g. iNOS) and mediators of inflammation (e.g. COX-2), scavenging reactive oxygen and nitrogen species, and modulation of xenobiotic-metabolizing enzymes (especially phase II enzyme induction). Some anti-inflammatory drugs have been tested in clinical trials to prevent human cancer at several sites. Better understanding of the molecular mechanisms by which chronic inflammation increases cancer risk will lead to further development of new strategies for cancer prevention at many sites.

  3. Coffee consumption modulates inflammatory processes in an individual fashion.

    Science.gov (United States)

    Muqaku, Besnik; Tahir, Ammar; Klepeisz, Philip; Bileck, Andrea; Kreutz, Dominique; Mayer, Rupert L; Meier, Samuel M; Gerner, Marlene; Schmetterer, Klaus; Gerner, Christopher

    2016-12-01

    Anti-inflammatory effects of coffee consumption have been reported to be caused by caffeine and adenosine receptor signaling. However, contradictory effects have been observed. Many kinds of chronic diseases are linked to inflammation; therefore a profound understanding of potential effects of coffee consumption is desirable. We performed ex vivo experiments with eight individuals investigating peripheral blood mononuclear cells isolated from venous blood before and after coffee consumption, as well as in vitro experiments applying caffeine on isolated cells. After in vitro inflammatory stimulation of the cells, released cytokines, chemokines, and eicosanoids were determined and quantified using targeted mass spectrometric methods. Remarkably, the release of inflammation mediators IL6, IL8, GROA, CXCL2, CXCL5 as well as PGA2, PGD2, prostaglandin E2 (PGE2), LTC4, LTE4, and 15S-HETE was significantly affected after coffee consumption. While in several individuals coffee consumption or caffeine treatment caused significant downregulation of most inflammation mediators, in other healthy individuals exactly the opposite effects were observed. Ruling out age, sex, coffee consumption habits, the metabolic kinetics of caffeine in blood and the individual amount of regulatory T cells or CD39 expression as predictive parameters, we demonstrated here that coffee consumption may have significant pro- or anti-inflammatory effects in an individual fashion. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Lycopene Modulates THP1 and Caco2 Cells Inflammatory State through Transcriptional and Nontranscriptional Processes

    Science.gov (United States)

    Makon-Sébastien, Njock; Francis, Fouchier; Eric, Seree; Henri, Villard Pierre; François, Landrier Jean; Laurent, Pechere; Yves, Barra; Serge, Champion

    2014-01-01

    We revisited the action of a carotenoid, the lycopene, on the expression of proinflammatory genes, reactive oxygen species (ROS) production, and metalloprotease (MMP9) activity. THP1 and Caco2 cell lines were used as in vitro models for the two main cell types found in intestine tissue, that is, monocytes and epithelial cells. Proinflammatory condition was induced using either phorbol ester acetate (PMA), lipopolysaccharide (LPS) or tumor necrosis factor (TNF). In THP1 cells, short term pretreatment (2 h) with a low concentration (2 μM) of lycopene reinforce proinflammatory gene expression. The extent of the effect of lycopene is dependent on the proinflammtory stimulus (PMA, LPS or TNF) used. Lycopene enhanced MMP9 secretion via a c-AMP-dependent process, and reduced ROS production at higher concentrations than 2 μM. Cell culture media, conditioned by PMA-treated monocytes and then transferred on CaCo-2 epithelial cells, induced a proinflammatory state in these cells. The extent of this inflammatory effect was reduced when cells has been pretreated (12 h) with lycopene. At low concentration (2 μM or less), lycopene appeared to promote an inflammatory state not correlated with ROS modulation. At higher concentration (5 μM–20 μM), an anti-inflammatory effect takes place as a decrease of ROS production was detected. So, both concentration and time have to be considered in order to define the exact issue of the effect of carotenoids present in meals. PMID:24891766

  5. Inflammatory Process Modulation by Homeopathic Arnica montana 6CH: The Role of Individual Variation

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    Ana Paula Kawakami

    2011-01-01

    Full Text Available The effects of Arnica montana 6cH on the individual modulation of acute inflammation kinetics in rats were evaluated. Adult male Wistar rats were inoculated with 1% carrageenan into the footpad and treated with Arnica montana 6cH, dexamethasone (4.0 mg/kg; positive control or 5% hydroalcoholic solution (negative control, per os, each 15 minutes, between 30 and 180 minutes after the irritant inoculation. Histopathological and immunohistochemistry procedures were done in order to get a panel of inflammatory positive cells for CD3 (T lymphocytes, CD45RA (B lymphocytes, CD18 (beta 2 integrin, CD163 (ED2 protein, CD54 (ICAM-1, and MAC 387 (monocytes and macrophages. The statistical treatment of data included a posteriori classification of animals from each group (N=20 in two subgroups presenting spontaneous precocious or late oedema. Animals that presented precocious oedema were less responsible to Arnica montana 6cH in relation to hemodynamic changes. Instead, rats that exhibited late oedema presented less intense oedema (P=.01, lower percentage of mast cell degranulation (P=.0001, and increase in lymphatic vessels diameter (P=.05. The data suggest an individually qualitative adjustment of inflammatory vascular events by Arnica montana 6cH.

  6. Rats Born to Mothers Treated with Dexamethasone 15 cH Present Changes in Modulation of Inflammatory Process

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    Leoni V. Bonamin

    2012-01-01

    Full Text Available As little information about the effect of ultra high dilutions of glucocorticoid in reproduction is available in the literature, pregnant female Wistar rats (N=12 were blindly subcutaneously treated during all gestational and lactation period with: dexamethasone 4 mg/kg diluted into dexamethasone 15 cH (mixed; or dexamethasone 4 mg/kg diluted in water; or dexamethasone 15 cH, or vehicle. Parental generation had body weight, food and water consumption monitored. The F1 generation was monitored regarding to newborn development. No birth occurred in both groups treated with dexamethasone 4 mg/kg. After 60 days from birth, 12 male F1 rats were randomly selected from each remaining group and inoculated subcutaneously with 1% carrageenan into the footpad, for evaluation of inflammatory performance. Edema and histopathology of the footpad were evaluated, using specific staining methods, immunohistochemistry and digital histomorphometry. Mothers treated with mixed dexamethasone presented reduced water consumption. F1 rats born to dexamethasone 15 cH treated females presented significant increase in mast cell degranulation, decrease in monocyte percentage, increase in CD18+ PMN cells, and early expression of ED2 protein, in relation to control. The results show that the exposure of parental generation to highly diluted dexamethasone interferes in inflammation modulation in the F1 generation.

  7. New approaches to the modulation of inflammatory processes in airway disease models: ATS 2001, May 18-23, San Francisco

    Directory of Open Access Journals (Sweden)

    Hele David J

    2001-07-01

    Full Text Available Abstract The 97th American Thoracic Society meeting proved to be an excellent meeting, providing a wealth of new information on inflammatory diseases of the airways. Once again there appeared to be an increased emphasis on chronic obstructive pulmonary disease (COPD with most of the major drug companies concentrating a large part of their efforts in this field. An assessment of the new British Thoracic Society guidelines, which are designed to promote better management of COPD, was also presented at the meeting. Potential new treatments for inflammatory diseases of the airways including COPD were described, ranging from phase III trial data with GlaxoSmithKline's PDE4 inhibitor, Cilomilast (Ariflo® to the development of AstraZeneca's novel dual dopamine D2-receptor/β2-adrenoreceptor agonist, Viozan™. Of particular interest was Byk Gulden's Ciclesonide, a new corticosteroid with equivalent efficacy to the market leaders but with an improved safety profile. The same company also presented data on their PDE4 inhibitor, Roflumilast, which is now in phase II/III. Bayer presented data on their PDE4 inhibitor, BAY 19-8004, in a smoking animal model and claimed greater anti-inflammatory efficacy than with a steroid. Asta Medica (now known as Elbion also described a new potent PDE4 inhibitor, AWD 12-281, with anti-inflammatory activity. In the bronchodilator field, an analysis of data from a one-year trial with Boehringer Ingelheim's Tiotropium revealed a possible improvement in lung function in COPD patients; this needs to be confirmed in a specifically designed study. Inhibitors of p38 (c-Jun NH2-terminal kinase and syk kinase were also discussed as anti-inflammatory agents with potential in the treatment of COPD and asthma. GlaxoSmithKline's p38 kinase inhibitor, SB 239063, appeared to be the most advanced of these with clinical data expected in two to three years. Lyn kinase was also discussed as a novel target for inflammatory airway diseases.

  8. Role of insulin hormone in modulation of inflammatory phenomena

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    Antonio Di Petta

    2011-09-01

    Full Text Available Evidence demonstrates the involvement of hormones in thedevelopment of inflammatory response. Inflammation evokes markedstructural alterations of microvasculature, besides migration ofleukocytes from microcirculation to the site of lesion. These alterations are caused primarily by release or activation of endogenous mediators, in which hormones play an integral role in this regulatory system. Binding sites for many hormones may be characterized by vascular structures and hematogenous cells involved with the inflammatory response. Quantitative alterations of inflammatory events involving the decrease in microvascular response to inflammatory mediators, deficiency in the leukocyte-endothelium interaction, reduction of cell concentration in the inflammatory exudate, and failure of the phagocyte function of mononuclear cells were observed in insulindeficient states. Therefore, inflammation is not merely a local response, but rather a process controlled by hormones in which insulin plays an essential role in modulation of these phenomena, and assures tissue repair and remodeling within the limits of normality.

  9. 9 CFR 381.86 - Inflammatory processes.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Inflammatory processes. 381.86 Section 381.86 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... Carcasses and Parts § 381.86 Inflammatory processes. Any organ or other part of a carcass which is affected...

  10. Markers of liver function and inflammatory cytokines modulation by ...

    African Journals Online (AJOL)

    Conclusion: Aerobic exercise training modulates inflammatory cytokine levels and markers of liver function in patients with nonalcoholic ... and is associated with over nutrition and under activity, ... of these subjects with leptin reduced liver fat and liver enzyme ... tissue, muscle-released interleukin-6 inhibition of tumor.

  11. Processing module operating methods, processing modules, and communications systems

    Science.gov (United States)

    McCown, Steven Harvey; Derr, Kurt W.; Moore, Troy

    2014-09-09

    A processing module operating method includes using a processing module physically connected to a wireless communications device, requesting that the wireless communications device retrieve encrypted code from a web site and receiving the encrypted code from the wireless communications device. The wireless communications device is unable to decrypt the encrypted code. The method further includes using the processing module, decrypting the encrypted code, executing the decrypted code, and preventing the wireless communications device from accessing the decrypted code. Another processing module operating method includes using a processing module physically connected to a host device, executing an application within the processing module, allowing the application to exchange user interaction data communicated using a user interface of the host device with the host device, and allowing the application to use the host device as a communications device for exchanging information with a remote device distinct from the host device.

  12. Melatonin as an Anti-Inflammatory Agent Modulating Inflammasome Activation

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    Gaia Favero

    2017-01-01

    Full Text Available Inflammation may be defined as the innate response to harmful stimuli such as pathogens, injury, and metabolic stress; its ultimate function is to restore the physiological homeostatic state. The exact aetiology leading to the development of inflammation is not known, but a combination of genetic, epigenetic, and environmental factors seems to play an important role in the pathogenesis of many inflammation-related clinical conditions. Recent studies suggest that the pathogenesis of different inflammatory diseases also involves the inflammasomes, intracellular multiprotein complexes that mediate activation of inflammatory caspases thereby inducing the secretion of proinflammatory cytokines. Melatonin, an endogenous indoleamine, is considered an important multitasking molecule with fundamental clinical applications. It is involved in mood modulation, sexual behavior, vasomotor control, and immunomodulation and influences energy metabolism; moreover, it acts as an oncostatic and antiaging molecule. Melatonin is an important antioxidant and also a widespread anti-inflammatory molecule, modulating both pro- and anti-inflammatory cytokines in different pathophysiological conditions. This review, first, gives an overview concerning the growing importance of melatonin in the inflammatory-mediated pathological conditions and, then, focuses on its roles and its protective effects against the activation of the inflammasomes and, in particular, of the NLRP3 inflammasome.

  13. Inflammatory Process in Alzheimer’s Disease

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    MARCO ANTONIO eMERAZ RIOS

    2013-08-01

    Full Text Available Alzheimer Disease (AD is a neurodegenerative disorder and the most common form of dementia. Histopathologically is characterized by the presence of two major hallmarks, the intracellular neurofibrillary tangles (NFTs and extracellular neuritic plaques (NPs surrounded by activated astrocytes and microglia. NFTs consist of paired helical filaments of truncated tau protein that is abnormally hyperphosphorylated. The main component in the NP is the amyloid-β peptide (Aβ, a small fragment of 40-42 amino acids with a molecular weight of 4kD. It has been proposed that the amyloid aggregates and microglia activation are able to favor the neurodegenerative process observed in AD patients. However, the role of inflammation in AD is controversial, because in early stages the inflammation could have a beneficial role in the pathology, since it has been thought that the microglia and astrocytes activated could be involved in Aβ clearance. Nevertheless the chronic activation of the microglia has been related with an increase of Aβ and possibly with tau phosphorylation. Studies in AD brains have shown an upregulation of complement molecules, pro-inflammatory cytokines, acute phase reactants and other inflammatory mediators that could contribute with the neurodegenerative process. Clinical trials and animal models with nonsteroidal anti-inflammatory drugs (NSAIDs indicate that these drugs may decrease the risk of developing AD and apparently reduce Aβ deposition. Finally, further studies are needed to determine whether treatment with anti-inflammatory strategies, may decrease the neurodegenerative process that affects these patients.

  14. Interferon-β Modulates Inflammatory Response in Cerebral Ischemia.

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    Kuo, Ping-Chang; Scofield, Barbara A; Yu, I-Chen; Chang, Fen-Lei; Ganea, Doina; Yen, Jui-Hung

    2016-01-08

    Stroke is a leading cause of death in the world. In >80% of strokes, the initial acute phase of ischemic injury is due to the occlusion of a blood vessel resulting in severe focal hypoperfusion, excitotoxicity, and oxidative damage. Interferon-β (IFNβ), a cytokine with immunomodulatory properties, was approved by the US Food and Drug Administration for the treatment of relapsing-remitting multiple sclerosis for more than a decade. Its anti-inflammatory properties and well-characterized safety profile suggest that IFNβ has therapeutic potential for the treatment of ischemic stroke. We investigated the therapeutic effect of IFNβ in the mouse model of transient middle cerebral artery occlusion/reperfusion. We found that IFNβ not only reduced infarct size in ischemic brains but also lessened neurological deficits in ischemic stroke animals. Further, multiple molecular mechanisms by which IFNβ modulates ischemic brain inflammation were identified. IFNβ reduced central nervous system infiltration of monocytes/macrophages, neutrophils, CD4(+) T cells, and γδ T cells; inhibited the production of inflammatory mediators; suppressed the expression of adhesion molecules on brain endothelial cells; and repressed microglia activation in the ischemic brain. Our results demonstrate that IFNβ exerts a protective effect against ischemic stroke through its anti-inflammatory properties and suggest that IFNβ is a potential therapeutic agent, targeting the reperfusion damage subsequent to the treatment with tissue plasminogen activator. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  15. Inflammatory Modulation Effect of Glycopeptide from Ganoderma capense (Lloyd Teng

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    Yan Zhou

    2014-01-01

    Full Text Available Glycopeptide from Ganoderma capense (Lloyd Teng (GCGP injection is widely used in kinds of immune disorders, but little is known about the molecular mechanisms of how GCGP could interfere with immune cell function. In the present study, we have found that GCGP had inflammatory modulation effects on macrophage cells to maintain NO production and iNOS expression at the normal level. Furthermore, western blot analysis showed that the underlying mechanism of immunomodulatory effect of GCGP involved NF-κB p65 translation, IκB phosphorylation, and degradation; NF-κB inhibitor assays also confirmed the results. In addition, competition study showed that GCGP could inhibit LPS from binding to macrophage cells. Our data indicates that GCGP, which may share the same receptor(s expressed by macrophage cells with LPS, exerted immunomodulatory effect in a NF-κB-dependent signaling pathway in macrophages.

  16. Inflammatory Modulation Effect of Glycopeptide from Ganoderma capense (Lloyd) Teng

    Science.gov (United States)

    Zhou, Yan; Chen, Song; Yao, Wenbing; Gao, Xiangdong

    2014-01-01

    Glycopeptide from Ganoderma capense (Lloyd) Teng (GCGP) injection is widely used in kinds of immune disorders, but little is known about the molecular mechanisms of how GCGP could interfere with immune cell function. In the present study, we have found that GCGP had inflammatory modulation effects on macrophage cells to maintain NO production and iNOS expression at the normal level. Furthermore, western blot analysis showed that the underlying mechanism of immunomodulatory effect of GCGP involved NF-κB p65 translation, IκB phosphorylation, and degradation; NF-κB inhibitor assays also confirmed the results. In addition, competition study showed that GCGP could inhibit LPS from binding to macrophage cells. Our data indicates that GCGP, which may share the same receptor(s) expressed by macrophage cells with LPS, exerted immunomodulatory effect in a NF-κB-dependent signaling pathway in macrophages. PMID:24966469

  17. Immuno-modulation and anti-inflammatory benefits of antibiotics: The example of tilmicosin

    OpenAIRE

    Buret, André G.

    2010-01-01

    Exagerated immune responses, such as those implicated in severe inflammatory reactions, are costly to the metabolism. Inflammation and pro-inflammatory mediators negatively affect production in the food animal industry by reducing growth, feed intake, reproduction, milk production, and metabolic health. An ever-increasing number of findings have established that antibiotics, macrolides in particular, may generate anti-inflammatory effects, including the modulation of pro-inflammatory cytokine...

  18. Anthocyanins as inflammatory modulators and the role of the gut microbiota.

    Science.gov (United States)

    Morais, Carina Almeida; de Rosso, Veridiana Vera; Estadella, Débora; Pisani, Luciana Pellegrini

    2016-07-01

    The health benefits of consuming fruits that are rich in polyphenols, especially anthocyanins, have been the focus of recent in vitro and in vivo investigations. Thus, greater attention is being directed to the reduction of the inflammatory process associated with the intestinal microbiota and the mechanism underlying these effects because the microbiota has been closely associated with the metabolism of these compounds in the gastrointestinal tract. Further interest lies in the ability of these metabolites to modulate the growth of specific intestinal bacteria. Thus, this review examines studies involving the action of the anthocyanins that are present in many fruits and their effect in the modulating the inflammatory process associated with the interaction between the host and the gut microbiota. The findings of both in vitro and in vivo studies suggest a potential antiinflammatory effect of these compounds, which seem to inhibit activation of the signaling pathway mediated by the transcription factor NFκB. This effect is associated with modulation of a beneficial gut microbiota, particularly an increase in Bifidobacterium strains. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Immune and inflammatory responses in the CNS : Modulation by astrocytes

    DEFF Research Database (Denmark)

    Penkowa, Milena; aschner, michael; hidalgo, juan

    2008-01-01

    Beyond their long-recognized support functions, astrocytes are active partners of neurons in processing information, synaptic integration, and production of trophic factors, just to name a few. Both microglia and astrocytes produce and secrete a number of cytokines, modulating and integrating...... the communication between hematogenous cells and resident cells of the central nervous system (CNS). This review will address (1) the functions of astrocytes in the normal brain and (2) their role in surveying noxious stimuli within the brain, with particular emphasis on astrocytic responses to damage or disease...

  20. Inflammatory cytokines and immune system modulation by aerobic ...

    African Journals Online (AJOL)

    Keywords: Immune function, inflammatory cytokines, aerobic exercise, resistance exercise, aging. ... Physical exercise is effective in reducing (or ameliorate) the ..... moderate resistance training program increases muscle .... Nutrition Metabo-.

  1. Targeting S1P in Inflammatory bowel disease: new avenues for modulating intestinal leukocyte migration.

    Science.gov (United States)

    Danese, Silvio; Furfaro, Federica; Vetrano, Stefania

    2017-07-28

    Sphingosine 1 phosphate (S1P) is a bioactive lipid mediator involved in the regulation of several cellular processes though the activation of a G protein-coupled receptor family known as the S1P receptors (S1PRs). Advances in the understanding of the biological activities mediated by S1PRs have sparked great interest in the S1P/S1PRs axes as new therapeutic targets for the modulation of several cellular processes. In particular, S1P/ S1PR1 axis has been identified as key regulator for the lymphocyte migration from lymph nodes. The blockade of this axis is emerging as a new therapeutic approach to control the aberrant leukocytes migration into the mucosa in inflammatory bowel disease (IBD). This review briefly summarizes the current evidence coming from clinical studies and discusses the future prospects of S1P inhibitors for treatment of inflammatory bowel disease. Copyright © 2017 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  2. Treating Gulf War Illness with Novel Anti-Inflammatories: A Screening of Botantical Microglia Modulators

    Science.gov (United States)

    2016-10-01

    AWARD NUMBER: W81XWH-14-1-0623 TITLE: Treating Gulf War Illness with Novel Anti-Inflammatories: A Screening of Botantical Microglia Modulators...Report 3. DATES COVERED 30 Sep 2015 - 29 Sep 2016 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Treating Gulf War Illness with Novel Anti...SUBJECT TERMS Gulf War Illness, botanical, anti-inflammatory, biomarker, microglia, improvement, treatment 16. SECURITY CLASSIFICATION OF: 17

  3. Chronic inflammatory and suppurative processes in lungs

    International Nuclear Information System (INIS)

    Rozenshtraukh, L.C.; Rybakova, N.I.; Vinner, M.G.

    1987-01-01

    Roentgenologic methods of diagnosis of chronic bronchitis, bronchiectatic disease, lung abscess and gangrene, chronic non-specific pneumonia and cancer of lung and other pathalogical changes at chronic processes in lungs are discussed in detail

  4. Myeloproliferative neoplasms and inflammation: whether to target the malignant clone or the inflammatory process or both.

    Science.gov (United States)

    Koschmieder, S; Mughal, T I; Hasselbalch, H C; Barosi, G; Valent, P; Kiladjian, J-J; Jeryczynski, G; Gisslinger, H; Jutzi, J S; Pahl, H L; Hehlmann, R; Maria Vannucchi, A; Cervantes, F; Silver, R T; Barbui, T

    2016-05-01

    The Philadelphia-negative myeloproliferative neoplasms (MPNs) are clonal disorders involving hematopoietic stem and progenitor cells and are associated with myeloproliferation, splenomegaly and constitutional symptoms. Similar signs and symptoms can also be found in patients with chronic inflammatory diseases, and inflammatory processes have been found to play an important role in the pathogenesis and progression of MPNs. Signal transduction pathways involving JAK1, JAK2, STAT3 and STAT5 are causally involved in driving both the malignant cells and the inflammatory process. Moreover, anti-inflammatory and immune-modulating drugs have been used successfully in the treatment of MPNs. However, to date, many unresoved issues remain. These include the role of somatic mutations that are present in addition to JAK2V617F, CALR and MPL W515 mutations, the interdependency of malignant and nonmalignant cells and the means to eradicate MPN-initiating and -maintaining cells. It is imperative for successful therapeutic approaches to define whether the malignant clone or the inflammatory cells or both should be targeted. The present review will cover three aspects of the role of inflammation in MPNs: inflammatory states as important differential diagnoses in cases of suspected MPN (that is, in the absence of a clonal marker), the role of inflammation in MPN pathogenesis and progression and the use of anti-inflammatory drugs for MPNs. The findings emphasize the need to separate the inflammatory processes from the malignancy in order to improve our understanding of the pathogenesis, diagnosis and treatment of patients with Philadelphia-negative MPNs.

  5. Space-time-modulated stochastic processes

    Science.gov (United States)

    Giona, Massimiliano

    2017-10-01

    Starting from the physical problem associated with the Lorentzian transformation of a Poisson-Kac process in inertial frames, the concept of space-time-modulated stochastic processes is introduced for processes possessing finite propagation velocity. This class of stochastic processes provides a two-way coupling between the stochastic perturbation acting on a physical observable and the evolution of the physical observable itself, which in turn influences the statistical properties of the stochastic perturbation during its evolution. The definition of space-time-modulated processes requires the introduction of two functions: a nonlinear amplitude modulation, controlling the intensity of the stochastic perturbation, and a time-horizon function, which modulates its statistical properties, providing irreducible feedback between the stochastic perturbation and the physical observable influenced by it. The latter property is the peculiar fingerprint of this class of models that makes them suitable for extension to generic curved-space times. Considering Poisson-Kac processes as prototypical examples of stochastic processes possessing finite propagation velocity, the balance equations for the probability density functions associated with their space-time modulations are derived. Several examples highlighting the peculiarities of space-time-modulated processes are thoroughly analyzed.

  6. Oak kombucha protects against oxidative stress and inflammatory processes.

    Science.gov (United States)

    Vázquez-Cabral, B D; Larrosa-Pérez, M; Gallegos-Infante, J A; Moreno-Jiménez, M R; González-Laredo, R F; Rutiaga-Quiñones, J G; Gamboa-Gómez, C I; Rocha-Guzmán, N E

    2017-06-25

    Black tea infusion is the common substrate for preparing kombucha; however other sources such as oak leaves infusions can be used for the same purpose. Almost any white oak species have been used for medicinal applications by some ethnic groups in Mexico and could be also suitable for preparing kombucha analogues from oak (KAO). The objective of this research was to investigate the antioxidant activity and anti-inflammatory effects of KAO by examining its modulation ability on macrophage-derived TNF-alpha and IL-6. Herbal infusions from oak and black tea were fermented by kombucha consortium during seven days at 28 °C. Chemical composition was determined by LC-ESI-MS/MS. The antioxidant activity of samples against oxidative damage caused by H 2 O 2 in monocytes activated (macrophages) was explored. Additionally, it was determined the anti-inflammatory activity using lipopolysaccharide (LPS) - stimulated macrophages; in particular, the nitric oxide (NO), TNF-alpha, and IL-6 production was assessed. Levels of pro-inflammatory cytokines IL-6 and TNF-alpha were significantly reduced by the sample treatment. Likewise, NO production was lower in treatment with kombucha and KAO compared with LPS-stimulated macrophages. Fermented beverages of oak effectively down-regulated the production of NO, while pro-inflammatory cytokines (TNF-alpha and IL-6) in macrophages were stimulated with LPS. Additionally, phytochemical compounds present in KAO decrease oxidative stress. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Curcumin Protects Against the Acute Inflammatory Process in Irradiated Rats

    International Nuclear Information System (INIS)

    El-Ghazaly, M.A.; Nada, A.S.; Hegazy, M.E.; Kenawy, S.A.

    2010-01-01

    Nutraceuticals that provide medical or health benefits, including prevention and treatment of disease may be advantageous in inflammation and exposure to radiation. The aim of this study was to investigate the potential of curcumin to modulate, counteract or prevent the inflammatory response induced in irradiated and non-irradiated rats using the carrageenan air-pouch model as an acute model. Diclofenac was used as a reference standard non-steroidal anti-inflammatory drug (NSAID). Results indicated that exposure of rats to a single dose of gamma-radiation (6 Gy) before induction of inflammation increased production of prostaglandin E2 (PGE2), tumour necrosis factor-alpha (TNF-alpha) and malondialdehyde (MDA) levels in serum. Blood glutathione (GSH) was shown to be reduced in irradiated animals. Curcumin suppressed the elevated levels of TNF-alpha, PGE2 and MDA and was able to restore blood GSH levels. Reduction in liver contents of copper (Cu), zinc (Zn), selenium (Se) and iron (Fe) was recorded after irradiation of animals before induction of inflammation. Curcumin restored the hepatic concentrations of these trace elements. The present results suggest that irradiation of rats caused marked changes in the inflammatory response while curcumin suppressed the inflammatory response in both irradiated and control animals.

  8. GanedenBC30™ cell wall and metabolites: anti-inflammatory and immune modulating effects in vitro

    Directory of Open Access Journals (Sweden)

    Carter Steve G

    2010-03-01

    also enhanced both the PHA- and the PWM-induced expression of IL-10. Conclusion The data suggest that consumption of GanedenBC30TM may introduce both cell wall components and metabolites that modulate inflammatory processes in the gut. Both the cell wall and the supernatant possess strong immune modulating properties in vitro. The anti-inflammatory effects, combined with direct induction of IL-10, are of interest with respect to possible treatment of inflammatory bowel diseases as well as in support of a healthy immune system.

  9. GanedenBC30™ cell wall and metabolites: anti-inflammatory and immune modulating effects in vitro

    Science.gov (United States)

    2010-01-01

    - and the PWM-induced expression of IL-10. Conclusion The data suggest that consumption of GanedenBC30TM may introduce both cell wall components and metabolites that modulate inflammatory processes in the gut. Both the cell wall and the supernatant possess strong immune modulating properties in vitro. The anti-inflammatory effects, combined with direct induction of IL-10, are of interest with respect to possible treatment of inflammatory bowel diseases as well as in support of a healthy immune system. PMID:20331905

  10. GanedenBC30 cell wall and metabolites: anti-inflammatory and immune modulating effects in vitro.

    Science.gov (United States)

    Jensen, Gitte S; Benson, Kathleen F; Carter, Steve G; Endres, John R

    2010-03-24

    -induced expression of IL-10. The data suggest that consumption of GanedenBC30TM may introduce both cell wall components and metabolites that modulate inflammatory processes in the gut. Both the cell wall and the supernatant possess strong immune modulating properties in vitro. The anti-inflammatory effects, combined with direct induction of IL-10, are of interest with respect to possible treatment of inflammatory bowel diseases as well as in support of a healthy immune system.

  11. Immuno-modulation and anti-inflammatory benefits of antibiotics: the example of tilmicosin.

    Science.gov (United States)

    Buret, André G

    2010-01-01

    Exaggerated immune responses, such as those implicated in severe inflammatory reactions, are costly to the metabolism. Inflammation and pro-inflammatory mediators negatively affect production in the food animal industry by reducing growth, feed intake, reproduction, milk production, and metabolic health. An ever-increasing number of findings have established that antibiotics, macrolides in particular, may generate anti-inflammatory effects, including the modulation of pro-inflammatory cytokines and the alteration of neutrophil function. The effects are time- and dose-dependent, and the mechanisms responsible for these phenomena remain incompletely understood. Recent studies, mostly using the veterinary macrolide tilmicosin, may have shed new light on the mode of action of some macrolides and their anti-inflammatory properties. Indeed, research findings demonstrate that this compound, amongst others, induces neutrophil apoptosis, which in turn provides anti-inflammatory benefits. Studies using tilmicosin model systems in vitro and in vivo demonstrate that this antibiotic has potent immunomodulatory effects that may explain why at least parts of its clinical benefits are independent of anti-microbial effects. More research is needed, using this antibiotic and others that may have similar properties, to clarify the biological mechanisms responsible for antibiotic-induced neutrophil apoptosis, and how this, in turn, may provide enhanced clinical benefits. Such studies may help establish a rational basis for the development of novel, efficacious, anti-microbial compounds that generate anti-inflammatory properties in addition to their antibacterial effects.

  12. Immuno-modulation and anti-inflammatory benefits of antibiotics: The example of tilmicosin

    Science.gov (United States)

    Buret, André G.

    2010-01-01

    Exagerated immune responses, such as those implicated in severe inflammatory reactions, are costly to the metabolism. Inflammation and pro-inflammatory mediators negatively affect production in the food animal industry by reducing growth, feed intake, reproduction, milk production, and metabolic health. An ever-increasing number of findings have established that antibiotics, macrolides in particular, may generate anti-inflammatory effects, including the modulation of pro-inflammatory cytokines and the alteration of neutrophil function. The effects are time- and dose-dependent, and the mechanisms responsible for these phenomena remain incompletely understood. Recent studies, mostly using the veterinary macrolide tilmicosin, may have shed new light on the mode of action of some macrolides and their anti-inflammatory properties. Indeed, research findings demonstrate that this compound, amongst others, induces neutrophil apoptosis, which in turn provides anti-inflammatory benefits. Studies using tilmicosin model systems in vitro and in vivo demonstrate that this antibiotic has potent immunomodulatory effects that may explain why at least parts of its clinical benefits are independent of anti-microbial effects. More research is needed, using this antibiotic and others that may have similar properties, to clarify the biological mechanisms responsible for antibiotic-induced neutrophil apoptosis, and how this, in turn, may provide enhanced clinical benefits. Such studies may help establish a rational basis for the development of novel, efficacious, anti-microbial compounds that generate anti-inflammatory properties in addition to their antibacterial effects. PMID:20357951

  13. Binaural processing of modulated interaural level differences

    DEFF Research Database (Denmark)

    Thompson, Eric Robert; Dau, Torsten

    2008-01-01

    Two experiments are presented that measure the acuity of binaural processing of modulated interaural level differences ILDs using psychoacoustic methods. In both experiments, dynamic ILDs were created by imposing an interaurally antiphasic sinusoidal amplitude modulation AM signal on high...... frequency, broadly tuned, bandpass-shaped patterns were obtained. Simulations with an existing binaural model show that a low-pass filter to limit the binaural temporal resolution is not sufficient to predict the results of the experiments....

  14. Physical exercise, inflammatory process and adaptive condition: an overview

    OpenAIRE

    Silva, Fernando Oliveira Catanho da; Macedo, Denise Vaz

    2011-01-01

    Physical exercise induces inflammation, a physiological response that is part of immune system activity and promotes tissue remodeling after exercise overload. The activation of the inflammatory process is local and systemic and is mediated by different cells and secreted compounds. The objective is to reestablish organ homeostasis after a single bout of exercise or after several exercise sessions. The acute-phase response involves the combined actions of activated leukocytes, cytokines, acut...

  15. Language and culture modulate online semantic processing.

    Science.gov (United States)

    Ellis, Ceri; Kuipers, Jan R; Thierry, Guillaume; Lovett, Victoria; Turnbull, Oliver; Jones, Manon W

    2015-10-01

    Language has been shown to influence non-linguistic cognitive operations such as colour perception, object categorization and motion event perception. Here, we show that language also modulates higher level processing, such as semantic knowledge. Using event-related brain potentials, we show that highly fluent Welsh-English bilinguals require significantly less processing effort when reading sentences in Welsh which contain factually correct information about Wales, than when reading sentences containing the same information presented in English. Crucially, culturally irrelevant information was processed similarly in both Welsh and English. Our findings show that even in highly proficient bilinguals, language interacts with factors associated with personal identity, such as culture, to modulate online semantic processing. © The Author (2015). Published by Oxford University Press.

  16. Neuropsychiatric comorbidity in obesity: role of inflammatory processes

    Directory of Open Access Journals (Sweden)

    Nathalie eCastanon

    2014-05-01

    Full Text Available Neuropsychiatric symptoms are frequent in obesity. In addition to their substantial economic and health impact, these symptoms significantly interfere with the quality of life and social function of obese individuals. While the pathophysiological mechanisms underlying obesity-related neuropsychiatric symptoms are still under investigation and remain to be clearly identified, there is increasing evidence for a role of inflammatory processes. Obesity is characterized by a chronic low-grade inflammatory state that is likely to influence neuropsychiatric status given the well-known and highly documented effects of inflammation on brain activity/function and behavior. This hypothesis is supported by recent findings emanating from clinical investigations in obese subjects and from experimentations conducted in animal models of obesity. These studies converge to show that obesity-related inflammatory processes, originating either from the adipose tissue or gut microbiota environment, spread to the brain where they lead to substantial changes in neurocircuitry, neuroendocrine activity, neurotransmitter metabolism and activity, and neurogenesis. Together, these alterations contribute to shape the propitious bases for the development of obesity-related neuropsychiatric comorbidities.

  17. Stress modulation of cognitive and affective processes

    Science.gov (United States)

    CAMPEAU, SERGE; LIBERZON, ISRAEL; MORILAK, DAVID; RESSLER, KERRY

    2012-01-01

    This review summarizes the major discussion points of a symposium on stress modulation of cognitive and affective processes, which was held during the 2010 workshop on the neurobiology of stress (Boulder, CO, USA). The four discussants addressed a number of specific cognitive and affective factors that are modulated by exposure to acute or repeated stress. Dr David Morilak discussed the effects of various repeated stress situations on cognitive flexibility, as assessed with a rodent model of attentional set-shifting task, and how performance on slightly different aspects of this test is modulated by different prefrontal regions through monoaminergic neurotransmission. Dr Serge Campeau summarized the findings of several studies exploring a number of factors and brain regions that regulate habituation of various autonomic and neuroendocrine responses to repeated audiogenic stress exposures. Dr Kerry Ressler discussed a body of work exploring the modulation and extinction of fear memories in rodents and humans, especially focusing on the role of key neurotransmitter systems including excitatory amino acids and brain-derived neurotrophic factor. Dr Israel Liberzon presented recent results on human decision-making processes in response to exogenous glucocorticoid hormone administration. Overall, these discussions are casting a wider framework on the cognitive/affective processes that are distinctly regulated by the experience of stress and some of the brain regions and neurotransmitter systems associated with these effects. PMID:21790481

  18. Polysaccharides from the fungus Scleroderma nitidum with anti-inflammatory potential modulate cytokine levels and the expression of Nuclear Factor kB

    Directory of Open Access Journals (Sweden)

    Marília S. Nascimento

    2012-02-01

    Full Text Available Several pharmacological properties are attributed to polysaccharides and glucans derived from fungi such as tumor, anti-inflammatory, and immunomodulatory activity. In this work, the anti-inflammatory potential of polysaccharides from the fungus Scleroderma nitidum and their possible action mechanism were studied. The effect of these polymers on the inflammatory process was tested using the carrageenan and histamine-induced paw edema model and the sodium thioglycolate and zymosan-induced model. The polysaccharides from S. nitidum were effective in reducing edema (73% at 50 mg/kg and cell infiltrate (37% at 10 mg/kg in both inflammation models tested. Nitric oxide, a mediator in the inflammatory process, showed a reduction of around 26% at 10 mg/kg of body weight. Analysis of pro-and anti-inflammatory cytokines showed that in the groups treated with polysaccharides from S. nitidum there was an increase in cytokines such as IL-1ra, IL-10, and MIP-1β concomitant with the decrease in INF-γ (75% and IL-2 (22%. We observed the influence of polysaccharides on the modulation of the expression of nuclear factor κB. This compound reduced the expression of NF-κB by up to 64%. The results obtained suggest that NF-κB modulation an mechanisms that explain the anti-inflammatory effect of polysaccharides from the fungus S. nitidum.

  19. Optogenetic exploration and modulation of pain processing.

    Science.gov (United States)

    Xie, Yu-Feng; Wang, Jing; Bonin, Robert P

    2018-08-01

    Intractable pain is the single most common cause of disability, affecting more than 20% of the population world-wide. There is accordingly a global effort to decipher how changes in nociceptive processing in the peripheral and central nervous systems contribute to the onset and maintenance of chronic pain. The past several years have brought rapid progress in the adaptation of optogenetic approaches to study and manipulate the activity of sensory afferents and spinal cord neurons in freely behaving animals, and to investigate cortical processing and modulation of pain responses. This review discusses methodological advances that underlie this recent progress, and discusses practical considerations for the optogenetic modulation of nociceptive sensory processing. Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.

  20. A3 Adenosine Receptor Allosteric Modulator Induces an Anti-Inflammatory Effect: In Vivo Studies and Molecular Mechanism of Action

    Directory of Open Access Journals (Sweden)

    Shira Cohen

    2014-01-01

    Full Text Available The A3 adenosine receptor (A3AR is overexpressed in inflammatory cells and in the peripheral blood mononuclear cells of individuals with inflammatory conditions. Agonists to the A3AR are known to induce specific anti-inflammatory effects upon chronic treatment. LUF6000 is an allosteric compound known to modulate the A3AR and render the endogenous ligand adenosine to bind to the receptor with higher affinity. The advantage of allosteric modulators is their capability to target specifically areas where adenosine levels are increased such as inflammatory and tumor sites, whereas normal body cells and tissues are refractory to the allosteric modulators due to low adenosine levels. LUF6000 administration induced anti-inflammatory effect in 3 experimental animal models of rat adjuvant induced arthritis, monoiodoacetate induced osteoarthritis, and concanavalin A induced liver inflammation in mice. The molecular mechanism of action points to deregulation of signaling proteins including PI3K, IKK, IκB, Jak-2, and STAT-1, resulting in decreased levels of NF-κB, known to mediate inflammatory effects. Moreover, LUF6000 induced a slight stimulatory effect on the number of normal white blood cells and neutrophils. The anti-inflammatory effect of LUF6000, mechanism of action, and the differential effects on inflammatory and normal cells position this allosteric modulator as an attractive and unique drug candidate.

  1. Development of coincidence processing module for PEM

    International Nuclear Information System (INIS)

    Feng Baotong; Shuai Lei; Li Ke

    2011-01-01

    For the breast cancer diagnosis and therapy, a prototype of positron emission mammography (PEM) was developed in Institute of High Energy Physics, Chinese Academy of Sciences. In this paper, the design of coincidence processing module (CPM) for this PEM was presented. Both the hardware architecture and the software logic were introduced. In this design, the CPM used the Rocket IO fast interface in FPGA and fiber technology to acquire the preprocessed data from the continuous sampling module (CSM) and then selected the valid event with the coincidence timing window method, which was performed in the FPGA on the daughter board. The CPM transmits the processed data to host computer via gigabit Ethernet. The whole system was controlled by CAN bus. The primary tests indicate that the performance of this design is good. (authors)

  2. Visible light communications modulation and signal processing

    CERN Document Server

    Wang, Zhaocheng; Huang, Wei; Xu, Zhengyuan

    2018-01-01

    This informative new book on state-of-the-art visible light communication (VLC) provides, for the first time, a systematical and advanced treatment of modulation and signal processing for VLC. Visible Light Communications: Modulation and Signal Processing offers a practical guide to designing VLC, linking academic research with commercial applications. In recent years, VLC has attracted attention from academia and industry since it has many advantages over the traditional radio frequency, including wide unregulated bandwidth, high security, and low cost. It is a promising complementary technique in 5G and beyond wireless communications, especially in indoor applications. However, lighting constraints have not been fully considered in the open literature when considering VLC system design, and its importance has been underestimated. That’s why this book—written by a team of experts with both academic research experience and industrial development experience in the field—is so welcome. To help readers u...

  3. Transintestinal transport of the anti-inflammatory drug 4F and the modulation of transintestinal cholesterol efflux[S

    Science.gov (United States)

    Meriwether, David; Sulaiman, Dawoud; Wagner, Alan; Grijalva, Victor; Kaji, Izumi; Williams, Kevin J.; Yu, Liqing; Fogelman, Spencer; Volpe, Carmen; Bensinger, Steven J.; Anantharamaiah, G. M.; Shechter, Ishaiahu; Fogelman, Alan M.; Reddy, Srinivasa T.

    2016-01-01

    The site and mechanism of action of the apoA-I mimetic peptide 4F are incompletely understood. Transintestinal cholesterol efflux (TICE) is a process involved in the clearance of excess cholesterol from the body. While TICE is responsible for at least 30% of the clearance of neutral sterols from the circulation into the intestinal lumen, few pharmacological agents have been identified that modulate this pathway. We show first that circulating 4F selectively targets the small intestine (SI) and that it is predominantly transported into the intestinal lumen. This transport of 4F into the SI lumen is transintestinal in nature, and it is modulated by TICE. We also show that circulating 4F increases reverse cholesterol transport from macrophages and cholesterol efflux from lipoproteins via the TICE pathway. We identify the cause of this modulation of TICE either as 4F being a cholesterol acceptor with respect to enterocytes, from which 4F enhances cholesterol efflux, or as 4F being an intestinal chaperone with respect to TICE. Our results assign a novel role for 4F as a modulator of the TICE pathway and suggest that the anti-inflammatory functions of 4F may be a partial consequence of the codependent intestinal transport of both 4F and cholesterol. PMID:27199144

  4. Resveratrol modulates the inflammatory response via an estrogen receptor-signal integration network

    Science.gov (United States)

    Nwachukwu, Jerome C; Srinivasan, Sathish; Bruno, Nelson E; Parent, Alexander A; Hughes, Travis S; Pollock, Julie A; Gjyshi, Olsi; Cavett, Valerie; Nowak, Jason; Garcia-Ordonez, Ruben D; Houtman, René; Griffin, Patrick R; Kojetin, Douglas J; Katzenellenbogen, John A; Conkright, Michael D; Nettles, Kendall W

    2014-01-01

    Resveratrol has beneficial effects on aging, inflammation and metabolism, which are thought to result from activation of the lysine deacetylase, sirtuin 1 (SIRT1), the cAMP pathway, or AMP-activated protein kinase. In this study, we report that resveratrol acts as a pathway-selective estrogen receptor-α (ERα) ligand to modulate the inflammatory response but not cell proliferation. A crystal structure of the ERα ligand-binding domain (LBD) as a complex with resveratrol revealed a unique perturbation of the coactivator-binding surface, consistent with an altered coregulator recruitment profile. Gene expression analyses revealed significant overlap of TNFα genes modulated by resveratrol and estradiol. Furthermore, the ability of resveratrol to suppress interleukin-6 transcription was shown to require ERα and several ERα coregulators, suggesting that ERα functions as a primary conduit for resveratrol activity. DOI: http://dx.doi.org/10.7554/eLife.02057.001 PMID:24771768

  5. Safety analysis of SISL process module

    International Nuclear Information System (INIS)

    1983-05-01

    This report provides an assessment of various postulated accidental occurrences within an experimental process module which is part of a Special Isotope Separation Laboratory (SISL) currently under construction at the Lawrence Livermore National Laboratory (LLNL). The process module will contain large amounts of molten uranium and various water-cooled structures within a vacuum vessel. Special emphasis is therefore given to potential accidental interactions of molten uranium with water leading to explosive and/or rapid steam formation, as well as uranium oxidation and the potential for combustion. Considerations are also given to the potential for vessel melt-through. Evaluations include mechanical and thermal interactions and design implications both in terms of design basis as well as once-in-a-lifetime accident scenarios. These scenarios include both single- and multiple-failure modes leading to various contact modes and locations within the process module for possible thermal interactions. The evaluations show that a vacuum vessel design based upon nominal operating conditions would appear sufficient to meet safety requirements in connection with both design basis as well as once-in-a-lifetime accidents. Controlled venting requirements for removal of steam and hydrogen in order to avoid possible long-term pressurization events are recommended. Depending upon the resulting accident conditions, the vacuum system (i.e., the roughing system) could also serve this purpose. Finally, based upon accident evaluations of this study, immediate shut-off of all coolant water following an incident leak is not recommended, as such action may have adverse effects in terms of cool-down requirements for the melt crucibles etc. These requirements have not been assessed as part of this study

  6. Melatonin modulates inflammatory response and suppresses burn-induced apoptotic injury

    Directory of Open Access Journals (Sweden)

    Ganka Bekyarova

    2017-04-01

    Full Text Available Introduction: Melatonin, the principal secretory product of the pineal gland, has antioxidant functions as a potent antioxidant and free radical scavenger. Objectives of the present study were to investigate the effect of melatonin against inflammatory response, burn-induced oxidative damage and apoptotic changes of rat liver. Methods: Melatonin (10 mg /kg, i.p. was applied immediately after 30% of total body surface area (TBSA burns on male Wistar rats. The level of malondialdehyde (MDA as a marker of an oxidative stress was quantified by thiobarbituric method. Hepatic TNFα and IL-10 as inflammatory markers were assayed by ELISA. Using light immunоchistochemistry the expression Ki67 proliferative marker was investigated. Results: Hepatic MDA and TNF-α levels increased significantly following burns without any change in IL-10 level. Intracellular vacuolization, hepatic cell degeneration and apoptosis occurred in rats after burns. The number of apoptotic cells was increased whereas no significant increase in Ki67 proliferative marker. Melatonin decreased the MDA and TNF-α content and increased the IL-10 level. It also limited the degenerative changes and formation of apoptotic cells in rat liver but did not increase expression of the marker of proliferation. In conclusion, our data show that melatonin relieves burn-induced hepatic damage associated with modulation of the proinflammatory/anti-inflammatory balance, mitigation of lipid peroxidation and hepatic apoptosis.

  7. Hepcidin mediates transcriptional changes that modulate acute cytokine-induced inflammatory responses in mice.

    Science.gov (United States)

    De Domenico, Ivana; Zhang, Tian Y; Koening, Curry L; Branch, Ryan W; London, Nyall; Lo, Eric; Daynes, Raymond A; Kushner, James P; Li, Dean; Ward, Diane M; Kaplan, Jerry

    2010-07-01

    Hepcidin is a peptide hormone that regulates iron homeostasis and acts as an antimicrobial peptide. It is expressed and secreted by a variety of cell types in response to iron loading and inflammation. Hepcidin mediates iron homeostasis by binding to the iron exporter ferroportin, inducing its internalization and degradation via activation of the protein kinase Jak2 and the subsequent phosphorylation of ferroportin. Here we have shown that hepcidin-activated Jak2 also phosphorylates the transcription factor Stat3, resulting in a transcriptional response. Hepcidin treatment of ferroportin-expressing mouse macrophages showed changes in mRNA expression levels of a wide variety of genes. The changes in transcript levels for half of these genes were a direct effect of hepcidin, as shown by cycloheximide insensitivity, and dependent on the presence of Stat3. Hepcidin-mediated transcriptional changes modulated LPS-induced transcription in both cultured macrophages and in vivo mouse models, as demonstrated by suppression of IL-6 and TNF-alpha transcript and secreted protein. Hepcidin-mediated transcription in mice also suppressed toxicity and morbidity due to single doses of LPS, poly(I:C), and turpentine, which is used to model chronic inflammatory disease. Most notably, we demonstrated that hepcidin pretreatment protected mice from a lethal dose of LPS and that hepcidin-knockout mice could be rescued from LPS toxicity by injection of hepcidin. The results of our study suggest a new function for hepcidin in modulating acute inflammatory responses.

  8. Leucocytes labelled with In-111-oxine in acute inflammatory processes

    International Nuclear Information System (INIS)

    Herranz, R.; Lomena, F.; Fernandez, R.M.; Del Rio, L.; Piera, C.; Vida, F.; Setoain, J.

    1982-01-01

    We used autologous leucocytes labelled with In-111-Oxine to diagnose inflammatory processes, located or scattered, in 60 patients. In 46 there was suspected located infection focus. Gammagraphy was abnormal in 38 cases (83%), 28 abdominally located (87%), 5 thorax located (71%) and 5 of several locations. In other 14 cases there was clinic suspicion of infection without located septic focus. In 5 of them gammagraphy was interpreted as positive but only in 3 patients it was found abdominal located abscess. The two other cases are considered as false positive ones. In the 9 remaining, with negative gammagraphy there was no clinic confirmation nor other diagnostic methods of abscess existence. In this paper we checked high sensitivity of leucocytes In-111-Oxine to diagnose and locate infectious focuses. In our casuistry there was only a false negative and two false positive ones

  9. Role of Nonneuronal TRPV4 Signaling in Inflammatory Processes.

    Science.gov (United States)

    Rajasekhar, Pradeep; Poole, Daniel P; Veldhuis, Nicholas A

    2017-01-01

    Transient receptor potential (TRP) ion channels are important signaling components in nociceptive and inflammatory pathways. This is attributed to their ability to function as polymodal sensors of environmental stimuli (chemical and mechanical) and as effector molecules in receptor signaling pathways. TRP vanilloid 4 (TRPV4) is a nonselective cation channel that is activated by multiple endogenous stimuli including shear stress, membrane stretch, and arachidonic acid metabolites. TRPV4 contributes to many important physiological processes and dysregulation of its activity is associated with chronic conditions of metabolism, inflammation, peripheral neuropathies, musculoskeletal development, and cardiovascular regulation. Mechanosensory and receptor- or lipid-mediated signaling functions of TRPV4 have historically been attributed to central and peripheral neurons. However, with the development of potent and selective pharmacological tools, transgenic mice and improved molecular and imaging techniques, many new roles for TRPV4 have been revealed in nonneuronal cells. In this chapter, we discuss these recent findings and highlight the need for greater characterization of TRPV4-mediated signaling in nonneuronal cell types that are either directly associated with neurons or indirectly control their excitability through release of sensitizing cellular factors. We address the integral role of these cells in sensory and inflammatory processes as well as their importance when considering undesirable on-target effects that may be caused by systemic delivery of TRPV4-selective pharmaceutical agents for treatment of chronic diseases. In future, this will drive a need for targeted drug delivery strategies to regulate such a diverse and promiscuous protein. © 2017 Elsevier Inc. All rights reserved.

  10. Potent anti-inflammatory effects of systemically-administered curcumin modulates periodontal disease in vivo

    Science.gov (United States)

    Guimarães, Morgana R.; Coimbra, Leila S.; de Aquino, Sabrina Garcia; Spolidorio, Luis C.; Kirkwood, Keith L.; Junior, Carlos Rossa

    2011-01-01

    Background Curcumin is a plant-derived dietary spice with various biological activities, including anti-tumoral and anti-inflammatory. Its therapeutic applications have been studied in a variety of conditions, including rheumatoid arthritis, colon cancer and depression; but no studies evaluated the effects of curcumin on periodontal disease in vivo. Methods Experimental periodontal disease was induced in rats by placing cotton ligatures around both lower first molars. Curcumin was given to the rats intragastrically daily in two doses (30 and 100 mg/Kg) during 15 days. Control animals received ligatures but only the corn oil vehicle by gavage and no treatment negative control animals were included. Bone resorption was assessed by microcomputer tomography and the inflammatory status was evaluated by stereometric analysis. RT-qPCR and ELISA were used to determine the expression of interleukin (IL)-6, tumor necrosis factor (TNF)-alpha and prostaglandin E2 (PGE2) synthase on the gingival tissues. Modulation of p38 mitogen-activated protein kinase (MAPK) and NK-kB activation was assessed by western blot. Results Bone resorption was effectively induced in the experimental period, but it was not affected by either dose of curcumin. Curcumin effectively inhibited cytokine gene expression at mRNA and protein levels and dose-dependently inhibited activation of NF-kB in the gingival tissues. p38 MAPK activation was not inhibited by curcumin. Curcumin-treated animals also presented a marked reduction on the inflammatory cell infiltrate and increased collagen content and fibroblastic cell numbers. Conclusions Curcumin did not prevent alveolar bone resorption, but its potent anti-inflammatory effect suggests it may have a therapeutic potential in periodontal diseases. PMID:21306385

  11. Potent anti-inflammatory effects of systemically administered curcumin modulate periodontal disease in vivo.

    Science.gov (United States)

    Guimarães, M R; Coimbra, L S; de Aquino, S G; Spolidorio, L C; Kirkwood, K L; Rossa, C

    2011-04-01

    Curcumin is a plant-derived dietary spice with various biological activities, including anticarcinogenic and anti-inflammatory effects. Its therapeutic applications have been studied in a variety of conditions, including rheumatoid arthritis, colon cancer and depression, but no studies have evaluated the effects of curcumin on periodontal disease in vivo. Experimental periodontal disease was induced in rats by placing cotton ligatures around both lower first molars. Curcumin was given to the rats by the intragastric route daily at two dosages (30 and 100 mg/kg) for 15 d. Control animals received ligatures but only the corn oil vehicle by gavage, and no treatment-negative control animals were included. Bone resorption was assessed by micro-computed tomography, and the inflammatory status was evaluated by stereometric analysis. Both RT-qPCR and ELISA were used to determine the expression of interleukin-6, tumor necrosis factor-α and prostaglandin E(2) synthase in the gingival tissues. Modulation of p38 MAPK and nuclear factor-κB activation were assessed by western blotting. Bone resorption was effectively induced in the experimental period, but it was not affected by either dose of curcumin. Curcumin effectively inhibited cytokine gene expression at both the mRNA and the protein level and produced a dose-dependent inhibition of the activation of nuclear factor-κB in the gingival tissues. Activation of p38 MAPK was not inhibited by curcumin. Curcumin-treated animals also presented a marked reduction of the inflammatory cell infiltrate and increased collagen content and fibroblastic cell numbers. Curcumin did not prevent alveolar bone resorption, but its potent anti-inflammatory effect suggests that it may have a therapeutic potential in periodontal diseases. © 2011 John Wiley & Sons A/S.

  12. Regulation of survival, proliferation, invasion, angiogenesis, and metastasis of tumor cells through modulation of inflammatory pathways by nutraceuticals

    Science.gov (United States)

    Gupta, Subash C.; Kim, Ji Hye; Prasad, Sahdeo

    2010-01-01

    Almost 25 centuries ago, Hippocrates, the father of medicine, proclaimed “Let food be thy medicine and medicine be thy food.” Exploring the association between diet and health continues today. For example, we now know that as many as 35% of all cancers can be prevented by dietary changes. Carcinogenesis is a multistep process involving the transformation, survival, proliferation, invasion, angiogenesis, and metastasis of the tumor and may take up to 30 years. The pathways associated with this process have been linked to chronic inflammation, a major mediator of tumor progression. The human body consists of about 13 trillion cells, almost all of which are turned over within 100 days, indicating that 70,000 cells undergo apoptosis every minute. Thus, apoptosis/cell death is a normal physiological process, and it is rare that a lack of apoptosis kills the patient. Almost 90% of all deaths due to cancer are linked to metastasis of the tumor. How our diet can prevent cancer is the focus of this review. Specifically, we will discuss how nutraceuticals, such as allicin, apigenin, berberine, butein, caffeic acid, capsaicin, catechin gallate, celastrol, curcumin, epigallocatechin gallate, fisetin, flavopiridol, gambogic acid, genistein, plumbagin, quercetin, resveratrol, sanguinarine, silibinin, sulforaphane, taxol, γ-tocotrienol, and zerumbone, derived from spices, legumes, fruits, nuts, and vegetables, can modulate inflammatory pathways and thus affect the survival, proliferation, invasion, angiogenesis, and metastasis of the tumor. Various cell signaling pathways that are modulated by these agents will also be discussed. PMID:20737283

  13. Renewal characterization of Markov modulated Poisson processes

    Directory of Open Access Journals (Sweden)

    Marcel F. Neuts

    1989-01-01

    Full Text Available A Markov Modulated Poisson Process (MMPP M(t defined on a Markov chain J(t is a pure jump process where jumps of M(t occur according to a Poisson process with intensity λi whenever the Markov chain J(t is in state i. M(t is called strongly renewal (SR if M(t is a renewal process for an arbitrary initial probability vector of J(t with full support on P={i:λi>0}. M(t is called weakly renewal (WR if there exists an initial probability vector of J(t such that the resulting MMPP is a renewal process. The purpose of this paper is to develop general characterization theorems for the class SR and some sufficiency theorems for the class WR in terms of the first passage times of the bivariate Markov chain [J(t,M(t]. Relevance to the lumpability of J(t is also studied.

  14. Serotonergic and dopaminergic modulation of attentional processes.

    Science.gov (United States)

    Boulougouris, Vasileios; Tsaltas, Eleftheria

    2008-01-01

    Disturbances in attentional processes are a common feature of several psychiatric disorders such as schizophrenia, attention deficit/hyperactivity disorder and Huntington's disease. The use of animal models has been useful in defining various candidate neural systems thus enabling us to translate basic laboratory science to the clinic and vice-versa. In this chapter, a comparative and integrated account is provided on the neuroanatomical and neurochemical modulation of basic behavioural operations such as selective attention, vigilance, set-shifting and executive control focusing on the comparative functions of the serotonin and dopamine systems in the cognitive control exerted by the prefrontal cortex. Specifically, we have reviewed evidence emerging from several behavioural paradigms in experimental animals and humans each of which centres on a different aspect of the attentional function. These paradigms offering both human and animal variants include the five-choice serial reaction time task (5CSRTT), attentional set-shifting and stop-signal reaction time task. In each case, the types of operation that are measured by the given paradigm and their neural correlates are defined. Then, the role of the ascending dopaminergic and serotonergic systems in the neurochemical modulation of its behavioural output are examined, and reference is made to clinical implications for neurological and neuropsychiatric disorders which exhibit deficits in these cognitive tests.

  15. Value conditioning modulates visual working memory processes.

    Science.gov (United States)

    Thomas, Paul M J; FitzGibbon, Lily; Raymond, Jane E

    2016-01-01

    Learning allows the value of motivationally salient events to become associated with stimuli that predict those events. Here, we asked whether value associations could facilitate visual working memory (WM), and whether such effects would be valence dependent. Our experiment was specifically designed to isolate value-based effects on WM from value-based effects on selective attention that might be expected to bias encoding. In a simple associative learning task, participants learned to associate the color of tinted faces with gaining or losing money or neither. Tinted faces then served as memoranda in a face identity WM task for which previously learned color associations were irrelevant and no monetary outcomes were forthcoming. Memory was best for faces with gain-associated tints, poorest for faces with loss-associated tints, and average for faces with no-outcome-associated tints. Value associated with 1 item in the WM array did not modulate memory for other items in the array. Eye movements when studying faces did not depend on the valence of previously learned color associations, arguing against value-based biases being due to differential encoding. This valence-sensitive value-conditioning effect on WM appears to result from modulation of WM maintenance processes. (c) 2015 APA, all rights reserved).

  16. Diminazene aceturate (Berenil modulates the host cellular and inflammatory responses to Trypanosoma congolense infection.

    Directory of Open Access Journals (Sweden)

    Shiby Kuriakose

    Full Text Available BACKGROUND: Trypanosoma congolense are extracellular and intravascular blood parasites that cause debilitating acute or chronic disease in cattle and other domestic animals. Diminazene aceturate (Berenil has been widely used as a chemotherapeutic agent for trypanosomiasis in livestock since 1955. As in livestock, treatment of infected highly susceptible BALB/c mice with Berenil leads to rapid control of parasitemia and survival from an otherwise lethal infection. The molecular and biochemical mechanisms of action of Berenil are still not very well defined and its effect on the host immune system has remained relatively unstudied. Here, we investigated whether Berenil has, in addition to its trypanolytic effect, a modulatory effect on the host immune response to Trypanosoma congolense. METHODOLOGY/PRINCIPAL FINDINGS: BALB/c and C57BL/6 mice were infected intraperitoneally with T. congolense, treated with Berenil and the expression of CD25 and FoxP3 on splenic cells was assessed directly ex vivo. In addition, serum levels and spontaneous and LPS-induced production of pro-inflammatory cytokines by splenic and hepatic CD11b⁺ cells were determined by ELISA. Berenil treatment significantly reduced the percentages of CD25⁺ cells, a concomitant reduction in the percentage of regulatory (CD4⁺Foxp3⁺ T cells and a striking reduction in serum levels of disease exacerbating pro-inflammatory cytokines including IL-6, IL-12, TNF and IFN-γ. Furthermore, Berenil treatment significantly suppressed spontaneous and LPS-induced production of inflammatory cytokines by splenic and liver macrophages and significantly ameliorated LPS-induced septic shock and the associated cytokine storm. CONCLUSIONS/SIGNIFICANCE: Collectively, these results provide evidence that in addition to its direct trypanolytic effect, Berenil also modulates the host immune response to the parasite in a manner that dampen excessive immune activation and production of pathology

  17. Cervicovaginal bacteria are a major modulator of host inflammatory responses in the female genital tract.

    Science.gov (United States)

    Anahtar, Melis N; Byrne, Elizabeth H; Doherty, Kathleen E; Bowman, Brittany A; Yamamoto, Hidemi S; Soumillon, Magali; Padavattan, Nikita; Ismail, Nasreen; Moodley, Amber; Sabatini, Mary E; Ghebremichael, Musie S; Nusbaum, Chad; Huttenhower, Curtis; Virgin, Herbert W; Ndung'u, Thumbi; Dong, Krista L; Walker, Bruce D; Fichorova, Raina N; Kwon, Douglas S

    2015-05-19

    Colonization by Lactobacillus in the female genital tract is thought to be critical for maintaining genital health. However, little is known about how genital microbiota influence host immune function and modulate disease susceptibility. We studied a cohort of asymptomatic young South African women and found that the majority of participants had genital communities with low Lactobacillus abundance and high ecological diversity. High-diversity communities strongly correlated with genital pro-inflammatory cytokine concentrations in both cross-sectional and longitudinal analyses. Transcriptional profiling suggested that genital antigen-presenting cells sense gram-negative bacterial products in situ via Toll-like receptor 4 signaling, contributing to genital inflammation through activation of the NF-κB signaling pathway and recruitment of lymphocytes by chemokine production. Our study proposes a mechanism by which cervicovaginal microbiota impact genital inflammation and thereby might affect a woman's reproductive health, including her risk of acquiring HIV. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Modulation of the Senescence-Associated Inflammatory Phenotype in Human Fibroblasts by Olive Phenols

    Directory of Open Access Journals (Sweden)

    Beatrice Menicacci

    2017-10-01

    Full Text Available Senescent cells display an increase in the secretion of growth factors, inflammatory cytokines and proteolytic enzymes, termed the “senescence-associated-secretory-phenotype” (SASP, playing a major role in many age-related diseases. The phenolic compounds present in extra-virgin olive oil are inhibitors of oxidative damage and have been reported to play a protective role in inflammation-related diseases. Particularly, hydroxytyrosol and oleuropein are the most abundant and more extensively studied. Pre-senescent human lung (MRC5 and neonatal human dermal (NHDF fibroblasts were used as cellular model to evaluate the effect of chronic (4–6 weeks treatment with 1 μM hydroxytyrosol (HT or 10 μM oleuropein aglycone (OLE on senescence/inflammation markers. Both phenols were effective in reducing β-galactosidase-positive cell number and p16 protein expression. In addition, senescence/inflammation markers such as IL-6 and metalloprotease secretion, and Ciclooxigenase type 2 (COX-2 and α-smooth-actin levels were reduced by phenol treatments. In NHDF, COX-2 expression, Nuclear Factor κ-light-chain-enhancer of activated B cells (NFκB protein level and nuclear localization were augmented with culture senescence and decreased by OLE and HT treatment. Furthermore, the inflammatory effect of Tumor Necrosis Factor α (TNFα exposure was almost completely abolished in OLE- and HT-pre-treated NHDF. Thus, the modulation of the senescence-associated inflammatory phenotype might be an important mechanism underlying the beneficial effects of olive oil phenols.

  19. Alginate micro-encapsulation of mesenchymal stromal cells enhances modulation of the neuro-inflammatory response.

    Science.gov (United States)

    Stucky, Elizabeth C; Schloss, Rene S; Yarmush, Martin L; Shreiber, David I

    2015-10-01

    Modulation of inflammation after brain trauma is a key therapeutic goal aimed at limiting the consequences of the subsequent injury cascade. Mesenchymal stromal cells (MSCs) have been demonstrated to dynamically regulate the inflammatory environment in several tissue systems, including the central nervous system. There has been limited success, however, with the use of direct implantation of cells in the brain caused by low viability and engraftment at the injury site. To circumvent this, we encapsulated MSCs in alginate microspheres and evaluated the ability of these encapsulated MSCs to attenuate inflammation in rat organotypic hippocampal slice cultures (OHSC). OHSC were administered lipopolysaccharide to induce inflammation and immediately co-cultured with encapsulated or monolayer human MSCs. After 24 h, culture media was assayed for the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α) produced by OHSC, as well as MSC-produced trophic mediators. Encapsulated MSCs reduced TNF-α more effectively than did monolayer MSCs. Additionally, there was a strong correlation between increased prostaglandin E2 (PGE2) and reduction of TNF-α. In contrast to monolayer MSCs, inflammatory signals were not required to stimulate PGE2 production by encapsulated MSCs. Further encapsulation-stimulated changes were revealed in a multiplex panel analyzing 27 MSC-produced cytokines and growth factors, from which additional mediators with strong correlations to TNF-α levels were identified. These results suggest that alginate encapsulation of MSCs may not only provide an improved delivery vehicle for transplantation but may also enhance MSC therapeutic benefit for treating neuro-inflammation. Copyright © 2015. Published by Elsevier Inc.

  20. Cucurbitacin IIb exhibits anti-inflammatory activity through modulating multiple cellular behaviors of mouse lymphocytes.

    Directory of Open Access Journals (Sweden)

    Yao Wang

    Full Text Available Cucurbitacin IIb (CuIIb is one of the major active compounds in Hemsleyadine tablets which have been used for clinical treatment of bacillary dysentery, enteritis and acute tonsilitis. However, its action mechanism has not been completely understood. This study aimed to explore the anti-inflammatory activity of CuIIb and its underlying mechanism in mitogen-activated lymphocytes isolated from mouse mesenteric lymph nodes. The results showed that CuIIb inhibited the proliferation of concanavalin A (Con A-activated lymphocytes in a time- and dose-dependent manner. CuIIb treatment arrested their cell cycle in S and G2/M phases probably due to the disruption of the actin cytoskeleton and the modulation of p27(Kip1 and cyclin levels. Moreover, the surface expression of activation markers CD69 and CD25 on Con A-activated CD3(+ T lymphocytes was suppressed by CuIIb treatment. Both Con A- and phorbol ester plus ionomycin-induced expression of TNF-α, IFN-γ and IL-6 proteins was attenuated upon exposure to CuIIb. Mechanistically, CuIIb treatment suppressed the phosphorylation of JNK and Erk1/2 but not p38 in Con A-activated lymphocytes. Although CuIIb unexpectedly enhanced the phosphorylation of IκB and NF-κB (p65, it blocked the nuclear translocation of NF-κB (p65. In support of this, CuIIb significantly decreased the mRNA levels of IκBα and TNF-α, two target genes of NF-κB, in Con A-activated lymphocytes. In addition, CuIIb downregulated Con A-induced STAT3 phosphorylation and increased cell apoptosis. Collectively, these results suggest that CuIIb exhibits its anti-inflammatory activity through modulating multiple cellular behaviors and signaling pathways, leading to the suppression of the adaptive immune response.

  1. Aerobic Exercise Modulates the Free Fatty Acids and Inflammatory Response During Obesity and Cancer Cachexia.

    Science.gov (United States)

    Teixeira, Alexandre Abilio de Souza; Lira, Fábio Santos; Pimentel, Gustavo D; Oliveira de Souza, Camila; Batatinha, Helena; Biondo, Luana A; Yamashita, Alex S; Junior, Edson A Lima; Neto, José Cesar Rosa

    2016-01-01

    White adipose tissue (WAT) is no longer considered a tissue whose main function is the storage of TAG. Since the discovery of leptin in 1994, several studies have elucidated the important role of WAT as an endocrine organ, the source of the adipokines. The low-grade inflammation observed in obese and cancer cachexia patients is explained, at least partially, by the exacerbated release of proinflammatory adipokines. Despite of the recent progress in the characterization of the various adipokines and lipokines produced by WAT, little is known about the mechanisms regulating the secretion of these molecules in different physiological and pathological circumstances. Chronic exercise is a nonpharmacological therapy employed in several chronic diseases and shows an anti-inflammatory effect through the regulation of the cytokine network. In this review, we address the potential mechanisms by which the aerobic physical exercise modulate the production and release of inflammatory adipokines, as well as the inflammation-lipolysis axis in WAT, with special focus in the therapeutic role of exercise in obesity-associated insulin resistance and cancer cachexia.

  2. Prediction of the anti-inflammatory mechanisms of curcumin by module-based protein interaction network analysis

    Directory of Open Access Journals (Sweden)

    Yanxiong Gan

    2015-11-01

    Full Text Available Curcumin, the medically active component from Curcuma longa (Turmeric, is widely used to treat inflammatory diseases. Protein interaction network (PIN analysis was used to predict its mechanisms of molecular action. Targets of curcumin were obtained based on ChEMBL and STITCH databases. Protein–protein interactions (PPIs were extracted from the String database. The PIN of curcumin was constructed by Cytoscape and the function modules identified by gene ontology (GO enrichment analysis based on molecular complex detection (MCODE. A PIN of curcumin with 482 nodes and 1688 interactions was constructed, which has scale-free, small world and modular properties. Based on analysis of these function modules, the mechanism of curcumin is proposed. Two modules were found to be intimately associated with inflammation. With function modules analysis, the anti-inflammatory effects of curcumin were related to SMAD, ERG and mediation by the TLR family. TLR9 may be a potential target of curcumin to treat inflammation.

  3. A New Population of Parvocellular Oxytocin Neurons Controlling Magnocellular Neuron Activity and Inflammatory Pain Processing.

    Science.gov (United States)

    Eliava, Marina; Melchior, Meggane; Knobloch-Bollmann, H Sophie; Wahis, Jérôme; da Silva Gouveia, Miriam; Tang, Yan; Ciobanu, Alexandru Cristian; Triana Del Rio, Rodrigo; Roth, Lena C; Althammer, Ferdinand; Chavant, Virginie; Goumon, Yannick; Gruber, Tim; Petit-Demoulière, Nathalie; Busnelli, Marta; Chini, Bice; Tan, Linette L; Mitre, Mariela; Froemke, Robert C; Chao, Moses V; Giese, Günter; Sprengel, Rolf; Kuner, Rohini; Poisbeau, Pierrick; Seeburg, Peter H; Stoop, Ron; Charlet, Alexandre; Grinevich, Valery

    2016-03-16

    Oxytocin (OT) is a neuropeptide elaborated by the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei. Magnocellular OT neurons of these nuclei innervate numerous forebrain regions and release OT into the blood from the posterior pituitary. The PVN also harbors parvocellular OT cells that project to the brainstem and spinal cord, but their function has not been directly assessed. Here, we identified a subset of approximately 30 parvocellular OT neurons, with collateral projections onto magnocellular OT neurons and neurons of deep layers of the spinal cord. Evoked OT release from these OT neurons suppresses nociception and promotes analgesia in an animal model of inflammatory pain. Our findings identify a new population of OT neurons that modulates nociception in a two tier process: (1) directly by release of OT from axons onto sensory spinal cord neurons and inhibiting their activity and (2) indirectly by stimulating OT release from SON neurons into the periphery. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Development of anti-inflammatory drugs - the research and development process.

    Science.gov (United States)

    Knowles, Richard Graham

    2014-01-01

    The research and development process for novel drugs to treat inflammatory diseases is described, and several current issues and debates relevant to this are raised: the decline in productivity, attrition, challenges and trends in developing anti-inflammatory drugs, the poor clinical predictivity of experimental models of inflammatory diseases, heterogeneity within inflammatory diseases, 'improving on the Beatles' in treating inflammation, and the relationships between big pharma and biotechs. The pharmaceutical research and development community is responding to these challenges in multiple ways which it is hoped will lead to the discovery and development of a new generation of anti-inflammatory medicines. © 2013 Nordic Pharmacological Society. Published by John Wiley & Sons Ltd.

  5. Inflammatory modulation of exercise salience: using hormesis to return to a healthy lifestyle

    Directory of Open Access Journals (Sweden)

    Bell Jimmy D

    2010-12-01

    Full Text Available Abstract Most of the human population in the western world has access to unlimited calories and leads an increasingly sedentary lifestyle. The propensity to undertake voluntary exercise or indulge in spontaneous physical exercise, which might be termed "exercise salience", is drawing increased scientific attention. Despite its genetic aspects, this complex behaviour is clearly modulated by the environment and influenced by physiological states. Inflammation is often overlooked as one of these conditions even though it is known to induce a state of reduced mobility. Chronic subclinical inflammation is associated with the metabolic syndrome; a largely lifestyle-induced disease which can lead to decreased exercise salience. The result is a vicious cycle that increases oxidative stress and reduces metabolic flexibility and perpetuates the disease state. In contrast, hormetic stimuli can induce an anti-inflammatory phenotype, thereby enhancing exercise salience, leading to greater biological fitness and improved functional longevity. One general consequence of hormesis is upregulation of mitochondrial function and resistance to oxidative stress. Examples of hormetic factors include calorie restriction, extreme environmental temperatures, physical activity and polyphenols. The hormetic modulation of inflammation, and thus, exercise salience, may help to explain the highly heterogeneous expression of voluntary exercise behaviour and therefore body composition phenotypes of humans living in similar obesogenic environments.

  6. Pacific ciguatoxin 1B-induced modulation of inflammatory mediators in a murine macrophage cell line.

    Science.gov (United States)

    Matsui, Mariko; Kumar-Roine, Shilpa; Darius, H Taiana; Chinain, Mireille; Laurent, Dominique; Pauillac, Serge

    2010-10-01

    Ciguatoxins, potent marine neurotoxins responsible for ciguatera, exert their numerous damaging effects through primary binding to the voltage-sensitive sodium channels of excitable cells. Using RAW 264.7 murine macrophages, we report the first experimental study presenting evidence that P-CTX-1B (the most potent congener from the Pacific) could modulate mRNA expression of pro- and anti-inflammatory cytokines as well as of inducible nitric oxide synthase (iNOS). P-CTX-1B, unlike other less potent marine polyether toxins, P-CTX-3C and PbTx-3, induced the overexpression of interleukin (IL)-1beta, IL-6, IL-10, tumor necrosis factor-alpha and iNOS with different magnitude and kinetic profiles, as compared to bacterial lipopolysaccharide (LPS). Unlike LPS, P-CTX-1B did not modulate IL-11 expression. In this report, we provide new evidence of the P-CTX-1B iNOS- and cytokines-inducing ability and shed new light on host response to potent neurotoxins. Copyright 2009 Elsevier Ltd. All rights reserved.

  7. Phycocyanobilin promotes PC12 cell survival and modulates immune and inflammatory genes and oxidative stress markers in acute cerebral hypoperfusion in rats

    Energy Technology Data Exchange (ETDEWEB)

    Marín-Prida, Javier [Centre for Research and Biological Evaluations (CEIEB), Institute of Pharmacy and Food, University of Havana, Ave. 23 e/ 214 y 222, La Lisa, PO Box: 430, Havana (Cuba); Pavón-Fuentes, Nancy [International Centre for Neurological Restoration (CIREN), Ave. 25 e/ 158 y 160, Playa, PO Box: 11300, Havana (Cuba); Llópiz-Arzuaga, Alexey; Fernández-Massó, Julio R. [Centre for Genetic Engineering and Biotechnology (CIGB), Ave. 31 e/158 y 190, Playa, PO Box: 6162, Havana (Cuba); Delgado-Roche, Liván [Centre for Research and Biological Evaluations (CEIEB), Institute of Pharmacy and Food, University of Havana, Ave. 23 e/ 214 y 222, La Lisa, PO Box: 430, Havana (Cuba); Mendoza-Marí, Yssel; Santana, Seydi Pedroso; Cruz-Ramírez, Alieski; Valenzuela-Silva, Carmen; Nazábal-Gálvez, Marcelo; Cintado-Benítez, Alberto [Centre for Genetic Engineering and Biotechnology (CIGB), Ave. 31 e/158 y 190, Playa, PO Box: 6162, Havana (Cuba); Pardo-Andreu, Gilberto L. [Centre for Research and Biological Evaluations (CEIEB), Institute of Pharmacy and Food, University of Havana, Ave. 23 e/ 214 y 222, La Lisa, PO Box: 430, Havana (Cuba); Polentarutti, Nadia [Istituto Clinico Humanitas (IRCCS), Rozzano (Italy); Riva, Federica [Department of Veterinary Science and Public Health (DIVET), University of Milano (Italy); Pentón-Arias, Eduardo [Centre for Genetic Engineering and Biotechnology (CIGB), Ave. 31 e/158 y 190, Playa, PO Box: 6162, Havana (Cuba); Pentón-Rol, Giselle [Centre for Genetic Engineering and Biotechnology (CIGB), Ave. 31 e/158 y 190, Playa, PO Box: 6162, Havana (Cuba)

    2013-10-01

    Since the inflammatory response and oxidative stress are involved in the stroke cascade, we evaluated here the effects of Phycocyanobilin (PCB, the C-Phycocyanin linked tetrapyrrole) on PC12 cell survival, the gene expression and the oxidative status of hypoperfused rat brain. After the permanent bilateral common carotid arteries occlusion (BCCAo), the animals were treated with saline or PCB, taking samples 24 h post-surgery. Global gene expression was analyzed with GeneChip Rat Gene ST 1.1 from Affymetrix; the expression of particular genes was assessed by the Fast SYBR Green RT-PCR Master Mix and Bioplex methods; and redox markers (MDA, PP, CAT, SOD) were evaluated spectrophotometrically. The PCB treatment prevented the H{sub 2}O{sub 2} and glutamate induced PC12 cell injury assessed by the MTT assay, and modulated 190 genes (93 up- and 97 down-regulated) associated to several immunological and inflammatory processes in BCCAo rats. Furthermore, PCB positively modulated 19 genes mostly related to a detrimental pro-inflammatory environment and counteracted the oxidative imbalance in the treated BCCAo animals. Our results support the view of an effective influence of PCB on major inflammatory mediators in acute cerebral hypoperfusion. These results suggest that PCB has a potential to be a treatment for ischemic stroke for which further studies are needed. - Highlights: • Phycocyanobilin (PCB) prevents H{sub 2}O{sub 2} and glutamate induced PC12 cell viability loss. • Anterior cortex and striatum are highly vulnerable to cerebral hypoperfusion (CH). • PCB modulates 190 genes associated to inflammation in acute CH. • PCB regulates 19 genes mostly related to a detrimental pro-inflammatory environment. • PCB restores redox and immune balances showing promise as potential stroke therapy.

  8. Phycocyanobilin promotes PC12 cell survival and modulates immune and inflammatory genes and oxidative stress markers in acute cerebral hypoperfusion in rats

    International Nuclear Information System (INIS)

    Marín-Prida, Javier; Pavón-Fuentes, Nancy; Llópiz-Arzuaga, Alexey; Fernández-Massó, Julio R.; Delgado-Roche, Liván; Mendoza-Marí, Yssel; Santana, Seydi Pedroso; Cruz-Ramírez, Alieski; Valenzuela-Silva, Carmen; Nazábal-Gálvez, Marcelo; Cintado-Benítez, Alberto; Pardo-Andreu, Gilberto L.; Polentarutti, Nadia; Riva, Federica; Pentón-Arias, Eduardo; Pentón-Rol, Giselle

    2013-01-01

    Since the inflammatory response and oxidative stress are involved in the stroke cascade, we evaluated here the effects of Phycocyanobilin (PCB, the C-Phycocyanin linked tetrapyrrole) on PC12 cell survival, the gene expression and the oxidative status of hypoperfused rat brain. After the permanent bilateral common carotid arteries occlusion (BCCAo), the animals were treated with saline or PCB, taking samples 24 h post-surgery. Global gene expression was analyzed with GeneChip Rat Gene ST 1.1 from Affymetrix; the expression of particular genes was assessed by the Fast SYBR Green RT-PCR Master Mix and Bioplex methods; and redox markers (MDA, PP, CAT, SOD) were evaluated spectrophotometrically. The PCB treatment prevented the H 2 O 2 and glutamate induced PC12 cell injury assessed by the MTT assay, and modulated 190 genes (93 up- and 97 down-regulated) associated to several immunological and inflammatory processes in BCCAo rats. Furthermore, PCB positively modulated 19 genes mostly related to a detrimental pro-inflammatory environment and counteracted the oxidative imbalance in the treated BCCAo animals. Our results support the view of an effective influence of PCB on major inflammatory mediators in acute cerebral hypoperfusion. These results suggest that PCB has a potential to be a treatment for ischemic stroke for which further studies are needed. - Highlights: • Phycocyanobilin (PCB) prevents H 2 O 2 and glutamate induced PC12 cell viability loss. • Anterior cortex and striatum are highly vulnerable to cerebral hypoperfusion (CH). • PCB modulates 190 genes associated to inflammation in acute CH. • PCB regulates 19 genes mostly related to a detrimental pro-inflammatory environment. • PCB restores redox and immune balances showing promise as potential stroke therapy

  9. Cerium dioxide nanoparticles do not modulate the lipopolysaccharide-induced inflammatory response in human monocytes

    Directory of Open Access Journals (Sweden)

    Hussain S

    2012-03-01

    Full Text Available Salik Hussain1,*, Faris Al-Nsour1,*, Annette B Rice1, Jamie Marshburn1, Zhaoxia Ji2, Jeffery I Zink2, Brenda Yingling1, Nigel J Walker3, Stavros Garantziotis11Clinical Research Unit, National Institute of Environmental Health Sciences/National Institute of Health, Research Triangle Park, NC, 2UC Center for Environmental Implications of Nanotechnology University of California, Los Angeles, CA, 3Division of National Toxicology Program, National Institute of Environmental Health Sciences/National Institute of Health, Research Triangle Park, NC, USA*Both are principal authorsBackground: Cerium dioxide (CeO2 nanoparticles have potential therapeutic applications and are widely used for industrial purposes. However, the effects of these nanoparticles on primary human cells are largely unknown. The ability of nanoparticles to exacerbate pre-existing inflammatory disorders is not well documented for engineered nanoparticles, and is certainly lacking for CeO2 nanoparticles. We investigated the inflammation-modulating effects of CeO2 nanoparticles at noncytotoxic concentrations in human peripheral blood monocytes.Methods: CD14+ cells were isolated from peripheral blood samples of human volunteers. Cells were exposed to either 0.5 or 1 µg/mL of CeO2 nanoparticles over a period of 24 or 48 hours with or without lipopolysaccharide (10 ng/mL prestimulation. Modulation of the inflammatory response was studied by measuring secreted tumor necrosis factor-alpha, interleukin-1beta, macrophage chemotactic protein-1, interferon-gamma, and interferon gamma-induced protein 10.Results: CeO2 nanoparticle suspensions were thoroughly characterized using dynamic light scattering analysis (194 nm hydrodynamic diameter, zeta potential analysis (-14 mV, and transmission electron microscopy (irregular-shaped particles. Transmission electron microscopy of CD14+ cells exposed to CeO2 nanoparticles revealed that these nanoparticles were efficiently internalized by monocytes and

  10. Modulation of magmatic processes by carbon dioxide

    Science.gov (United States)

    Caricchi, L.; Sheldrake, T. E.; Blundy, J. D.

    2017-12-01

    Volatile solubility in magmas increases with pressure, although the solubility of CO2 is much lower than that of H2O. Consequently, magmas rising from depth release CO2-rich fluids, which inevitably interact with H2O-poor magmas in the upper crust (CO2-flushing). CO2-flushing triggers the exsolution of H2O-rich fluids, leading to an increase of volume and magma crystallisation. While the analyses of eruptive products demonstrates that this process operates in virtually all magmatic system, its impact on magmatic and volcanic processes has not been quantified. Here we show that depending on the initial magma crystallinity, and the depth of magma storage, CO2-flushing can lead to volcanic eruptions or promote conditions that favour the impulsive release of mineralising fluids. Our calculations show that the interaction between a few hundred ppm of carbonic fluids, and crystal-poor magmas stored at shallow depths, produces rapid pressurisation that can potentially lead to an eruption. Further addition of CO2 increases magma compressibility and crystallinity, reducing the potential for volcanic activity, promoting the formation of ore deposits. Increasing the depth of fluid-magma interaction dampens the impact of CO2-flushing on the pressurisation of a magma reservoir. CO2-flushing may result in surface inflation and increases in surface CO2 fluxes, which are commonly considered signs of an impending eruption, but may not necessarily result in eruption depending on the initial crystallnity and depth of the magmatic reservoir. We propose that CO2-flushing is a powerful agent modulating the pressurisation of magma reservoirs and the release of mineralising fluids from upper crustal magma reservoirs.

  11. Systemic Inflammatory Load in Young and Old Ringdoves Is Modulated by Consumption of a Jerte Valley Cherry-Based Product

    Science.gov (United States)

    Delgado, Jonathan; Terrón, María del Pilar; Garrido, María; Barriga, Carmen; Paredes, Sergio Damián; Espino, Javier

    2012-01-01

    Abstract A chronic subclinical inflammatory status that coexists with immune dysfunction is commonly found in the elderly population. Consumption of foods rich in antioxidants (e.g., cherries) is an attractive strategy to reduce risk from chronic diseases. Based on previous studies showing the antioxidant effect of a Jerte Valley cherry derivative product in humans, the objective of this work was to evaluate the effect of the intake of a Jerte Valley cherry-based beverage on inflammatory load in both young and old ringdoves (Streptopelia risoria). To this purpose, circulating levels of pro-inflammatory and anti-inflammatory cytokines as well as serum levels of different acute-phase proteins were measured before and after a 10-day treatment with the Jerte Valley cherry-based beverage. Thus, the 10-day treatment with the cherry-based beverage modulated the balance of pro- and anti-inflammatory cytokines in both young and old ringdoves by down-regulating the levels of pro-inflammatory cytokines (interleukin [IL]-1β, tumor necrosis factor-α, and interferon-γ) and up-regulating the levels of anti-inflammatory cytokines (IL-4, IL-2, and IL-10). Moreover, the 10-day treatment with the Jerte Valley cherry-based product reduced the levels of several proteins involved in acute-phase responses, such as C-reactive protein, haptoglobin, α2-macroglobulin, and serum amyloid P component. On the other hand, old birds showed imbalanced levels of inflammatory markers toward a pro-inflammatory status, thereby underlining the fact that aging is usually accompanied by systemic inflammation and inflammation-related chronic diseases. To sum up, the data suggest a potential health benefit by consuming the cherry-based beverage, especially in aged populations, through their anti-inflammatory properties. PMID:22846077

  12. The chemokine Bv8/prokineticin 2 is up-regulated in inflammatory granulocytes and modulates inflammatory pain

    OpenAIRE

    Giannini, Elisa; Lattanzi, Roberta; Nicotra, Annalisa; Campese, Antonio F.; Grazioli, Paola; Screpanti, Isabella; Balboni, Gianfranco; Salvadori, Severo; Sacerdote, Paola; Negri, Lucia

    2009-01-01

    Neutrophil migration into injured tissues is invariably accompanied by pain. Bv8/prokineticin 2 (PK2), a chemokine characterized by a unique structural motif comprising five disulfide bonds, is highly expressed in inflamed tissues associated to infiltrating cells. Here, we demonstrate the fundamental role of granulocyte-derived PK2 (GrPK2) in initiating inflammatory pain and driving peripheral sensitization. In animal models of complete Freund's adjuvant-induced paw inflammation the developme...

  13. Sequential inflammatory processes define human progression from M. tuberculosis infection to tuberculosis disease.

    Science.gov (United States)

    Scriba, Thomas J; Penn-Nicholson, Adam; Shankar, Smitha; Hraha, Tom; Thompson, Ethan G; Sterling, David; Nemes, Elisa; Darboe, Fatoumatta; Suliman, Sara; Amon, Lynn M; Mahomed, Hassan; Erasmus, Mzwandile; Whatney, Wendy; Johnson, John L; Boom, W Henry; Hatherill, Mark; Valvo, Joe; De Groote, Mary Ann; Ochsner, Urs A; Aderem, Alan; Hanekom, Willem A; Zak, Daniel E

    2017-11-01

    Our understanding of mechanisms underlying progression from Mycobacterium tuberculosis infection to pulmonary tuberculosis disease in humans remains limited. To define such mechanisms, we followed M. tuberculosis-infected adolescents longitudinally. Blood samples from forty-four adolescents who ultimately developed tuberculosis disease (“progressors”) were compared with those from 106 matched controls, who remained healthy during two years of follow up. We performed longitudinal whole blood transcriptomic analyses by RNA sequencing and plasma proteome analyses using multiplexed slow off-rate modified DNA aptamers. Tuberculosis progression was associated with sequential modulation of immunological processes. Type I/II interferon signalling and complement cascade were elevated 18 months before tuberculosis disease diagnosis, while changes in myeloid inflammation, lymphoid, monocyte and neutrophil gene modules occurred more proximally to tuberculosis disease. Analysis of gene expression in purified T cells also revealed early suppression of Th17 responses in progressors, relative to M. tuberculosis-infected controls. This was confirmed in an independent adult cohort who received BCG re-vaccination; transcript expression of interferon response genes in blood prior to BCG administration was associated with suppression of IL-17 expression by BCG-specific CD4 T cells 3 weeks post-vaccination. Our findings provide a timeline to the different immunological stages of disease progression which comprise sequential inflammatory dynamics and immune alterations that precede disease manifestations and diagnosis of tuberculosis disease. These findings have important implications for developing diagnostics, vaccination and host-directed therapies for tuberculosis. Clincialtrials.gov, NCT01119521.

  14. Digital intermediate frequency QAM modulator using parallel processing

    Science.gov (United States)

    Pao, Hsueh-Yuan [Livermore, CA; Tran, Binh-Nien [San Ramon, CA

    2008-05-27

    The digital Intermediate Frequency (IF) modulator applies to various modulation types and offers a simple and low cost method to implement a high-speed digital IF modulator using field programmable gate arrays (FPGAs). The architecture eliminates multipliers and sequential processing by storing the pre-computed modulated cosine and sine carriers in ROM look-up-tables (LUTs). The high-speed input data stream is parallel processed using the corresponding LUTs, which reduces the main processing speed, allowing the use of low cost FPGAs.

  15. Anti-inflammatory activity of Momordica charantia in edema paw and in cortisol seric modulation

    International Nuclear Information System (INIS)

    Magnata, Simey S.L.P.; Correia, Marilia B.L.; Brandao, Jose Odinilson C.; Souza, Grace M.L.; Catanho, Maria Teresa J.A.; Terra, Daniele A.; Amorim, Lucia F.

    2005-01-01

    The first sources that the humanity disposed to disease's treatment was plants and herbs. The Momordica charantia, Melao de Sao Caetano (bitter melon), occur in South and Central America and in East, it has been used as an anti-diabetic agent, anti-tumor, anti-helmintic and anti-ulcerogenic. The objective of this study is to research the Momordica charantia's activity on inflammatory process and the change on cortisol hormone seric concentration. To evaluate the anti-inflammatory activity were used mice (n=5) in test groups (30,60,100,250 mg/kg of extract) and control (negative and positive) groups (AAS 250 mg/kg and NaCl 0,9%); the inflammatory agent (carrageenan 1% p/v, 0,1 mL) was injected into right hind paw planter surface, 30 min after, the groups received each dose IP of extract, AAS and solution saline respectively; 4 hour after the mice was sacrificed and the difference between right and left hind foot mass was measured. There was a significant reduction (p<0,05)in carrageenan-induced edema paw at test from control group, the best result was obtained at 60 mg/kg dose which inhibits edema formation by 50%. To determinate the cortisol concentrations male Wistar rats, were divided in three groups: control, test A (2 hours of treatment) and test B (4 hours of treatment). The control group received 0,25 mL of saline solution (NaCl) 0,9% and the test groups 0,25 mL of Momordica charantia's aqueous extract, obtained by decoction of green leaves, (31,16 mg/kg animal); all by via IP. After the treatment, the animals were sacrificed and the serum obtained for realization of dosages. The cortisol was determined through radioimmunoassay. The results showed a reduction on a average by 83,9% from control group. The Momordica charantia's extract showed a high anti-inflammatory effect and was capable of reducing the seric cortisol on normal rats. (author)

  16. Optical metrology for advanced process control: full module metrology solutions

    Science.gov (United States)

    Bozdog, Cornel; Turovets, Igor

    2016-03-01

    Optical metrology is the workhorse metrology in manufacturing and key enabler to patterning process control. Recent advances in device architecture are gradually shifting the need for process control from the lithography module to other patterning processes (etch, trim, clean, LER/LWR treatments, etc..). Complex multi-patterning integration solutions, where the final pattern is the result of multiple process steps require a step-by-step holistic process control and a uniformly accurate holistic metrology solution for pattern transfer for the entire module. For effective process control, more process "knobs" are needed, and a tighter integration of metrology with process architecture.

  17. Rosiglitazone inhibits chlorpyrifos-induced apoptosis via modulation of the oxidative stress and inflammatory response in SH-SY5Y cells

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jeong Eun [Department of Pharmacology, College of Medicine, Hanyang University, Seoul (Korea, Republic of); Hanyang Biomedical Research Institute, Seoul (Korea, Republic of); Park, Jae Hyeon; Jang, Sea Jeong [Hanyang Biomedical Research Institute, Seoul (Korea, Republic of); Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul (Korea, Republic of); Koh, Hyun Chul, E-mail: hckoh@hanyang.ac.kr [Department of Pharmacology, College of Medicine, Hanyang University, Seoul (Korea, Republic of); Hanyang Biomedical Research Institute, Seoul (Korea, Republic of); Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul (Korea, Republic of)

    2014-07-15

    Oxidative stress can lead to expression of inflammatory transcription factors, which are important regulatory elements in the induction of inflammatory responses. One of the transcription factors, nuclear transcription factor kappa-B (NF-κB) plays a significant role in the inflammation regulatory process. Inflammatory cell death has been implicated in neuronal cell death in some neurodegenerative disorders such as Parkinson's disease (PD). In this study, we investigated the molecular mechanisms underlying apoptosis initiated by chlorpyrifos (CPF)-mediated oxidative stress. Based on the cytotoxic mechanism of CPF, we examined the neuroprotective effects of rosiglitazone (RGZ), a peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist, against CPF-induced neuronal cell death. The treatment of SH-SY5Y cells with CPF induced oxidative stress. In addition, CPF activated the p38, JNK and ERK mitogen-activated protein kinases (MAPKs), and induced increases in the inflammatory genes such as COX-2 and TNF-α. CPF also induced nuclear translocation of NF-κB and inhibitors of NF-κB abolished the CPF-induced COX-2 expression. Pretreatment with RGZ significantly reduced ROS generation and enhanced HO-1 expression in CPF-exposed cells. RGZ blocked the activation of both p38 and JNK signaling, while ERK activation was strengthened. RGZ also attenuated CPF-induced cell death through the reduction of NF-κB-mediated proinflammatory factors. Results from this study suggest that RGZ may exert an anti-apoptotic effect against CPF-induced cytotoxicity by attenuation of oxidative stress as well as inhibition of the inflammatory cascade via inactivation of signaling by p38 and JNK, and NF-κB. - Highlights: • CPF induces apoptotic cell death in SH-SY5Y cells • ROS involved in CPF-mediated apoptotic cell death • Inflammation involved in CPF-mediated apoptotic cell death • Rosiglitazone modulates ROS and inflammatory response in CPF-treated cells.

  18. Processing abstract language modulates motor system activity.

    Science.gov (United States)

    Glenberg, Arthur M; Sato, Marc; Cattaneo, Luigi; Riggio, Lucia; Palumbo, Daniele; Buccino, Giovanni

    2008-06-01

    Embodiment theory proposes that neural systems for perception and action are also engaged during language comprehension. Previous neuroimaging and neurophysiological studies have only been able to demonstrate modulation of action systems during comprehension of concrete language. We provide neurophysiological evidence for modulation of motor system activity during the comprehension of both concrete and abstract language. In Experiment 1, when the described direction of object transfer or information transfer (e.g., away from the reader to another) matched the literal direction of a hand movement used to make a response, speed of responding was faster than when the two directions mismatched (an action-sentence compatibility effect). In Experiment 2, we used single-pulse transcranial magnetic stimulation to study changes in the corticospinal motor pathways to hand muscles while reading the same sentences. Relative to sentences that do not describe transfer, there is greater modulation of activity in the hand muscles when reading sentences describing transfer of both concrete objects and abstract information. These findings are discussed in relation to the human mirror neuron system.

  19. Phototherapy with low intensity laser in carrageenan-induced acute inflammatory process in mice paw - dosimetry studies

    International Nuclear Information System (INIS)

    Meneguzzo, Daiane Thais

    2010-01-01

    The importance of modulation of inflammation on the treatment of inflammatory diseases and the difficulty in determining the laser irradiation parameters has led us to study the effects of different protocols of phototherapy with low intensity laser (power, energy, time and place of irradiation) in the treatment and prevention of edema in acute inflammatory process using the experimental model of paw edema induced by carrageenan (CGN) in three strains of mice (Balb-c, Swiss and C57BL/6). The first stage of the study evaluated different combinations of energy (1J and 3J) with different powers (30, 60 and 100mW) in Balb-C mice paw irradiated 1 and 2h after injection of CGN. The second stage studied different combinations of location (foot, inguinal lymph nodes and both) and exposure time (2 and 1h before, 1h and immediately before the CGN, 1 and 2h and 3.5 and 4.5h after CGN) using fixed irradiation parameters (1J, 100mW, 35J/cm 2 , spot area of 0.028 cm 2 ). The third stage compared different strains of mice Balb-c and C57BL/6) in the best local and time parameters found in step 2. At all stages, we evaluated the change in paw volume by plethysmography and inflammatory infiltrate by histomorphometry or analysis of myeloperoxidase (MPO). The results showed that laser phototherapy treated and prevented edema and modulated the inflammatory process with paw and inguinal lymph nodes irradiations accordingly with the parameters and mice strain used. (author)

  20. Immune and Inflammatory Responses in the Central Nervous System: Modulation by Astrocytes

    DEFF Research Database (Denmark)

    Penkowa, Milena; hidalgo, juan; aschner, michael

    2008-01-01

    Beyond their long-recognized support functions, astrocytes are active partners of neurons in processing information, synaptic integration, and production of trophic factors, just to name a few. Both microglia and astrocytes produce and secrete a number of cytokines, modulating and integrating...... the communication between hematogenous cells and resident cells of the central nervous system (CNS). This review will address (1) the functions of astrocytes in the normal brain and (2) their role in surveying noxious stimuli within the brain, with particular emphasis on astrocytic responses to damage or disease...

  1. Modulation of immunity and inflammatory gene expression in the gut, in inflammatory diseases of the gut and in the liver by probiotics

    Science.gov (United States)

    Plaza-Diaz, Julio; Gomez-Llorente, Carolina; Fontana, Luis; Gil, Angel

    2014-01-01

    The potential for the positive manipulation of the gut microbiome through the introduction of beneficial microbes, as also known as probiotics, is currently an active area of investigation. The FAO/WHO define probiotics as live microorganisms that confer a health benefit to the host when administered in adequate amounts. However, dead bacteria and bacterial molecular components may also exhibit probiotic properties. The results of clinical studies have demonstrated the clinical potential of probiotics in many pathologies, such as allergic diseases, diarrhea, inflammatory bowel disease and viral infection. Several mechanisms have been proposed to explain the beneficial effects of probiotics, most of which involve gene expression regulation in specific tissues, particularly the intestine and liver. Therefore, the modulation of gene expression mediated by probiotics is an important issue that warrants further investigation. In the present paper, we performed a systematic review of the probiotic-mediated modulation of gene expression that is associated with the immune system and inflammation. Between January 1990 to February 2014, PubMed was searched for articles that were published in English using the MeSH terms “probiotics" and "gene expression" combined with “intestines", "liver", "enterocytes", "antigen-presenting cells", "dendritic cells", "immune system", and "inflammation". Two hundred and five original articles matching these criteria were initially selected, although only those articles that included specific gene expression results (77) were later considered for this review and separated into three major topics: the regulation of immunity and inflammatory gene expression in the gut, in inflammatory diseases of the gut and in the liver. Particular strains of Bifidobacteria, Lactobacilli, Escherichia coli, Propionibacterium, Bacillus and Saccharomyces influence the gene expression of mucins, Toll-like receptors, caspases, nuclear factor-κB, and

  2. Taurine protects cisplatin induced cardiotoxicity by modulating inflammatory and endoplasmic reticulum stress responses.

    Science.gov (United States)

    Chowdhury, Sayantani; Sinha, Krishnendu; Banerjee, Sharmistha; Sil, Parames C

    2016-11-12

    Oxidative stress, ER stress, inflammation, and apoptosis results in the pathogenesis of cisplatin-induced cardiotoxicity. The present study was designed to investigate the signaling mechanisms involved in the ameliorating effect of taurine, a conditionally essential amino acid, against cisplatin-mediated cardiac ER stress dependent apoptotic death and inflammation. Mice were simultaneously treated with taurine (150 mg kg -1 body wt, i.p.) and cisplatin (10 mg kg -1 body wt, i.p.) for a week. Cisplatin exposure significantly altered serum creatine kinase and troponin T levels. In addition, histological studies revealed disintegration in the normal radiation pattern of cardiac muscle fibers. However, taurine administration could abate such adverse effects of cisplatin. Taurine administration significantly mitigated the reactive oxygen species production, alleviated the overexpression of nuclear factor-κB (NF-κB), and inhibited the elevation of proinflammatoy cytokines, adhesion molecules, and chemokines. Cisplatin exposure resulted in the unfolded protein response (UPR)-regulated CCAAT/enhancer binding protein (CHOP) up-regulation, induction of GRP78: a marker of ER stress and eIF2α signaling. Increase in calpain-1 expression level, activation of caspase-12 and caspase-3, cleavage of the PARP protein as well as the inhibition of antiapoptotic protein Bcl-2 were reflected on cisplatin-triggered apoptosis. Taurine could, however, combat against such cisplatin induced cardiac-abnormalities. The above mentioned findings suggest that taurine plays a beneficial role in providing protection against cisplatin-induced cardiac damage by modulating inflammatory responses and ER stress. © 2016 BioFactors, 42(6):647-664, 2016. © 2016 International Union of Biochemistry and Molecular Biology.

  3. 279 Watt Metal-Wrap-Through module using industrial processes

    Energy Technology Data Exchange (ETDEWEB)

    Guillevin, N.; Heurtault, B.; Geerligs, L.J.; Anker, J.; Van Aken, B.B.; Bennett, I.J.; Jansen, M.J.; Berkeveld, L.D.; Weeber, A.W.; Bultman, J.H. [ECN Solar Energy, PO Box 1, 1755 ZG Petten (Netherlands); Wenchao, Zhao; Jianming, Wang; Ziqian, Wang; Yingle, Chen; Yanlong, Shen; Zhiyan, Hu; Gaofei, Li; Jianhui, Chen; Bo, Yu; Shuquan, Tian; Jingfeng, Xiong [Yingli Solar, 3399 Chaoyang North Street, Baoding (China)

    2012-09-15

    This paper describes results of metal wrap through (MWT) cells produced from n-type Czochralski silicon wafers, and modules produced from those cells. The use of n-type silicon as base material allows for high efficiencies: for front emitter contacted industrial cells, efficiencies up to 20% have been reported. MWT cells allow even higher cell efficiency due to reduced front metal coverage, and additionally full back-contacting of the MWT cells in a module results in reduced cell to module (CTM) fill factor losses. MWT cells were produced by industrial process technologies. The efficiency of the MWT cells reproducibly exceeds the efficiency of front contact cells based on the same technology by about 0.2-0.3%, and routes for further improvement are analyzed. 60-cell modules were produced from both types of cells (MWT and H-pattern front emitter). In a direct module performance comparison, the MWT module, based on integrated backfoil, produced 3% higher power output than the comparable tabbed front emitter contact module. CTM current differences arise from the higher packing density, and in this experiment from a lower reflectance of the backfoil, in MWT modules. CTM FF differences are related to resistive losses in copper circuitry on the backfoil versus tabs. The CTM FF loss of the MWT module was reduced by 2.2%abs compared to the tabbed front emitter contact module. Finally, simple process optimizations were tested to improve the n-type MWT cell and module efficiency. A module made using MWT cells of 19.6% average efficiency resulted in a power output of 279W. The cell and module results are analyzed and routes for improvements are discussed.

  4. Microeconomics of 300-mm process module control

    Science.gov (United States)

    Monahan, Kevin M.; Chatterjee, Arun K.; Falessi, Georges; Levy, Ady; Stoller, Meryl D.

    2001-08-01

    Simple microeconomic models that directly link metrology, yield, and profitability are rare or non-existent. In this work, we validate and apply such a model. Using a small number of input parameters, we explain current yield management practices in 200 mm factories. The model is then used to extrapolate requirements for 300 mm factories, including the impact of simultaneous technology transitions to 130nm lithography and integrated metrology. To support our conclusions, we use examples relevant to factory-wide photo module control.

  5. Information processing systems, reasoning modules, and reasoning system design methods

    Science.gov (United States)

    Hohimer, Ryan E; Greitzer, Frank L; Hampton, Shawn D

    2014-03-04

    Information processing systems, reasoning modules, and reasoning system design methods are described. According to one aspect, an information processing system includes working memory comprising a semantic graph which comprises a plurality of abstractions, wherein the abstractions individually include an individual which is defined according to an ontology and a reasoning system comprising a plurality of reasoning modules which are configured to process different abstractions of the semantic graph, wherein a first of the reasoning modules is configured to process a plurality of abstractions which include individuals of a first classification type of the ontology and a second of the reasoning modules is configured to process a plurality of abstractions which include individuals of a second classification type of the ontology, wherein the first and second classification types are different.

  6. Information processing systems, reasoning modules, and reasoning system design methods

    Energy Technology Data Exchange (ETDEWEB)

    Hohimer, Ryan E.; Greitzer, Frank L.; Hampton, Shawn D.

    2016-08-23

    Information processing systems, reasoning modules, and reasoning system design methods are described. According to one aspect, an information processing system includes working memory comprising a semantic graph which comprises a plurality of abstractions, wherein the abstractions individually include an individual which is defined according to an ontology and a reasoning system comprising a plurality of reasoning modules which are configured to process different abstractions of the semantic graph, wherein a first of the reasoning modules is configured to process a plurality of abstractions which include individuals of a first classification type of the ontology and a second of the reasoning modules is configured to process a plurality of abstractions which include individuals of a second classification type of the ontology, wherein the first and second classification types are different.

  7. Information processing systems, reasoning modules, and reasoning system design methods

    Energy Technology Data Exchange (ETDEWEB)

    Hohimer, Ryan E.; Greitzer, Frank L.; Hampton, Shawn D.

    2015-08-18

    Information processing systems, reasoning modules, and reasoning system design methods are described. According to one aspect, an information processing system includes working memory comprising a semantic graph which comprises a plurality of abstractions, wherein the abstractions individually include an individual which is defined according to an ontology and a reasoning system comprising a plurality of reasoning modules which are configured to process different abstractions of the semantic graph, wherein a first of the reasoning modules is configured to process a plurality of abstractions which include individuals of a first classification type of the ontology and a second of the reasoning modules is configured to process a plurality of abstractions which include individuals of a second classification type of the ontology, wherein the first and second classification types are different.

  8. Time-dependent LXR/RXR pathway modulation characterizes capillary remodeling in inflammatory corneal neovascularization.

    Science.gov (United States)

    Mukwaya, Anthony; Lennikov, Anton; Xeroudaki, Maria; Mirabelli, Pierfrancesco; Lachota, Mieszko; Jensen, Lasse; Peebo, Beatrice; Lagali, Neil

    2018-05-01

    Inflammation in the normally immune-privileged cornea can initiate a pathologic angiogenic response causing vision-threatening corneal neovascularization. Inflammatory pathways, however, are numerous, complex and are activated in a time-dependent manner. Effective resolution of inflammation and associated angiogenesis in the cornea requires knowledge of these pathways and their time dependence, which has, to date, remained largely unexplored. Here, using a model of endogenous resolution of inflammation-induced corneal angiogenesis, we investigate the time dependence of inflammatory genes in effecting capillary regression and the return of corneal transparency. Endogenous capillary regression was characterized by a progressive thinning and remodeling of angiogenic capillaries and inflammatory cell retreat in vivo in the rat cornea. By whole-genome longitudinal microarray analysis, early suppression of VEGF ligand-receptor signaling and inflammatory pathways preceded an unexpected later-phase preferential activation of LXR/RXR, PPARα/RXRα and STAT3 canonical pathways, with a concurrent attenuation of LPS/IL-1 inhibition of RXR function and Wnt/β-catenin signaling pathways. Potent downstream inflammatory cytokines such as Cxcl5, IL-1β, IL-6 and Ccl2 were concomitantly downregulated during the remodeling phase. Upstream regulators of the inflammatory pathways included Socs3, Sparc and ApoE. A complex and coordinated time-dependent interplay between pro- and anti-inflammatory signaling pathways highlights a potential anti-inflammatory role of LXR/RXR, PPARα/RXRα and STAT3 signaling pathways in resolving inflammatory corneal angiogenesis.

  9. Morita-Baylis-Hillman Adducts Display Anti-Inflammatory Effects by Modulating Inflammatory Mediator Expression in RAW264.7 Cells

    Directory of Open Access Journals (Sweden)

    Glaucia V. Faheina-Martins

    2017-01-01

    Full Text Available Inflammatory response plays an important role not only in the normal physiology but also in pathologies such as cancers. The Morita-Baylis-Hillman adducts (MBHA are a novel group of synthetic molecules that have demonstrated many biological activities against some parasitic cells such as Plasmodium falciparum, Leishmania amazonensis, and Leishmania chagasi, and antimitotic activity against sea urchin embryonic cells was also related. However, little is known about the mechanisms induced by MBHA in inflammatory process and its relation with anticancer activity. The present work investigated the cytotoxicity of three MBHA derivatives (A2CN, A3CN, and A4CN, on human colorectal adenocarcinoma, HT-29 cells, and their anti-inflammatory activities were examined in lipopolysaccharide- (LPS- stimulated RAW264.7 macrophage cells, being these derivatives potentially cytotoxic to HT-29 cells. Coincubation with A2CN, A3CN, or A4CN and LPS in RAW264.7 cells inhibited NO production, as well as the production of reactive oxygen species (ROS was also repressed. The mRNA expressions of IL-1β and IL-6 were significantly downregulated by such MBHA compounds in RAW264.7 cells, but only A2CN was able to inhibit the COX-2 gene expression. We also showed that MBHA compounds decreased almost to zero the production of IL-1β and IL-6. These findings display that such MBHA compounds exhibit anticancer and anti-inflammatory activities.

  10. Chagas disease: modulation of the inflammatory response by acetylcholinesterase in hematological cells and brain tissue.

    Science.gov (United States)

    Silva, Aniélen D; Bottari, Nathieli B; do Carmo, Guilherme M; Baldissera, Matheus D; Souza, Carine F; Machado, Vanessa S; Morsch, Vera M; Schetinger, Maria Rosa C; Mendes, Ricardo E; Monteiro, Silvia G; Da Silva, Aleksandro S

    2018-01-01

    Chagas disease is an acute or chronic illness that causes severe inflammatory response, and consequently, it may activate the inflammatory cholinergic pathway, which is regulated by cholinesterases, including the acetylcholinesterase. This enzyme is responsible for the regulation of acetylcholine levels, an anti-inflammatory molecule linked to the inflammatory response during parasitic diseases. Thus, the aim of this study was to investigate whether Trypanosoma cruzi infection can alter the activity of acetylcholinesterase and acetylcholine levels in mice, and whether these alterations are linked to the inflammatory cholinergic signaling pathway. Twenty-four mice were divided into two groups: uninfected (control group, n = 12) and infected by T. cruzi, Y strain (n = 12). The animals developed acute disease with a peak of parasitemia on day 7 post-infection (PI). Blood, lymphocytes, and brain were analyzed on days 6 and 12 post-infection. In the brain, acetylcholine and nitric oxide levels, myeloperoxidase activity, and histopathology were analyzed. In total blood and brain, acetylcholinesterase activity decreased at both times. On the other hand, acetylcholinesterase activity in lymphocytes increased on day 6 PI compared with the control group. Infection by T. cruzi increased acetylcholine and nitric oxide levels and histopathological damage in the brain of mice associated to increased myeloperoxidase activity. Therefore, an intense inflammatory response in mice with acute Chagas disease in the central nervous system caused an anti-inflammatory response by the activation of the cholinergic inflammatory pathway.

  11. Neuroendocrine modulation of the inflammatory response in common carp: adrenaline regulates leukocyte profile and activity

    NARCIS (Netherlands)

    Kepka, M.; Verburg-van Kemenade, B.M.L.; Chadzinska, M.K.

    2013-01-01

    Inflammatory responses have to be carefully controlled, as high concentrations and/or prolonged action of inflammation-related molecules (e.g. reactive oxygen species, nitric oxide and pro-inflammatory cytokines) can be detrimental to host tissue and organs. One of the potential regulators of the

  12. Facilitating an Elementary Engineering Design Process Module

    Science.gov (United States)

    Hill-Cunningham, P. Renee; Mott, Michael S.; Hunt, Anna-Blair

    2018-01-01

    STEM education in elementary school is guided by the understanding that engineering represents the application of science and math concepts to make life better for people. The Engineering Design Process (EDP) guides the application of creative solutions to problems. Helping teachers understand how to apply the EDP to create lessons develops a…

  13. The time course of attentional modulation on emotional conflict processing.

    Science.gov (United States)

    Zhou, Pingyan; Yang, Guochun; Nan, Weizhi; Liu, Xun

    2016-01-01

    Cognitive conflict resolution is critical to human survival in a rapidly changing environment. However, emotional conflict processing seems to be particularly important for human interactions. This study examined whether the time course of attentional modulation on emotional conflict processing was different from cognitive conflict processing during a flanker task. Results showed that emotional N200 and P300 effects, similar to colour conflict processing, appeared only during the relevant task. However, the emotional N200 effect preceded the colour N200 effect, indicating that emotional conflict can be identified earlier than cognitive conflict. Additionally, a significant emotional N100 effect revealed that emotional valence differences could be perceived during early processing based on rough aspects of input. The present data suggest that emotional conflict processing is modulated by top-down attention, similar to cognitive conflict processing (reflected by N200 and P300 effects). However, emotional conflict processing seems to have more time advantages during two different processing stages.

  14. Mechanisms Modulating Inflammatory Osteolysis: A Review with Insights into Therapeutic Targets

    OpenAIRE

    Wei, Shi; Siegal, Gene P.

    2008-01-01

    Inflammatory osteolysis is a relatively frequent and incapacitating complication of rheumatoid arthritis and multiple other inflammation-associated bone diseases. It is thought to operate through an ultimate common pathway of accelerated osteoclast recruitment and activation under the control of cytokines produced in the inflammatory environment. Over the past decade, there have been major advances in our understanding of the mechanisms of osteoclastogenesis. It is now clear that the interact...

  15. Modulation of intestinal inflammation by yeasts and cell wall extracts: strain dependence and unexpected anti-inflammatory role of glucan fractions.

    Directory of Open Access Journals (Sweden)

    Samir Jawhara

    Full Text Available Yeasts and their glycan components can have a beneficial or adverse effect on intestinal inflammation. Previous research has shown that the presence of Saccharomyces cerevisiae var. boulardii (Sb reduces intestinal inflammation and colonization by Candida albicans. The aim of this study was to identify dietary yeasts, which have comparable effects to the anti-C. albicans and anti-inflammatory properties of Sb and to assess the capabilities of yeast cell wall components to modulate intestinal inflammation. Mice received a single oral challenge of C. albicans and were then given 1.5% dextran-sulphate-sodium (DSS for 2 weeks followed by a 3-day restitution period. S. cerevisiae strains (Sb, Sc1 to Sc4, as well as mannoprotein (MP and β-glucan crude fractions prepared from Sc2 and highly purified β-glucans prepared from C. albicans were used in this curative model, starting 3 days after C. albicans challenge. Mice were assessed for the clinical, histological and inflammatory responses related to DSS administration. Strain Sc1-1 gave the same level of protection against C. albicans as Sb when assessed by mortality, clinical scores, colonization levels, reduction of TNFα and increase in IL-10 transcription. When Sc1-1 was compared with the other S. cerevisiae strains, the preparation process had a strong influence on biological activity. Interestingly, some S. cerevisiae strains dramatically increased mortality and clinical scores. Strain Sc4 and MP fraction favoured C. albicans colonization and inflammation, whereas β-glucan fraction was protective against both. Surprisingly, purified β-glucans from C. albicans had the same protective effect. Thus, some yeasts appear to be strong modulators of intestinal inflammation. These effects are dependent on the strain, species, preparation process and cell wall fraction. It was striking that β-glucan fractions or pure β-glucans from C. albicans displayed the most potent anti-inflammatory effect in the

  16. Roles of inflammatory caspases during processing of zebrafish interleukin-1β in Francisella noatunensis infection

    Science.gov (United States)

    Vojtech, Lucia N.; Scharping, Nichole; Woodson, James C.; Hansen, John D.

    2012-01-01

    The interleukin-1 family of cytokines are essential for the control of pathogenic microbes but are also responsible for devastating autoimmune pathologies. Consequently, tight regulation of inflammatory processes is essential for maintaining homeostasis. In mammals, interleukin-1 beta (IL-1β) is primarily regulated at two levels, transcription and processing. The main pathway for processing IL-1β is the inflammasome, a multiprotein complex that forms in the cytosol and which results in the activation of inflammatory caspase (caspase 1) and the subsequent cleavage and secretion of active IL-1β. Although zebrafish encode orthologs of IL-1β and inflammatory caspases, the processing of IL-1β by activated caspase(s) has never been examined. Here, we demonstrate that in response to infection with the fish-specific bacterial pathogen Francisella noatunensis, primary leukocytes from adult zebrafish display caspase-1-like activity that results in IL-1β processing. Addition of caspase 1 or pancaspase inhibitors considerably abrogates IL-1β processing. As in mammals, this processing event is concurrent with the secretion of cleaved IL-1β into the culture medium. Furthermore, two putative zebrafish inflammatory caspase orthologs, caspase A and caspase B, are both able to cleave IL-1β, but with different specificities. These results represent the first demonstration of processing and secretion of zebrafish IL-1β in response to a pathogen, contributing to our understanding of the evolutionary processes governing the regulation of inflammation.                   

  17. Omega-3 fatty acids and inflammatory processes: from molecules to man.

    Science.gov (United States)

    Calder, Philip C

    2017-10-15

    Inappropriate, excessive or uncontrolled inflammation contributes to a range of human diseases. Inflammation involves a multitude of cell types, chemical mediators and interactions. The present article will describe nutritional and metabolic aspects of omega-6 (n-6) and omega-3 (n-3) fatty acids and explain the roles of bioactive members of those fatty acid families in inflammatory processes. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are n-3 fatty acids found in oily fish and fish oil supplements. These fatty acids are capable of partly inhibiting many aspects of inflammation including leucocyte chemotaxis, adhesion molecule expression and leucocyte-endothelial adhesive interactions, production of eicosanoids like prostaglandins and leukotrienes from the n-6 fatty acid arachidonic acid and production of pro-inflammatory cytokines. In addition, EPA gives rise to eicosanoids that often have lower biological potency than those produced from arachidonic acid, and EPA and DHA give rise to anti-inflammatory and inflammation resolving mediators called resolvins, protectins and maresins. Mechanisms underlying the anti-inflammatory actions of EPA and DHA include altered cell membrane phospholipid fatty acid composition, disruption of lipid rafts, inhibition of activation of the pro-inflammatory transcription factor nuclear factor κB so reducing expression of inflammatory genes and activation of the anti-inflammatory transcription factor peroxisome proliferator-activated receptor γ. Animal experiments demonstrate benefit from EPA and DHA in a range of models of inflammatory conditions. Human trials demonstrate benefit of oral n-3 fatty acids in rheumatoid arthritis and in stabilizing advanced atherosclerotic plaques. Intravenous n-3 fatty acids may have benefits in critically ill patients through reduced inflammation. The anti-inflammatory and inflammation resolving actions of EPA, DHA and their derivatives are of clinical relevance. © 2017 The Author

  18. Effective Thermal Analysis of Using Peltier Module for Desalination Process

    OpenAIRE

    Hayder Al-Madhhachi

    2018-01-01

    The key objective of this study is to analyse the heat transfer processes involved in the evaporation and condensation of water in a water distillation system employing a thermoelectric module. This analysis can help to increase the water production and to enhance the system performance. For the analysis, a water distillation unit prototype integrated with a thermoelectric module was designed and fabricated. A theoretical model is developed to study the effect of the heat added, transferred a...

  19. Effects of short-term dietary restriction and glutamine supplementation in vitro on the modulation of inflammatory properties.

    Science.gov (United States)

    C de Oliveira, Dalila; Santos, Ed Wilson; Nogueira-Pedro, Amanda; Xavier, José Guilherme; Borelli, Primavera; Fock, Ricardo Ambrósio

    2018-04-01

    Dietary restriction (DR) is a nutritional intervention that exerts profound effects on biochemical and immunologic parameters, modulating some inflammatory properties. Glutamine (GLN) is a conditionally essential amino acid that can modulate inflammatory properties. However, there is a lack of data evaluating the effects of DR and GLN supplementation, especially in relation to inflammatory cytokine production and the expression of transcription factors such as nuclear factor (NF)-κB. We subjected 3-mo-old male Balb/c mice to DR by reducing their food intake by 30%. DR animals lost weight and showed reduced levels of serum triacylglycerols, glucose, cholesterol, and calcium as well as a reduction in bone density. Additionally, blood, peritoneal, and spleen cellularity were reduced, lowering the number of peritoneal F4/80- and CD86-positive cells and the total number of splenic CD4- and CD8-positive cells. The production of interleukin (IL)-10 and the expression of NF-κB in splenic cells were not affected by DR or by GLN supplementation. However, peritoneal macrophages from DR animals showed reduced IL-12 and tumor necrosis factor-α production and increased IL-10 production with reduced phosphorylation of NF-κB expression. Additionally, GLN was able to modulate cytokine production by peritoneal cells from the control group, although no effects were observed in cells from the DR group. DR induces biochemical and immunologic changes, in particular by reducing IL-12 and tumor necrosis factor-α production by macrophages and clearly upregulating IL-10 production, whereas GLN supplementation did not modify these parameters in cells from DR animals. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. The transcription factor GLI1 modulates the inflammatory response during pancreatic tissue remodeling.

    Science.gov (United States)

    Mathew, Esha; Collins, Meredith A; Fernandez-Barrena, Maite G; Holtz, Alexander M; Yan, Wei; Hogan, James O; Tata, Zachary; Allen, Benjamin L; Fernandez-Zapico, Martin E; di Magliano, Marina Pasca

    2014-10-03

    Pancreatic cancer, one of the deadliest human malignancies, is almost uniformly associated with a mutant, constitutively active form of the oncogene Kras. Studies in genetically engineered mouse models have defined a requirement for oncogenic KRAS in both the formation of pancreatic intraepithelial neoplasias, the most common precursor lesions to pancreatic cancer, and in the maintenance and progression of these lesions. Previous work using an inducible model allowing tissue-specific and reversible expression of oncogenic Kras in the pancreas indicates that inactivation of this GTPase at the pancreatic intraepithelial neoplasia stage promotes pancreatic tissue repair. Here, we extend these findings to identify GLI1, a transcriptional effector of the Hedgehog pathway, as a central player in pancreatic tissue repair upon Kras inactivation. Deletion of a single allele of Gli1 results in improper stromal remodeling and perdurance of the inflammatory infiltrate characteristic of pancreatic tumorigenesis. Strikingly, this partial loss of Gli1 affects activated fibroblasts in the pancreas and the recruitment of immune cells that are vital for tissue recovery. Analysis of the mechanism using expression and chromatin immunoprecipitation assays identified a subset of cytokines, including IL-6, mIL-8, Mcp-1, and M-csf (Csf1), as direct GLI1 target genes potentially mediating this phenomenon. Finally, we demonstrate that canonical Hedgehog signaling, a known regulator of Gli1 activity, is required for pancreas recovery. Collectively, these data delineate a new pathway controlling tissue repair and highlight the importance of GLI1 in regulation of the pancreatic microenvironment during this cellular process. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  1. Complementary and Alternative Medicine Strategies for Therapeutic Gut Microbiota Modulation in Inflammatory Bowel Disease and their Next-Generation Approaches.

    Science.gov (United States)

    Basson, Abigail R; Lam, Minh; Cominelli, Fabio

    2017-12-01

    The human gut microbiome exerts a major impact on human health and disease, and therapeutic gut microbiota modulation is now a well-advocated strategy in the management of many diseases, including inflammatory bowel disease (IBD). Scientific and clinical evidence in support of complementary and alternative medicine, in targeting intestinal dysbiosis among patients with IBD, or other disorders, has increased dramatically over the past years. Delivery of "artificial" stool replacements for fecal microbiota transplantation (FMT) could provide an effective, safer alternative to that of human donor stool. Nevertheless, optimum timing of FMT administration in IBD remains unexplored, and future investigations are essential. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Anti-Inflammatory Effects of Spirulina platensis Extract via the Modulation of Histone Deacetylases

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    Tho X. Pham

    2016-06-01

    Full Text Available We previously demonstrated that the organic extract of Spirulina platensis (SPE, an edible blue-green alga, possesses potent anti-inflammatory effects. In this study, we investigated if the regulation of histone deacetylases (HDACs play a role in the anti-inflammatory effect of SPE in macrophages. Treatment of macrophages with SPE rapidly and dose-dependently reduced HDAC2, 3, and 4 proteins which preceded decreases in their mRNA levels. Degradation of HDAC4 protein was attenuated in the presence of inhibitors of calpain proteases, lysosomal acidification, and Ca2+/calmodulin-dependent protein kinase II, respectively, but not a proteasome inhibitor. Acetylated histone H3 was increased in SPE-treated macrophages to a similar level as macrophages treated with a pan-HDAC inhibitor, with concomitant inhibition of inflammatory gene expression upon LPS stimulation. Knockdown of HDAC3 increased basal and LPS-induced pro-inflammatory gene expression, while HDAC4 knockdown increased basal expression of interleukin-1β (IL-1β, but attenuated LPS-induced inflammatory gene expression. Chromatin immunoprecipitation showed that SPE decreased p65 binding and H3K9/K14 acetylation at the Il-1β and tumor necrosis factor α (Tnfα promoters. Our results suggest that SPE increased global histone H3 acetylation by facilitating HDAC protein degradation, but decreases histone H3K9/K14 acetylation and p65 binding at the promoters of Il-1β and Tnfα to exert its anti-inflammatory effect.

  3. Effective Thermal Analysis of Using Peltier Module for Desalination Process

    Directory of Open Access Journals (Sweden)

    Hayder Al-Madhhachi

    2018-01-01

    Full Text Available The key objective of this study is to analyse the heat transfer processes involved in the evaporation and condensation of water in a water distillation system employing a thermoelectric module. This analysis can help to increase the water production and to enhance the system performance. For the analysis, a water distillation unit prototype integrated with a thermoelectric module was designed and fabricated. A theoretical model is developed to study the effect of the heat added, transferred and removed, in forced convection and laminar flow, during the evaporation and condensation processes. The thermoelectric module is used to convert electricity into heat under Peltier effect and control precisely the absorbed and released heat at the cold and hot sides of the module, respectively. Temperatures of water, vapour, condenser, cold and hot sides of the thermoelectric module and water production have been measured experimentally under steady state operation. The theoretical and experimental water production were found to be in agreement. The amount of heat that needs to be evaporated from water-vapour interface and transferred through the condenser surface to the thermoelectric module is crucial for the design and optimization of distillation systems.

  4. Block of the Mevalonate Pathway Triggers Oxidative and Inflammatory Molecular Mechanisms Modulated by Exogenous Isoprenoid Compounds

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    Paola Maura Tricarico

    2014-04-01

    Full Text Available Deregulation of the mevalonate pathway is known to be involved in a number of diseases that exhibit a systemic inflammatory phenotype and often neurological involvements, as seen in patients suffering from a rare disease called mevalonate kinase deficiency (MKD. One of the molecular mechanisms underlying this pathology could depend on the shortage of isoprenoid compounds and the subsequent mitochondrial damage, leading to oxidative stress and pro-inflammatory cytokines’ release. Moreover, it has been demonstrated that cellular death results from the balance between apoptosis and pyroptosis, both driven by mitochondrial damage and the molecular platform inflammasome. In order to rescue the deregulated pathway and decrease inflammatory markers, exogenous isoprenoid compounds were administered to a biochemical model of MKD obtained treating a murine monocytic cell line with a compound able to block the mevalonate pathway, plus an inflammatory stimulus. Our results show that isoprenoids acted in different ways, mainly increasing the expression of the evaluated markers [apoptosis, mitochondrial dysfunction, nucleotide-binding oligomerization-domain protein-like receptors 3 (NALP3, cytokines and nitric oxide (NO]. Our findings confirm the hypothesis that inflammation is triggered, at least partially, by the shortage of isoprenoids. Moreover, although further studies are necessary, the achieved results suggest a possible role for exogenous isoprenoids in the treatment of MKD.

  5. [TLR2 modulates Staphylococcus aureus-induced inflammatory response and autophagy in macrophages through PI3K signaling pathway].

    Science.gov (United States)

    Li, Shuai; Fang, Lei; Wang, Jiong; Liu, Rongyu

    2017-09-01

    Objective To investigate the molecular mechanisms of Toll-like receptor 2 (TLR2) taking part in inflammatory response in Staphylococcus aureus (SA)-induced asthma. Methods We established the cell inflammatory response model through stimulating mouse RAW264.7 macrophages with SA. The TLR2, myeloid differentiation factor 88 (MyD88), phosphoinositide-3 kinase (PI3K), nuclear factor κBp65 (NF-κBp65), phospho-NF-κBp65, beclin-1 and microtubule-associated protein 1 light chain 3B (LC3B) were detected by Western blot analysis after treatment with TLR2 small interfering RNA (siRNA) and 3-methyladenine (3-MA), and the tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) were determined by ELISA. In addition, the number of autolysosomes was observed by the laser scanning confocal microscope. Results SA-stimulated macrophages activated various signaling pathways including TLR2. TLR2 siRNA markedly repressed the expressions of PI3K, phospho-NF-κBp65, the autophagy protein beclin-1 and LC3B as well as the number of autolysosomes and the production of TNF- and IL-6. We also demonstrated that 3-MA had the same effect on autophagy and inflammation as TLR2 siRNA did. Conclusion TLR2 modulates SA-induced inflammatory response and autophagy in macrophages through PI3K signaling pathway.

  6. Functional imaging of interleukin 1 beta expression in inflammatory process using bioluminescence imaging in transgenic mice

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    Liu Zhihui

    2008-08-01

    Full Text Available Abstract Background Interleukin 1 beta (IL-1β plays an important role in a number of chronic and acute inflammatory diseases. To understand the role of IL-1β in disease processes and develop an in vivo screening system for anti-inflammatory drugs, a transgenic mouse line was generated which incorporated the transgene firefly luciferase gene driven by a 4.5-kb fragment of the human IL-1β gene promoter. Luciferase gene expression was monitored in live mice under anesthesia using bioluminescence imaging in a number of inflammatory disease models. Results In a LPS-induced sepsis model, dramatic increase in luciferase activity was observed in the mice. This transgene induction was time dependent and correlated with an increase of endogenous IL-1β mRNA and pro-IL-1β protein levels in the mice. In a zymosan-induced arthritis model and an oxazolone-induced skin hypersensitivity reaction model, luciferase expression was locally induced in the zymosan injected knee joint and in the ear with oxazolone application, respectively. Dexamethasone suppressed the expression of luciferase gene both in the acute sepsis model and in the acute arthritis model. Conclusion Our data suggest that the transgenic mice model could be used to study transcriptional regulation of the IL-1β gene expression in the inflammatory process and evaluation the effect of anti-inflammatory drug in vivo.

  7. Purinergic signaling modulates the cerebral inflammatory response in experimentally infected fish with Streptococcus agalactiae: an attempt to improve the immune response.

    Science.gov (United States)

    Souza, Carine F; Baldissera, Matheus D; Bottari, Nathiele B; Moreira, Karen L S; da Rocha, Maria Izabel U M; da Veiga, Marcelo L; Santos, Roberto C V; Baldisserotto, Bernardo

    2018-06-01

    Appropriate control of the immune response is a critical determinant of fish health, and the purinergic cascade has an important role in the immune and inflammatory responses. This cascade regulates the levels of adenosine triphosphate (ATP), adenosine diphosphate, adenosine monophosphate and adenosine (Ado), molecules involved in physiological or pathological events as inflammatory and anti-inflammatory mediators. Thus, the aim of this study was to evaluate whether purinergic signaling, through the activities of nucleoside triphosphate diphosphohydrolase (NTPDase), 5'-nucleotidase, and adenosine deaminase (ADA), is capable of modulating the cerebral immune and inflammatory responses in silver catfish that is experimentally infected with Streptococcus agalactiae. Cerebral NTPDase (with ATP as substrate) and 5'-nucleotidase activities increased, while ADA activity decreased in silver catfish that is experimentally infected with S. agalactiae, compared to the control group. Moreover, the cerebral levels of ATP and Ado increased in infected animals compared to the uninfected control group. Brain histopathology in infected animals revealed inflammatory demyelination (the presence of occasional bubbly collections), increased cellular density in the area near to pia-mater and intercellular edema. Based on this evidence, the modulation of the purinergic cascade by the enzymes NTPDase, 5'-nucleotidase, and ADA exerts an anti-inflammatory profile due to the regulation of ATP and Ado levels. This suggests involvement of purinergic enzymes on streptococcosis pathogenesis, through regulating cerebral ATP and Ado levels, molecules known to participate in physiological or pathological events as inflammatory and anti-inflammatory mediators, respectively. In summary, the modulation of the cerebral purinergic cascade exerts an anti-inflammatory profile in an attempt to reduce inflammatory damage.

  8. Cyanidin-3-O-Glucoside Modulates the In Vitro Inflammatory Crosstalk between Intestinal Epithelial and Endothelial Cells

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    Daniela Ferrari

    2017-01-01

    Full Text Available Intestinal epithelium represents a protective physical barrier and actively contributes to the mucosal immune system. Polarized basolateral intestinal secretion of inflammatory mediators, followed by activation of NF-κB signaling and inflammatory pathways in endothelial cells, efficiently triggers extravasation of neutrophils from the vasculature, therefore contributing to the development and maintenance of intestinal inflammation. Proper regulation of NF-κB activation at the epithelial interface is crucial for the maintenance of physiological tissue homeostasis. Many papers reported that anthocyanins, a group of compounds belonging to flavonoids, possess anti-inflammatory effects and modulate NF-κB activity. In this study, by using a coculture in vitro system, we aimed to evaluate the effects of TNF-α-stimulated intestinal cells on endothelial cells activation, as well as the protective effects of cyanidin-3-glucoside (C3G. In this model, TNF-α induced nuclear translocation of NF-κB and TNF-α and IL-8 gene expression in Caco-2 cells, whereas C3G pretreatment dose-dependently reduced these effects. Furthermore, TNF-α-stimulated Caco-2 cells induced endothelial cells activation with increased E-selectin and VCAM-1 mRNA, leukocyte adhesion, and NF-κB levels in HUVECs, which were inhibited by C3G. We demonstrated that selective inhibition of the NF-κB pathway in epithelial cells represents the main mechanism by which C3G exerts these protective effects. Thus, anthocyanins could contribute to the management of chronic gut inflammatory diseases.

  9. Distortions caused by the signal processing in analog AM modulators

    International Nuclear Information System (INIS)

    Njau, E.C.

    1988-08-01

    Complete analytical expressions for distortions caused by signal processing in analog AM modulators are developed. The salient features in these expressions are shown to be consistent with displays of actual spectra of AM signals. Finally suggestions are given on how the distortions may be practically minimized. (author). 6 refs, 3 figs

  10. Bone scan in diagnosis of inflammatory processes of the foot bones in diabetes mellitus

    International Nuclear Information System (INIS)

    Slavnov, V.M.; Markov, V.V.; Bolgars'ka, S.V.

    2003-01-01

    The radionuclide technique for early diagnosis of inflammatory process in the bones of the foot was developed for diabetes mellitus (DM) patients. The most important diagnostic criterion of the bone lesion in patients with DM is area asymmetry and total activity percentage between the lesion focus and symmetrical zone

  11. Optical modulation techniques for analog signal processing and CMOS compatible electro-optic modulation

    Science.gov (United States)

    Gill, Douglas M.; Rasras, Mahmoud; Tu, Kun-Yii; Chen, Young-Kai; White, Alice E.; Patel, Sanjay S.; Carothers, Daniel; Pomerene, Andrew; Kamocsai, Robert; Beattie, James; Kopa, Anthony; Apsel, Alyssa; Beals, Mark; Mitchel, Jurgen; Liu, Jifeng; Kimerling, Lionel C.

    2008-02-01

    Integrating electronic and photonic functions onto a single silicon-based chip using techniques compatible with mass-production CMOS electronics will enable new design paradigms for existing system architectures and open new opportunities for electro-optic applications with the potential to dramatically change the management, cost, footprint, weight, and power consumption of today's communication systems. While broadband analog system applications represent a smaller volume market than that for digital data transmission, there are significant deployments of analog electro-optic systems for commercial and military applications. Broadband linear modulation is a critical building block in optical analog signal processing and also could have significant applications in digital communication systems. Recently, broadband electro-optic modulators on a silicon platform have been demonstrated based on the plasma dispersion effect. The use of the plasma dispersion effect within a CMOS compatible waveguide creates new challenges and opportunities for analog signal processing since the index and propagation loss change within the waveguide during modulation. We will review the current status of silicon-based electrooptic modulators and also linearization techniques for optical modulation.

  12. Modulation of the Inflammatory Response by Ionizing Radiation and the Possible Role of Curcumin

    International Nuclear Information System (INIS)

    Hegazy, M.El.A.

    2009-01-01

    The increasing use of radiation and the recent incidents of massive radiation exposure give an importance to study possible radiation hazards. Radiation-induced cell changes may result in death of the organism, death of the cells, modulation of physiological activity, or cancers that have no features distinguishing them from those induced by other types of cell injury (Valko et al., 2004). Electromagnetic radiation is divided into non-ionizing and ionizing radiation according to the energy required to eject electrons from molecules (Bessonov, 2006). Ionizing radiation, which may exhibit the properties of both waves and particles, has sufficient energy to produce ionization in matter. The ionizing radiation that exhibits corpuscular properties include alpha and beta particles, while those that behave more like waves of energy include x-rays and gamma-rays (γ-rays) (Bessonov, 2006). Radiation exposure comes from many sources and may be directly or indirectly ionizing. Directly ionizing radiation carries an electric charge that directly interacts, by electrostatic attraction or repulsion, with atoms in the tissue or the exposed medium. On the other hand, indirectly ionizing radiation is not electrically charged but results in production of charged particles by which its energy is absorbed (Metting et al., 1988). One of the characteristics of charged particles produced directly or indirectly is the linear energy transfer (LET), the energy loss per unit of distance traveled, usually expressed in kilo-electron volts (keV) per micrometer (μm). The LET, depending on the velocity and charge of the particles, may vary from about 0.2 to more than 1000 keV/μm (Table (1)). Radiation interacts with matter by direct and indirect processes to form ion pairs, some of which may be free radicals. These ion pairs rapidly interact with themselves and other surrounding molecules to produce free radicals. Both the indirect and direct activities of ionizing radiation lead to molecular

  13. The Role of CD39 in Modulating Effector Immune Responses in Inflammatory Bowel Disease

    OpenAIRE

    Huang, Huang

    2015-01-01

    Inflammatory bowel disease is associated with excessive inflammation of the bowel and intestinal tissues in genetically susceptible individuals. IBD can manifest in two major forms, ulcerative colitis and Crohn’s disease. T helper type 17 cells (Th17) are effector lymphocytes that have been linked to intestinal inflammation in both mice and humans. Effector Th17 cells and regulatory T cells (Treg) – a subset pivotal to immune-tolerance maintenance – derive from the same CD4 progenitors. Our i...

  14. Protein kinase CK2 modulates IL-6 expression in inflammatory breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Drygin, Denis, E-mail: ddrygin@cylenepharma.com; Ho, Caroline B.; Omori, Mayuko; Bliesath, Joshua; Proffitt, Chris; Rice, Rachel; Siddiqui-Jain, Adam; O' Brien, Sean; Padgett, Claire; Lim, John K.C.; Anderes, Kenna; Rice, William G.; Ryckman, David

    2011-11-11

    Highlights: Black-Right-Pointing-Pointer We examine the potential cross-talk between CK2 and IL-6. Black-Right-Pointing-Pointer Inhibition of CK2 by siRNA or CX-4945 inhibits expression of IL-6 in models of IBC. Black-Right-Pointing-Pointer Treatment of IBC patient in the clinic with CX-4945 reduces her IL-6 plasma levels. Black-Right-Pointing-Pointer We demonstrate that CK2 is a potential therapeutic target for IL-6 driven diseases. -- Abstract: Inflammatory breast cancer is driven by pro-angiogenic and pro-inflammatory cytokines. One of them Interleukin-6 (IL-6) is implicated in cancer cell proliferation and survival, and promotes angiogenesis, inflammation and metastasis. While IL-6 has been shown to be upregulated by several oncogenes, the mechanism behind this phenomenon is not well characterized. Here we demonstrate that the pleotropic Serine/Threonine kinase CK2 is implicated in the regulation of IL-6 expression in a model of inflammatory breast cancer. We used siRNAs targeted toward CK2 and a selective small molecule inhibitor of CK2, CX-4945, to inhibit the expression and thus suppress the secretion of IL-6 in in vitro as well as in vivo models. Moreover, we report that in a clinical trial, CX-4945 was able to dramatically reduce IL-6 levels in plasma of an inflammatory breast cancer patient. Our data shed a new light on the regulation of IL-6 expression and position CX-4945 and potentially other inhibitors of CK2, for the treatment of IL-6-driven cancers and possibly other diseases where IL-6 is instrumental, including rheumatoid arthritis.

  15. Identification of Therapeutic Targets of Inflammatory Monocyte Recruitment to Modulate the Allogeneic Injury to Donor Cornea

    OpenAIRE

    Lapp, T.; Zaher, S. S.; Haas, C. T.; Becker, D. L.; Thrasivoulou, C.; Chain, B. M.; Larkin, D. F. P.; Noursadeghi, M.

    2015-01-01

    Purpose: We sought to test the hypothesis that monocytes contribute to the immunopathogenesis of corneal allograft rejection and identify therapeutic targets to inhibit monocyte recruitment. Methods: Monocytes and proinflammatory mediators within anterior chamber samples during corneal graft rejection were quantified by flow cytometry and multiplex protein assays. Lipopolysaccharide or IFN-γ stimulation of monocyte-derived macrophages (MDMs) was used to generate inflammatory conditioned me...

  16. Involvement of Visceral Adipose Tissue in Immunological Modulation of Inflammatory Cascade in Preeclampsia

    Directory of Open Access Journals (Sweden)

    Katsuhiko Naruse

    2015-01-01

    Full Text Available Objectives. The pathophysiology of preeclampsia is characterized by abnormal placentation, an exaggerated inflammatory response, and generalized dysfunction of the maternal endothelium. We investigated the effects of preeclampsia serum on the expression of inflammation-related genes by adipose tissue. Materials and Methods. Visceral adipose tissue was obtained from the omentum of patients with early ovarian cancer without metastasis. Adipose tissue was incubated with sera obtained from either five women affected with severe preeclampsia or five women from control pregnant women at 37°C in a humidified incubator at 5% CO2 for 24 hours. 370 genes in total mRNA were analyzed with quantitative RT-PCR (Inflammatory Response & Autoimmunity gene set. Results. Gene expression analysis revealed changes in the expression levels of 30 genes in adipose tissue treated with preeclampsia sera. Some genes are related to immune response, oxidative stress, insulin resistance, and adipogenesis, which plays a central role in excessive systemic inflammatory response of preeclampsia. In contrast, other genes have shown beneficial effects in the regulation of Th2 predominance, antioxidative stress, and insulin sensitivity. Conclusion. In conclusion, visceral adipose tissue offers protection against inflammation, oxidative insults, and other forms of cellular stress that are central to the pathogenesis of preeclampsia.

  17. Platelet-Released Growth Factors Modulate the Secretion of Cytokines in Synoviocytes under Inflammatory Joint Disease

    Science.gov (United States)

    Rasuo, Biljana; Hock, Jennifer Vanessa Phi; Kweider, Nisreen; Fragoulis, Athanassios; Sönmez, Tolga Taha; Jahr, Holger; Pufe, Thomas; Lippross, Sebastian

    2017-01-01

    The etiology and pathogenesis of rheumatoid arthritis (RA) are marked by a complex interplay of various cell populations and is mediated by different signaling pathways. Traditionally, therapies have primarily focused on pain relief, reducing inflammation and the recovery of joint function. More recently, however, researchers have discussed the therapeutic efficacy of autologous platelet-rich plasma (PRP). The main objective of this work is to examine the influences of platelet-released growth factor (PRGF) on human synoviocytes under inflammatory conditions. Additionally, it is checked to which extend treatment with platelet concentrate influences the release of cytokines form synoviocytes. For this purpose, an in vitro RA model was created by stimulating the cells with the TNF-α. The release of cytokines was measured by ELISA. The cytokine gene expression was analyzed by real-time PCR. It has been observed that the stimulation concentration of 10 ng/ml TNF-α resulted in a significantly increased endogenous secretion and gene expression of IL-6 and TNF-α. The anti-inflammatory effect of PRGF could be confirmed through significant reduction of TNF-α and IL-1β. An induced inflammatory condition seems to cause PRGF to inhibit the release of proinflammatory cytokines. Further study is required to understand the exact effect mechanism of PRGF on synoviocytes. PMID:29348703

  18. Platelet-Released Growth Factors Modulate the Secretion of Cytokines in Synoviocytes under Inflammatory Joint Disease

    Directory of Open Access Journals (Sweden)

    Mersedeh Tohidnezhad

    2017-01-01

    Full Text Available The etiology and pathogenesis of rheumatoid arthritis (RA are marked by a complex interplay of various cell populations and is mediated by different signaling pathways. Traditionally, therapies have primarily focused on pain relief, reducing inflammation and the recovery of joint function. More recently, however, researchers have discussed the therapeutic efficacy of autologous platelet-rich plasma (PRP. The main objective of this work is to examine the influences of platelet-released growth factor (PRGF on human synoviocytes under inflammatory conditions. Additionally, it is checked to which extend treatment with platelet concentrate influences the release of cytokines form synoviocytes. For this purpose, an in vitro RA model was created by stimulating the cells with the TNF-α. The release of cytokines was measured by ELISA. The cytokine gene expression was analyzed by real-time PCR. It has been observed that the stimulation concentration of 10 ng/ml TNF-α resulted in a significantly increased endogenous secretion and gene expression of IL-6 and TNF-α. The anti-inflammatory effect of PRGF could be confirmed through significant reduction of TNF-α and IL-1β. An induced inflammatory condition seems to cause PRGF to inhibit the release of proinflammatory cytokines. Further study is required to understand the exact effect mechanism of PRGF on synoviocytes.

  19. Effect of exposure to radiation on the inflammatory process and its influence by diclofenac

    International Nuclear Information System (INIS)

    El-Ghazaly, M.; Kenawy, S.; Khayyal, M.T.; Roushdy, H.; Saleh, S.

    1985-01-01

    The effect of radiation exposure on the inflammatory process was studied in rats using the carrageenan-induced paw oedema and adjuvant-induced arthritis tests. Irradiation (0.5,1 and 2 Grays) resulted in a significant augmentation of the tissue response to carrageenan and the early phase of adjuvant-induced arthritis, but suppressed the late phase. Diclofenac(1-5 mg kg -1 ) effectively reduced the exaggerated inflammatory response in irradiated animals in both the carrageenan paw oedema and adjuvant-induced arthritis tests. The drug also had a prophylactic value in guarding against the induction of radiation damage. The inflammatory responses produced by irradiation and the benefits obtained by drug treatment may be related to changes in tissue prostaglandin levels and/or changes in the immune system. (author)

  20. The impact of maternal obesity on inflammatory processes and consequences for later offspring health outcomes.

    Science.gov (United States)

    Segovia, S A; Vickers, M H; Reynolds, C M

    2017-10-01

    Obesity is a global epidemic, affecting both developed and developing countries. The related metabolic consequences that arise from being overweight or obese are a paramount global health concern, and represent a significant burden on healthcare systems. Furthermore, being overweight or obese during pregnancy increases the risk of offspring developing obesity and other related metabolic complications in later life, which can therefore perpetuate a transgenerational cycle of obesity. Obesity is associated with a chronic state of low-grade metabolic inflammation. However, the role of maternal obesity-mediated alterations in inflammatory processes as a mechanism underpinning developmental programming in offspring is less understood. Further, the use of anti-inflammatory agents as an intervention strategy to ameliorate or reverse the impact of adverse developmental programming in the setting of maternal obesity has not been well studied. This review will discuss the impact of maternal obesity on key inflammatory pathways, impact on pregnancy and offspring outcomes, potential mechanisms and avenues for intervention.

  1. Modulation of PPAR-γ by Nutraceutics as Complementary Treatment for Obesity-Related Disorders and Inflammatory Diseases

    Directory of Open Access Journals (Sweden)

    D. Ortuño Sahagún

    2012-01-01

    Full Text Available A direct correlation between adequate nutrition and health is a universally accepted truth. The Western lifestyle, with a high intake of simple sugars, saturated fat, and physical inactivity, promotes pathologic conditions. The main adverse consequences range from cardiovascular disease, type 2 diabetes, and metabolic syndrome to several cancers. Dietary components influence tissue homeostasis in multiple ways and many different functional foods have been associated with various health benefits when consumed. Natural products are an important and promising source for drug discovery. Many anti-inflammatory natural products activate peroxisome proliferator-activated receptors (PPAR; therefore, compounds that activate or modulate PPAR-gamma (PPAR-γ may help to fight all of these pathological conditions. Consequently, the discovery and optimization of novel PPAR-γ agonists and modulators that would display reduced side effects is of great interest. In this paper, we present some of the main naturally derived products studied that exert an influence on metabolism through the activation or modulation of PPAR-γ, and we also present PPAR-γ-related diseases that can be complementarily treated with nutraceutics from functional foods.

  2. Coconut water of different maturity stages ameliorates inflammatory processes in model of inflammation

    Science.gov (United States)

    Rao, Sadia Saleem; Najam, Rahila

    2016-01-01

    Aim: Coconut water is a natural beverage that is a part of daily diet of many people. This study was designed to explore the anti-inflammatory activity of coconut water of different maturation stages (young and mature) with rat paw edema model of inflammation using plethysmometer. Methodology: For this study, albino rats were selected and divided into four equal groups (10 rats in each group). Group 1 was set as control and administered distilled water 1 ml orally; Groups 2 and 3 were treated with young and mature coconut water, respectively, at 4 ml/100 g dose orally. Group 4 was treated with the standard drug (ibuprofen) at 400 mg/70 kg. 0.1 ml of 1% w/v acetic acid was administered in the subplantar tissue of rat paw 30 min after oral treatments of groups. Plethysmometer was used to measure rat paw edema. Results: Results revealed that both coconut water possess significant anti-inflammatory activity (P coconut water was 20.22%, 35.13%, 42.52%, and 36% at 1, 2, 3, and 4 h of acetic acid administration, respectively. However, maximum percent inhibition (42.52%) was observed in the second phase of the inflammatory process. On the other hand, percent inhibition by mature coconut water was 18.80%, 25.94%, 24.13%, and 18.66% at 1, 2, 3, and 4 h of acetic acid administration, respectively. However, maximum percent inhibition (25.94%) was observed in the first phase of the inflammatory process. Conclusions: This study strongly suggests the use of young coconut water for potent anti-inflammatory effect and mature coconut water for moderate anti-inflammatory effect. PMID:27366350

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

    Science.gov (United States)

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

    2018-01-01

    inflammatory processes (e.g., "Fcγ Receptor-mediated Phagocytosis in Macrophages and Monocytes," "PI3K signaling in B Lymphocytes") and master regulators (e.g., TNF, CSF2, TGFB1). The majority of these processes and regulators are modulated in the same direction in Ldlr -/- .Leiden mice fed HFD with a human-like macronutrient composition, thus demonstrating that specific experimental conditions recapitulate human disease on the molecular level of disease pathways and upstream/master regulators.

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

    Science.gov (United States)

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

    2018-01-01

    inflammatory processes (e.g., “Fcγ Receptor-mediated Phagocytosis in Macrophages and Monocytes,” “PI3K signaling in B Lymphocytes”) and master regulators (e.g., TNF, CSF2, TGFB1). The majority of these processes and regulators are modulated in the same direction in Ldlr−/−.Leiden mice fed HFD with a human-like macronutrient composition, thus demonstrating that specific experimental conditions recapitulate human disease on the molecular level of disease pathways and upstream/master regulators. PMID:29527177

  5. Curcumin mitigates lithium-induced thyroid dysfunction by modulating antioxidant status, apoptosis and inflammatory cytokines

    Directory of Open Access Journals (Sweden)

    Sanaa M. Abd El-Twab

    2016-08-01

    Full Text Available Lithium is an integral drug used in the management of acute mania, unipolar and bipolar depression and prophylaxis of bipolar disorders. It has also been shown to reduce suicidal risk and short term mortality. Few experimental studies have demonstrated the thyroid toxicity caused by lithium as well as the possible protective effect of curcumin. Twenty four male albino rats were divided into three groups; group I (control group, group II received lithium carbonate daily for 6 weeks and group III received the same dose of lithium carbonate as group II concomitantly with curcumin for 6 weeks. The specimens were prepared for histopathological, immunohistochemical and biochemical examination. Lithium-induced thyroid dysfunction evidenced by the histopathological and immunohistochemical changes represented by detached cells and vacuolated cytoplasm of some follicular cells and highly significant increase in positive immunostained of thyroglobulin and caspase-3 respectively. Moreover, a significant decrease in serum free triiodothyonine (FT3, free thyroxine (FT4 concomitant with significantly increased thyroid stimulating hormone (TSH and pro-inflammatory cytokines, and thyroid lipid peroxidation (MDA and nitric oxide (NO levels. Curcumin counteracted lithium-induced oxidative stress and inflammation as assessed by restoration of the antioxidant defenses and diminishing of pro-inflammatory cytokines and improvements in the degenerative changes of the thyroid gland. In conclusion, the present study provides evidence that curcumin exerts thyroprotective effects against lithium carbonate mediated by its antioxidant, anti-inflammatory and anti-apoptotic effect as indicated by caspase-3. This report also confers that the use of this drug should be justified for long treatment under direct medical supervision.

  6. Human mesenchymal stem cells modulate inflammatory cytokines after spinal cord injury in rat

    Czech Academy of Sciences Publication Activity Database

    Machová-Urdzíková, Lucia; Růžička, Jiří; LaBagnara, M.; Kárová, Kristýna; Kubinová, Šárka; Jiráková, Klára; Murali, R.; Syková, Eva; Jhanwar-Uniyal, M.; Jendelová, Pavla

    2014-01-01

    Roč. 15, č. 7 (2014), s. 11275-11293 E-ISSN 1422-0067 R&D Projects: GA ČR GP13-15031P; GA ČR(CZ) GA13-00939S; GA MŠk LH12024; GA MŠk EE2.3.30.0018; GA MŠk(CZ) ED1.1.00/02.0109 Grant - others:GAUK(CZ) 521712 Institutional support: RVO:68378041 Keywords : mesenchymal stem cells * spinal cord injury * inflammatory cytokines Subject RIV: FH - Neurology Impact factor: 2.862, year: 2014

  7. Kaempferol modulates pro-inflammatory NF-κB activation by suppressing advanced glycation endproducts-induced NADPH oxidase

    Science.gov (United States)

    Kim, Ji Min; Lee, Eun Kyeong; Kim, Dae Hyun; Yu, Byung Pal

    2010-01-01

    Advanced glycation endproducts (AGE) are oxidative products formed from the reaction between carbohydrates and a free amino group of proteins that are provoked by reactive species (RS). It is also known that AGE enhance the generation of RS and that the binding of AGE to a specific AGE receptor (RAGE) induces the activation of the redox-sensitive, pro-inflammatory transcription factor, nuclear factor-kappa B (NF-ĸB). In this current study, we investigated the anti-oxidative effects of short-term kaempferol supplementation on the age-related formation of AGE and the binding activity of RAGE in aged rat kidney. We further investigated the suppressive action of kaempferol against AGE's ability to stimulate activation of pro-inflammatory NF-ĸB and its molecular mechanisms. For this study, we utilized young (6 months old), old (24 months old), and kaempferol-fed (2 and 4 mg/kg/day for 10 days) old rats. In addition, for the molecular work, the rat endothelial cell line, YPEN-1 was used. The results show that AGE and RAGE were increased during aging and that these increases were blunted by kaempferol. In addition, dietary kaempferol reduced age-related increases in NF-κB activity and NF-ĸB-dependant pro-inflammatory gene activity. The most significant new finding from this study is that kaempferol supplementation prevented age-related NF-κB activation by suppressing AGE-induced nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase). Taken together, our results demonstrated that dietary kaempferol exerts its anti-oxidative and anti-inflammatory actions by modulating the age-related NF-κB signaling cascade and its pro-inflammatory genes by suppressing AGE-induced NADPH oxidase activation. Based on these data, dietary kaempferol is proposed as a possible anti-AGE agent that may have the potential for use in anti-inflammation therapies. PMID:20431987

  8. MicroRNA-27b Modulates Inflammatory Response and Apoptosis during Mycobacterium tuberculosis Infection.

    Science.gov (United States)

    Liang, Shuxin; Song, Zhigang; Wu, Yongyan; Gao, Yuanpeng; Gao, Mingqing; Liu, Fayang; Wang, Fengyu; Zhang, Yong

    2018-04-16

    Mycobacterium tuberculosis poses a significant global health threat. MicroRNAs play an important role in regulating host anti-mycobacterial defense; however, their role in apoptosis-mediated mycobacterial elimination and inflammatory response remains unclear. In this study, we explored the role of microRNA-27b (miR-27b) in murine macrophage responses to M. tuberculosis infection. We uncovered that the TLR-2/MyD88/NF-κB signaling pathway induced the expression of miR-27b and miR-27b suppressed the production of proinflammatory factors and the activity of NF-κB, thereby avoiding an excessive inflammation during M. tuberculosis infection. Luciferase reporter assay and Western blotting showed that miR-27b directly targeted Bcl-2-associated athanogene 2 (Bag2) in macrophages. Overexpression of Bag2 reversed miR-27b-mediated inhibition of the production of proinflammatory factors. In addition, miR-27b increased p53-dependent cell apoptosis and the production of reactive oxygen species and decreased the bacterial burden. We also showed that Bag2 interacts with p53 and negatively regulates its activity, thereby controlling cell apoptosis and facilitating bacterial survival. In summary, we revealed a novel role of the miR-27b/Bag2 axis in the regulation of inflammatory response and apoptosis and provide a potential molecular host defense mechanism against mycobacteria. Copyright © 2018 by The American Association of Immunologists, Inc.

  9. Bioactive Fraction of Geopropolis from Melipona scutellaris Decreases Neutrophils Migration in the Inflammatory Process: Involvement of Nitric Oxide Pathway

    Directory of Open Access Journals (Sweden)

    Marcelo Franchin

    2013-01-01

    Full Text Available The aim of this study was to evaluate the activity of the ethanolic extract of geopropolis (EEGP from Melipona scutellaris and its fractions on the modulation of neutrophil migration in the inflammatory process, and the participation of nitric oxide (NO pathway, as well as to check the chemical profile of the bioactive fraction. EEGP and its aqueous fraction decreased neutrophil migration in the peritoneal cavity and also the interaction of leukocytes (rolling and adhesion with endothelial cells. The levels of chemokines CXCL1/KC and CXCL2/MIP-2 were not altered after treatment with EEGP and the aqueous fraction. It was found that the injection of NO pathway antagonists abolished the EEGP and the aqueous fraction inhibitory activity on the neutrophil migration. The expression of intercellular adhesion molecule type 1 (ICAM-1 was reduced, and nitrite levels increased after treatment with EEGP and aqueous fraction. In the carrageenan-induced paw edema model, EEGP and the aqueous fraction showed antiedema activity. No pattern of flavonoid and phenolic acid commonly found in propolis samples of Apis mellifera could be detected in the aqueous fraction samples. These data indicate that the aqueous fraction found has promising bioactive substances with anti-inflammatory activity.

  10. Bioactive Fraction of Geopropolis from Melipona scutellaris Decreases Neutrophils Migration in the Inflammatory Process: Involvement of Nitric Oxide Pathway.

    Science.gov (United States)

    Franchin, Marcelo; da Cunha, Marcos Guilherme; Denny, Carina; Napimoga, Marcelo Henrique; Cunha, Thiago Mattar; Bueno-Silva, Bruno; Matias de Alencar, Severino; Ikegaki, Masaharu; Luiz Rosalen, Pedro

    2013-01-01

    The aim of this study was to evaluate the activity of the ethanolic extract of geopropolis (EEGP) from Melipona scutellaris and its fractions on the modulation of neutrophil migration in the inflammatory process, and the participation of nitric oxide (NO) pathway, as well as to check the chemical profile of the bioactive fraction. EEGP and its aqueous fraction decreased neutrophil migration in the peritoneal cavity and also the interaction of leukocytes (rolling and adhesion) with endothelial cells. The levels of chemokines CXCL1/KC and CXCL2/MIP-2 were not altered after treatment with EEGP and the aqueous fraction. It was found that the injection of NO pathway antagonists abolished the EEGP and the aqueous fraction inhibitory activity on the neutrophil migration. The expression of intercellular adhesion molecule type 1 (ICAM-1) was reduced, and nitrite levels increased after treatment with EEGP and aqueous fraction. In the carrageenan-induced paw edema model, EEGP and the aqueous fraction showed antiedema activity. No pattern of flavonoid and phenolic acid commonly found in propolis samples of Apis mellifera could be detected in the aqueous fraction samples. These data indicate that the aqueous fraction found has promising bioactive substances with anti-inflammatory activity.

  11. Human, donkey and cow milk differently affects energy efficiency and inflammatory state by modulating mitochondrial function and gut microbiota.

    Science.gov (United States)

    Trinchese, Giovanna; Cavaliere, Gina; Canani, Roberto Berni; Matamoros, Sebastien; Bergamo, Paolo; De Filippo, Chiara; Aceto, Serena; Gaita, Marcello; Cerino, Pellegrino; Negri, Rossella; Greco, Luigi; Cani, Patrice D; Mollica, Maria Pina

    2015-11-01

    Different nutritional components are able, by modulating mitochondrial function and gut microbiota composition, to influence body composition, metabolic homeostasis and inflammatory state. In this study, we aimed to evaluate the effects produced by the supplementation of different milks on energy balance, inflammatory state, oxidative stress and antioxidant/detoxifying enzyme activities and to investigate the role of the mitochondrial efficiency and the gut microbiota in the regulation of metabolic functions in an animal model. We compared the intake of human milk, gold standard for infant nutrition, with equicaloric supplementation of donkey milk, the best substitute for newborns due to its nutritional properties, and cow milk, the primary marketed product. The results showed a hypolipidemic effect produced by donkey and human milk intake in parallel with enhanced mitochondrial activity/proton leakage. Reduced mitochondrial energy efficiency and proinflammatory signals (tumor necrosis factor α, interleukin-1 and lipopolysaccharide levels) were associated with a significant increase of antioxidants (total thiols) and detoxifying enzyme activities (glutathione-S-transferase, NADH quinone oxidoreductase) in donkey- and human milk-treated animals. The beneficial effects were attributable, at least in part, to the activation of the nuclear factor erythroid-2-related factor-2 pathway. Moreover, the metabolic benefits induced by human and donkey milk may be related to the modulation of gut microbiota. In fact, milk treatments uniquely affected the proportions of bacterial phyla and genera, and we hypothesized that the increased concentration of fecal butyrate in human and donkey milk-treated rats was related to the improved lipid and glucose metabolism and detoxifying activities. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  12. Modulating the innate immune response to influenza A virus: potential therapeutic use of anti-inflammatory drugs

    Directory of Open Access Journals (Sweden)

    Irene eRamos

    2015-07-01

    Full Text Available Infection by influenza A viruses (IAV is frequently characterized by robust inflammation that is usually more pronounced in the case of avian influenza. It is becoming clearer that the morbidity and pathogenesis caused by IAV is a consequence of this inflammatory response, with several components of the innate immune system acting as the main players. It has been postulated that using a therapeutic approach to limit the innate immune response in combination with antiviral drugs has the potential to diminish symptoms and tissue damage caused by IAV infection. Indeed, some anti-inflammatory agents have been shown to be effective in animal models at reducing IAV pathology as a proof of principle. The main challenge in developing such therapies is to selectively modulate signaling pathways that contribute to lung injury while maintaining the ability of the host cells to mount an antiviral response to control virus replication. However, the dissection of those pathways is very complex given the numerous components regulated by the same factors (i.e. NF kappa B transcription factors and the large number of players involved in this regulation, some of which may be undescribed or unknown. This article provides a comprehensive review of the current knowledge regarding the innate immune responses associated with tissue damage by IAV infection, the understanding of which is essential for the development of effective immunomodulatory drugs. Furthermore, we summarize the recent advances on the development and evaluation of such drugs as well as the lessons learned from those studies.

  13. Kinetic Assessment and Therapeutic Modulation of Metabolic and Inflammatory Profiles in Mice on a High-Fat and Cholesterol Diet

    Directory of Open Access Journals (Sweden)

    Laura W. Engstrom

    2010-01-01

    Full Text Available The kinetics of metabolic and inflammatory parameters associated with obesity were evaluated in a murine diet-induced obesity (DIO model using a diet high in fat and cholesterol. Cellular infiltration and mediator production were assessed and shown to be therapeutically modulated by the PPARgamma agonist rosiglitazone. C57BL/6 mice were maintained on a 45% fat/0.12% cholesterol (HF/CH or Chow diet for 3, 6, 16, or 27 weeks. Flow cytometry was employed to monitor peripheral blood monocytes and adipose tissue macrophages (ATM. Gene expression and protein analysis methods were used to evaluate mediator production from total epididymal fat (EF, stromal vascular fraction (SVF, and sorted SVF cells. To investigate therapeutic intervention, mice were fed a HF/CH diet for 12 weeks and then a diet formulated with rosiglitazone (5 mg/kg for an additional 6 weeks. A HF/CH diet correlated with obesity and a dramatic proinflammatory state. Therapeutic intervention with rosiglitazone attenuated the HF/CH induced inflammation. In addition, a novel population was found that expressed the highest levels of the pro-inflammatory mediators CCL2 and IL-6.

  14. Low cost solar array project production process and equipment task. A Module Experimental Process System Development Unit (MEPSDU)

    Science.gov (United States)

    1981-01-01

    Technical readiness for the production of photovoltaic modules using single crystal silicon dendritic web sheet material is demonstrated by: (1) selection, design and implementation of solar cell and photovoltaic module process sequence in a Module Experimental Process System Development Unit; (2) demonstration runs; (3) passing of acceptance and qualification tests; and (4) achievement of a cost effective module.

  15. External and internal limitations in amplitude-modulation processing

    DEFF Research Database (Denmark)

    Ewert, Stephan; Dau, Torsten

    2004-01-01

    Three experiments are presented to explore the relative role of "external" signal variability and "internal" resolution limitations of the auditory system in the detection and discrimination of amplitude modulations (AM). In the first experiment, AM-depth discrimination performance was determined......-filterbank models. The predictions revealed that AM-depth discrimination and AM detection are limited by a combination of the external signal variability and an internal "Weber-fraction" noise process....

  16. Cryotherapy Reduces Inflammatory Response Without Altering Muscle Regeneration Process and Extracellular Matrix Remodeling of Rat Muscle.

    Science.gov (United States)

    Vieira Ramos, Gracielle; Pinheiro, Clara Maria; Messa, Sabrina Peviani; Delfino, Gabriel Borges; Marqueti, Rita de Cássia; Salvini, Tania de Fátima; Durigan, Joao Luiz Quagliotti

    2016-01-04

    The application of cryotherapy is widely used in sports medicine today. Cooling could minimize secondary hypoxic injury through the reduction of cellular metabolism and injury area. Conflicting results have also suggested cryotherapy could delay and impair the regeneration process. There are no definitive findings about the effects of cryotherapy on the process of muscle regeneration. The aim of the present study was to evaluate the effects of a clinical-like cryotherapy on inflammation, regeneration and extracellular matrix (ECM) remodeling on the Tibialis anterior (TA) muscle of rats 3, 7 and 14 days post-injury. It was observed that the intermittent application of cryotherapy (three 30-minute sessions, every 2 h) in the first 48 h post-injury decreased inflammatory processes (mRNA levels of TNF-α, NF-κB, TGF-β and MMP-9 and macrophage percentage). Cryotherapy did not alter regeneration markers such as injury area, desmin and Myod expression. Despite regulating Collagen I and III and their growth factors, cryotherapy did not alter collagen deposition. In summary, clinical-like cryotherapy reduces the inflammatory process through the decrease of macrophage infiltration and the accumulation of the inflammatory key markers without influencing muscle injury area and ECM remodeling.

  17. Utility-based early modulation of processing distracting stimulus information.

    Science.gov (United States)

    Wendt, Mike; Luna-Rodriguez, Aquiles; Jacobsen, Thomas

    2014-12-10

    Humans are selective information processors who efficiently prevent goal-inappropriate stimulus information to gain control over their actions. Nonetheless, stimuli, which are both unnecessary for solving a current task and liable to cue an incorrect response (i.e., "distractors"), frequently modulate task performance, even when consistently paired with a physical feature that makes them easily discernible from target stimuli. Current models of cognitive control assume adjustment of the processing of distractor information based on the overall distractor utility (e.g., predictive value regarding the appropriate response, likelihood to elicit conflict with target processing). Although studies on distractor interference have supported the notion of utility-based processing adjustment, previous evidence is inconclusive regarding the specificity of this adjustment for distractor information and the stage(s) of processing affected. To assess the processing of distractors during sensory-perceptual phases we applied EEG recording in a stimulus identification task, involving successive distractor-target presentation, and manipulated the overall distractor utility. Behavioral measures replicated previously found utility modulations of distractor interference. Crucially, distractor-evoked visual potentials (i.e., posterior N1) were more pronounced in high-utility than low-utility conditions. This effect generalized to distractors unrelated to the utility manipulation, providing evidence for item-unspecific adjustment of early distractor processing to the experienced utility of distractor information. Copyright © 2014 the authors 0270-6474/14/3416720-06$15.00/0.

  18. Processing and characterization of device solder interconnection and module attachment for power electronics modules

    Science.gov (United States)

    Haque, Shatil

    This research is focused on the processing of an innovative three-dimensional packaging architecture for power electronics building blocks with soldered device interconnections and subsequent characterization of the module's critical interfaces. A low-cost approach termed metal posts interconnected parallel plate structure (MPIPPS) was developed for packaging high-performance modules of power electronics building blocks (PEBB). The new concept implemented direct bonding of copper posts, not wire bonding of fine aluminum wires, to interconnect power devices as well as joining the different circuit planes together. We have demonstrated the feasibility of this packaging approach by constructing PEBB modules (consisting of Insulated Gate Bipolar Transistors (IGBTs), diodes, and a few gate driver elements and passive components). In the 1st phase of module fabrication with IGBTs with Si3N 4 passivation, we had successfully fabricated packaged devices and modules using the MPIPPS technique. These modules were tested electrically and thermally, and they operated at pulse-switch and high power stages up to 6kW. However, in the 2nd phase of module fabrication with polyimide passivated devices, we experienced significant yield problems due to metallization difficulties of these devices. The under-bump metallurgy scheme for the development of a solderable interface involved sputtering of Ti-Ni-Cu and Cr-Cu, and an electroless deposition of Zn-Ni-Au metallization. The metallization process produced excellent yield in the case of Si3N4 passivated devices. However, under the same metallization schemes, devices with a polyimide passivation exhibited inconsistent electrical contact resistance. We found that organic contaminants such as hydrocarbons remain in the form of thin monolayers on the surface, even in the case of as-received devices from the manufacturer. Moreover, in the case of polyimide passivated devices, plasma cleaning introduced a few carbon constituents on the

  19. Diagnosis of intra abdominal inflammatory processes with 111In-labelled leucocytes

    International Nuclear Information System (INIS)

    Roevekamp, M.H.; Brummelkamp, W.H.; Schoot, J.B. van der; Reinders Folmer, S.Chr.C.; Royen, E.A. van

    1982-01-01

    Over a two and a half year period, 225 scintigrams with indium-111 oxinate labelled leukocytes were performed in 184 patients suspected of an intra-abdominal, retroperitoneal or pelvic inflammatory process. In patients suspected of an upper abdominal process, an indium-111 leukocyte-99Tc-Sn colloid subtraction was performed, in order to eliminate the normal liver and spleen uptake. 123 Scintigrams were considered true positive and 73 true negative. A diagnostic accuracy of 87% was calculated. With 18 false-positive scans an 80%-specificity and with 11 false-negative a 92%-sensitivity were obtained. False-positive results in the majority of the scintigrams were based on leukocyte accumulations, due to aspecific cellular inflammatory reactions. False-negative results were mainly related to intra-hepatic, intra-splenic or older lesions. In 150 patients, ultrasonography and/or computed tomography was also performed. A higher diagnostic accuracy was observed with leukocyte scintigraphy compared to ultrasonography. (Auth.)

  20. DEFINITION OF ETIOLOGICAL ANTIBIOTIC SENSITIVITY FACTORS IN PURULENT-INFLAMMATORY PROCESSES.

    Science.gov (United States)

    Dubovyk, O; Mishyna, М; Malanchuk, S; Kuzmenko, A; Kozlov, O

    2017-10-01

    The purpose of the study - assessment of purulent-inflammatory processes etiologic factors and determination of microbial agents' in forms of plankton and biofilms sensitivity to antibiotics. Clinical microbial strains isolated from patients with purulent-inflammatory processes were the subject of the study. The study material comprised of wound tissue, pus, bandage and suture, catheters and drainage devices. Sensitivity of isolates to antimicrobial preparations with various mechanism of activity on the microbial cells was studied with the help of micro-test system. Formation of biofilms was studied with the help of definition of bacteria strains ability to adhesion to the surface of polystyrene flatbeds. It was revealed that one of the leading factors of purulent-inflammatory process development is S.aureus, which disseminated in 36,5% of cases; E.coli disseminated in 17,3% of cases. Among the agents of purulent-inflammatory processes the specific gravity attributed to: Proteus spp. - 14,6%, S.рyogenes - 12,8%, P.aeruginosa - 6,9%, K.pneumoniae - 6,7%. It was revealed that all isolates formed dense biofilms. It was demonstrated that most isolates in plankton form were sensitive to Novapime, Cefepime, Gatifloxacin, Imipenem; sensitive strains were registered in a smaller quantity to Gentamicin, Clindamycin and Doxycycline. In terms of sensitivity of isolates in the form of biofilm to antibacterial preparations it was revealed that most isolates were polyresistant to them. Thus, the study of the sensitivity of allotted microbial strains to antimicrobial preparations demonstrated, that there were strains among cultures with multiple resistances which was the consequence of a wide and not always effective use of antimicrobial preparations.

  1. Unified microprocessor CAMAC module for preliminary data processing

    International Nuclear Information System (INIS)

    Zaushitsin, V.L.; Kulik, O.V.; Repin, V.M.

    1984-01-01

    The UP-80 unified active module is described. It is made in the CAMAC standard on the base of the K580IK80 microprocessor allowing to increase the rate of large-volume experimental spectroscopic data processing by an order. Loading of 5 different programs for data processing is possible. Data from the operative storage with 1K capacity (8 bits) are recorded and read out trhough the CAMAC line (the regime of unit exchange is possible) or through the joint of the external line

  2. Criticality classification of waste receiving and processing module 2A

    International Nuclear Information System (INIS)

    Boothe, G.F.

    1994-10-01

    The purpose of this document is to evaluate the criticality potential of the Waste Receiving and Processing Module 2A (WRAP 2A) and to demonstrate that the facility is an exempt facility, under the provisions of the Nuclear Criticality Safety Manual. The WRAP 2A maximum potential transuranic (TRU) contents of feedstreams and product inventories are discussed. Total plant fissionable materials are estimated and compared with the fissionable material exempt quantity. The WRAP 2A operations and processes are also described, relative to the potential for concentrating or accumulating fissionable material within the facility

  3. Malignant transformation of oral lichen planus by a chronic inflammatory process. Use of topical corticosteroids to prevent this progression?

    Science.gov (United States)

    Otero-Rey, Eva Maria; Suarez-Alen, Fatima; Peñamaria-Mallon, Manuel; Lopez-Lopez, Jose; Blanco-Carrion, Andres

    2014-11-01

    Oral lichen planus is a potentially malignant disorder with a capacity, although low, for malignant transformation. Of all the factors related to the process of malignant transformation, it is believed that the chronic inflammatory process plays a key role in the development of oral cancer. This inflammatory process is capable of providing a microenvironment based on different inflammatory cells and molecules that affect cellular growth, proliferation and differentiation. The objectives of our study are: to review the available evidence about the possible relationship between the chronic inflammatory process present in oral lichen planus and its malignant transformation, to discuss the potential therapeutic implications derived from this relationship and to study the role that topical corticosteroids play in the control of oral lichen planus inflammation and its possible progression to malignant transformation. The maintenance of a minimum dose of topical corticosteroids could prevent the inflammatory progression of oral lichen planus to oral cancer.

  4. Adiponectin and pro-inflammatory cytokines are modulated in Vietnamese patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Tong, Hoang Van; Luu, Nguyen Kim; Son, Ho Anh; Hoan, Nguyen Van; Hung, Trinh Thanh; Velavan, Thirumalaisamy P; Toan, Nguyen Linh

    2017-05-01

    Adipose tissue-derived hormones are associated with metabolic disorders including type 2 diabetes mellitus. The present study investigated the levels of adiponectin and pro-inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-1 beta (IL-1β) and IL-10 in Vietnamese patients with type 2 diabetes mellitus, and their correlations with clinical parameters of overweight and type 2 diabetes mellitus. Based on body mass index, 73 patients with type 2 diabetes mellitus were categorized either as overweight or non-overweight. As healthy controls, 57 overweight and non-overweight individuals without type 2 diabetes mellitus were included. The adiponectin, TNF-α, IL-1β and IL-10 levels were measured in the sera samples in all study participants by enzyme-linked immunosorbent assay and were correlated with clinical parameters. The adiponectin levels were lower in patients with type 2 diabetes mellitus (2.5 ± 1.5 μg/mL) compared with controls (16 ± 18.6 μg/mL; P < 0.0001), and were decreased in overweight individuals compared with those who were not overweight. The TNF-α and IL-1β levels were increased, whereas the IL-10 levels were decreased in patients with type 2 diabetes mellitus and in overweight controls compared with non-overweight controls (P < 0.0001). The adiponectin levels were correlated with the TNF-α, IL-1β, IL-10 levels, and the clinical parameters of overweight and type 2 diabetes mellitus. The quantitative insulin sensitivity check index and homeostasis model assessment insulin resistance indexes were correlated with the relative ratios of adiponectin/TNF-α, adiponectin/IL-1β, adiponectin/IL-10, TNF-α/IL-10 and IL-1β/IL-10. Adiponectin and pro-inflammatory cytokines are associated with type 2 diabetes mellitus, and might serve as a prognostic marker and a therapeutic intervention for overweight-related type 2 diabetes mellitus. © 2016 The Authors. Journal of Diabetes Investigation published by Asian Association for the

  5. Cucurbita ficifolia (Cucurbitaceae) modulates inflammatory cytokines and IFN-γ in obese mice.

    Science.gov (United States)

    Fortis-Barrera, Á; García-Macedo, R; Almanza-Perez, J C; Blancas-Flores, G; Zamilpa-Alvarez, A; Flores-Sáenz, J L; Cruz, M; Román-Ramos, R; Alarcón-Aguilar, F J

    2017-02-01

    This study investigated the effect of aqueous extract of Cucurbita ficifolia Bouché on systemic chronic inflammation in an obesity model induced by monosodium glutamate (MSG) via modulating the expression of adipokines (TNF-α, IL-6, resistin, and adiponectin) and immune-regulatory cytokines (IFN-γ and IL-10). Cucurbita ficifolia extract was administered daily by gavage to lean and MSG-obese mice for 30 days. At the end of treatment, cytokine mRNA expression in adipose tissue was determined by real-time polymerase chain reaction (PCR), and the protein levels of these cytokines were also quantified by enzyme-linked immunosorbent assay (ELISA). Cucurbita ficifolia extract decreased body mass and inflammation in MSG-obese mice by reducing the expression of TNF-α and IL-6; these decreases were parallel to significant reductions in protein levels. The extract also increased protein levels of IL-10 in lean mice and IFN-γ in both lean and MSG-obese mice. In conclusion, C. ficifolia extract modulates systemic chronic inflammation in MSG-obese mice and could have a beneficial effect on the adaptive immune system in obesity.

  6. Odontogenic Inflammatory Processes of Head and Neck in Computed Tomography Examinations

    International Nuclear Information System (INIS)

    Wabik, Aleksandra; Hendrich, Barbara K.; Nienartowicz, Jan; Guziński, Maciej; Sąsiadek, Marek J.

    2014-01-01

    Infections of odontogenic origin are the most common cause of inflammatory disease of head and neck region. Computed tomography allows for defining localization and extent of inflammatory lesions, visualizes soft tissue involvement, presence of an abscess or an osteolytic lesion around causative tooth. The aim of this study was to assess pathways, by which odontogenic infections spread into respective deep head and neck structures in computed tomography examination, taking into account the following criteria: frequency of involvement of respective deep cervical spaces, possibility to determine a probable causative tooth and concordance with the results of clinical examination. Thirty-eight patients cervicofacial inflammatory disease had undergone CT examination of head and neck region with a 64-slice CT scanner after intravenous contrast administration. Abscess was reported in 30 (79%) cases, while inflammatory infiltration was diagnosed in remaining 8 (21%) patients. There was full concordance between radiological report and intraoperative report In 33 cases (87%). The most commonly involved cervical space was masticator space – 31 patients (82%), followed by submandibular space – 27 patients (71%). Dental examination was impossible in 29 patient because of trismus. During analysis of CT studies we evaluated maxillary and mandibular alveolar processes for presence of osteolytic bone lesions around causative teeth roots and we found them in 30 cases (79%). In 32 cases (84%) cervicofacial infection were of mandibular odontogenic origin. In most cases CT study in patients suspected of odontogenic craniofacial infection revealed presence of an abscess, needing urgent surgery. Inflammatory infiltration of dental origin most frequently involves masticator space, followed by submandibular space. In most cases CT scanning allows for identification of causative teeth, especially when trismus makes detailed clinical examination impossible

  7. Vagus Nerve as Modulator of the Brain–Gut Axis in Psychiatric and Inflammatory Disorders

    Directory of Open Access Journals (Sweden)

    Sigrid Breit

    2018-03-01

    Full Text Available The vagus nerve represents the main component of the parasympathetic nervous system, which oversees a vast array of crucial bodily functions, including control of mood, immune response, digestion, and heart rate. It establishes one of the connections between the brain and the gastrointestinal tract and sends information about the state of the inner organs to the brain via afferent fibers. In this review article, we discuss various functions of the vagus nerve which make it an attractive target in treating psychiatric and gastrointestinal disorders. There is preliminary evidence that vagus nerve stimulation is a promising add-on treatment for treatment-refractory depression, posttraumatic stress disorder, and inflammatory bowel disease. Treatments that target the vagus nerve increase the vagal tone and inhibit cytokine production. Both are important mechanism of resiliency. The stimulation of vagal afferent fibers in the gut influences monoaminergic brain systems in the brain stem that play crucial roles in major psychiatric conditions, such as mood and anxiety disorders. In line, there is preliminary evidence for gut bacteria to have beneficial effect on mood and anxiety, partly by affecting the activity of the vagus nerve. Since, the vagal tone is correlated with capacity to regulate stress responses and can be influenced by breathing, its increase through meditation and yoga likely contribute to resilience and the mitigation of mood and anxiety symptoms.

  8. Rational modulation of neuronal processing with applied electric fields.

    Science.gov (United States)

    Bikson, Marom; Radman, Thomas; Datta, Abhishek

    2006-01-01

    Traditional approaches to electrical stimulation, using trains of supra-threshold pulses to trigger action potentials, may be replaced or augmented by using 'rational' sub-threshold stimulation protocols that incorporate knowledge of single neuron geometry, inhomogeneous tissue properties, and nervous system information coding. Sub-threshold stimulation, at intensities (well) below those sufficient to trigger action potentials, may none-the-less exert a profound effect on brain function through modulation of concomitant neuronal activity. For example, small DC fields may coherently polarize a network of neurons and thus modulate the simultaneous processing of afferent synaptic input as well as resulting changes in synaptic plasticity. Through 'activity-dependent plasticity', sub-threshold fields may allow specific targeting of pathological networks and are thus particularly suitable to overcome the poor anatomical focus of noninvasive (transcranial) electrical stimulation. Additional approaches to improve targeting in transcranial stimulation using novel electrode configurations are also introduced.

  9. Interleukin-1β modulates smooth muscle cell phenotype to a distinct inflammatory state relative to PDGF-DD via NF-κB-dependent mechanisms.

    Science.gov (United States)

    Alexander, Matthew R; Murgai, Meera; Moehle, Christopher W; Owens, Gary K

    2012-04-02

    Smooth muscle cell (SMC) phenotypic modulation in atherosclerosis and in response to PDGF in vitro involves repression of differentiation marker genes and increases in SMC proliferation, migration, and matrix synthesis. However, SMCs within atherosclerotic plaques can also express a number of proinflammatory genes, and in cultured SMCs the inflammatory cytokine IL-1β represses SMC marker gene expression and induces inflammatory gene expression. Studies herein tested the hypothesis that IL-1β modulates SMC phenotype to a distinct inflammatory state relative to PDGF-DD. Genome-wide gene expression analysis of IL-1β- or PDGF-DD-treated SMCs revealed that although both stimuli repressed SMC differentiation marker gene expression, IL-1β distinctly induced expression of proinflammatory genes, while PDGF-DD primarily induced genes involved in cell proliferation. Promoters of inflammatory genes distinctly induced by IL-1β exhibited over-representation of NF-κB binding sites, and NF-κB inhibition in SMCs reduced IL-1β-induced upregulation of proinflammatory genes as well as repression of SMC differentiation marker genes. Interestingly, PDGF-DD-induced SMC marker gene repression was not NF-κB dependent. Finally, immunofluorescent staining of mouse atherosclerotic lesions revealed the presence of cells positive for the marker of an IL-1β-stimulated inflammatory SMC, chemokine (C-C motif) ligand 20 (CCL20), but not the PDGF-DD-induced gene, regulator of G protein signaling 17 (RGS17). Results demonstrate that IL-1β- but not PDGF-DD-induced phenotypic modulation of SMC is characterized by NF-κB-dependent activation of proinflammatory genes, suggesting the existence of a distinct inflammatory SMC phenotype. In addition, studies provide evidence for the possible utility of CCL20 and RGS17 as markers of inflammatory and proliferative state SMCs within atherosclerotic plaques in vivo.

  10. A Versatile Multichannel Digital Signal Processing Module for Microcalorimeter Arrays

    Science.gov (United States)

    Tan, H.; Collins, J. W.; Walby, M.; Hennig, W.; Warburton, W. K.; Grudberg, P.

    2012-06-01

    Different techniques have been developed for reading out microcalorimeter sensor arrays: individual outputs for small arrays, and time-division or frequency-division or code-division multiplexing for large arrays. Typically, raw waveform data are first read out from the arrays using one of these techniques and then stored on computer hard drives for offline optimum filtering, leading not only to requirements for large storage space but also limitations on achievable count rate. Thus, a read-out module that is capable of processing microcalorimeter signals in real time will be highly desirable. We have developed multichannel digital signal processing electronics that are capable of on-board, real time processing of microcalorimeter sensor signals from multiplexed or individual pixel arrays. It is a 3U PXI module consisting of a standardized core processor board and a set of daughter boards. Each daughter board is designed to interface a specific type of microcalorimeter array to the core processor. The combination of the standardized core plus this set of easily designed and modified daughter boards results in a versatile data acquisition module that not only can easily expand to future detector systems, but is also low cost. In this paper, we first present the core processor/daughter board architecture, and then report the performance of an 8-channel daughter board, which digitizes individual pixel outputs at 1 MSPS with 16-bit precision. We will also introduce a time-division multiplexing type daughter board, which takes in time-division multiplexing signals through fiber-optic cables and then processes the digital signals to generate energy spectra in real time.

  11. NPY2-receptor variation modulates iconic memory processes.

    Science.gov (United States)

    Arning, Larissa; Stock, Ann-Kathrin; Kloster, Eugen; Epplen, Jörg T; Beste, Christian

    2014-08-01

    Sensory memory systems are modality-specific buffers that comprise information about external stimuli, which represent the earliest stage of information processing. While these systems have been the subject of cognitive neuroscience research for decades, little is known about the neurobiological basis of sensory memory. However, accumulating evidence suggests that the glutamatergic system and systems influencing glutamatergic neural transmission are important. In the current study we examine if functional promoter variations in neuropeptide Y (NPY) and its receptor gene NPY2R affect iconic memory processes using a partial report paradigm. We found that iconic memory decayed much faster in individuals carrying the rare promoter NPY2R G allele which is associated with increased expression of the Y2 receptor. Possibly this effect is due to altered presynaptic inhibition of glutamate release, known to be modulated by Y2 receptors. Altogether, our results provide evidence that the functionally relevant single nucleotide polymorphism (SNP) in the NPY2R promoter gene affect circumscribed processes of early sensory processing, i.e. only the stability of information in sensory memory buffers. This leads us to suggest that especially the stability of information in sensory memory buffers depends on glutamatergic neural transmission and factors modulating glutamatergic turnover. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

  12. [The contribution of inflammatory process in pathogenesis and natural history of atrial fibrillation].

    Science.gov (United States)

    Zyśko, Dorota; Gajek, Jacek; Mazurek, Walentyna

    2005-02-01

    The inflammatory process plays important role in pathogenesis of some cardiovascular diseases. Atrial fibrillation is atrial arrhythmia with rapid, asynchronous activation of atrial myocytes. The inflammatory process can be responsible for atrial electrical and anatomical remodeling and therefore shifts towards arrhythmia persistence. The presence of systemic inflammation may be assessed by means of C-reactive protein (CRP) measurement. Maximal concentration of CRP coincidences with the peak of paroxysmal atrial fibrillation occurrence in patients after cardiac surgery. In patients with sinus rhythm the concentration of CRP is a risk factor for this arrhythmia in long-term follow-up. In patients with atrial fibrillation mean CRP concentration is 2-fold higher comparing to control group. CRP concentration is higher in patients with chronic than paroxysmal form of this arrhythmia. High CRP level predicts worse results of direct current cardioversion and more frequent paroxysms of atrial fibrillation during follow-up. Besides of, the patients with echocardiographic signs of thromboembolic risk have higher CRP levels than control subjects. There is no data about the influence of anti-inflammatory therapy on atrial fibrillation or its recurrences.

  13. Suppression of Tumorigenesis: Modulation of Inflammatory Cytokines by Oral Administration of Microencapsulated Probiotic Yogurt Formulation

    Directory of Open Access Journals (Sweden)

    Aleksandra Malgorzata Urbanska

    2010-01-01

    Full Text Available The objective of this study was to examine the ability of a novel microencapsulated probiotic yogurt formulation to suppress the intestinal inflammation. We assessed its anticancer activity by screening interleukin-1, 6, and 12 (IL-1, 6, 12, secretory levels of tumor necrosis factor-alpha (TNF-α, interferon-gamma (IFN-γ, prostaglandin E2  (PGE2, and thromboxane B2 in the digesta obtained from the duodenum, jejunum, proximal, and distal segments of the ileum of C57BL/6J-ApcMin/J mice. Formulation-receiving animals showed consistently lower proinflammatory cytokines' levels when compared to control group animals receiving empty alginate-poly-L-lysine-alginate (APA microcapsules suspended in saline. The concentrations of IL-12 found in serum in control and treatment group animals were significant: 46.58±16.96 pg/mL and 158.58±28.56 pg/mL for control and treatment animals, respectively. We determined a significant change in plasma C-reactive protein: 81.04±23.73 ng/mL in control group and 64.21±16.64 ng/mL in treatment group. Western blots showed a 71% downregulation of cyclooxygenase-2 (COX-2 protein in treatment group animals compared to control. These results point to the possibility of using this yogurt formulation in anticancer therapies, in addition to chronic gut diseases such as Crohn's disease, irritable bowel syndrome (IBS, and inflammatory bowel disease (IBD thanks to its inflammation lowering properties.

  14. Trehalose: a biophysics approach to modulate the inflammatory response during endotoxic shock.

    Science.gov (United States)

    Minutoli, Letteria; Altavilla, Domenica; Bitto, Alessandra; Polito, Francesca; Bellocco, Ersilia; Laganà, Giuseppina; Fiumara, Tiziana; Magazù, Salvatore; Migliardo, Federica; Venuti, Francesco Saverio; Squadrito, Francesco

    2008-07-28

    We evaluated the effects of trehalose against endotoxic shock, a condition in which the loss of bio-membrane integrity plays a pivotal role. In addition we performed a biophysics experiment by quasi elastic neutron scattering (QENS) study, to investigate whether the membrane stability effect of trehalose might be correlated with its high capability to switch-off the water diffusive dynamics and, hence, the kinetic mechanisms of interaction. Endotoxic shock was induced in male rats by a single injection of Salmonella enteritidis lipopolysaccharide (LPS; 20 mg/kg/i.p.). Thirty minutes before and 2 h after LPS injection, the animals were randomized to receive vehicle (1 ml/kg/i.p. 0.9%NaCl), sucrose (1 g/kg/i.p.) or trehalose (1 g/kg/i.p.). Mean arterial blood pressure, nuclear factor-kappaB (NF-kappaB) binding activity, Ikappa-Balpha and toll-like receptor-4 (TLR-4) activation were evaluated in both liver and lung. Plasmatic tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), interleukin-6 (IL-6) and malondialdehyde (MDA) were also investigated. We studied liver injury by means of blood alanine aminotransferase activity (ALT); inducible nitric oxide synthase (iNOS) expression, myeloperoxidase (MPO) activity and tissue edema evaluation. Lung injury was investigated by means of tissue monocyte chemoattractant protein-1 (MCP-1) levels, MPO activity, iNOS expression and edema formation. Trehalose reduced hypotension, NF-kappaB binding activity, IkappaBalpha protein loss and TLR-4 activation. In addition trehalose reduced TNF-alpha, IL-1, IL-6 and MDA levels. Trehalose also blunted liver and lung injury. QENS measurements showed also that trehalose possesses a high "switching off" capability. Sucrose did not modify endotoxic shock-induced sequelae. Trehalose blocked the inflammatory cascade triggered by endotoxin shock, stabilizing the bio-membranes and switching off the water diffusive dynamics.

  15. Structural Basis for Carbohydrate Recognition and Anti-inflammatory Modulation by Gastrointestinal Nematode Parasite Toxascaris leonina Galectin*

    Science.gov (United States)

    Hwang, Eun Young; Jeong, Mi Suk; Park, Sang Kyun; Ha, Sung Chul; Yu, Hak Sun; Jang, Se Bok

    2016-01-01

    Toxascaris leonina galectin (Tl-gal) is a galectin-9 homologue protein isolated from an adult worm of the canine gastrointestinal nematode parasite, and Tl-gal-vaccinated challenge can inhibit inflammation in inflammatory bowel disease-induced mice. We determined the first X-ray structures of full-length Tl-gal complexes with carbohydrates (lactose, N-acetyllactosamine, lacto-N-tetraose, sialyllactose, and glucose). Bonds were formed on concave surfaces of both carbohydrate recognition domains (CRDs) in Tl-gal. All binding sites were found in the HXXXR and WGXEER motifs. Charged Arg61/Arg196 and Glu80/Glu215 on the conserved motif of Tl-gal N-terminal CRD and C-terminal CRD are critical amino acids for recognizing carbohydrate binding, and the residues can affect protein folding and structure. The polar amino acids His, Asn, and Trp are also important residues for the interaction with carbohydrates through hydrogen bonding. Hemagglutination activities of Tl-gal were inhibited by interactions with carbohydrates and mutations. We found that the mutation of Tl-gal (E80A/E215A) at the carbohydrate binding region induced protein aggregation and could be caused in many diseases. The short linker region between the N-terminal and C-terminal CRDs of Tl-gal was very stable against proteolysis and maintained its biological activity. This structural information is expected to elucidate the carbohydrate recognition mechanism of Tl-gal and improve our understanding of anti-inflammatory mediators and modulators of immune response. PMID:27742836

  16. Markov modulated Poisson process models incorporating covariates for rainfall intensity.

    Science.gov (United States)

    Thayakaran, R; Ramesh, N I

    2013-01-01

    Time series of rainfall bucket tip times at the Beaufort Park station, Bracknell, in the UK are modelled by a class of Markov modulated Poisson processes (MMPP) which may be thought of as a generalization of the Poisson process. Our main focus in this paper is to investigate the effects of including covariate information into the MMPP model framework on statistical properties. In particular, we look at three types of time-varying covariates namely temperature, sea level pressure, and relative humidity that are thought to be affecting the rainfall arrival process. Maximum likelihood estimation is used to obtain the parameter estimates, and likelihood ratio tests are employed in model comparison. Simulated data from the fitted model are used to make statistical inferences about the accumulated rainfall in the discrete time interval. Variability of the daily Poisson arrival rates is studied.

  17. Atorvastatin restores arsenic-induced vascular dysfunction in rats: Modulation of nitric oxide signaling and inflammatory mediators

    International Nuclear Information System (INIS)

    Kesavan, Manickam; Sarath, Thengumpallil Sasindran; Kannan, Kandasamy; Suresh, Subramaniyam; Gupta, Priyanka; Vijayakaran, Karunakaran; Sankar, Palanisamy; Kurade, Nitin Pandurang; Mishra, Santosh Kumar; Sarkar, Souvendra Nath

    2014-01-01

    We evaluated whether atorvastatin, an extensively prescribed statin for reducing the risks of cardiovascular diseases, can reduce the risk of arsenic-induced vascular dysfunction and inflammation in rats and whether the modulation could be linked to improvement in vascular NO signaling. Rats were exposed to sodium arsenite (100 ppm) through drinking water for 90 consecutive days. Atorvastatin (10 mg/kg bw, orally) was administered once daily during the last 30 days of arsenic exposure. On the 91 st day, blood was collected for measuring serum C-reactive protein. Thoracic aorta was isolated for assessing reactivity to phenylephrine, sodium nitroprusside and acetylcholine; evaluating eNOS and iNOS mRNA expression and measuring NO production, while abdominal aorta was used for ELISA of cytokines, chemokine and vascular cell adhesion molecules. Histopathology was done in aortic arches. Arsenic did not alter phenylephrine-elicited contraction. Atorvastatin inhibited E max of phenylephrine, but it augmented the contractile response in aortic rings from arsenic-exposed animals. Sodium nitroprusside-induced relaxation was not altered with any treatment. However, arsenic reduced acetylcholine-induced relaxation and affected aortic eNOS at the levels of mRNA expression, protein concentration, phosphorylation and NO production. Further, it increased aortic iNOS mRNA expression, iNOS-derived NO synthesis, production of pro-inflammatory mediators (IL-1β, IL-6, MCP-1, VCAM, sICAM) and serum C-reactive protein and aortic vasculopathic lesions. Atorvastatin attenuated these arsenic-mediated functional, biochemical and structural alterations. Results show that atorvastatin has the potential to ameliorate arsenic-induced vascular dysfunction and inflammation by restoring endothelial function with improvement in NO signaling and attenuating production of pro-inflammatory mediators and cell adhesion molecules. - Highlights: • We evaluated if atorvastatin reduce arsenic

  18. Atorvastatin restores arsenic-induced vascular dysfunction in rats: Modulation of nitric oxide signaling and inflammatory mediators

    Energy Technology Data Exchange (ETDEWEB)

    Kesavan, Manickam; Sarath, Thengumpallil Sasindran; Kannan, Kandasamy; Suresh, Subramaniyam; Gupta, Priyanka; Vijayakaran, Karunakaran; Sankar, Palanisamy; Kurade, Nitin Pandurang; Mishra, Santosh Kumar; Sarkar, Souvendra Nath, E-mail: snsarkar1911@rediffmail.com

    2014-10-01

    We evaluated whether atorvastatin, an extensively prescribed statin for reducing the risks of cardiovascular diseases, can reduce the risk of arsenic-induced vascular dysfunction and inflammation in rats and whether the modulation could be linked to improvement in vascular NO signaling. Rats were exposed to sodium arsenite (100 ppm) through drinking water for 90 consecutive days. Atorvastatin (10 mg/kg bw, orally) was administered once daily during the last 30 days of arsenic exposure. On the 91{sup st} day, blood was collected for measuring serum C-reactive protein. Thoracic aorta was isolated for assessing reactivity to phenylephrine, sodium nitroprusside and acetylcholine; evaluating eNOS and iNOS mRNA expression and measuring NO production, while abdominal aorta was used for ELISA of cytokines, chemokine and vascular cell adhesion molecules. Histopathology was done in aortic arches. Arsenic did not alter phenylephrine-elicited contraction. Atorvastatin inhibited E{sub max} of phenylephrine, but it augmented the contractile response in aortic rings from arsenic-exposed animals. Sodium nitroprusside-induced relaxation was not altered with any treatment. However, arsenic reduced acetylcholine-induced relaxation and affected aortic eNOS at the levels of mRNA expression, protein concentration, phosphorylation and NO production. Further, it increased aortic iNOS mRNA expression, iNOS-derived NO synthesis, production of pro-inflammatory mediators (IL-1β, IL-6, MCP-1, VCAM, sICAM) and serum C-reactive protein and aortic vasculopathic lesions. Atorvastatin attenuated these arsenic-mediated functional, biochemical and structural alterations. Results show that atorvastatin has the potential to ameliorate arsenic-induced vascular dysfunction and inflammation by restoring endothelial function with improvement in NO signaling and attenuating production of pro-inflammatory mediators and cell adhesion molecules. - Highlights: • We evaluated if atorvastatin reduce arsenic

  19. The NJOY nuclear data processing system: The MICROR module

    International Nuclear Information System (INIS)

    Mathews, D.R.; Stepanek, J.; Pelloni, S.; Higgs, C.E.

    1984-12-01

    The NJOY nuclear data processing system is a comprehensive computer code package for producing pointwise and multigroup neutron and photon cross sections and related nuclear parameters from ENDF/B-IV and V evaluated nuclear data. The MICROR overlay is a reformatting module that produces cross sections library files for the MICROX, MICROX-2 and MICROBURN postprocessor codes. Using the data on the pointwise and groupwise NJOY tapes, MICROR produces the tapes containing basic nuclear data, FDTAPE, GAR and GGTAPE used by two-region spectrum codes MICROX and MICROX-2 and by two-region spectrum burn-up code MICROBURN. (author)

  20. Neural pulse frequency modulation of an exponentially correlated Gaussian process

    Science.gov (United States)

    Hutchinson, C. E.; Chon, Y.-T.

    1976-01-01

    The effect of NPFM (Neural Pulse Frequency Modulation) on a stationary Gaussian input, namely an exponentially correlated Gaussian input, is investigated with special emphasis on the determination of the average number of pulses in unit time, known also as the average frequency of pulse occurrence. For some classes of stationary input processes where the formulation of the appropriate multidimensional Markov diffusion model of the input-plus-NPFM system is possible, the average impulse frequency may be obtained by a generalization of the approach adopted. The results are approximate and numerical, but are in close agreement with Monte Carlo computer simulation results.

  1. Apparel Research Network (ARN); Apparel Order Processing Module (AOPM): Field User Manual, Version 1

    Science.gov (United States)

    1997-09-30

    changes. Cancel Button Closes the Site Information Screen, abandoning changes. APPAREL ORDER PROCESSING MODULE FIELD USER MANUAL Ordering Official...on the Ordering Official Information Screen. APPAREL ORDER PROCESSING MODULE FIELD USER MANUAL Ordering Official Information Screen (Jjj

  2. Associations of Heart Rate With Inflammatory Markers Are Modulated by Gender and Obesity in Older Adults.

    Science.gov (United States)

    Laudisio, Alice; Bandinelli, Stefania; Gemma, Antonella; Ferrucci, Luigi; Incalzi, Raffaele Antonelli

    2015-07-01

    Faster resting heart rate (HR), which is associated with inflammation and elevated cortisol levels, is a risk factor for excess cardiovascular morbidity and mortality. Obesity is associated with increased cardiovascular morbidity and mortality, inflammation, and elevated cortisol levels. The aim of the present study was to evaluate the interaction of Body Mass Index (BMI) with inflammation and cortisol in modulating HR in older subjects. We analyzed data of 895 participants aged 65+ enrolled in the "InCHIANTI" study, in sinus rhythm, and not taking beta blockers or digoxin. Linear regression was performed to assess the adjusted association between HR, IL-6, and cortisol levels. The model was also analyzed stratifying for BMI tertiles. Logistic regression was adopted for evaluating the association of HR exceeding the mean value with Il-6 and serum cortisol. According to multivariable linear regression, IL-6 and cortisol levels were associated with HR (B = 1.42, 95% CI = 0.43-2.42; p = .005 and B = .34, 95% CI = 0.17-.51; p cortisol). Logistic regression confirmed that IL-6 and cortisol levels were associated with HR above the mean value in the highest BMI tertile (OR = 2.13, 95% CI = 1.15-3.97; p = .009 and OR = 1.14, 95% CI = 1.03-1.25; p = .009, respectively). Faster HR is associated with proinflammatory state in elderly patients; this association seems to be limited to women with higher BMI. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  3. A biomimetic membrane device that modulates the excessive inflammatory response to sepsis.

    Directory of Open Access Journals (Sweden)

    Feng Ding

    Full Text Available OBJECTIVE: Septic shock has a clinical mortality rate approaching fifty percent. The major clinical manifestations of sepsis are due to the dysregulation of the host's response to infection rather than the direct consequences of the invading pathogen. Central to this initial immunologic response is the activation of leukocytes and microvascular endothelium resulting in cardiovascular instability, lung injury and renal dysfunction. Due to the primary role of leukocyte activation in the sepsis syndrome, a synthetic biomimetic membrane, called a selective cytopheretic device (SCD, was developed to bind activated leukocytes. The incorporation of the SCD along an extracorporeal blood circuit coupled with regional anticoagulation with citrate to lower blood ionized calcium was devised to modulate leukocyte activation in sepsis. DESIGN: Laboratory investigation. SETTING: University of Michigan Medical School. SUBJECTS: Pigs weighing 30-35 kg. INTERVENTIONS: To assess the effect of the SCD in septic shock, pigs were administered 30×10(10 bacteria/kg body weight of Escherichia coli into the peritoneal cavity and within 1 hr were immediately placed in an extracorporeal circuit containing SCD. MEASUREMENTS AND MAIN RESULTS: In this animal model, the SCD with citrate compared to control groups without the SCD or with heparin anticoagulation ameliorated the cardiovascular instability and lung sequestration of activated leukocytes, reduced renal dysfunction and improved survival time compared to various control groups. This effect was associated with minimal elevations of systemic circulating neutrophil activation. CONCLUSIONS: These preclinical studies along with two favorable exploratory clinical trials form the basis of an FDA-approved investigational device exemption for a pivotal multicenter, randomized control trial currently underway.

  4. WISP3 (CCN6 Is a Secreted Tumor-Suppressor Protein that Modulates IGF Signaling in Inflammatory Breast Cancer

    Directory of Open Access Journals (Sweden)

    Celina G. Kleer

    2004-03-01

    Full Text Available Inflammatory breast cancer (IBC is the most lethal form of locally advanced breast cancer. We have found that WISP3 is lost in 80% of human IBC tumors and that it has growth- and angiogenesis-inhibitory functions in breast cancer in vitro and in vivo. WISP3 is a cysteine-rich, putatively secreted protein that belongs to the CCN family. It contains a signal peptide at the N-terminus and four highly conserved motifs. Here, for the first time, we investigate the function of WISP3 protein in relationship to its structural features. We found that WISP3 is secreted into the conditioned media and into the lumens of normal breast ducts. Once secreted, WISP3 was able to decrease, directly or through induction of other molecule(s, the IGF-1-induced activation of the IGF-IR, and two of its main downstream signaling molecules, IRS1 and ERK-1/2, in SUM149 IBC cells. Furthermore, WISP3 containing conditioned media decreased the growth rate of SUM149 cells. This work sheds light into the mechanism of WISP3 function by demonstrating that it is secreted and that, once in the extracellular media, it induces a series of molecular events that leads to modulation of IGF-IR signaling pathways and cellular growth in IBC cells.

  5. Evaluation of the effect of Punica granatum juice and punicalagin on NFκB modulation in inflammatory bowel disease.

    Science.gov (United States)

    Shah, Tanmay A; Parikh, Mihir; Patel, Kirti V; Patel, Kalpana G; Joshi, Chaitanya G; Gandhi, Tejal R

    2016-08-01

    Punica granatum L. (Lythraceae) inhibits cancer cell proliferation and apoptosis through the modulation of cellular transcription factors and signaling proteins. No pharmacological work is reported on the effects of P. granatum juice on the cellular signaling pathways involved in initiation and progression of inflammation. The present investigation evaluates the effect of P. granatum juice (PJ) and purified punicalagin (PW) on nuclear factor kappa B (NFκB) and the signaling pathways leading to its expression in colon inflammation. Male Sprague-Dawley rats were divided into six groups: positive and negative control, vehicle (50 % ethanol), standard (5-ASA 100 mg/kg, p.o.), PJ (400 mg/kg, p.o.), PW (4 mg/kg, p.o.). Colitis was induced with 2,4-dinitrobenzene sulfonic acid and animals were euthanized on 18th day. Colon samples collected were subjected to various histological assessment (CMDI, DAI), and biochemical parameters (MPO, MDA, SOD, NO). Gene expression study was carried out using RT-PCR for cytokines (TNF-α, IL-1β, IL-18 and NF-κβ). Pretreatment with PJ and PW significantly (p granatum juice is more biologically active over punicalagin alone and can be potentially used for the treatment of inflammatory bowel disease.

  6. Evolutionary conserved mechanisms pervade structure and transcriptional modulation of allograft inflammatory factor-1 from sea anemone Anemonia viridis.

    Science.gov (United States)

    Cuttitta, Angela; Ragusa, Maria Antonietta; Costa, Salvatore; Bennici, Carmelo; Colombo, Paolo; Mazzola, Salvatore; Gianguzza, Fabrizio; Nicosia, Aldo

    2017-08-01

    Gene family encoding allograft inflammatory factor-1 (AIF-1) is well conserved among organisms; however, there is limited knowledge in lower organisms. In this study, the first AIF-1 homologue from cnidarians was identified and characterised in the sea anemone Anemonia viridis. The full-length cDNA of AvAIF-1 was of 913 bp with a 5' -untranslated region (UTR) of 148 bp, a 3'-UTR of 315 and an open reading frame (ORF) of 450 bp encoding a polypeptide with149 amino acid residues and predicted molecular weight of about 17 kDa. The predicted protein possesses evolutionary conserved EF hand Ca 2+ binding motifs, post-transcriptional modification sites and a 3D structure which can be superimposed with human members of AIF-1 family. The AvAIF-1 transcript was constitutively expressed in all tested tissues of unchallenged sea anemone, suggesting that AvAIF-1 could serve as a general protective factor under normal physiological conditions. Moreover, we profiled the transcriptional activation of AvAIF-1 after challenges with different abiotic/biotic stresses showing induction by warming conditions, heavy metals exposure and immune stimulation. Thus, mechanisms associated to inflammation and immune challenges up-regulated AvAIF-1 mRNA levels. Our results suggest its involvement in the inflammatory processes and immune response of A. viridis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Selective modulation of nociceptive processing due to noise distraction.

    Science.gov (United States)

    Boyle, Yvonne; El-Deredy, Wael; Martínez Montes, Eduardo; Bentley, Deborah E; Jones, Anthony K P

    2008-09-15

    This study investigates the effects of noise distraction on the different components and sources of laser-evoked potentials (LEPs) whilst attending to either the spatial component (localisation performance task) or the affective component (unpleasantness rating task) of pain. LEPs elicited by CO2 laser stimulation of the right forearm were recorded from 64 electrodes in 18 consenting healthy volunteers. Subjects reported either pain location or unpleasantness, in the presence and absence of distraction by continuous 85 dBa white noise. Distributed sources of the LEP peaks were identified using Low Resolution Electromagnetic Tomography (LORETA). Pain unpleasantness ratings and P2 (430 ms) peak amplitude were significantly reduced by distraction during the unpleasantness task, whereas the localisation ability and the corresponding N1/N2 (310 ms) peak amplitude remained unchanged. Noise distraction (at 310 ms) reduced activation in the anterior cingulate cortex (ACC) and precuneus during attention to localisation and unpleasantness, respectively. This suggests a complimentary role for these two areas in the control of attention to pain. In contrast, activation of the occipital pole and SII were enhanced by noise during the localisation and unpleasantness task, respectively, suggesting that the presence of noise was associated with increased spatial attentional load. This study has shown selective modulation of affective pain processing by noise distraction, indicated by a reduction in the unpleasantness ratings and P2 peak amplitude and associated activity within the medial pain system. These results show that processing of the affective component of pain can be differentially modulated by top-down processes, providing a potential mechanism for therapeutic intervention.

  8. Simulated Microgravity Modulates Differentiation Processes of Embryonic Stem Cells

    Directory of Open Access Journals (Sweden)

    Vaibhav Shinde

    2016-04-01

    Full Text Available Background/Aims: Embryonic developmental studies under microgravity conditions in space are very limited. To study the effects of altered gravity on the embryonic development processes we established an in vitro methodology allowing differentiation of mouse embryonic stem cells (mESCs under simulated microgravity within a fast-rotating clinostat (clinorotation and capture of microarray-based gene signatures. Methods: The differentiating mESCs were cultured in a 2D pipette clinostat. The microarray and bioinformatics tools were used to capture genes that are deregulated by simulated microgravity and their impact on developmental biological processes. Results: The data analysis demonstrated that differentiation of mESCs in pipettes for 3 days resultet to early germ layer differentiation and then to the different somatic cell types after further 7 days of differentiation in the Petri dishes. Clinorotation influences differentiation as well as non-differentiation related biological processes like cytoskeleton related 19 genes were modulated. Notably, simulated microgravity deregulated genes Cyr61, Thbs1, Parva, Dhrs3, Jun, Tpm1, Fzd2 and Dll1 are involved in heart morphogenesis as an acute response on day 3. If the stem cells were further cultivated under normal gravity conditions (1 g after clinorotation, the expression of cardiomyocytes specific genes such as Tnnt2, Rbp4, Tnni1, Csrp3, Nppb and Mybpc3 on day 10 was inhibited. This correlated well with a decreasing beating activity of the 10-days old embryoid bodies (EBs. Finally, we captured Gadd45g, Jun, Thbs1, Cyr61and Dll1 genes whose expressions were modulated by simulated microgravity and by real microgravity in various reported studies. Simulated microgravity also deregulated genes belonging to the MAP kinase and focal dhesion signal transduction pathways. Conclusion: One of the most prominent biological processes affected by simulated microgravity was the process of cardiomyogenesis. The

  9. HLA-B27-Homodimer-Specific Antibody Modulates the Expansion of Pro-Inflammatory T-Cells in HLA-B27 Transgenic Rats.

    Directory of Open Access Journals (Sweden)

    Osiris Marroquin Belaunzaran

    Full Text Available HLA-B27 is a common genetic risk factor for the development of Spondyloarthritides (SpA. HLA-B27 can misfold to form cell-surface heavy chain homodimers (B272 and induce pro-inflammatory responses that may lead to SpA pathogenesis. The presence of B272 can be detected on leukocytes of HLA-B27+ Ankylosing spondylitis (AS patients and HLA-B27 transgenic rats. We characterized a novel B272-specific monoclonal antibody to study its therapeutic use in HLA-B27 associated disorders.The monoclonal HD5 antibody was selected from a phage library to target cell-surface B272 homodimers and characterized for affinity, specificity and ligand binding. The immune modulating effect of HD5 was tested in HLA-B27 transgenic rats. Onset and progression of disease profiles were monitored during therapy. Cell-surface B272 and expansion of pro-inflammatory cells from blood, spleen and draining lymph nodes were assessed by flow cytometry.HD5 bound B272 with high specificity and affinity (Kd = 0.32 nM. HD5 blocked cell-surface interaction of B272 with immune regulatory receptors KIR3DL2, LILRB2 and Pirb. In addition, HD5 modulated the production of TNF from CD4+ T-cells by limiting B272 interactions in vitro. In an HLA-B27 transgenic rat model repetitive dosing of HD5 reduced the expansion of pro-inflammatory CD4+ T-cells, and decreased the levels of soluble TNF and number of cell-surface B272 molecules.HD5 predominantly inhibits early TNF production and expansion of pro-inflammatory CD4+ T-cells in HLA-B27 transgenic rats. Monoclonal antibodies targeting cell-surface B272 propose a new concept for the modulation of inflammatory responses in HLA-B27 related disorders.

  10. HLA-B27-Homodimer-Specific Antibody Modulates the Expansion of Pro-Inflammatory T-Cells in HLA-B27 Transgenic Rats

    Science.gov (United States)

    Marroquin Belaunzaran, Osiris; Kleber, Sascha; Schauer, Stefan; Hausmann, Martin; Nicholls, Flora; Van den Broek, Maries; Payeli, Sravan; Ciurea, Adrian; Milling, Simon; Stenner, Frank; Shaw, Jackie; Kollnberger, Simon; Bowness, Paul; Petrausch, Ulf; Renner, Christoph

    2015-01-01

    Objectives HLA-B27 is a common genetic risk factor for the development of Spondyloarthritides (SpA). HLA-B27 can misfold to form cell-surface heavy chain homodimers (B272) and induce pro-inflammatory responses that may lead to SpA pathogenesis. The presence of B272 can be detected on leukocytes of HLA-B27+ Ankylosing spondylitis (AS) patients and HLA-B27 transgenic rats. We characterized a novel B272–specific monoclonal antibody to study its therapeutic use in HLA-B27 associated disorders. Methods The monoclonal HD5 antibody was selected from a phage library to target cell-surface B272 homodimers and characterized for affinity, specificity and ligand binding. The immune modulating effect of HD5 was tested in HLA-B27 transgenic rats. Onset and progression of disease profiles were monitored during therapy. Cell-surface B272 and expansion of pro-inflammatory cells from blood, spleen and draining lymph nodes were assessed by flow cytometry. Results HD5 bound B272 with high specificity and affinity (Kd = 0.32 nM). HD5 blocked cell-surface interaction of B272 with immune regulatory receptors KIR3DL2, LILRB2 and Pirb. In addition, HD5 modulated the production of TNF from CD4+ T-cells by limiting B272 interactions in vitro. In an HLA-B27 transgenic rat model repetitive dosing of HD5 reduced the expansion of pro-inflammatory CD4+ T-cells, and decreased the levels of soluble TNF and number of cell-surface B272 molecules. Conclusion HD5 predominantly inhibits early TNF production and expansion of pro-inflammatory CD4+ T-cells in HLA-B27 transgenic rats. Monoclonal antibodies targeting cell-surface B272 propose a new concept for the modulation of inflammatory responses in HLA-B27 related disorders. PMID:26125554

  11. Natural Modulators of Amyloid-Beta Precursor Protein Processing

    Science.gov (United States)

    Zhang, Can; Tanzi, Rudolph E.

    2013-01-01

    Alzheimer’s disease (AD) is a devastating neurodegenerative disease and the primary cause of dementia, with no cure currently available. The pathogenesis of AD is believed to be primarily driven by Aβ, the principal component of senile plaques. Aβ is an ~4 kDa peptide generated from the amyloid-β precursor protein (APP) through proteolytic secretases. Natural products, particularly those utilized in traditional Chinese medicine (TCM), have a long history alleviating common clinical disorders, including dementia. However, the cell/molecular pathways mediated by these natural products are largely unknown until recently when the underlying molecular mechanisms of the disorders begin to be elucidated. Here, the mechanisms with which natural products modulate the pathogenesis of AD are discussed, in particular, by focusing on their roles in the processing of APP. PMID:22998566

  12. Microstructure fabrication process induced modulations in CVD graphene

    Science.gov (United States)

    Matsubayashi, Akitomo; Zhang, Zhenjun; Lee, Ji Ung; LaBella, Vincent P.

    2014-12-01

    The systematic Raman spectroscopic study of a "mimicked" graphene device fabrication is presented. Upon photoresist baking, compressive stress is induced in the graphene which disappears after it is removed. The indirect irradiation from the electron beam (through the photoresist) does not significantly alter graphene characteristic Raman peaks indicating that graphene quality is preserved upon the exposure. The 2D peak shifts and the intensity ratio of 2D and G band, I(2D)/I(G), decreases upon direct metal deposition (Co and Py) suggesting that the electronic modulation occurs due to sp2 C-C bond weakening. In contrast, a thin metal oxide film deposited graphene does not show either the significant 2D and G peaks shift or I(2D)/I(G) decrease upon the metal deposition suggesting the oxide protect the graphene quality in the fabrication process.

  13. Microstructure fabrication process induced modulations in CVD graphene

    Energy Technology Data Exchange (ETDEWEB)

    Matsubayashi, Akitomo, E-mail: amatsubayashi@albany.edu; Zhang, Zhenjun; Lee, Ji Ung; LaBella, Vincent P., E-mail: vlabella@albany.edu [College of Nanoscale Science and Engineering, University at Albany, SUNY, Albany, New York 12203 (United States)

    2014-12-15

    The systematic Raman spectroscopic study of a “mimicked” graphene device fabrication is presented. Upon photoresist baking, compressive stress is induced in the graphene which disappears after it is removed. The indirect irradiation from the electron beam (through the photoresist) does not significantly alter graphene characteristic Raman peaks indicating that graphene quality is preserved upon the exposure. The 2D peak shifts and the intensity ratio of 2D and G band, I(2D)/I(G), decreases upon direct metal deposition (Co and Py) suggesting that the electronic modulation occurs due to sp{sup 2} C-C bond weakening. In contrast, a thin metal oxide film deposited graphene does not show either the significant 2D and G peaks shift or I(2D)/I(G) decrease upon the metal deposition suggesting the oxide protect the graphene quality in the fabrication process.

  14. Modulation of Autophagy-Like Processes by Tumor Viruses

    Directory of Open Access Journals (Sweden)

    Karl Munger

    2012-06-01

    Full Text Available Autophagy is an intracellular degradation pathway for long-lived proteins and organelles. This process is activated above basal levels upon cell intrinsic or environmental stress and dysregulation of autophagy has been linked to various human diseases, including those caused by viral infection. Many viruses have evolved strategies to directly interfere with autophagy, presumably to facilitate their replication or to escape immune detection. However, in some cases, modulation of autophagy appears to be a consequence of the virus disturbing the cell’s metabolic signaling networks. Here, we summarize recent advances in research at the interface of autophagy and viral infection, paying special attention to strategies that human tumor viruses have evolved.

  15. Modulated neural processing of Western harmony in folk musicians.

    Science.gov (United States)

    Brattico, Elvira; Tupala, Tiina; Glerean, Enrico; Tervaniemi, Mari

    2013-07-01

    A chord deviating from the conventions of Western tonal music elicits an early right anterior negativity (ERAN) in inferofrontal brain regions. Here, we tested whether the ERAN is modulated by expertise in more than one music culture, as typical of folk musicians. Finnish folk musicians and nonmusicians participated in electroencephalography recordings. The cadences consisted of seven chords. In incongruous cadences, the third, fifth, or seventh chord was a Neapolitan. The ERAN to the Neapolitans was enhanced in folk musicians compared to nonmusicians. Folk musicians showed an enhanced P3a for the ending Neapolitan. The Neapolitan at the fifth position was perceived differently and elicited a late enhanced ERAN in folk musicians. Hence, expertise in more than one music culture seems to modify chord processing by enhancing the ERAN to ambivalent chords and the P3a to incongruous chords, and by altering their perceptual attributes. Copyright © 2013 Society for Psychophysiological Research.

  16. Modulation of Human Time Processing by Subthalamic Deep Brain Stimulation

    Science.gov (United States)

    Timmermann, Lars; Reck, Christiane; Maarouf, Mohammad; Jörgens, Silke; Ploner, Markus; Südmeyer, Martin; Groiss, Stefan Jun; Sturm, Volker; Niedeggen, Michael; Schnitzler, Alfons

    2011-01-01

    Timing in the range of seconds referred to as interval timing is crucial for cognitive operations and conscious time processing. According to recent models of interval timing basal ganglia (BG) oscillatory loops are involved in time interval recognition. Parkinsońs disease (PD) is a typical disease of the basal ganglia that shows distortions in interval timing. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a powerful treatment of PD which modulates motor and cognitive functions depending on stimulation frequency by affecting subcortical-cortical oscillatory loops. Thus, for the understanding of BG-involvement in interval timing it is of interest whether STN-DBS can modulate timing in a frequency dependent manner by interference with oscillatory time recognition processes. We examined production and reproduction of 5 and 15 second intervals and millisecond timing in a double blind, randomised, within-subject repeated-measures design of 12 PD-patients applying no, 10-Hz- and ≥130-Hz-STN-DBS compared to healthy controls. We found under(re-)production of the 15-second interval and a significant enhancement of this under(re-)production by 10-Hz-stimulation compared to no stimulation, ≥130-Hz-STN-DBS and controls. Milliseconds timing was not affected. We provide first evidence for a frequency-specific modulatory effect of STN-DBS on interval timing. Our results corroborate the involvement of BG in general and of the STN in particular in the cognitive representation of time intervals in the range of multiple seconds. PMID:21931767

  17. Modulation of human time processing by subthalamic deep brain stimulation.

    Science.gov (United States)

    Wojtecki, Lars; Elben, Saskia; Timmermann, Lars; Reck, Christiane; Maarouf, Mohammad; Jörgens, Silke; Ploner, Markus; Südmeyer, Martin; Groiss, Stefan Jun; Sturm, Volker; Niedeggen, Michael; Schnitzler, Alfons

    2011-01-01

    Timing in the range of seconds referred to as interval timing is crucial for cognitive operations and conscious time processing. According to recent models of interval timing basal ganglia (BG) oscillatory loops are involved in time interval recognition. Parkinsońs disease (PD) is a typical disease of the basal ganglia that shows distortions in interval timing. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a powerful treatment of PD which modulates motor and cognitive functions depending on stimulation frequency by affecting subcortical-cortical oscillatory loops. Thus, for the understanding of BG-involvement in interval timing it is of interest whether STN-DBS can modulate timing in a frequency dependent manner by interference with oscillatory time recognition processes. We examined production and reproduction of 5 and 15 second intervals and millisecond timing in a double blind, randomised, within-subject repeated-measures design of 12 PD-patients applying no, 10-Hz- and ≥ 130-Hz-STN-DBS compared to healthy controls. We found under(re-)production of the 15-second interval and a significant enhancement of this under(re-)production by 10-Hz-stimulation compared to no stimulation, ≥ 130-Hz-STN-DBS and controls. Milliseconds timing was not affected. We provide first evidence for a frequency-specific modulatory effect of STN-DBS on interval timing. Our results corroborate the involvement of BG in general and of the STN in particular in the cognitive representation of time intervals in the range of multiple seconds.

  18. GanedenBC30™ cell wall and metabolites: anti-inflammatory and immune modulating effects in vitro

    OpenAIRE

    Carter Steve G; Benson Kathleen F; Jensen Gitte S; Endres John R

    2010-01-01

    Abstract Background This study was performed to evaluate anti-inflammatory and immune modulating properties of the probiotic, spore-forming bacterial strain: Bacillus coagulans: GBI-30, (PTA-6086, GanedenBC30TM). In addition, cell wall and metabolite fractions were assayed separately to address whether biological effects were due to cell wall components only, or whether secreted compounds from live bacteria had additional biological properties. The spores were heat-activated, and bacterial cu...

  19. Curcumin modulates the inflammatory response and inhibits subsequent fibrosis in a mouse model of viral-induced acute respiratory distress syndrome.

    Science.gov (United States)

    Avasarala, Sreedevi; Zhang, Fangfang; Liu, Guangliang; Wang, Ruixue; London, Steven D; London, Lucille

    2013-01-01

    Acute Respiratory Distress Syndrome (ARDS) is a clinical syndrome characterized by diffuse alveolar damage usually secondary to an intense host inflammatory response of the lung to a pulmonary or extrapulmonary infectious or non-infectious insult often leading to the development of intra-alveolar and interstitial fibrosis. Curcumin, the principal curcumoid of the popular Indian spice turmeric, has been demonstrated as an anti-oxidant and anti-inflammatory agent in a broad spectrum of diseases. Using our well-established model of reovirus 1/L-induced acute viral pneumonia, which displays many of the characteristics of the human ALI/ARDS, we evaluated the anti-inflammatory and anti-fibrotic effects of curcumin. Female CBA/J mice were treated with curcumin (50 mg/kg) 5 days prior to intranasal inoculation with 10(7)pfu reovirus 1/L and daily, thereafter. Mice were evaluated for key features associated with ALI/ARDS. Administration of curcumin significantly modulated inflammation and fibrosis, as revealed by histological and biochemical analysis. The expression of IL-6, IL-10, IFNγ, and MCP-1, key chemokines/cytokines implicated in the development of ALI/ARDS, from both the inflammatory infiltrate and whole lung tissue were modulated by curcumin potentially through a reduction in the phosphorylated form of NFκB p65. While the expression of TGFß1 was not modulated by curcumin, TGFß Receptor II, which is required for TGFß signaling, was significantly reduced. In addition, curcumin also significantly inhibited the expression of α-smooth muscle actin and Tenascin-C, key markers of myofibroblast activation. This data strongly supports a role for curcumin in modulating the pathogenesis of viral-induced ALI/ARDS in a pre-clinical model potentially manifested through the alteration of inflammation and myofibroblast differentiation.

  20. Attention Modulates the Neural Processes Underlying Multisensory Integration of Emotion

    Directory of Open Access Journals (Sweden)

    Hao Tam Ho

    2011-10-01

    Full Text Available Integrating emotional information from multiple sensory modalities is generally assumed to be a pre-attentive process (de Gelder et al., 1999. This assumption, however, presupposes that the integrative process occurs independent of attention. Using event-potentials (ERP the present study investigated whether the neural processes underlying the integration of dynamic facial expression and emotional prosody is indeed unaffected by attentional manipulations. To this end, participants were presented with congruent and incongruent face-voice combinations (eg, an angry face combined with a neutral voice and performed different two-choice tasks in four consecutive blocks. Three of the tasks directed the participants' attention to emotion expressions in the face, the voice or both. The fourth task required participants to attend to the synchronicity between voice and lip movements. The results show divergent modulations of early ERP components by the different attentional manipulations. For example, when attention was directed to the face (or the voice, incongruent stimuli elicited a reduced N1 as compared to congruent stimuli. This effect was absent, when attention was diverted away from the emotionality in both face and voice suggesting that the detection of emotional incongruence already requires attention. Based on these findings, we question whether multisensory integration of emotion occurs indeed pre-attentively.

  1. Structure Characterization of Honey-Processed Astragalus Polysaccharides and Its Anti-Inflammatory Activity In Vitro

    Directory of Open Access Journals (Sweden)

    Jingzhu Liao

    2018-01-01

    Full Text Available Honey-processed Astragalus is a dosage form of Radix Astragalus mixed with honey by a traditional Chinese medicine processing method which strengthens the tonic effect. Astragalus polysaccharide (APS, perform its immunomodulatory effects by relying on the tonic effect of Radix Astragalus, therefore, the improved pharmacological activity of honey-processed Astragalus polysaccharide (HAPS might be due to structural changes during processing. The molecular weights of HAPS and APS were 1,695,788 Da, 2,047,756 Da, respectively, as determined by high performance gel filtration chromatography combined with evaporative light scattering detection (HPGFC-ELSD. The monosaccharide composition was determined by ultra-performance liquid chromatogram quadrupole time-of-flight mass spectrometry (UPLC/ESI-Q-TOF-MS after pre-column derivatization with 1-phenyl-3-methyl-5-pyrazolone (PMP. The results showed that the essential components were mannose, glucose, xylose, arabinose, glucuronic acid and rhamnose, is molar ratios of 0.06:28.34:0.58:0.24:0.33:0.21 and 0.27:12.83:1.63:0.71:1.04:0.56, respectively. FT-IR and NMR analysis of HAPS results showed the presence of uronic acid and acetyl groups. The anti-inflammatory activities of HAPS were more effective than those of APS according to the NO contents and the expression of IFN-γ, IL-1β, IL-22 and TNF-α in lipopolysaccharide (LPS-induced RAW264.7 cells. This findings suggest that the anti-inflammatory and bioactivity improvement might be associated with molecular structure changes, bearing on the potential immunomodulatory action.

  2. Structure Characterization of Honey-Processed Astragalus Polysaccharides and Its Anti-Inflammatory Activity In Vitro.

    Science.gov (United States)

    Liao, Jingzhu; Li, Chanyi; Huang, Jing; Liu, Wuping; Chen, Hongce; Liao, Shuangye; Chen, Hongyuan; Rui, Wen

    2018-01-15

    Honey-processed Astragalus is a dosage form of Radix Astragalus mixed with honey by a traditional Chinese medicine processing method which strengthens the tonic effect. Astragalus polysaccharide (APS), perform its immunomodulatory effects by relying on the tonic effect of Radix Astragalus , therefore, the improved pharmacological activity of honey-processed Astragalus polysaccharide (HAPS) might be due to structural changes during processing. The molecular weights of HAPS and APS were 1,695,788 Da, 2,047,756 Da, respectively, as determined by high performance gel filtration chromatography combined with evaporative light scattering detection (HPGFC-ELSD). The monosaccharide composition was determined by ultra-performance liquid chromatogram quadrupole time-of-flight mass spectrometry (UPLC/ESI-Q-TOF-MS) after pre-column derivatization with 1-phenyl-3-methyl-5-pyrazolone (PMP). The results showed that the essential components were mannose, glucose, xylose, arabinose, glucuronic acid and rhamnose, is molar ratios of 0.06:28.34:0.58:0.24:0.33:0.21 and 0.27:12.83:1.63:0.71:1.04:0.56, respectively. FT-IR and NMR analysis of HAPS results showed the presence of uronic acid and acetyl groups. The anti-inflammatory activities of HAPS were more effective than those of APS according to the NO contents and the expression of IFN-γ, IL-1β, IL-22 and TNF-α in lipopolysaccharide (LPS)-induced RAW264.7 cells. This findings suggest that the anti-inflammatory and bioactivity improvement might be associated with molecular structure changes, bearing on the potential immunomodulatory action.

  3. Adjuvant effect of Asparagus racemosus Willd. derived saponins in antibody production, allergic response and pro-inflammatory cytokine modulation.

    Science.gov (United States)

    Tiwari, Nimisha; Gupta, Vivek Kumar; Pandey, Pallavi; Patel, Dinesh Kumar; Banerjee, Suchitra; Darokar, Mahendra Pandurang; Pal, Anirban

    2017-02-01

    The study manifests the immunoadjuvant potential of saponin rich fraction from Asparagus racemosus in terms of cellular and humoral immune response that can be exploited against microbial infections. Asparagus racemosus (AR) has been attributed as an adaptogen and rasayana in traditional medication systems for enhancing the host defence mechanism. Spectrophotometric and HPTLC analysis ensured the presence of saponins. The saponin rich fractions were tested for immunoadjuvant property in ovalbumin immunised mice for the humoral response, quantified in terms of prolonged antibody production upto a duration of 56days. Proinflammatory cytokines (IL-6 and TNF) were estimated for the cellular immune response in LPS stimulated primary murine macrophages. The safety evaluation in terms of cytotoxicity and allergic response has also been evaluated through in-vitro (MTT) and in-vivo (IgE) respectively. ARS significantly inhibited the pro-inflammatory cytokines, in LPS stimulated murine macrophages with no intrinsic cytotoxicity. The significant increase in IgG production infers the utility of ARS for prolonged humoral response. Further, the antigen specific response of IL-12 at early stage and IgE titres also suggests the generation of cellular immune response and low allergic reaction respectively, as compared to conventional adjuvants. IL-6 and TNF fluctuations in LPS stimulated and non-stimulated macrophages along with IgG and IL-12 also confirmed the Th1/Th2 modulating effect of ARS. The study indicates potential effect of ARS as an adjuvant for the stimulation of cellular immune response in addition to generating a sustained adaptive response without any adverse effects paving way for further validation with pathogenic organisms. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  4. Altered joint tribology in osteoarthritis: Reduced lubricin synthesis due to the inflammatory process. New horizons for therapeutic approaches.

    Science.gov (United States)

    Szychlinska, M A; Leonardi, R; Al-Qahtani, M; Mobasheri, A; Musumeci, G

    2016-06-01

    Osteoarthritis (OA) is the most common form of joint disease. This review aimed to consolidate the current evidence that implicates the inflammatory process in the attenuation of synovial lubrication and joint tissue homeostasis in OA. Moreover, with these findings, we propose some evidence for novel therapeutic strategies for preventing and/or treating this complex disorder. The studies reviewed support that inflammatory mediators participate in the onset and progression of OA after joint injury. The flow of pro-inflammatory cytokines following an acute injury seems to be directly associated with altered lubricating ability in the joint tissue. The latter is associated with reduced level of lubricin, one of the major joint lubricants. Future research should focus on the development of new therapies that attenuate the inflammatory process and restore lubricin synthesis and function. This approach could support joint tribology and synovial lubrication leading to improved joint function and pain relief. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  5. Oxidized low-density lipoproteins induced inflammatory process during atherogenesis with aging

    International Nuclear Information System (INIS)

    Larbi, Anis; Khalil, Abdelouahed; Douziech, Nadine; Guerard, Karl-Philippe; Fueloep, Tamas

    2005-01-01

    Atherosclerosis is a chronic disease developing through decades with two life-threatening complications: myocardial infarction and stroke. Oxidized low-density lipoproteins (oxLDL) produced by oxidative modifications of LDL in the subendothelial space have been demonstrated to be critically involved in atherogenesis through their intensive pro-inflammatory activity. Recently, it was shown that oxLDL have an apoptosis-inducing effect in T cells depending on time and degree of oxidation. The goal of the current study is to elucidate the molecular mechanisms underlying the apoptotic-inducing effects of oxLDL on T lymphocytes. T cells of young and elderly subjects were incubated for various periods of time with LDL oxidized to various degrees. The proliferation, the apoptosis, the MAPK ERK1/2 activation and the expression of the Bcl-2 protein family members were measured upon different LDL treatments. Thus, more the LDL are oxidized more they induce apoptosis and this effect is highly accentuated with aging. The oxLDL decrease the activation of the surviving molecule ERK1/2 and modulate the ratio of Bax/Bcl-2 towards a pro-apoptotic profile, which is also accentuated with aging. These results partly explain why atherosclerosis is increasing with aging concomitantly to its complications

  6. Oral fungal immunomodulatory protein-Flammulina velutipes has influence on pulmonary inflammatory process and potential treatment for allergic airway disease: A mouse model

    Directory of Open Access Journals (Sweden)

    Po-Yu Chu

    2017-06-01

    Conclusion: Oral FIP-fve had an anti-inflammatory effect on the acute phase of the airway inflammatory process induced by HDM in the mouse model and might have a potentially therapeutic role for allergic airway diseases.

  7. Computer tomography of inflammatory rheumatic degenerative and reparative affections and transformation processes in the region of the sacroiliac joints

    International Nuclear Information System (INIS)

    Heller, M.; Guertler, K.F.; Dihlmann, W.; Allgemeines Krankenhaus Barmbek, Hamburg

    1980-01-01

    Inflammatory rheumatic, degenerative and reparative affections and transformation processes in the region of the sacroiliac joints can be demonstrated via computer tomography and/or conventinal roentgenology. It is found that computer tomography is superior to plain roentgenography diagnosis, including tomography, in respect of malpositioning of the articulating bones and reparative phenomena. On the other hand, early diagnosis of inflammatory rheumatic changes does not yield any additional information via computer tomography. (orig.) [de

  8. Visualization of inflammatory processes using 'in vitro' and in vivo' labelled leucocytes

    International Nuclear Information System (INIS)

    Kostadinova, I.; Milanov, S.; Kovacheva, S.

    1993-01-01

    The labelled leucocytes have become a means of choice for the diagnosis of a variety of active inflammatory conditions. The aim of the study was to evaluate 'in vivo' and 'in vitro' methods for labelling of leucocytes. A total of 146 patients, suspected of having various inflammatory lesions were examined. In 95 of them 'in vitro' method with 99m Tc-HMPAO or 111 In-oxine was used, in 29 'in vivo' method with 99m Tc-MAB (BW 250/183) and in 22 both methods. The obtained results of sensitivity, specificity and accuracy were 87,3%, 96,5%, 89,5% for 'in vitro' method and 83,3%, 93,8%, 86,2% for 'in vivo' method. Taking into consideration the received data and comparable results, we think that in seriously ill patients and in cases of urgency, the use of easier 'in vivo' method is more suitable, while in chronic processes or in such with unclear localisation, 'in vitro' method is recommended, which sometimes gives images with better quality. (orig.) [de

  9. Is SPECT useful in imaging of abdominal inflammatory processes using 99mTc-HMPAO-WBCs?

    International Nuclear Information System (INIS)

    Smole, M.S.; Stantic, T.S.; Fettich, J.F.

    2002-01-01

    Aim: The aim of the study is to determine whether SPECT gives additional information in the assessment of inflammation of the abdominal region with labelled white blood cells as compared with usual planar imaging. Patients And Methods: SPECT and planar imaging was performed in 26 patients with suspected inflammatory process in the abdomen, within three hours after injection of autologous white blood cells labelled with 99m Tc HMPAO. Planar images where acquired as static spot images using high resolution low energy collimator on 256 x 256 matrix. SPECT was performed using the same collimator on 128 x 128 matrix in 128 projections. Filtered back projection was used for reconstruction and volume rendering was performed. Results: The lesions in the abdomen were classified as jejunum, colon ascendents, colon transversum, colon descendents, sigmoid, and lesions outside GIT. All lesions, which were seen on planar images, except one, were also seen on SPECT. Five equivocal lesions seen on planar images were reconfirmed as pathological on SPECT. Additionally SPECT revealed three lesions not seen on planar images. Fourteen lesions were seen by both imaging techniques. All together SPECT improved diagnostic accuracy of 99m Tc - HMPAO - WBC scintigraphy in 7/28 patients. Conclusion: more inflammatory lesions in the abdomen are revealed by SPECT and volume rendering, than by planar imaging equivocal lesions seen on planar images can be characterised as positive or negative by SPECT. SPECT artefacts can cause possible false positive results; therefore usual planar imaging cannot be omitted if SPECT is performed

  10. Emotional sounds modulate early neural processing of emotional pictures

    Directory of Open Access Journals (Sweden)

    Antje B M Gerdes

    2013-10-01

    Full Text Available In our natural environment, emotional information is conveyed by converging visual and auditory information; multimodal integration is of utmost importance. In the laboratory, however, emotion researchers have mostly focused on the examination of unimodal stimuli. Few existing studies on multimodal emotion processing have focused on human communication such as the integration of facial and vocal expressions. Extending the concept of multimodality, the current study examines how the neural processing of emotional pictures is influenced by simultaneously presented sounds. Twenty pleasant, unpleasant, and neutral pictures of complex scenes were presented to 22 healthy participants. On the critical trials these pictures were paired with pleasant, unpleasant and neutral sounds. Sound presentation started 500 ms before picture onset and each stimulus presentation lasted for 2s. EEG was recorded from 64 channels and ERP analyses focused on the picture onset. In addition, valence, and arousal ratings were obtained. Previous findings for the neural processing of emotional pictures were replicated. Specifically, unpleasant compared to neutral pictures were associated with an increased parietal P200 and a more pronounced centroparietal late positive potential (LPP, independent of the accompanying sound valence. For audiovisual stimulation, increased parietal P100 and P200 were found in response to all pictures which were accompanied by unpleasant or pleasant sounds compared to pictures with neutral sounds. Most importantly, incongruent audiovisual pairs of unpleasant pictures and pleasant sounds enhanced parietal P100 and P200 compared to pairings with congruent sounds. Taken together, the present findings indicate that emotional sounds modulate early stages of visual processing and, therefore, provide an avenue by which multimodal experience may enhance perception.

  11. Acute fluoxetine modulates emotional processing in young adult volunteers.

    Science.gov (United States)

    Capitão, L P; Murphy, S E; Browning, M; Cowen, P J; Harmer, C J

    2015-08-01

    Fluoxetine is generally regarded as the first-line pharmacological treatment for young people, as it is believed to show a more favourable benefit:risk ratio than other antidepressants. However, the mechanisms through which fluoxetine influences symptoms in youth have been little investigated. This study examined whether acute administration of fluoxetine in a sample of young healthy adults altered the processing of affective information, including positive, sad and anger cues. A total of 35 male and female volunteers aged between 18 and 21 years old were randomized to receive a single 20 mg dose of fluoxetine or placebo. At 6 h after administration, participants completed a facial expression recognition task, an emotion-potentiated startle task, an attentional dot-probe task and the Rapid Serial Visual Presentation. Subjective ratings of mood, anxiety and side effects were also taken pre- and post-fluoxetine/placebo administration. Relative to placebo-treated participants, participants receiving fluoxetine were less accurate at identifying anger and sadness and did not show the emotion-potentiated startle effect. There were no overall significant effects of fluoxetine on subjective ratings of mood. Fluoxetine can modulate emotional processing after a single dose in young adults. This pattern of effects suggests a potential cognitive mechanism for the greater benefit:risk ratio of fluoxetine in adolescent patients.

  12. Modulation of magmatic processes by CO2 flushing

    Science.gov (United States)

    Caricchi, Luca; Sheldrake, Tom E.; Blundy, Jon

    2018-06-01

    Magmatic systems are the engines driving volcanic eruptions and the source of fluids responsible for the formation of porphyry-type ore deposits. Sudden variations of pressure, temperature and volume in magmatic systems can produce unrest, which may culminate in a volcanic eruption and/or the abrupt release of ore-forming fluids. Such variations of the conditions within magmatic systems are commonly ascribed to the injection of new magma from depth. However, as magmas fractionating at depth or rising to the upper crust release CO2-rich fluids, the interaction between carbonic fluids and H2O-rich magmas stored in the upper crust (CO2 flushing), must also be a common process affecting the evolution of subvolcanic magma reservoirs. Here, we investigate the effect of gas injection on the stability and chemical evolution of magmatic systems. We calculate the chemical and physical evolution of magmas subjected to CO2-flushing using rhyolite-MELTS. We compare the calculations with a set of melt inclusion data for Mt. St. Helens, Merapi, Etna, and Stromboli volcanoes. We provide an approach that can be used to distinguish between melt inclusions trapped during CO2 flushing, magma ascent and decompression, or those affected by post-entrapment H2O-loss. Our results show that CO2 flushing is a widespread process in both felsic and mafic magmatic systems. Depending upon initial magma crystallinity and duration of CO2 input, flushing can either lead to volcanic eruption or fluid release. We suggest that CO2 flushing is a fundamental process modulating the behaviour and chemical evolution of crustal magmatic systems.

  13. Transcranial direct current stimulation improves long-term memory deficits in an animal model of attention-deficit/hyperactivity disorder and modulates oxidative and inflammatory parameters.

    Science.gov (United States)

    Leffa, Douglas Teixeira; Bellaver, Bruna; Salvi, Artur Alban; de Oliveira, Carla; Caumo, Wolnei; Grevet, Eugenio Horacio; Fregni, Felipe; Quincozes-Santos, André; Rohde, Luis Augusto; Torres, Iraci L S

    2018-04-05

    Transcranial direct current stimulation (tDCS) is a technique that modulates neuronal activity and has been proposed as a potential therapeutic tool for attention-deficit/hyperactivity disorder (ADHD) symptoms. Although pilot studies have shown evidence of efficacy, its mechanism of action remains unclear. We evaluated the effects of tDCS on behavioral (working and long-term memory) and neurochemical (oxidative and inflammatory parameters) outcomes related to ADHD pathophysiology. We used the most widely accepted animal model of ADHD: spontaneously hypertensive rats (SHR). The selected behavioral outcomes have been shown to be altered in both ADHD patients and animal models, and were chosen for their relation to the proposed mechanistic action of tDCS. Adult male SHR and their control, the Wistar Kyoto rats (WKY), were subjected to 20 min of bicephalic tDCS or sham stimulation for 8 consecutive days. Working memory, long-term memory, and neurochemical outcomes were evaluated. TDCS improved long-term memory deficits presented by the SHR. No change in working memory performance was observed. In the hippocampus, tDCS increased both the production of reactive oxygen species in SHR and the levels of the antioxidant molecule glutathione in both strains. TDCS also modulated inflammatory response in the brains of WKY by downregulating pro-inflammatory cytokines. TDCS had significant effects that were specific for strain, type of behavioral and neurochemical outcomes. The long-term memory improvement in the SHR may point to a possible therapeutic role of tDCS in ADHD that does not seem to be mediated by inflammatory markers. Additionally, the anti-inflammatory effects observed in the brain of WKY after tDCS needs to be further explored. Copyright © 2018 Elsevier Inc. All rights reserved.

  14. Human Milk and Donkey Milk, Compared to Cow Milk, Reduce Inflammatory Mediators and Modulate Glucose and Lipid Metabolism, Acting on Mitochondrial Function and Oleylethanolamide Levels in Rat Skeletal Muscle.

    Science.gov (United States)

    Trinchese, Giovanna; Cavaliere, Gina; De Filippo, Chiara; Aceto, Serena; Prisco, Marina; Chun, Jong Tai; Penna, Eduardo; Negri, Rossella; Muredda, Laura; Demurtas, Andrea; Banni, Sebastiano; Berni-Canani, Roberto; Mattace Raso, Giuseppina; Calignano, Antonio; Meli, Rosaria; Greco, Luigi; Crispino, Marianna; Mollica, Maria P

    2018-01-01

    Scope: Milk from various species differs in nutrient composition. In particular, human milk (HM) and donkey milk (DM) are characterized by a relative high level of triacylglycerol enriched in palmitic acid in sn-2 position. These dietary fats seem to exert beneficial nutritional properties through N-acylethanolamine tissue modulation. The aim of this study is to compare the effects of cow milk (CM), DM, and HM on inflammation and glucose and lipid metabolism, focusing on mitochondrial function, efficiency, and dynamics in skeletal muscle, which is the major determinant of resting metabolic rate. Moreover, we also evaluated the levels of endocannabinoids and N-acylethanolamines in liver and skeletal muscle, since tissue fatty acid profiles can be modulated by nutrient intervention. Procedures: To this aim, rats were fed with CM, DM, or HM for 4 weeks. Then, glucose tolerance and insulin resistance were analyzed. Pro-inflammatory and anti-inflammatory cytokines were evaluated in serum and skeletal muscle. Skeletal muscle was also processed to estimate mitochondrial function, efficiency, and dynamics, oxidative stress, and antioxidant/detoxifying enzyme activities. Fatty acid profiles, endocannabinoids, and N-acylethanolamine congeners were determined in liver and skeletal muscle tissue. Results: We demonstrated that DM or HM administration reducing inflammation status, improves glucose disposal and insulin resistance and reduces lipid accumulation in skeletal muscle. Moreover, HM or DM administration increases redox status, and mitochondrial uncoupling, affecting mitochondrial dynamics in the skeletal muscle. Interestingly, HM and DM supplementation increase liver and muscle levels of the N-oleoylethanolamine (OEA), a key regulator of lipid metabolism and inflammation. Conclusions: HM and DM have a healthy nutritional effect, acting on inflammatory factors and glucose and lipid metabolism. This beneficial effect is associated to a modulation of mitochondrial function

  15. Human Milk and Donkey Milk, Compared to Cow Milk, Reduce Inflammatory Mediators and Modulate Glucose and Lipid Metabolism, Acting on Mitochondrial Function and Oleylethanolamide Levels in Rat Skeletal Muscle

    Directory of Open Access Journals (Sweden)

    Giovanna Trinchese

    2018-01-01

    Full Text Available Scope: Milk from various species differs in nutrient composition. In particular, human milk (HM and donkey milk (DM are characterized by a relative high level of triacylglycerol enriched in palmitic acid in sn-2 position. These dietary fats seem to exert beneficial nutritional properties through N-acylethanolamine tissue modulation. The aim of this study is to compare the effects of cow milk (CM, DM, and HM on inflammation and glucose and lipid metabolism, focusing on mitochondrial function, efficiency, and dynamics in skeletal muscle, which is the major determinant of resting metabolic rate. Moreover, we also evaluated the levels of endocannabinoids and N-acylethanolamines in liver and skeletal muscle, since tissue fatty acid profiles can be modulated by nutrient intervention.Procedures: To this aim, rats were fed with CM, DM, or HM for 4 weeks. Then, glucose tolerance and insulin resistance were analyzed. Pro-inflammatory and anti-inflammatory cytokines were evaluated in serum and skeletal muscle. Skeletal muscle was also processed to estimate mitochondrial function, efficiency, and dynamics, oxidative stress, and antioxidant/detoxifying enzyme activities. Fatty acid profiles, endocannabinoids, and N-acylethanolamine congeners were determined in liver and skeletal muscle tissue.Results: We demonstrated that DM or HM administration reducing inflammation status, improves glucose disposal and insulin resistance and reduces lipid accumulation in skeletal muscle. Moreover, HM or DM administration increases redox status, and mitochondrial uncoupling, affecting mitochondrial dynamics in the skeletal muscle. Interestingly, HM and DM supplementation increase liver and muscle levels of the N-oleoylethanolamine (OEA, a key regulator of lipid metabolism and inflammation.Conclusions: HM and DM have a healthy nutritional effect, acting on inflammatory factors and glucose and lipid metabolism. This beneficial effect is associated to a modulation of

  16. Morin protects gastric mucosa from nonsteroidal anti-inflammatory drug, indomethacin induced inflammatory damage and apoptosis by modulating NF-κB pathway.

    Science.gov (United States)

    Sinha, Krishnendu; Sadhukhan, Pritam; Saha, Sukanya; Pal, Pabitra Bikash; Sil, Parames C

    2015-04-01

    Deregulation in prostaglandin (PG) biosynthesis, severe oxidative stress, inflammation and apoptosis contribute to the pathogenesis of nonsteroidal anti-inflammatory drug (NSAID)-induced gastropathy. Unfortunately, most of the prescribed anti-ulcer drugs generate various side effects. In this scenario, we could consider morin as a safe herbal potential agent against IND-gastropathy and rationalize its action systematically. Rats were pretreated with morin for 30 min followed by IND (48 mgkg(-1)) administration for 4 h. The anti-ulcerogenic nature of morin was assessed by morphological and histological analysis. Its effects on the inflammatory (MPO, cytokines, adhesion molecules), ulcer-healing (COXs, PGE(2)), and signaling parameters (NF-κB and apoptotic signaling) were assessed by biochemical, RP-HPLC, immunoblots, IHC, RT-PCR, and ELISA at the time points of their maximal changes due to IND administration. IND induced NF-κB and apoptotic signaling in rat's gastric mucosa. These increased proinflammatory responses, but reduced the antioxidant enzymes and other protective factors. Morin reversed all the adverse effects to prevent IND-induced gastric ulceration in a PGE2 independent manner. Also, it did not affect the absorption and/or primary pharmacological activity of IND. The gastroprotective action of morin is primarily attributed to its potent antioxidant nature that also helps in controlling several IND-induced inflammatory responses. For the first time, the study reveals a mechanistic basis of morin mediated protective action against IND-induced gastropathy. As morin is a naturally abundant safe antioxidant, future detailed pharmacokinetic and pharmacodynamic studies are expected to establish it as a gastroprotective agent. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Waste Receiving and Processing Module 2A waste certification strategy

    International Nuclear Information System (INIS)

    LeClair, M.D.; Pottmeyer, J.A.; Hyre, R.A.

    1994-01-01

    This document addresses the certification of Mixed Low Level Waste (MLLW) that will be treated in the Waste Receiving and Processing Facility Module 2A (WRAP 2A) and is destined for disposal in the MLLW trench of the Low Level Burial Grounds (LLBG). The MLLW that will be treated in WRAP 2A contains land disposal restricted and radioactive constituents. Certification of the treated waste is dependent on numerous waste management activities conducted throughout the WRAP 2A operation. These activities range from waste treatability testing conducted prior to WRAP 2A waste acceptance to overchecking final waste form quality prior to transferring waste to disposal. This document addresses the high level strategies and methodologies for certifying the final waste form. Integration among all design and verification activities that support final waste form quality assurance is also discussed. The information generated from this effort may directly support other ongoing activities including the WRAP 2A Waste Characterization Study, WRAP 2A Waste Analysis Plan development, Sample Plan development, and the WRAP 2A Data Management System functional requirements definition

  18. Physiological Aspects of Aging. Module A-5. Block A. Basic Knowledge of the Aging Process.

    Science.gov (United States)

    Harvey, Dexter; Cap, Orest

    This instructional module on physiological aspects of aging is one in a block of 10 modules designed to provide the human services worker who works with older adults with basic information regarding the aging process. An introduction provides an overview of the module content. A listing of general objectives follows. Nine sections present…

  19. Nuclear Technology. Course 28: Welding Inspection. Module 28-6, Process Controls.

    Science.gov (United States)

    Espy, John

    This sixth in a series of ten modules for a course titled Welding Inspection describes procedures review, process monitoring, and weld defect analysis. The module follows a typical format that includes the following sections: (1) introduction, (2) module prerequisites, (3) objectives, (4) notes to instructor/student, (5) subject matter, (6)…

  20. Empathy Modulates the Evaluation Processing of Altruistic Outcomes

    Directory of Open Access Journals (Sweden)

    Xin Liu

    2018-04-01

    Full Text Available Empathy plays a central role in social decisions involving psychological conflict, such as whether to help another person at the cost of one’s own interests. Using the event-related potential (ERP technique, the current study explored the neural mechanisms underlying the empathic effect on the evaluation processing of outcomes in conflict-of-interest situations, in which the gain of others resulted in the performer’s loss. In the high-empathy condition, the beneficiaries were underprivileged students who were living in distress (stranger in need. In the low-empathy condition, the beneficiaries were general students without miserable information (stranger not in need. ERP results showed that the FRN was more negative-going for self no-gain than self gain, but showed reversed pattern for other’s outcome (i.e., more negative for gain than no-gain in the low-empathy condition, indicating that participants interpreted the gain of others as the loss of themselves. However, the reversed FRN pattern was not observed in the high-empathy condition, suggesting that the neural responses to one’s own loss are buffered by empathy. In addition, the P3 valence effect was observed only in the self condition, but not in the two stranger conditions, indicating that the P3 is more sensitive to self-relevant information. Moreover, the results of subjective rating showed that more empathic concern and altruistic motivation were elicited in the high-empathy condition than in the low-empathy condition, and these scores had negative linear correlations only with the FRN, but not with the P3. These findings suggest that when outcomes following altruistic decisions involve conflict of interest, the early stage of the processing of outcome evaluation could be modulated by the empathic level.

  1. Contribution of PPARγ in modulation of acrolein-induced inflammatory signaling in gp91phox knock-out mice.

    Science.gov (United States)

    Yousefipour, Zivar; Chug, Neha; Marek, Katarzyna; Nesbary, Alicia; Mathew, Joseph; Ranganna, Kasturi; Newaz, Mohammad A

    2017-08-01

    Oxidative stress and inflammation are major contributors to acrolein toxicity. Peroxisome proliferator activated receptor gamma (PPARγ) has antioxidant and anti-inflammatory effects. We investigated the contribution of PPARγ ligand GW1929 to the attenuation of oxidative stress in acrolein-induced insult. Male gp91 phox knock-out (KO) mice were treated with acrolein (0.5 mg·(kg body mass) -1 by intraperitoneal injection for 7 days) with or without GW1929 (GW; 0.5 mg·(kg body mass) -1 ·day -1 , orally, for 10 days). The livers were processed for further analyses. Acrolein significantly increased 8-isoprostane and reduced PPARγ activity (P acrolein-treated WT mice, and was reduced by GW1929 (by 65%). KO mice exhibited higher xanthine oxidase (XO). Acrolein increased XO and COX in WT mice and XO in KO mice. GW1929 significantly reduced COX in WT and KO mice and reduced XO in KO mice. Acrolein significantly reduced the total antioxidant status in WT and KO mice (P acrolein-treated WT mice. GW1929 reduced NF-κB levels (by 51%) in KO mice. Acrolein increased CD36 in KO mice (by 43%), which was blunted with GW1929. Data confirms that the generation of free radicals by acrolein is mainly through NAD(P)H, but other oxygenates play a role too. GW1929 may alleviate the toxicity of acrolein by attenuating NF-κB, COX, and CD36.

  2. Persistent Oxytetracycline Exposure Induces an Inflammatory Process That Improves Regenerative Capacity in Zebrafish Larvae

    Science.gov (United States)

    Barros-Becker, Francisco; Romero, Jaime; Pulgar, Alvaro; Feijóo, Carmen G.

    2012-01-01

    Background The excessive use of antibiotics in aquaculture can adversely affect not only the environment, but also fish themselves. In this regard, there is evidence that some antibiotics can activate the immune system and reduce their effectiveness. None of those studies consider in detail the adverse inflammatory effect that the antibiotic remaining in the water may cause to the fish. In this work, we use the zebrafish to analyze quantitatively the effects of persistent exposure to oxytetracycline, the most common antibiotic used in fish farming. Methodology We developed a quantitative assay in which we exposed zebrafish larvae to oxytetracycline for a period of 24 to 96 hrs. In order to determinate if the exposure causes any inflammation reaction, we evaluated neutrophils infiltration and quantified their total number analyzing the Tg(mpx:GFP)i114 transgenic line by fluorescence stereoscope, microscope and flow cytometry respectively. On the other hand, we characterized the process at a molecular level by analyzing several immune markers (il-1β, il-10, lysC, mpx, cyp1a) at different time points by qPCR. Finally, we evaluated the influence of the inflammation triggered by oxytetracycline on the regeneration capacity in the lateral line. Conclusions Our results suggest that after 48 hours of exposure, the oxytetracycline triggered a widespread inflammation process that persisted until 96 hours of exposure. Interestingly, larvae that developed an inflammation process showed an improved regeneration capacity in the mechanosensory system lateral line. PMID:22590621

  3. Hass avocado modulates postprandial vascular reactivity and postprandial inflammatory responses to a hamburger meal in healthy volunteers.

    Science.gov (United States)

    Li, Zhaoping; Wong, Angela; Henning, Susanne M; Zhang, Yanjun; Jones, Alexis; Zerlin, Alona; Thames, Gail; Bowerman, Susan; Tseng, Chi-Hong; Heber, David

    2013-02-26

    Hass avocados are rich in monounsaturated fatty acids (oleic acid) and antioxidants (carotenoids, tocopherols, polyphenols) and are often eaten as a slice in a sandwich containing hamburger or other meats. Hamburger meat forms lipid peroxides during cooking. After ingestion, the stomach functions as a bioreactor generating additional lipid peroxides and this process can be inhibited when antioxidants are ingested together with the meat. The present pilot study was conducted to investigate the postprandial effect of the addition of 68 g of avocado to a hamburger on vasodilation and inflammation. Eleven healthy subjects on two separate occasions consumed either a 250 g hamburger patty alone (ca. 436 cal and 25 g fat) or together with 68 grams of avocado flesh (an additional 114 cal and 11 g of fat for a total of 550 cal and 36 g fat), a common culinary combination, to assess effects on vascular health. Using the standard peripheral arterial tonometry (PAT) method to calculate the PAT index, we observed significant vasoconstriction 2 hours following hamburger ingestion (2.19 ± 0.36 vs. 1.56 ± 0.21, p = 0.0007), which did not occur when the avocado flesh was ingested together with the burger (2.17 ± 0.57 vs. 2.08 ± 0.51, NS p = 0.68). Peripheral blood mononuclear cells were isolated from postprandial blood samples and the Ikappa-B alpha (IκBα) protein concentration was determined to assess effects on inflammation. At 3 hours, there was a significant preservation of IκBα (131% vs. 58%, p = 0.03) when avocado was consumed with the meat compared to meat alone, consistent with reduced activation of the NF-kappa B (NFκB) inflammatory pathway. IL-6 increased significantly at 4 hours in postprandial serum after consumption of the hamburger, but no change was observed when avocado was added. Postprandial serum triglyceride concentration increased, but did not further increase when avocado was ingested with the burger compared to burger alone despite the added fat and

  4. ANKRD1 modulates inflammatory responses in C2C12 myoblasts through feedback inhibition of NF-κB signaling activity

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Xin-Hua [National Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States); Bauman, William A. [National Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States); Department of Rehabilitation Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States); Cardozo, Christopher, E-mail: chris.cardozo@va.gov [National Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States); Department of Rehabilitation Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States); Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States)

    2015-08-14

    Transcription factors of the nuclear factor-kappa B (NF-κB) family play a pivotal role in inflammation, immunity and cell survival responses. Recent studies revealed that NF-κB also regulates the processes of muscle atrophy. NF-κB activity is regulated by various factors, including ankyrin repeat domain 2 (AnkrD2), which belongs to the muscle ankyrin repeat protein family. Another member of this family, AnkrD1 is also a transcriptional effector. The expression levels of AnkrD1 are highly upregulated in denervated skeletal muscle, suggesting an involvement of AnkrD1 in NF-κB mediated cellular responses to paralysis. However, the molecular mechanism underlying the interactive role of AnkrD1 in NF-κB mediated cellular responses is not well understood. In the current study, we examined the effect of AnkrD1 on NF-κB activity and determined the interactions between AnkrD1 expression and NF-κB signaling induced by TNFα in differentiating C2C12 myoblasts. TNFα upregulated AnkrD1 mRNA and protein levels. AnkrD1-siRNA significantly increased TNFα-induced transcriptional activation of NF-κB, whereas overexpression of AnkrD1 inhibited TNFα-induced NF-κB activity. Co-immunoprecipitation studies demonstrated that AnkrD1 was able to bind p50 subunit of NF-κB and vice versa. Finally, CHIP assays revealed that AnkrD1 bound chromatin at a NF-κB binding site in the AnrkD2 promoter and required NF-κB to do so. These results provide evidence of signaling integration between AnkrD1 and NF-κB pathways, and suggest a novel anti-inflammatory role of AnkrD1 through feedback inhibition of NF-κB transcriptional activity by which AnkrD1 modulates the balance between physiological and pathological inflammatory responses in skeletal muscle. - Highlights: • AnkrD1 is upregulated by TNFα and represses NF-κB-induced transcriptional activity. • AnkrD1 binds to p50 subunit of NF-κB and is recruited to NF-κB bound to chromatin. • AnkrD1 mediates a feed-back inhibitory loop

  5. Platelet-activating factor acether (PAF-acether) involvement in acute inflammatory and pain processes.

    Science.gov (United States)

    Bonnet, J; Loiseau, A M; Orvoen, M; Bessin, P

    1981-12-01

    PAF-acether is a potent aggregating agent released by various cells involved in acute inflammatory process. In this paper, exogenous PAF-acether has been investigated for its ability to generate signs of inflammation (edema measured by plethysmometry) and hyperalgesia (Randall-Sellito test) by standard subplantar injection in the rat paw. From 0.005 microgram. PAF-acether induced significant edema of the paw, maximal 1 hour after injection; it was dose-dependent from 0.1 to 5 microgram. Significant dose-dependent hyperalgesia occurred from 1.25 microgram; it reached a plateau from 2 to 4 hours after injection. Both phenomena were long-lasting (greater than 6 h). PAF-acether was 1.5 to 10 times stronger than PGI2 and PGE2 in inducing edema, pain, and in increasing vascular permeability. We investigated the interaction of miscellaneous drugs with the edema and the hyperalgesia caused by 2.5 microgram of PAF-acether. Non-steroidal anti-inflammatory (NSAI) drugs exerted only moderate effects on the edema without affecting hyperalgesia. Edema was highly reduced by various agents: prednisolone, L-cysteine, anti-calcic drugs, theophylline, PGI2, salbutamol, clonidine. All of them, except clonidine, and in contrast to NSAI drugs, were more potent on PAF-acether edema than on kaolin edema; a possible link between these agents is their ability to increase cyclic AMP levels in the cells and consequently to reduce lysosomal enzyme release. PAF-acether itself, injected intra-peritoneally, inhibited PAF-acether edema without preventing pain, at doses inactive on arterial pressure and hematocrit, but inducing marked gastric mucosal damage. Among the drugs tested, including analgesics, only PGI2 and imidazole improved PAF-induced hyperalgesia, showing a dissociation between edema and hyperalgesia not only in their induction (doses of PAF required, time course of the phenomena), but in the drugs able to antagonize their development too.

  6. Medial prefrontal cortex stimulation modulates the processing of conditioned fear

    Directory of Open Access Journals (Sweden)

    Anne eGuhn

    2014-02-01

    Full Text Available The extinction of conditioned fear is dependent on an efficient interplay between the amygdala and the medial prefrontal cortex (mPFC. In rats, high-frequency electrical mPFC stimulation was shown to improve extinction by a reduction of amygdala activity. However, so far it is unclear whether stimulation of homologues regions in humans might have similar beneficial effects.Healthy volunteers received one-session of either active or sham repetitive transcranial magnetic stimulation (rTMS covering the mPFC while undergoing a two-day fear conditioning and extinction paradigm. rTMS was applied offline after fear acquisition in which one of two faces (CS+ but not CS- was associated with an aversive scream (UCS. Immediate extinction learning (day 1 and extinction recall (day 2 were conducted without UCS delivery. Conditioned responses were assessed in a multimodal approach using fear-potentiated startle (FPS, skin conductance responses (SCR, functional near-infrared spectroscopy (fNIRS and self-report scales. Consistent with the hypothesis of a modulated processing of conditioned fear after high-frequency rTMS, the active group showed a reduced CS+/CS- discrimination during extinction learning as evident in FPS as well as in SCR and arousal ratings. FPS responses to CS+ further showed a linear decrement throughout both extinction sessions. This study describes the first experimental approach of influencing conditioned fear by using rTMS which can be a basis for future studies investigating a complementation of mPFC stimulation to cognitive behavioral therapy.

  7. A Review of Inflammatory Processes of the Breast with a Focus on Diagnosis in Core Biopsy Samples

    Directory of Open Access Journals (Sweden)

    Timothy M. D’Alfonso

    2015-07-01

    Full Text Available Inflammatory and reactive lesions of the breast are relatively uncommon among benign breast lesions and can be the source of an abnormality on imaging. Such lesions can simulate a malignant process, based on both clinical and radiographic findings, and core biopsy is often performed to rule out malignancy. Furthermore, some inflammatory processes can mimic carcinoma or other malignancy microscopically, and vice versa. Diagnostic difficulty may arise due to the small and fragmented sample of a core biopsy. This review will focus on the pertinent clinical, radiographic, and histopathologic features of the more commonly encountered inflammatory lesions of the breast that can be characterized in a core biopsy sample. These include fat necrosis, mammary duct ectasia, granulomatous lobular mastitis, diabetic mastopathy, and abscess. The microscopic differential diagnoses for these lesions when seen in a core biopsy sample will be discussed.

  8. A Review of Inflammatory Processes of the Breast with a Focus on Diagnosis in Core Biopsy Samples.

    Science.gov (United States)

    D'Alfonso, Timothy M; Ginter, Paula S; Shin, Sandra J

    2015-07-01

    Inflammatory and reactive lesions of the breast are relatively uncommon among benign breast lesions and can be the source of an abnormality on imaging. Such lesions can simulate a malignant process, based on both clinical and radiographic findings, and core biopsy is often performed to rule out malignancy. Furthermore, some inflammatory processes can mimic carcinoma or other malignancy microscopically, and vice versa. Diagnostic difficulty may arise due to the small and fragmented sample of a core biopsy. This review will focus on the pertinent clinical, radiographic, and histopathologic features of the more commonly encountered inflammatory lesions of the breast that can be characterized in a core biopsy sample. These include fat necrosis, mammary duct ectasia, granulomatous lobular mastitis, diabetic mastopathy, and abscess. The microscopic differential diagnoses for these lesions when seen in a core biopsy sample will be discussed.

  9. Interactions between amplitude modulation and frequency modulation processing: Effects of age and hearing loss.

    Science.gov (United States)

    Paraouty, Nihaad; Ewert, Stephan D; Wallaert, Nicolas; Lorenzi, Christian

    2016-07-01

    Frequency modulation (FM) and amplitude modulation (AM) detection thresholds were measured for a 500-Hz carrier frequency and a 5-Hz modulation rate. For AM detection, FM at the same rate as the AM was superimposed with varying FM depth. For FM detection, AM at the same rate was superimposed with varying AM depth. The target stimuli always contained both amplitude and frequency modulations, while the standard stimuli only contained the interfering modulation. Young and older normal-hearing listeners, as well as older listeners with mild-to-moderate sensorineural hearing loss were tested. For all groups, AM and FM detection thresholds were degraded in the presence of the interfering modulation. AM detection with and without interfering FM was hardly affected by either age or hearing loss. While aging had an overall detrimental effect on FM detection with and without interfering AM, there was a trend that hearing loss further impaired FM detection in the presence of AM. Several models using optimal combination of temporal-envelope cues at the outputs of off-frequency filters were tested. The interfering effects could only be predicted for hearing-impaired listeners. This indirectly supports the idea that, in addition to envelope cues resulting from FM-to-AM conversion, normal-hearing listeners use temporal fine-structure cues for FM detection.

  10. Supradural inflammatory soup in awake and freely moving rats induces facial allodynia that is blocked by putative immune modulators.

    Science.gov (United States)

    Wieseler, Julie; Ellis, Amanda; McFadden, Andrew; Stone, Kendra; Brown, Kimberley; Cady, Sara; Bastos, Leandro F; Sprunger, David; Rezvani, Niloofar; Johnson, Kirk; Rice, Kenner C; Maier, Steven F; Watkins, Linda R

    2017-06-01

    Facial allodynia is a migraine symptom that is generally considered to represent a pivotal point in migraine progression. Treatment before development of facial allodynia tends to be more successful than treatment afterwards. As such, understanding the underlying mechanisms of facial allodynia may lead to a better understanding of the mechanisms underlying migraine. Migraine facial allodynia is modeled by applying inflammatory soup (histamine, bradykinin, serotonin, prostaglandin E2) over the dura. Whether glial and/or immune activation contributes to such pain is unknown. Here we tested if trigeminal nucleus caudalis (Sp5C) glial and/or immune cells are activated following supradural inflammatory soup, and if putative glial/immune inhibitors suppress the consequent facial allodynia. Inflammatory soup was administered via bilateral indwelling supradural catheters in freely moving rats, inducing robust and reliable facial allodynia. Gene expression for microglial/macrophage activation markers, interleukin-1β, and tumor necrosis factor-α increased following inflammatory soup along with robust expression of facial allodynia. This provided the basis for pursuing studies of the behavioral effects of 3 diverse immunomodulatory drugs on facial allodynia. Pretreatment with either of two compounds broadly used as putative glial/immune inhibitors (minocycline, ibudilast) prevented the development of facial allodynia, as did treatment after supradural inflammatory soup but prior to the expression of facial allodynia. Lastly, the toll-like receptor 4 (TLR4) antagonist (+)-naltrexone likewise blocked development of facial allodynia after supradural inflammatory soup. Taken together, these exploratory data support that activated glia and/or immune cells may drive the development of facial allodynia in response to supradural inflammatory soup in unanesthetized male rats. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Angiotensin II modulates interleukin-1β-induced inflammatory gene expression in vascular smooth muscle cells via interfering with ERK-NF-κB crosstalk

    International Nuclear Information System (INIS)

    Xu, Shanqin; Zhi, Hui; Hou, Xiuyun; Jiang, Bingbing

    2011-01-01

    Highlights: → We examine how angiotensin II modulates ERK-NF-κB crosstalk and gene expression. → Angiotensin II suppresses IL-1β-induced prolonged ERK and NF-κB activation. → ERK-RSK1 signaling is required for IL-1β-induced prolonged NF-κB activation. → Angiotensin II modulates NF-κB responsive genes via regulating ERK-NF-κB crosstalk. → ERK-NF-κB crosstalk is a novel mechanism regulating inflammatory gene expression. -- Abstract: Angiotensin II is implicated in cardiovascular diseases, which is associated with a role in increasing vascular inflammation. The present study investigated how angiotensin II modulates vascular inflammatory signaling and expression of inducible nitric oxide synthase (iNOS) and vascular cell adhesion molecule (VCAM)-1. In cultured rat aortic vascular smooth muscle cells (VSMCs), angiotensin II suppressed interleukin-1β-induced prolonged phosphorylation of extracellular signal-regulated kinase (ERK) and ribosomal S6 kinase (RSK)-1, and nuclear translocation of nuclear factor (NF)-κB, leading to decreased iNOS but enhanced VCAM-1 expression, associated with an up-regulation of mitogen-activated protein kinase phosphatase-1 expression. Knock-down of RSK1 selectively down regulated interleukin-1β-induced iNOS expression without influencing VCAM-1 expression. In vivo experiments showed that interleukin-1β, iNOS, and VCAM-1 expression were detectable in the aortic arches of both wild-type and apolipoprotein E-deficient (ApoE -/- ) mice. VCAM-1 and iNOS expression were higher in ApoE -/- than in wild type mouse aortic arches. Angiotensin II infusion (3.2 mg/kg/day, for 6 days, via subcutaneous osmotic pump) in ApoE -/- mice enhanced endothelial and adventitial VCAM-1 and iNOS expression, but reduced medial smooth muscle iNOS expression associated with reduced phosphorylation of ERK and RSK-1. These results indicate that angiotensin II can differentially modulate inflammatory gene expression in aortic smooth muscle cells

  12. Atorvastatin attenuates contrast-induced nephropathy by modulating inflammatory responses through the regulation of JNK/p38/Hsp27 expression

    Directory of Open Access Journals (Sweden)

    Xuyu He

    2016-05-01

    Our study demonstrates that high-dosage atorvastatin treatment attenuates both the inflammatory processes and apoptosis in contrast-induced acute kidney injury, and that the JNK/p38 MAPK pathway participates in the contrast-induced apoptosis of renal tubular cells. Finally, atorvastatin reduces CIN by suppression of apoptosis, which may be through inhibition of JNK/p38 MAPK pathways.

  13. Project T.E.A.M. (Technical Education Advancement Modules). Introduction to Statistical Process Control.

    Science.gov (United States)

    Billings, Paul H.

    This instructional guide, one of a series developed by the Technical Education Advancement Modules (TEAM) project, is a 6-hour introductory module on statistical process control (SPC), designed to develop competencies in the following skill areas: (1) identification of the three classes of SPC use; (2) understanding a process and how it works; (3)…

  14. Process, Voltage and Temperature Compensation Technique for Cascode Modulated PAs

    DEFF Research Database (Denmark)

    Sira, Daniel; Larsen, Torben

    2013-01-01

    , that represents a transistor level model (empirical model) of the cascode modulated PA, is utilized in a PA analog predistorter. The analog predistorter linearizes and compensates for PVT variation of the cascode modulated PA. The empirical model is placed in the negative feedback of an operational...... transconductance amplifier. The predistorted varying envelope signal is applied to the cascode gate of the PA. It is shown that the proposed PVT compensation technique significantly reduces the PVT spread of the PA linearity indicators and improves the PA linearity. Simulations were performed in a 0.13 μm CMOS...

  15. Developmental endothelial locus-1 modulates platelet-monocyte interactions and instant blood-mediated inflammatory reaction in islet transplantation.

    Science.gov (United States)

    Kourtzelis, Ioannis; Kotlabova, Klara; Lim, Jong-Hyung; Mitroulis, Ioannis; Ferreira, Anaisa; Chen, Lan-Sun; Gercken, Bettina; Steffen, Anja; Kemter, Elisabeth; Klotzsche-von Ameln, Anne; Waskow, Claudia; Hosur, Kavita; Chatzigeorgiou, Antonios; Ludwig, Barbara; Wolf, Eckhard; Hajishengallis, George; Chavakis, Triantafyllos

    2016-04-01

    Platelet-monocyte interactions are strongly implicated in thrombo-inflammatory injury by actively contributing to intravascular inflammation, leukocyte recruitment to inflamed sites, and the amplification of the procoagulant response. Instant blood-mediated inflammatory reaction (IBMIR) represents thrombo-inflammatory injury elicited upon pancreatic islet transplantation (islet-Tx), thereby dramatically affecting transplant survival and function. Developmental endothelial locus-1 (Del-1) is a functionally versatile endothelial cell-derived homeostatic factor with anti-inflammatory properties, but its potential role in IBMIR has not been previously addressed. Here, we establish Del-1 as a novel inhibitor of IBMIR using a whole blood-islet model and a syngeneic murine transplantation model. Indeed, Del-1 pre-treatment of blood before addition of islets diminished coagulation activation and islet damage as assessed by C-peptide release. Consistently, intraportal islet-Tx in transgenic mice with endothelial cell-specific overexpression of Del-1 resulted in a marked decrease of monocytes and platelet-monocyte aggregates in the transplanted tissues, relative to those in wild-type recipients. Mechanistically, Del-1 decreased platelet-monocyte aggregate formation, by specifically blocking the interaction between monocyte Mac-1-integrin and platelet GPIb. Our findings reveal a hitherto unknown role of Del-1 in the regulation of platelet-monocyte interplay and the subsequent heterotypic aggregate formation in the context of IBMIR. Therefore, Del-1 may represent a novel approach to prevent or mitigate the adverse reactions mediated through thrombo-inflammatory pathways in islet-Tx and perhaps other inflammatory disorders involving platelet-leukocyte aggregate formation.

  16. Hepatocyte growth factor modulates interleukin-6 production in bone marrow derived macrophages: implications for inflammatory mediated diseases.

    Directory of Open Access Journals (Sweden)

    Gina M Coudriet

    2010-11-01

    Full Text Available The generation of the pro-inflammatory cytokines IL-6, TNF-α, and IL-1β fuel the acute phase response (APR. To maintain body homeostasis, the increase of inflammatory proteins is resolved by acute phase proteins via presently unknown mechanisms. Hepatocyte growth factor (HGF is transcribed in response to IL-6. Since IL-6 production promotes the generation of HGF and induces the APR, we posited that accumulating HGF might be a likely candidate for quelling excess inflammation under non-pathological conditions. We sought to assess the role of HGF and how it influences the regulation of inflammation utilizing a well-defined model of inflammatory activation, lipopolysaccharide (LPS-stimulation of bone marrow derived macrophages (BMM. BMM were isolated from C57BL6 mice and were stimulated with LPS in the presence or absence of HGF. When HGF was present, there was a decrease in production of the pro-inflammatory cytokine IL-6, along with an increase in the anti-inflammatory cytokine IL-10. Altered cytokine production correlated with an increase in phosphorylated GSK3β, increased retention of the phosphorylated NFκB p65 subunit in the cytoplasm, and an enhanced interaction between CBP and phospho-CREB. These changes were a direct result of signaling through the HGF receptor, MET, as effects were reversed in the presence of a selective inhibitor of MET (SU11274 or when using BMM from macrophage-specific conditional MET knockout mice. Combined, these data provide compelling evidence that under normal circumstances, HGF acts to suppress the inflammatory response.

  17. Serine protease inhibitors containing a Kunitz domain: their role in modulation of host inflammatory responses and parasite survival.

    Science.gov (United States)

    de Magalhães, Mariana T Q; Mambelli, Fábio S; Santos, Bruno P O; Morais, Suellen B; Oliveira, Sergio C

    2018-03-31

    Proteins containing a Kunitz domain have the typical serine protease inhibition function ranging from sea anemone to man. Protease inhibitors play major roles in infection, inflammation disorders and cancer. This review discusses the role of serine proteases containing a Kunitz domain in immunomodulation induced by helminth parasites. Helminth parasites are associated with protection from inflammatory conditions. Therefore, interest has raised whether worm parasites or their products hold potential as drugs for treatment of immunological disorders. Finally, we also propose the use of recombinant SmKI-1 from Schistosoma mansoni as a potential therapeutic molecule to treat inflammatory diseases. Copyright © 2018 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  18. Motivational priming and processing interrupt: startle reflex modulation during shallow and deep processing of emotional words.

    Science.gov (United States)

    Herbert, Cornelia; Kissler, Johanna

    2010-05-01

    Valence-driven modulation of the startle reflex, that is larger eyeblinks during viewing of unpleasant pictures and inhibited blinks while viewing pleasant pictures, is well documented. The current study investigated, whether this motivational priming pattern also occurs during processing of unpleasant and pleasant words, and to what extent it is influenced by shallow vs. deep encoding of verbal stimuli. Emotional and neutral adjectives were presented for 5s, and the acoustically elicited startle eyeblink response was measured while subjects memorized the words by means of shallow or deep processing strategies. Results showed blink potentiation to unpleasant and blink inhibition to pleasant adjectives in subjects using shallow encoding strategies. In subjects using deep-encoding strategies, blinks were larger for pleasant than unpleasant or neutral adjectives. In line with this, free recall of pleasant words was also better in subjects who engaged in deep processing. The results suggest that motivational priming holds as long as processing is perceptual. However, during deep processing the startle reflex appears to represent a measure of "processing interrupt", facilitating blinks to those stimuli that are more deeply encoded. Copyright 2010 Elsevier B.V. All rights reserved.

  19. Post-Lamination Manufacturing Process Automation for Photovoltaic Modules; Annual Technical Progress Report: 15 June 1999--14 July 2000

    Energy Technology Data Exchange (ETDEWEB)

    Nowlan, M. J.; Murach, J. M.; Sutherland, S. F.; Lewis, E. R.; Hogan, S. J.

    2000-09-29

    Spire is addressing the PVMaT project goals of photovoltaic (PV) module cost reduction and improved module manufacturing process technology. New cost-effective automation processes are being developed for post-lamination PV module assembly, where post-lamination is defined as the processes after the solar cells are encapsulated. These processes apply to both crystalline and thin-film solar cell modules. Four main process areas are being addressed: (1) Module buffer storage and handling between steps; (2) Module edge trimming, edge sealing, and framing; (3) Junction-box installation; and (4) Testing for module performance, electrical isolation, and ground-path continuity.

  20. In vitro studies on the relationship between the anti-inflammatory activity of Physalis peruviana extracts and the phagocytic process.

    Science.gov (United States)

    Martínez, Willington; Ospina, Luis Fernando; Granados, Diana; Delgado, Gabriela

    2010-03-01

    The study of plants used in traditional medicine has drawn the attention of researchers as an alternative in the development of new therapeutics agents, such as the American Solanaceae Physalis peruviana, which has significant anti-inflammatory activity. The Physalis peruviana anti-inflammatory effect of ethanol or ether calyces extracts on the phagocytic process was assessed by using an in vitro phagocytosis model (Leishmania panamensis infection to murine macrophages). The Physalis peruviana extracts do not inhibit microorganism internalization and have no parasiticide effect. Most ET and EP extracts negatively affected the parasite's invasion of macrophages (Infected cells increased.). This observation might result from a down-regulation of the macrophage's microbicide ability associated with a selective reduction of proinflammatory cytokines levels. Physalis peruviana's anti-inflammatory activity described in this model is related to an immunomodulatory effect exerted on macrophages infected, which directly or indirectly "blocks" their ability to secrete soluble proinflammatory mediators.

  1. Waste Receiving and Processing (WRAP) Module 1 Hazards Assessment

    International Nuclear Information System (INIS)

    CAMPBELL, L.R.

    1999-01-01

    This document establishes the technical basis in support of Emergency Planning activities for the WRAP Module 1 Facility on the Hanford Site. Through this document, the technical basis for the development of facility specific Emergency Action Levels and Emergency Planning Zone is demonstrated

  2. Waste Receiving and Processing (WRAP) Module 1 Hazards Assessment

    Energy Technology Data Exchange (ETDEWEB)

    CAMPBELL, L.R.

    1999-09-29

    This document establishes the technical basis in support of Emergency Planning activities for the WRAP Module 1 Facility on the Hanford Site. Through this document, the technical basis for the development of facility specific Emergency Action Levels and Emergency Planning Zone is demonstrated.

  3. PET molecular imaging of peripheral and central inflammatory processes targeting the TSPO 18 kDa

    International Nuclear Information System (INIS)

    Bernards, Nicholas

    2014-01-01

    The purpose of this study was to determine the in vivo potential of the TSPO 18 kDa as a bio-marker of inflammation, with the use of its radioligand [ 18 F]DPA-714, to non-invasively quantify the inflammatory state within the scope of various pathologies. Multiple animal models of various inflammatory diseases, to include: inflammatory bowel disease, neuro-inflammation, and septic shock, were developed and put in place by adapted measures. The animals well-being and the subsequent inflammation was evaluated. The inflammatory state was measured using quantitative PET imaging with the TSPO radioligand [ 18 F]DPA-714 and correlated to the expression of conventional inflammatory markers using microscopy. Based on the observed data, we were able to distinguish control groups from treated groups when using [ 18 F]DPA-714. This TSPO radioligand permitted us to quantify the inflammatory level and to observe evolutionary changes in the inflammatory state of the disease in multiple models. The PET results, using the [ 18 F]DPA-714 signal was correlated with an increased TSPO expression at cellular level. Results indicate that [ 18 F]DPA-714 is a suitable tracer for studying inflammation of multiple diseases. [ 18 F]DPA-714 could be a good molecular probe to non-invasively evaluate the level and localization of inflammation. Moreover, in vivo imaging using this TSPO ligand is potentially a powerful tool to stage and certainly to follow the evolution and therapeutic efficiency at molecular level in inflammatory diseases. (author) [fr

  4. Inhibitory Effects of North American Wild Rice on Monocyte Adhesion and Inflammatory Modulators in Low-Density Lipoprotein Receptor-Knockout Mice.

    Science.gov (United States)

    Moghadasian, Mohammed H; Zhao, Ruozhi; Ghazawwi, Nora; Le, Khuong; Apea-Bah, Franklin B; Beta, Trust; Shen, Garry X

    2017-10-18

    The present study examined the effects of wild rice on monocyte adhesion, inflammatory and fibrinolytic mediators in low-density lipoprotein receptor-knockout (LDLr-KO) mice. Male LDLr-KO mice received a cholesterol (0.06%, w/w)-supplemented diet with or without white or wild rice (60%, w/w) for 20 weeks. White rice significantly increased monocyte adhesion and abundances of monocyte chemoattractant protein-1, tissue necrosis factor-α, intracellular cell adhesion molecule-1, plasminogen activator inhibitor-1, urokinase plasminogen activator (uPA), and uPA receptor in aortae and hearts of LDLr-KO mice compared to the control diet. Wild rice inhibited monocyte adhesion to the aorta, atherosclerosis, and abundances of the inflammatory and fibrinolytic regulators in the cardiovascular tissue of LDLr-KO mice compared to white rice. White or wild rice did not significantly alter the levels of cholesterol, triglycerides, or antioxidant enzymes in plasma. The anti-atherosclerotic effect of wild rice may result from its inhibition on monocyte adhesion and inflammatory modulators in LDLr-KO mice.

  5. Carvedilol alleviates adjuvant-induced arthritis and subcutaneous air pouch edema: Modulation of oxidative stress and inflammatory mediators

    International Nuclear Information System (INIS)

    Arab, Hany H.; El-Sawalhi, Maha M.

    2013-01-01

    Rheumatoid arthritis (RA) is a systemic inflammatory disease with cardiovascular complications as the leading cause of morbidity. Carvedilol is an adrenergic antagonist which has been safely used in treatment of several cardiovascular disorders. Given that carvedilol has powerful antioxidant/anti-inflammatory properties, we aimed to investigate its protective potential against arthritis that may add further benefits for its clinical usefulness especially in RA patients with concomitant cardiovascular disorders. Two models were studied in the same rat; adjuvant arthritis and subcutaneous air pouch edema. Carvedilol (10 mg/kg/day p.o. for 21 days) effectively suppressed inflammation in both models with comparable efficacy to the standard anti-inflammatory diclofenac (5 mg/kg/day p.o.). Notably, carvedilol inhibited paw edema and abrogated the leukocyte invasion to air pouch exudates. The latter observation was confirmed by the histopathological assessment of the pouch lining that revealed mitigation of immuno-inflammatory cell influx. Carvedilol reduced/normalized oxidative stress markers (lipid peroxides, nitric oxide and protein thiols) and lowered the release of inflammatory cytokines (TNF-α and IL-6), and eicosanoids (PGE 2 and LTB 4 ) in sera and exudates of arthritic rats. Interestingly, carvedilol, per se, didn't present any effect on assessed biochemical parameters in normal rats. Together, the current study highlights evidences for the promising anti-arthritic effects of carvedilol that could be mediated through attenuation of leukocyte migration, alleviation of oxidative stress and suppression of proinflammatory cytokines and eicosanoids. - Highlights: ► Carvedilol possesses promising anti-arthritic properties. ► It markedly suppressed inflammation in adjuvant arthritis and air pouch edema. ► It abrogated the leukocyte invasion to air pouch exudates and linings. ► It reduced/normalized oxidative stress markers in sera and exudates of arthritic rats

  6. Carvedilol alleviates adjuvant-induced arthritis and subcutaneous air pouch edema: Modulation of oxidative stress and inflammatory mediators

    Energy Technology Data Exchange (ETDEWEB)

    Arab, Hany H., E-mail: hany_h_arab@yahoo.com [Biochemistry Division, Department of Pharmacology and Toxicology, Faculty of Pharmacy, Taif University, Taif (Saudi Arabia); Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo (Egypt); El-Sawalhi, Maha M. [Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo (Egypt)

    2013-04-15

    Rheumatoid arthritis (RA) is a systemic inflammatory disease with cardiovascular complications as the leading cause of morbidity. Carvedilol is an adrenergic antagonist which has been safely used in treatment of several cardiovascular disorders. Given that carvedilol has powerful antioxidant/anti-inflammatory properties, we aimed to investigate its protective potential against arthritis that may add further benefits for its clinical usefulness especially in RA patients with concomitant cardiovascular disorders. Two models were studied in the same rat; adjuvant arthritis and subcutaneous air pouch edema. Carvedilol (10 mg/kg/day p.o. for 21 days) effectively suppressed inflammation in both models with comparable efficacy to the standard anti-inflammatory diclofenac (5 mg/kg/day p.o.). Notably, carvedilol inhibited paw edema and abrogated the leukocyte invasion to air pouch exudates. The latter observation was confirmed by the histopathological assessment of the pouch lining that revealed mitigation of immuno-inflammatory cell influx. Carvedilol reduced/normalized oxidative stress markers (lipid peroxides, nitric oxide and protein thiols) and lowered the release of inflammatory cytokines (TNF-α and IL-6), and eicosanoids (PGE{sub 2} and LTB{sub 4}) in sera and exudates of arthritic rats. Interestingly, carvedilol, per se, didn't present any effect on assessed biochemical parameters in normal rats. Together, the current study highlights evidences for the promising anti-arthritic effects of carvedilol that could be mediated through attenuation of leukocyte migration, alleviation of oxidative stress and suppression of proinflammatory cytokines and eicosanoids. - Highlights: ► Carvedilol possesses promising anti-arthritic properties. ► It markedly suppressed inflammation in adjuvant arthritis and air pouch edema. ► It abrogated the leukocyte invasion to air pouch exudates and linings. ► It reduced/normalized oxidative stress markers in sera and exudates of

  7. The NJOY nuclear data processing system: Volume 2, The NJOY, RECONR, BROADR, HEATR, and THERMR modules

    International Nuclear Information System (INIS)

    MacFarlane, R.E.; Muir, D.W.; Boicourt, R.M.

    1982-05-01

    The NJOY nuclear data processing system is a comprehensive computer code package for producing cross sections and related nuclear parameters from ENDF/B evaluated nuclear data. This volume provides detailed descriptions of the NJOY module, which contains the executive program and utility subroutines used by the other modules, and it discusses the theory and computational methods of four of the modules used for producing pointwise cross sections: RECONR, BROADR, HEATR, and THERMR

  8. Vibrio cholerae cytolysin causes an inflammatory response in human intestinal epithelial cells that is modulated by the PrtV protease.

    Directory of Open Access Journals (Sweden)

    Gangwei Ou

    Full Text Available BACKGROUND: Vibrio cholerae is the causal intestinal pathogen of the diarrheal disease cholera. It secretes the protease PrtV, which protects the bacterium from invertebrate predators but reduces the ability of Vibrio-secreted factor(s to induce interleukin-8 (IL-8 production by human intestinal epithelial cells. The aim was to identify the secreted component(s of V. cholerae that induces an epithelial inflammatory response and to define whether it is a substrate for PrtV. METHODOLOGY/PRINCIPAL FINDINGS: Culture supernatants of wild type V. cholerae O1 strain C6706, its derivatives and pure V. cholerae cytolysin (VCC were analyzed for the capacity to induce changes in cytokine mRNA expression levels, IL-8 and tumor necrosis factor-alpha (TNF-alpha secretion, permeability and cell viability when added to the apical side of polarized tight monolayer T84 cells used as an in vitro model for human intestinal epithelium. Culture supernatants were also analyzed for hemolytic activity and for the presence of PrtV and VCC by immunoblot analysis. CONCLUSIONS/SIGNIFICANCE: We suggest that VCC is capable of causing an inflammatory response characterized by increased permeability and production of IL-8 and TNF-alpha in tight monolayers. Pure VCC at a concentration of 160 ng/ml caused an inflammatory response that reached the magnitude of that caused by Vibrio-secreted factors, while higher concentrations caused epithelial cell death. The inflammatory response was totally abolished by treatment with PrtV. The findings suggest that low doses of VCC initiate a local immune defense reaction while high doses lead to intestinal epithelial lesions. Furthermore, VCC is indeed a substrate for PrtV and PrtV seems to execute an environment-dependent modulation of the activity of VCC that may be the cause of V. cholerae reactogenicity.

  9. THE ASSESSMENT OF BIOLOGICAL MARKERS IN PATIENTS WITH PREECLAMPSIA WHEN AN INFLAMMATORY PROCESS APPEARS

    Directory of Open Access Journals (Sweden)

    Eduard Crauciuc

    2015-07-01

    Full Text Available Preeclampsia represents a pathological state that is specific to regnancy, is characterized by high blood pressure de novo and significant proteinuria and appears after 20 weeks of pregnancy. The continuously increasing mortality caused by preeclampsia in our country totally justifies the fact that all efforts are directed towards primary and secondary prevention of the disease and underlines the necessity of urgent intervention at population level, together withthe implementation of a screening programme that is able to reduce the impact of this condition on the mother and the baby. The cases were gathered between 2003 and 2014. The patients were selected by studying the observation charts of the pregnant women hospitalized in ”Cuza Vodă” Clinical Hospital of Obstetrics and Gynecology Iaşi, having a pregnancy over 20 weeks, who came for a specialized consult and who were harvested CRP, without an infectious context or prematurely and spontaneously ruptured membranes. The comparison of the lab markers for the pregnantwomen with severe preeclampsia, depending on the plasmatic level of CRP over 12 mg/l, showed significantly higher values of fibrinogen, LDH, GOT, GPT, serum blood urea nitrogen, creatinine and urine proteins, while the mean number of white cells was significantly reduced (p<0,05. The study confirms the change in the inflammatory process markers, the hepatic and kidney function, associated with a high plasmatic level of CRP for pregnant women with severe preeclampsia.

  10. Post-Lamination Manufacturing Process Automation for Photovoltaic Modules: Final Subcontract Report, April 1998 - April 2002

    Energy Technology Data Exchange (ETDEWEB)

    Nowlan, M. J.; Murach, J. M.; Sutherland, S. F.; Miller, D. C.; Moore, S. B.; Hogan, S. J.

    2002-11-01

    This report describes the automated systems developed for PV module assembly and testing processes after lamination. These processes are applicable to a broad range of module types, including those made with wafer-based and thin-film solar cells. Survey data and input from module manufacturers gathered during site visits were used to define system capabilities and process specifications. Spire completed mechanical, electrical, and software engineering for four automation systems: a module edge trimming system, the SPI-TRIM 350; an edge sealing and framing system, the SPI-FRAMER 350; an integrated module testing system, the SPI-MODULE QA 350; and a module buffer storage system, the SPI-BUFFER 350. A fifth system for junction-box installation, the SPI-BOXER 350, was nearly completed during the program. A new-size solar simulator, the SPI-SUN SIMULATOR 350i, was designed as part of the SPI-MODULE QA 350. This simulator occupies minimal production floor space, and its test area is large enough to handle most production modules. The automated systems developed in this program are designed for integration to create automated production lines.

  11. Modeling auditory processing of amplitude modulation I. Detection and masking with narrow-band carriers

    NARCIS (Netherlands)

    Dau, T.; Kollmeier, B.; Kohlrausch, A.G.

    1997-01-01

    This paper presents a quantitative model for describing data from modulation-detection and modulation-masking experiments, which extends the model of the "effective" signal processing of the auditory system described in Dau et al. [J. Acoust. Soc. Am. 99, 3615–3622 (1996)]. The new element in the

  12. Febrile syndrome of unknown origin: Indications for 18F-FDG PET/CT in inflammatory and infectious processes.

    Science.gov (United States)

    García, J R

    Fever of unknown origin is defined as a body temperature greater than 38.3°C lasting more than three weeks for which the cause could not be found within one week of hospital admission. More than 200 causes have been reported, and these can be classified into four categories: infections, inflammatory diseases, oncologic processes, and miscellaneous conditions. Noninvasive diagnostic techniques are used in 69.2% of cases and invasive techniques in 30.8%. Structural imaging techniques show the morphological changes from infectious, inflammatory, and tumor-related processes, but they do not allow the detection of the early changes brought about by these processes. The metabolic information provided by 18 F-FDG PET/CT has a promising role in these patients. 18 F-FDG uptake is based on the cells' use of glucose as a source of energy, so it can be observed in infectious, inflammatory, and tumor-related processes. The established non-oncologic indications for 18 F-FDG PET/CT are sarcoidosis, osteomyelitis, spondylodiscitis, fever of unknown origin, and vasculitis, which together account for more than 85% of studies. Copyright © 2016 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

  13. Lactobacillus rhamnosus GG and its SpaC pilus adhesin modulate inflammatory responsiveness and TLR-related gene expression in the fetal human gut

    Science.gov (United States)

    Ganguli, Kriston; Collado, Maria Carmen; Rautava, Jaana; Lu, Lei; Satokari, Reetta; von Ossowski, Ingemar; Reunanen, Justus; de Vos, Willem M.; Palva, Airi; Isolauri, Erika; Salminen, Seppo; Walker, W. Allan; Rautava, Samuli

    2015-01-01

    Background Bacterial contact in utero modulates fetal and neonatal immune responses. Maternal probiotic supplementation reduces the risk of immune-mediated disease in the infant. We investigated the immunomodulatory properties of live Lactobacillus rhamnosus GG and its SpaC pilus adhesin in human fetal intestinal models. Methods TNF-α mRNA expression was measured by qPCR in a human fetal intestinal organ culture model exposed to live L. rhamnosus GG and proinflammatory stimuli. Binding of recombinant SpaC pilus protein to intestinal epithelial cells was assessed in human fetal intestinal organ culture and the human fetal intestinal epithelial cell line H4 by immunohistochemistry and immunofluorescence, respectively. TLR-related gene expression in fetal ileal organ culture after exposure to recombinant SpaC was assessed by qPCR. Results Live L. rhamnosus GG significantly attenuates pathogen-induced TNF-α mRNA expression in the human fetal gut. Recombinant SpaC protein was found to adhere to the fetal gut and to modulate varying levels of TLR-related gene expression. Conclusion The human fetal gut is responsive to luminal microbes. L. rhamnosus GG significantly attenuates fetal intestinal inflammatory responses to pathogenic bacteria. The L. rhamnosus GG pilus adhesin SpaC binds to immature human intestinal epithelial cells and directly modulates intestinal epithelial cell innate immune gene expression. PMID:25580735

  14. Safety Assessment of Commonly Used Nanoparticles in Biomedical Applications: Impact on Inflammatory Processes

    Science.gov (United States)

    Alnasser, Yossef

    Nanotechnology offers great promise in the biomedical field. Current knowledge of nanoparticles' (NPs) safety and possible mechanisms of various particle types' toxicity is insufficient. The role of particle properties and the route of particles administration in toxic reactions remain unexplored. In this thesis, we aimed to inspect the interrelationship between particle size, chemical composition and toxicological effects of four candidate NPs for drug delivery systems: gold (Au), chitosan, silica, and poly (lactide-co-glycolide) (PLGA). Mice model was combined with in vitro study to explore NPs' safety. We investigated mice survival, weight, behavior, and pro-inflammatory changes. NF-kappaB induction was assessed in vitro using the Luciferase Assay System. As observed in mice, Au NPs had a higher toxicity profile at a shorter duration than the other NPs. This was significantly in concordance with pro-inflammatory changes which may be the key routes of Au NPs toxicity. Although silica NPs induced NF-kappaB, they were less toxic to the mice than Au NPs and did not lead to the pro-inflammatory changes. Chitosan NPs were toxic to the mice but failed to cause significant NF-kappaB induction and pro-inflammatory changes. These findings indicate that chitosan NPs might not have the same pathophysiologic mechanism as the Au NPs. Comparative analysis in this model demonstrated that PLGA NPs is the safest drug delivery candidate to be administered subcutaneously.

  15. Salsalate attenuates diet induced non-alcoholic steatohepatitis in mice by decreasing lipogenic and inflammatory processes

    NARCIS (Netherlands)

    Liang, W.; Verschuren, L.; Mulder, P.; Hoorn, J.W.A. van der; Verheij, J.; Dam, A.D. van; Boon, M.R.; Princen, H.M.G.; Havekes, L.M.; Kleemann, R.; Hoek, A.M. van den

    2015-01-01

    BACKGROUND AND PURPOSE: Salsalate (salicylsalicylic acid) is an anti-inflammatory drug that was recently found to exert beneficial metabolic effects on glucose and lipid metabolism. Although its utility in the prevention and management of a wide range of vascular disorders, including type 2 diabetes

  16. Salsalate attenuates diet induced non-alcoholic steatohepatitis in mice by decreasing lipogenic and inflammatory processes

    NARCIS (Netherlands)

    Liang, Wen; Verschuren, Lars; Mulder, Petra; van der Hoorn, José W. A.; Verheij, Joanne; van Dam, Andrea D.; Boon, Mariette R.; Princen, Hans M. G.; Havekes, Louis M.; Kleemann, Robert; van den Hoek, Anita M.

    2015-01-01

    Salsalate (salicylsalicylic acid) is an anti-inflammatory drug that was recently found to exert beneficial metabolic effects on glucose and lipid metabolism. Although its utility in the prevention and management of a wide range of vascular disorders, including type 2 diabetes and metabolic syndrome

  17. Platelet CD40L mediates thrombotic and inflammatory processes in atherosclerosis

    NARCIS (Netherlands)

    Lievens, Dirk; Zernecke, Alma; Seijkens, Tom; Soehnlein, Oliver; Beckers, Linda; Munnix, Imke C. A.; Wijnands, Erwin; Goossens, Pieter; van Kruchten, Roger; Thevissen, Larissa; Boon, Louis; Flavell, Richard A.; Noelle, Randolph J.; Gerdes, Norbert; Biessen, Erik A.; Daemen, Mat J. A. P.; Heemskerk, Johan W. M.; Weber, Christian; Lutgens, Esther

    2010-01-01

    CD40 ligand (CD40L), identified as a costimulatory molecule expressed on T cells, is also expressed and functional on platelets. We investigated the thrombotic and inflammatory contributions of platelet CD40L in atherosclerosis. Although CD40L-deficient (Cd40l(-/-)) platelets exhibited impaired

  18. Bio-Electro-Fenton process for the degradation of Non-Steroidal Anti-Inflammatory Drugs in wastewater

    DEFF Research Database (Denmark)

    Nadais, Helena; Li, Xiaohu; Alves, Nadine

    2018-01-01

    Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are ubiquitous municipal wastewater pollutants of which several are resistant to degradation in conventional wastewater treatment, and represent a major environmental health concern worldwide. An alternative treatment, the bio-electro-Fenton process......, has received increasing attention in past years. In this process the strong oxidant •HO is formed using the electrons derived from bacterial oxidation of organic substrate. In this work, a laboratory scale microbial electrolysis cell based bio-electro-Fenton process was developed for the treatment...

  19. Intramuscular administration of paliperidone palmitate extended-release injectable microsuspension induces a subclinical inflammatory reaction modulating the pharmacokinetics in rats.

    Science.gov (United States)

    Darville, Nicolas; van Heerden, Marjolein; Vynckier, An; De Meulder, Marc; Sterkens, Patrick; Annaert, Pieter; Van den Mooter, Guy

    2014-07-01

    The present study aims at elucidating the intricate nature of the drug release and absorption following intramuscular (i.m.) injection of sustained-release prodrug nanocrystals/microcrystals. A paliperidone palmitate (PPP) long-acting suspension was characterized with regard to particle size (Dv,50 = 1.09 μm) and morphology prior to i.m. injection in rats. The local disposition was rigorously investigated by means of (immuno)histochemistry and transmission electron microscopy while the concurrent multiphasic pharmacokinetics was linked to the microanatomy. A transient (24 h) trauma-induced inflammation promptly evolved into a subclinical but chronic granulomatous inflammatory reaction initiated by the presence of solid material. The dense inflammatory envelope (CD68(+) macrophages) led to particle agglomeration with subsequent drop in dissolution rate beyond 24 h postinjection. This was associated with a decrease in apparent paliperidone (PP) absorption (near-zero order) until 96 h and a delayed time of occurrence of observed maximum drug plasma concentration (168 h). The infiltrating macrophages phagocytosed large fractions of the depot, thereby influencing the (pro)drug release. Radial angiogenesis (CD31(+)) was observed throughout the inflammatory rim from 72 h onwards and presumably contributed to the sustained systemic PP concentrations by maintaining a sufficient absorptive capacity. No solid-state transitions of the retrieved formulation were recorded with X-ray diffraction analysis. In summary, the initial formulation-driven prodrug (PPP) dissolution and drug (PP) absorption were followed by a complex phase determined by the relative contribution of formulation factors and dynamic physiological variables. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  20. Kefir-isolated bacteria and yeasts inhibit Shigella flexneri invasion and modulate pro-inflammatory response on intestinal epithelial cells.

    Science.gov (United States)

    Bolla, P A; Abraham, A G; Pérez, P F; de Los Angeles Serradell, M

    2016-02-01

    The aim of this work was to evaluate the ability of a kefir-isolated microbial mixture containing three bacterial and two yeast strains (MM) to protect intestinal epithelial cells against Shigella flexneri invasion, as well as to analyse the effect on pro-inflammatory response elicited by this pathogen. A significant decrease in S. flexneri strain 72 invasion was observed on both HT-29 and Caco-2 cells pre-incubated with MM. Pre-incubation with the individual strains Saccharomyces cerevisiae CIDCA 8112 or Lactococcus lactis subsp. lactis CIDCA 8221 also reduced the internalisation of S. flexneri into HT-29 cells although in a lesser extent than MM. Interestingly, Lactobacillus plantarum CIDCA 83114 exerted a protective effect on the invasion of Caco-2 and HT-29 cells by S. flexneri. Regarding the pro-inflammatory response on HT-29 cells, S. flexneri infection induced a significant activation of the expression of interleukin 8 (IL-8), chemokine (C-C motif) ligand 20 (CCL20) and tumour necrosis factor alpha (TNF-α) encoding genes (P<0.05), whereas incubation of cells with MM did not induce the expression of any of the mediators assessed. Interestingly, pre-incubation of HT-29 monolayer with MM produced an inhibition of S. flexneri-induced IL-8, CCL20 and TNF-α mRNA expression. In order to gain insight on the effect of MM (or the individual strains) on this pro-inflammatory response, a series of experiments using a HT-29-NF-κB-hrGFP reporter system were performed. Pre-incubation of HT-29-NF-κB-hrGFP cells with MM significantly dampened Shigella-induced activation. Our results showed that the contribution of yeast strain Kluyveromyces marxianus CIDCA 8154 seems to be crucial in the observed effect. In conclusion, results presented in this study demonstrate that pre-treatment with a microbial mixture containing bacteria and yeasts isolated from kefir, resulted in inhibition of S. flexneri internalisation into human intestinal epithelial cells, along with the

  1. Vitamin D mitigates age-related cognitive decline through the modulation of pro-inflammatory state and decrease in amyloid burden

    Directory of Open Access Journals (Sweden)

    Briones Teresita L

    2012-10-01

    Full Text Available Abstract Background Increasing evidence shows an association between the use of vitamin D and improvement in age-related cognitive decline. In this study, we investigated the possible mechanisms involved in the neuroprotective effects of vitamin D on age-related brain changes and cognitive function. Methods Male F344 rats aged 20 months (old and 6 months (young were used and randomly assigned to either vitamin D supplementation or no supplementation (control. A total of n = 39 rats were used in the study. Rats were individually housed and the supplementation group received a subcutaneous injection of vitamin D (1, α25-dihydroxyvitamin D3 42 I.U./Kg for 21 days. Control animals received equal volume of normal saline. Behavioral testing in water maze and spontaneous object recognition tasks started on day 14. Levels of interleukin (IL-1β and IL-10 were quantified to assess inflammatory state. Also, beta amyloid (Aβ clearance and Aβ load were measured. Results Our results show that: (1 aged rats demonstrated significant learning and memory impairment overall compared to younger animals. However, the age-related decline in learning and memory was ameliorated by the supplementation of vitamin D. No vitamin D effect on learning and memory was seen in the young animals; 2 the pro-inflammatory cytokine IL-1β is significantly increased while the anti-inflammatory cytokine IL-10 is significantly decreased in the aged rats compared to the young animals; but this age-related change in inflammatory state was mitigated by vitamin D supplementation. No effects of vitamin D were seen on the IL-1β and IL-10 expression in the young rats; (3 vitamin D increased Aβ clearance and decreased amyloid burden in the aged rats while no significant difference was seen between the young animal groups. Conclusions Our data suggest that vitamin D supplementation modulated age-related increase in pro-inflammatory state and amyloid burden. It is possible that these

  2. Modulation of inflammatory and catabolic responses in severely burned children by early burn wound excision in the first 24 hours

    NARCIS (Netherlands)

    Barret, JP; Herndon, DN

    Hypothesis: Early burn wound excision modulates the hypermetabolic response in severe pediatric burn injuries. Design: Before-after trial. Setting: A 30-bed burn referral center in a private, university-affiliated hospital. Methods: We studied 35 severely burned children who were divided into 2

  3. Soluble Iron in Alveolar Macrophages Modulates Iron Oxide Particle-Induced Inflammatory Response via Prostaglandin E2 Synthesis

    Science.gov (United States)

    Ambient particulate matter (PM)-associated metals have been shown to play an important role in cardiopulmonary health outcomes. To study the modulation of inflammation by PM-associated soluble metal, we investigated intracellular solubility of radiolabelled iron oxide (59

  4. Quality control of roll-to-roll processed polymer solar modules by complementary imaging methods

    DEFF Research Database (Denmark)

    Rösch, R.; Krebs, Frederik C; Tanenbaum, D.M.

    2012-01-01

    We applied complementary imaging methods to investigate processing failures of roll-to-roll solution processed polymer solar modules based on polymer:fullerene bulk heterojunctions. For investigation of processing deficiencies in solar modules we employed dark lock-in thermography (DLIT......), electroluminescence (ELI) and photoluminescence/reflection imaging (PLI/RI) complemented by optical imaging (OI). The combination of all high resolution images allowed us to allocate the origin of processing errors to a specific deposition process, i.e. the insufficient coverage of an electrode interlayer...

  5. Fisetin Modulates Antioxidant Enzymes and Inflammatory Factors to Inhibit Aflatoxin-B1 Induced Hepatocellular Carcinoma in Rats

    Directory of Open Access Journals (Sweden)

    Brajesh Kumar Maurya

    2016-01-01

    Full Text Available Fisetin, a known antioxidant, has been found to be cytotoxic against certain cell lines. However, the mechanism by which it inhibits tumor growth in vivo remains unexplored. Recently, we have demonstrated that Aflatoxin-B1 (AFB1 induced hepatocarcinogenesis is associated with activation of oxidative stress-inflammatory pathway in rat liver. The present paper describes the effect of in vivo treatment with 20 mg/kg b.w. Fisetin on antioxidant enzymes vis-a-vis oxidative stress level and on the profile of certain proinflammatory cytokines in the hepatocellular carcinoma (HCC induced by two doses of 1 mg/kg b.w. AFB1 i.p. in rats. The reduced levels of most of the antioxidant enzymes, coinciding with the enhanced level of reactive oxygen species in the HCC liver, were observed to regain their normal profiles due to Fisetin treatment. Also, Fisetin treatment could normalize the enhanced expression of TNFα and IL1α, the two proinflammatory cytokines, reported to be involved in HCC pathogenesis. These observations were consistent with the regression of neoplastic lesion and declined GST-pi (placental type glutathione-S-transferase level, a HCC marker, in the liver of the Fisetin treated HCC rats. The findings suggest that Fisetin attenuates oxidative stress-inflammatory pathway of AFB1 induced hepatocarcinogenesis.

  6. Fisetin Modulates Antioxidant Enzymes and Inflammatory Factors to Inhibit Aflatoxin-B1 Induced Hepatocellular Carcinoma in Rats

    Science.gov (United States)

    Maurya, Brajesh Kumar; Trigun, Surendra Kumar

    2016-01-01

    Fisetin, a known antioxidant, has been found to be cytotoxic against certain cell lines. However, the mechanism by which it inhibits tumor growth in vivo remains unexplored. Recently, we have demonstrated that Aflatoxin-B1 (AFB1) induced hepatocarcinogenesis is associated with activation of oxidative stress-inflammatory pathway in rat liver. The present paper describes the effect of in vivo treatment with 20 mg/kg b.w. Fisetin on antioxidant enzymes vis-a-vis oxidative stress level and on the profile of certain proinflammatory cytokines in the hepatocellular carcinoma (HCC) induced by two doses of 1 mg/kg b.w. AFB1 i.p. in rats. The reduced levels of most of the antioxidant enzymes, coinciding with the enhanced level of reactive oxygen species in the HCC liver, were observed to regain their normal profiles due to Fisetin treatment. Also, Fisetin treatment could normalize the enhanced expression of TNFα and IL1α, the two proinflammatory cytokines, reported to be involved in HCC pathogenesis. These observations were consistent with the regression of neoplastic lesion and declined GST-pi (placental type glutathione-S-transferase) level, a HCC marker, in the liver of the Fisetin treated HCC rats. The findings suggest that Fisetin attenuates oxidative stress-inflammatory pathway of AFB1 induced hepatocarcinogenesis. PMID:26682000

  7. Modulation of oxidative and inflammatory cardiac response by nonselective 1- and 2-cyclooxygenase inhibitor and benznidazole in mice.

    Science.gov (United States)

    Santos, Eliziária C; Novaes, Rômulo D; Bastos, Daniel S S; Oliveira, Jerusa M; Penitente, Arlete R; Gonçalves, Wagner G; Cardoso, Silvia A; Talvani, André; Oliveira, Leandro L

    2015-11-01

    This study investigated the combined effects of benznidazole (BZ) and ibuprofen (IB) on the oxidative and inflammatory status of the cardiac tissue in vivo. Swiss mice were randomized in groups receiving BZ (100 mg/kg) and IB (400 mg/kg) alone or combined (BZ + IB 200 or 400 mg/kg). Control animals were concurrently treated with 1% carboxymethyl cellulose. All treatments were administered orally for 7 days. BZ treatment increased cardiac production of nitrogen/oxygen-reactive species, malondialdeyde, carbonyl proteins, prostaglandins as well as the activities of catalase, superoxide dismutase and glutathione peroxidase. These parameters were attenuated by IB, with the best results at higher dose. Individually, BZ and IB significantly reduced the tissue levels of chemokine ligand 2, tumour necrosis factor-α and IL-10, but no reduction was observed when the treatments were combined. BZ triggers an oxidative and nitrosative route, which is associated with increased prostaglandin synthesis and marked damages to the lipids and proteins of the cardiac tissue. IB treatment attenuated reactive stresses triggered by BZ, which was an independent effects of this drug on the endogenous antioxidant enzymes. Individually, but not together, BZ and IB reduced the cardiac inflammatory status, indicating a beneficial and complex drug interaction. © 2015 Royal Pharmaceutical Society.

  8. Reasoning strategies modulate gender differences in emotion processing.

    Science.gov (United States)

    Markovits, Henry; Trémolière, Bastien; Blanchette, Isabelle

    2018-01-01

    The dual strategy model of reasoning has proposed that people's reasoning can be understood asa combination of two different ways of processing information related to problem premises: a counterexample strategy that examines information for explicit potential counterexamples and a statistical strategy that uses associative access to generate a likelihood estimate of putative conclusions. Previous studies have examined this model in the context of basic conditional reasoning tasks. However, the information processing distinction that underlies the dual strategy model can be seen asa basic description of differences in reasoning (similar to that described by many general dual process models of reasoning). In two studies, we examine how these differences in reasoning strategy may relate to processing very different information, specifically we focus on previously observed gender differences in processing negative emotions. Study 1 examined the intensity of emotional reactions to a film clip inducing primarily negative emotions. Study 2 examined the speed at which participants determine the emotional valence of sequences of negative images. In both studies, no gender differences were observed among participants using a counterexample strategy. Among participants using a statistical strategy, females produce significantly stronger emotional reactions than males (in Study 1) and were faster to recognize the valence of negative images than were males (in Study 2). Results show that the processing distinction underlying the dual strategy model of reasoning generalizes to the processing of emotions. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Mas-related G protein coupled receptor-X2: A potential new target for modulating mast cell-mediated allergic and inflammatory diseases.

    Science.gov (United States)

    Ali, Hydar

    2016-12-01

    Mast cells (MCs) are tissue resident immune cells that are best known for their roles in allergic and inflammatory diseases. In addition to the high affinity IgE receptor (FcεRI), MCs express numerous G protein coupled receptors (GPCRs), which are the most common targets of drug therapy. Neurokinin 1 receptor (NK-1R) is expressed on MCs and contributes to IgE and non-IgE-mediated responses in mice. Although NK-1R antagonists are highly effective in modulating experimental allergic and inflammatory responses in mice they lack efficacy in humans. This article reviews recent findings that demonstrate that while neuropeptides (NPs) activate murine MCs via NK-1R and Mas related G protein coupled receptor B2 (MrgprB2), they activate human MCs via Mas-related G protein coupled receptor X2 (MRGPRX2). Interestingly, conventional NK-1R antagonists have off-target activity against mouse MrgprB2 but not human MRGPRX2. These findings suggest that the failure to translate studies with NK-1R antagonists from in vivo mouse studies to the clinic likely reflects their lack of effect on human MRGPRX2. A unique feature of MRGPRX2 that distinguishes it from other GPCRs is that it is activated by a diverse group of ligands that include; neuropeptides, cysteine proteases, antimicrobial peptides and cationic proteins released from activated eosinophils. Thus, the development of small molecule MRGPRX2-specific antagonists or neutralizing antibodies may provide new targets for the treatment of MC-mediated allergic and inflammatory diseases.

  10. Tumor necrosis factor-alpha activates signal transduction in hypothalamus and modulates the expression of pro-inflammatory proteins and orexigenic/anorexigenic neurotransmitters.

    Science.gov (United States)

    Amaral, Maria E; Barbuio, Raquel; Milanski, Marciane; Romanatto, Talita; Barbosa, Helena C; Nadruz, Wilson; Bertolo, Manoel B; Boschero, Antonio C; Saad, Mario J A; Franchini, Kleber G; Velloso, Licio A

    2006-07-01

    Tumor necrosis factor-alpha (TNF-alpha) is known to participate in the wastage syndrome that accompanies cancer and severe infectious diseases. More recently, a role for TNF-alpha in the pathogenesis of type 2 diabetes mellitus and obesity has been shown. Much of the regulatory action exerted by TNF-alpha upon the control of energy stores depends on its action on the hypothalamus. In this study, we show that TNF-alpha activates canonical pro-inflammatory signal transduction pathways in the hypothalamus of rats. These signaling events lead to the transcriptional activation of an early responsive gene and to the induction of expression of cytokines and a cytokine responsive protein such as interleukin-1beta, interleukin-6, interleukin-10 and suppressor of cytokine signalling-3, respectively. In addition, TNF-alpha induces the expression of neurotransmitters involved in the control of feeding and thermogenesis. Thus, TNF-alpha may act directly in the hypothalamus inducing a pro-inflammatory response and the modulation of expression of neurotransmitters involved in energy homeostasis.

  11. Centella asiatica modulates cancer cachexia associated inflammatory cytokines and cell death in leukaemic THP-1 cells and peripheral blood mononuclear cells (PBMC's).

    Science.gov (United States)

    Naidoo, Dhaneshree Bestinee; Chuturgoon, Anil Amichund; Phulukdaree, Alisa; Guruprasad, Kanive Parashiva; Satyamoorthy, Kapaettu; Sewram, Vikash

    2017-08-01

    Cancer cachexia is associated with increased pro-inflammatory cytokine levels. Centella asiatica (C. asiatica) possesses antioxidant, anti-inflammatory and anti-tumour potential. We investigated the modulation of antioxidants, cytokines and cell death by C. asiatica ethanolic leaf extract (C LE ) in leukaemic THP-1 cells and normal peripheral blood mononuclear cells (PBMC's). Cytotoxcity of C LE was determined at 24 and 72 h (h). Oxidant scavenging activity of C LE was evaluated using the 2, 2-diphenyl-1 picrylhydrazyl (DPPH) assay. Glutathione (GSH) levels, caspase (-8, -9, -3/7) activities and adenosine triphosphate (ATP) levels (Luminometry) were then assayed. The levels of tumour necrosis factor-α (TNF-α), interleukin (IL)-6, IL-1β and IL-10 were also assessed using enzyme-linked immunosorbant assay. C LE decreased PBMC viability between 33.25-74.55% (24 h: 0.2-0.8 mg/ml C LE and 72 h: 0.4-0.8 mg/ml C LE ) and THP-1 viability by 28.404% (72 h: 0.8 mg/ml C LE ) (p cachexia.

  12. The antioxidants curcumin and quercetin inhibit inflammatory processes associated with arthritis.

    Science.gov (United States)

    Jackson, J K; Higo, T; Hunter, W L; Burt, H M

    2006-04-01

    Curcumin and quercetin are antioxidant molecules with anti-proliferative, anti-inflammatory and immunosuppressive activities. The objective of this study was to investigate the inhibitory activity of these agents using four assays of inflammatory aspects of arthritis. Crystal-induced neutrophil activation was measured by luminol-dependent chemiluminescence. Synoviocyte proliferation was measured by an MTS assay using HIG-82 rabbit synoviocytes in cell culture. Chondrocyte (cultured primary cells) expression of the matrix metalloproteinases collagenase and stromelysin was measured by Northern Blot analysis. Angiogenesis was measured using the chorioallantoic membrane of the chick embryo. Both agents inhibited neutrophil activation, synoviocyte proliferation and angiogenesis. Curcumin strongly inhibited collagenase and stromelysin expression at micromolar concentrations whereas quercetin had no effect in this assay. These studies suggest that curcumin and to a lesser extent quercetin may offer therapeutic potential for the treatment of crystal-induced arthritis or rheumatoid arthritis.

  13. Identification of inflammatory processes in temporomandibular joint (TMJ) by 99mTc-HMPAO in animal model

    International Nuclear Information System (INIS)

    Brasileiro, Claudia Borges; Cardoso, Valbert Nascimento; Lima, Carla Flavia de; Campos, Tarcisio Passos Ribeiro de

    2005-01-01

    Temporomandibular joint (TMJ) is a synovial joint that represents the junction of mandible with skull. TMJ and mastication muscles are affected by temporomandibular disorders (TMDs). During the last two decades the advances in imaging diagnostic of TMJ have greatly contributed to the assessment of the TMJ disorders. Labelled leukocytes with technetium- 99m hexamethyl propylene amine oxime ( 99m Tc-HMPAO) represent an efficient method that generates images based in physiological and/or biochemical changes related to inflammation. The aim of this study was to investigate the potential usefulness of technetium-99m labelled leukocytes scintigraphy in the diagnosis of TMJ inflammatory process applying a rabbit TMJ arthritis model. Arthritis was induced unilaterally with an intra-articular injection of ovalbumin in left ATM. On the contra-lateral side, the same dose of saline was injected. After five days, leukocytes were labeled with HMPAO and 99m Tc-HMPAO TMJ scintigraphic images were made. After twelve days a computed tomography was realized. Scintigraphic images obtained five days after induction of TMJ inflammation showed the localization of inflammatory process. The results were expressed as cpm of activity found in left ATM and contra-lateral side. Significant differences of activity were found between inflamed articulation and contra-lateral side (P = 0,0073). In conclusion, the method of leukocytes labeled with 99m Tc showed to be sensitive in detection of inflammatory disorders of TMJ and can be of great value in early diagnostic of these disorders. (author)

  14. The role of trophic factors and inflammatory processes in physical activity-induced neuroprotection in Parkinson’s disease

    Directory of Open Access Journals (Sweden)

    Ewelina Pałasz

    2017-01-01

    Full Text Available Glial cells and neurotrophins play an important role in maintaining homeostasis of the CNS. Disturbances of their function can lead to a number of nervous system diseases, including Parkinson’s disease (PD. Current clinical studies provide evidence that moderate physical activity adapted to the health status of PD patients can support pharmacological treatment, slow down the onset of motor impairments, and extend the patients period of independence. Physical activity, by stimulating the production and release of endogenous trophic factors, prevents the neurodegeneration of dopaminergic neurons via inhibition of inflammatory processes and the reduction of oxidative stress. The aim of this study is to present the current state of knowledge for the anti-inflammatory and neuroprotective properties of physical activity as a supportive therapy in Parkinson’s disease.

  15. [Function and modulation of type Ⅱ innate lymphoid cells and their role in chronic upper airway inflammatory diseases].

    Science.gov (United States)

    Liu, Y; Liu, Z

    2017-02-07

    Type Ⅱ innate lymphoid cells (ILC2) is a family of innate immune lymphocytes, which provide effective immune responses to cytokines. ILC2 are regulated by the nuclear transcription factor ROR alpha and GATA3, secreting cytokines IL-5 and IL-13, etc. Animal models have shown that ILC2 are involved in allergic diseases, such as asthma and atopic dermatitis, and also play a very important role in the metabolic balance. In addition, recent reports suggest that ILC2 not only play a role in the initial stages of the disease, but also can lead to chronic pathological changes in the disease, such as fibrosis, and may have an effect on acquired immunity. This paper mainly focus in the role and regulation of ILC2 cells, and review the research status of ILC2 in the field of chronic upper airway inflammatory diseases including allergic rhinitis and chronic rhinosinusitis.

  16. Temporal texture of associative encoding modulates recall processes.

    Science.gov (United States)

    Tibon, Roni; Levy, Daniel A

    2014-02-01

    Binding aspects of an experience that are distributed over time is an important element of episodic memory. In the current study, we examined how the temporal complexity of an experience may govern the processes required for its retrieval. We recorded event-related potentials during episodic cued recall following pair associate learning of concurrently and sequentially presented object-picture pairs. Cued recall success effects over anterior and posterior areas were apparent in several time windows. In anterior locations, these recall success effects were similar for concurrently and sequentially encoded pairs. However, in posterior sites clustered over parietal scalp the effect was larger for the retrieval of sequentially encoded pairs. We suggest that anterior aspects of the mid-latency recall success effects may reflect working-with-memory operations or direct access recall processes, while more posterior aspects reflect recollective processes which are required for retrieval of episodes of greater temporal complexity. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Eye Contact Modulates Cognitive Processing Differently in Children with Autism

    Science.gov (United States)

    Falck-Ytter, Terje; Carlström, Christoffer; Johansson, Martin

    2015-01-01

    In humans, effortful cognitive processing frequently takes place during social interaction, with eye contact being an important component. This study shows that the effect of eye contact on memory for nonsocial information is different in children with typical development than in children with autism, a disorder of social communication. Direct…

  18. Attentional Capture by Emotional Stimuli Is Modulated by Semantic Processing

    Science.gov (United States)

    Huang, Yang-Ming; Baddeley, Alan; Young, Andrew W.

    2008-01-01

    The attentional blink paradigm was used to examine whether emotional stimuli always capture attention. The processing requirement for emotional stimuli in a rapid sequential visual presentation stream was manipulated to investigate the circumstances under which emotional distractors capture attention, as reflected in an enhanced attentional blink…

  19. Ureaplasma Species Differentially Modulate Pro- and Anti-Inflammatory Cytokine Responses in Newborn and Adult Human Monocytes Pushing the State Toward Pro-Inflammation

    Science.gov (United States)

    Glaser, Kirsten; Silwedel, Christine; Fehrholz, Markus; Waaga-Gasser, Ana M.; Henrich, Birgit; Claus, Heike; Speer, Christian P.

    2017-01-01

    Background: Ureaplasma species have been associated with chorioamnionitis and preterm birth and have been implicated in the pathogenesis of neonatal short and long-term morbidity. However, being mostly commensal bacteria, controversy remains on the pro-inflammatory capacity of Ureaplasma. Discussions are ongoing on the incidence and impact of prenatal, perinatal, and postnatal infection. The present study addressed the impact of Ureaplasma isolates on monocyte-driven inflammation. Methods: Cord blood monocytes of term neonates and adult monocytes, either native or LPS-primed, were cultured with Ureaplasma urealyticum (U. urealyticum) serovar 8 (Uu8) and Ureaplasma parvum serovar 3 (Up3). Using qRT-PCR, cytokine flow cytometry, and multi-analyte immunoassay, we assessed mRNA and protein expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-8, IL-12p40, IL-10, and IL-1 receptor antagonist (IL-1ra) as well as Toll-like receptor (TLR) 2 and TLR4. Results: Uu8 and Up3 induced mRNA expression and protein release of TNF-α, IL-1β and IL-8 in term neonatal and adult monocytes (p Ureaplasma-stimulated cells paralleled those results. Ureaplasma-induced cytokine levels did not significantly differ from LPS-mediated levels except for lower intracellular IL-1β in adult monocytes (Uu8: p ureaplasmas did not induce IL-12p40 response and promoted lower amounts of anti-inflammatory IL-10 and IL-1ra than LPS, provoking a cytokine imbalance more in favor of pro-inflammation (IL-1β/IL-10, IL-8/IL-10 and IL-8/IL-1ra: p Ureaplasma isolates in human monocytes. Stimulating pro-inflammatory cytokine responses while hardly inducing immunomodulatory and anti-inflammatory cytokines, ureaplasmas might push monocyte immune responses toward pro-inflammation. Inhibition of LPS-induced cytokines in adult monocytes in contrast to sustained inflammation in term neonatal monocytes indicates a differential modulation of host immune responses to a second stimulus. Modification of

  20. Calcium supplementation decreases BCP-induced inflammatory processes in blood cells through the NLRP3 inflammasome down-regulation.

    Science.gov (United States)

    Lagadec, Patricia; Balaguer, Thierry; Boukhechba, Florian; Michel, Grégory; Bouvet-Gerbettaz, Sébastien; Bouler, Jean-Michel; Scimeca, Jean-Claude; Rochet, Nathalie

    2017-07-15

    Interaction of host blood with biomaterials is the first event occurring after implantation in a bone defect. This study aimed at investigating the cellular and molecular consequences arising at the interface between whole blood and biphasic calcium phosphate (BCP) particles. We observed that, due to calcium capture, BCP inhibited blood coagulation, and that this inhibition was reversed by calcium supplementation. Therefore, we studied the impact of calcium supplementation on BCP effects on blood cells. Comparative analysis of BCP and calcium supplemented-BCP (BCP/Ca) effects on blood cells showed that BCP as well as BCP/Ca induced monocyte proliferation, as well as a weak but significant hemolysis. Our data showed for the first time that calcium supplementation of BCP microparticles had anti-inflammatory properties compared to BCP alone that induced an inflammatory response in blood cells. Our results strongly suggest that the anti-inflammatory property of calcium supplemented-BCP results from its down-modulating effect on P2X7R gene expression and its capacity to inhibit ATP/P2X7R interactions, decreasing the NLRP3 inflammasome activation. Considering that monocytes have a vast regenerative potential, and since the excessive inflammation often observed after bone substitutes implantation limits their performance, our results might have great implications in terms of understanding the mechanisms leading to an efficient bone reconstruction. Although scaffolds and biomaterials unavoidably come into direct contact with blood during bone defect filling, whole blood-biomaterials interactions have been poorly explored. By studying in 3D the interactions between biphasic calcium phosphate (BCP) in microparticulate form and blood, we showed for the first time that calcium supplementation of BCP microparticles (BCP/Ca) has anti-inflammatory properties compared to BCP-induced inflammation in whole blood cells and provided information related to the molecular mechanisms

  1. Spectrotemporal processing in spectral tuning modules of cat primary auditory cortex.

    Directory of Open Access Journals (Sweden)

    Craig A Atencio

    Full Text Available Spectral integration properties show topographical order in cat primary auditory cortex (AI. Along the iso-frequency domain, regions with predominantly narrowly tuned (NT neurons are segregated from regions with more broadly tuned (BT neurons, forming distinct processing modules. Despite their prominent spatial segregation, spectrotemporal processing has not been compared for these regions. We identified these NT and BT regions with broad-band ripple stimuli and characterized processing differences between them using both spectrotemporal receptive fields (STRFs and nonlinear stimulus/firing rate transformations. The durations of STRF excitatory and inhibitory subfields were shorter and the best temporal modulation frequencies were higher for BT neurons than for NT neurons. For NT neurons, the bandwidth of excitatory and inhibitory subfields was matched, whereas for BT neurons it was not. Phase locking and feature selectivity were higher for NT neurons. Properties of the nonlinearities showed only slight differences across the bandwidth modules. These results indicate fundamental differences in spectrotemporal preferences--and thus distinct physiological functions--for neurons in BT and NT spectral integration modules. However, some global processing aspects, such as spectrotemporal interactions and nonlinear input/output behavior, appear to be similar for both neuronal subgroups. The findings suggest that spectral integration modules in AI differ in what specific stimulus aspects are processed, but they are similar in the manner in which stimulus information is processed.

  2. Modulation of the tissue regenerative process in fish by ß-glucans

    DEFF Research Database (Denmark)

    Nielsen, Michael Engelbrecht; Jiménez, Natalia Ivonne Vera; Przybylska, Dominika Alicja

    the importance of fibroblasts, macrophages, reactive oxygen species (especially hydrogen peroxide) and certain cytokines during wound healing processes. In fish however, only a few studies have been devoted tissue regeneration and modulation of cell proliferation during wound healing, even though mechanical...... the immune response towards pathogen eradication or tissue repair....... but not in animals. are commonly used as immune modulators, but the mechanisms through which the modulation is achieved remains to be understood. Wound healing and tissue regeneration are essential mechanisms to ensure the survival and health of any organism. Studies from the mammalian systems have shown...

  3. Alteration of the digestive motility linked with radiation-induced inflammatory processes in rats

    International Nuclear Information System (INIS)

    Picard, C.

    2000-12-01

    Exposure to ionizing radiation, whether accidental or for medical reasons, may lead to gastro-intestinal injury, characterized by nausea, vomiting, diarrhea and abdominal cramps. The aetiology of radiation-induced diarrhea remains to date unclear. In this study, we have investigated the acute effects of a 10 Gy abdominal irradiation on rat digestive functions. The objective of the first study was to evaluate the role of sensory afferent neurons, capsaicin-sensitive, on morphological changes and the inflammatory response following exposure. Three days after irradiation, we observed an inflammatory response characterized by neutrophils infiltration and mast cells de-granulation. No effect of capsaicin pre-treatment was seen on these parameters. However, neutrophils infiltration was increased as early as one day after irradiation in capsaicin-treated rats. No difference in severity of diarrhea was observed after denervation nor in morphological changes. These data demonstrate that abdominal irradiation results in diarrhea concomitant with an inflammatory response, and that sensory innervation does not play a major protective role. The objective of the rest of the work was in the first instance to characterize radiation-induced alterations of intestinal and colonic motility leading to diarrhea and secondly to evaluate the role of serotonin in such disorders. Perturbations in intestinal (MMC) and colonic (LSB) motor profiles were observed from the first day onwards. Migrating motor complexes (MMC) were completely disrupted at three days at the same time as the onset of diarrhea. In addition to inhibition of LSB, colonic fluid absorptive capacity was decreased and serotonin colonic tissue levels were increased three days after irradiation. Radiation-induced diarrhea was reduced by treatment with an antagonist of 5-HT 3 receptors, granisetron, as were alterations of colonic motility and serotonin tissue levels. However, this treatment did not significantly ameliorate

  4. Guinea-pig interpubic joint (symphysis pubica relaxation at parturition: Underlying cellular processes that resemble an inflammatory response

    Directory of Open Access Journals (Sweden)

    Muñoz-de-Toro Mónica

    2003-11-01

    Full Text Available Abstract Background At term, cervical ripening in coordination with uterine contractions becomes a prerequisite for a normal vaginal delivery. Currently, cervical ripening is considered to occur independently from uterine contractions. Many evidences suggest that cervical ripening resembles an inflammatory process. Comparatively little attention has been paid to the increased flexibility of the pelvic symphysis that occurs in many species to enable safe delivery. The aim of this study was to investigate whether the guinea-pig interpubic joint relaxation process observed during late pregnancy and parturition resembles an inflammatory process. Methods Samples of pubic symphysis were taken from pregnant guinea-pigs sacrificed along gestation, parturition and postpartum. Serial sections of paraffin-embedded tissues were used to measure the interpubic distance on digitalized images, stained with Giemsa to quantify leukocyte infiltration and to describe the vascular area changes, or studied by the picrosirius-polarization method to evaluate collagen remodeling. P4 and E2 serum levels were measured by a sequential immunometric assay. Results Data showed that the pubic relaxation is associated with an increase in collagen remodeling. In addition, a positive correlation between E2 serum levels and the increase in the interpubic distance was found. On the other hand, a leukocyte infiltration in the interpubic tissue around parturition was described, with the presence of almost all inflammatory cells types. At the same time, histological images show an increase in vascular area (angiogenesis. Eosinophils reached their highest level immediately before parturition; whereas for the neutrophilic and mononuclear infiltration higher values were recorded one day after parturition. Correlation analysis showed that eosinophils and mononuclear cells were positively correlated with E2 levels, but only eosinophilic infiltration was associated with collagen remodeling

  5. Disgust-specific modulation of early attention processes.

    Science.gov (United States)

    van Hooff, Johanna C; van Buuringen, Melanie; El M'rabet, Ihsane; de Gier, Margot; van Zalingen, Lilian

    2014-10-01

    Although threatening images are known to attract and keep our attention, little is known about the existence of emotion-specific attention effects. In this study (N=46), characteristics of an anticipated, disgust-specific effect were investigated by means of a covert orienting paradigm incorporating pictures that were either disgust-evoking, fear-evoking, happiness-evoking or neutral. Attention adhesion to these pictures was measured by the time necessary to identify a peripheral target, presented 100, 200, 500, or 800 ms after picture onset. Main results showed that reaction times were delayed for targets following the disgust-evoking pictures by 100 and 200 ms, suggesting that only these pictures temporarily grabbed hold of participants' attention. These delays were similar for ignore- and attend-instructions, and they were not affected by the participants' anxiety levels or disgust sensitivity. The disgust-specific influence on early attention processes thus appeared very robust, occurring in the majority of participants and without contribution of voluntary- and strategic-attention processes. In contrast, a smaller and less reliable effect of all emotional (arousing) pictures was present in the form of delayed responding in the 100 ms cue-target interval. This effect was more transitory and apparent only in participants with relatively high state-anxiety scores. Practical and theoretical consequences of these findings are discussed. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Kisspeptin modulates sexual and emotional brain processing in humans.

    Science.gov (United States)

    Comninos, Alexander N; Wall, Matthew B; Demetriou, Lysia; Shah, Amar J; Clarke, Sophie A; Narayanaswamy, Shakunthala; Nesbitt, Alexander; Izzi-Engbeaya, Chioma; Prague, Julia K; Abbara, Ali; Ratnasabapathy, Risheka; Salem, Victoria; Nijher, Gurjinder M; Jayasena, Channa N; Tanner, Mark; Bassett, Paul; Mehta, Amrish; Rabiner, Eugenii A; Hönigsperger, Christoph; Silva, Meire Ribeiro; Brandtzaeg, Ole Kristian; Lundanes, Elsa; Wilson, Steven Ray; Brown, Rachel C; Thomas, Sarah A; Bloom, Stephen R; Dhillo, Waljit S

    2017-02-01

    Sex, emotion, and reproduction are fundamental and tightly entwined aspects of human behavior. At a population level in humans, both the desire for sexual stimulation and the desire to bond with a partner are important precursors to reproduction. However, the relationships between these processes are incompletely understood. The limbic brain system has key roles in sexual and emotional behaviors, and is a likely candidate system for the integration of behavior with the hormonal reproductive axis. We investigated the effects of kisspeptin, a recently identified key reproductive hormone, on limbic brain activity and behavior. Using a combination of functional neuroimaging and hormonal and psychometric analyses, we compared the effects of kisspeptin versus vehicle administration in 29 healthy heterosexual young men. We demonstrated that kisspeptin administration enhanced limbic brain activity specifically in response to sexual and couple-bonding stimuli. Furthermore, kisspeptin's enhancement of limbic brain structures correlated with psychometric measures of reward, drive, mood, and sexual aversion, providing functional significance. In addition, kisspeptin administration attenuated negative mood. Collectively, our data provide evidence of an undescribed role for kisspeptin in integrating sexual and emotional brain processing with reproduction in humans. These results have important implications for our understanding of reproductive biology and are highly relevant to the current pharmacological development of kisspeptin as a potential therapeutic agent for patients with common disorders of reproductive function. National Institute for Health Research (NIHR), Wellcome Trust (Ref 080268), and the Medical Research Council (MRC).

  7. Tuned by experience: How orientation probability modulates early perceptual processing.

    Science.gov (United States)

    Jabar, Syaheed B; Filipowicz, Alex; Anderson, Britt

    2017-09-01

    Probable stimuli are more often and more quickly detected. While stimulus probability is known to affect decision-making, it can also be explained as a perceptual phenomenon. Using spatial gratings, we have previously shown that probable orientations are also more precisely estimated, even while participants remained naive to the manipulation. We conducted an electrophysiological study to investigate the effect that probability has on perception and visual-evoked potentials. In line with previous studies on oddballs and stimulus prevalence, low-probability orientations were associated with a greater late positive 'P300' component which might be related to either surprise or decision-making. However, the early 'C1' component, thought to reflect V1 processing, was dampened for high-probability orientations while later P1 and N1 components were unaffected. Exploratory analyses revealed a participant-level correlation between C1 and P300 amplitudes, suggesting a link between perceptual processing and decision-making. We discuss how these probability effects could be indicative of sharpening of neurons preferring the probable orientations, due either to perceptual learning, or to feature-based attention. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Edaravone alleviates cisplatin-induced neurobehavioral deficits via modulation of oxidative stress and inflammatory mediators in the rat hippocampus.

    Science.gov (United States)

    Jangra, Ashok; Kwatra, Mohit; Singh, Tavleen; Pant, Rajat; Kushwah, Pawan; Ahmed, Sahabuddin; Dwivedi, Durgesh; Saroha, Babita; Lahkar, Mangala

    2016-11-15

    Cisplatin is a chemotherapeutic agent used in the treatment of malignant tumors. A major clinical limitation of cisplatin is its potential toxic effects, including neurotoxicity. Edaravone, a potent free radical scavenger, has been reported to have the neuroprotective effect against neurological deficits. The aim of the present study was to determine the neuroprotective effect of edaravone against cisplatin-induced behavioral and biochemical anomalies in male Wistar rats. Our results showed that cisplatin (5mg/kg/week, i.p.) administration for seven weeks caused marked cognitive deficits and motor incoordination in rats. This was accompanied by oxido-nitrosative stress, neuroinflammation, NF-κB activation and down-regulation of Nrf2/HO-1 gene expression level in the hippocampus. Edaravone (10mg/kg/week, i.p.) treatment for seven weeks inhibited the aforementioned neurobehavioral and neurochemical deficits. Furthermore, edaravone was found to up-regulate the gene expression level of Nrf2/HO-1 and prevented the cisplatin-induced NF-κB activation. These findings demonstrated that oxido-nitrosative stress and inflammatory signaling mediators play a key role in the development of cisplatin-induced neurobehavioral deficits which were prevented by edaravone treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Chronic oral infection with major periodontal bacteria Tannerella forsythia modulates systemic atherosclerosis risk factors and inflammatory markers.

    Science.gov (United States)

    Chukkapalli, Sasanka S; Rivera-Kweh, Mercedes F; Velsko, Irina M; Chen, Hao; Zheng, Donghang; Bhattacharyya, Indraneel; Gangula, Pandu R; Lucas, Alexandra R; Kesavalu, Lakshmyya

    2015-04-01

    Tannerella forsythia is a Gram-negative anaerobic organism that inhabits the subgingival cavity and initiates connective tissue destruction and alveolar bone resorption in periodontal disease (PD). PD is a chronic immunoinflammatory disease and has been linked to several systemic diseases including atherosclerosis. This study evaluated the effects of a chronic oral infection with T. forsythia ATCC 43037 on the induction of PD, inflammatory markers and atherosclerosis risk factors in hyperlipidemic ApoE(null) mice. Mice were orally infected for 12 and 24 weeks prior to euthanasia. Bacterial colonization of the oral cavity and bacteremia was confirmed via isolation of genomic DNA from oral plaque and tissues. Oral infection elicited significantly elevated levels of serum IgG and IgM antibodies and alveolar bone resorption compared to control mice. Tannerella forsythia-infected mice had increased serum amyloid A, and significantly reduced serum nitric oxide when compared to controls. Tannerella forsythia chronic infection also significantly increased serum lipoproteins suggesting altered cholesterol metabolism and potential for aortic inflammation. Despite enhanced acute phase reactants and altered lipid profiles, T. forsythia infection was associated with decreased aortic plaque. This study investigates the potential of a known periodontal bacterial pathogen found in atherosclerotic plaque in humans to accelerate atherosclerosis in hyperlipdemic mice. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  10. Project T.E.A.M. (Technical Education Advancement Modules). Advanced Statistical Process Control.

    Science.gov (United States)

    Dunlap, Dale

    This instructional guide, one of a series developed by the Technical Education Advancement Modules (TEAM) project, is a 20-hour advanced statistical process control (SPC) and quality improvement course designed to develop the following competencies: (1) understanding quality systems; (2) knowing the process; (3) solving quality problems; and (4)…

  11. On stochastic integration for volatility modulated Brownian-driven Volterra processes via white noise analysis

    DEFF Research Database (Denmark)

    E. Barndorff-Nielsen, Ole; Benth, Fred Espen; Szozda, Benedykt

    This paper generalizes the integration theory for volatility modulated Brownian-driven Volterra processes onto the space G* of Potthoff-Timpel distributions. Sufficient conditions for integrability of generalized processes are given, regularity results and properties of the integral are discussed...

  12. On stochastic integration for volatility modulated Brownian-driven Volterra processes via white noise analysis

    DEFF Research Database (Denmark)

    Barndorff-Nielsen, Ole E.; Benth, Fred Espen; Szozda, Benedykt

    This paper generalizes the integration theory for volatility modulated Brownian-driven Volterra processes onto the space G∗ of Potthoff--Timpel distributions. Sufficient conditions for integrability of generalized processes are given, regularity results and properties of the integral are discusse...

  13. A Study on Signal Group Processing of AUTOSAR COM Module

    International Nuclear Information System (INIS)

    Lee, Jeong-Hwan; Hwang, Hyun Yong; Han, Tae Man; Ahn, Yong Hak

    2013-01-01

    In vehicle, there are many ECU(Electronic Control Unit)s, and ECUs are connected to networks such as CAN, LIN, FlexRay, and so on. AUTOSAR COM(Communication) which is a software platform of AUTOSAR(AUTomotive Open System ARchitecture) in the international industry standards of automotive electronic software processes signals and signal groups for data communications between ECUs. Real-time and reliability are very important for data communications in the vehicle. Therefore, in this paper, we analyze functions of signals and signal groups used in COM, and represent that functions of signal group are more efficient than signals in real-time data synchronization and network resource usage between the sender and receiver.

  14. A Study on Signal Group Processing of AUTOSAR COM Module

    Science.gov (United States)

    Lee, Jeong-Hwan; Hwang, Hyun Yong; Han, Tae Man; Ahn, Yong Hak

    2013-06-01

    In vehicle, there are many ECU(Electronic Control Unit)s, and ECUs are connected to networks such as CAN, LIN, FlexRay, and so on. AUTOSAR COM(Communication) which is a software platform of AUTOSAR(AUTomotive Open System ARchitecture) in the international industry standards of automotive electronic software processes signals and signal groups for data communications between ECUs. Real-time and reliability are very important for data communications in the vehicle. Therefore, in this paper, we analyze functions of signals and signal groups used in COM, and represent that functions of signal group are more efficient than signals in real-time data synchronization and network resource usage between the sender and receiver.

  15. Acoustic richness modulates the neural networks supporting intelligible speech processing.

    Science.gov (United States)

    Lee, Yune-Sang; Min, Nam Eun; Wingfield, Arthur; Grossman, Murray; Peelle, Jonathan E

    2016-03-01

    The information contained in a sensory signal plays a critical role in determining what neural processes are engaged. Here we used interleaved silent steady-state (ISSS) functional magnetic resonance imaging (fMRI) to explore how human listeners cope with different degrees of acoustic richness during auditory sentence comprehension. Twenty-six healthy young adults underwent scanning while hearing sentences that varied in acoustic richness (high vs. low spectral detail) and syntactic complexity (subject-relative vs. object-relative center-embedded clause structures). We manipulated acoustic richness by presenting the stimuli as unprocessed full-spectrum speech, or noise-vocoded with 24 channels. Importantly, although the vocoded sentences were spectrally impoverished, all sentences were highly intelligible. These manipulations allowed us to test how intelligible speech processing was affected by orthogonal linguistic and acoustic demands. Acoustically rich speech showed stronger activation than acoustically less-detailed speech in a bilateral temporoparietal network with more pronounced activity in the right hemisphere. By contrast, listening to sentences with greater syntactic complexity resulted in increased activation of a left-lateralized network including left posterior lateral temporal cortex, left inferior frontal gyrus, and left dorsolateral prefrontal cortex. Significant interactions between acoustic richness and syntactic complexity occurred in left supramarginal gyrus, right superior temporal gyrus, and right inferior frontal gyrus, indicating that the regions recruited for syntactic challenge differed as a function of acoustic properties of the speech. Our findings suggest that the neural systems involved in speech perception are finely tuned to the type of information available, and that reducing the richness of the acoustic signal dramatically alters the brain's response to spoken language, even when intelligibility is high. Copyright © 2015 Elsevier

  16. Waste receiving and processing facility module 1, detailed design report

    International Nuclear Information System (INIS)

    1993-10-01

    WRAP 1 baseline documents which guided the technical development of the Title design included: (a) A/E Statement of Work (SOW) Revision 4C: This DOE-RL contractual document specified the workscope, deliverables, schedule, method of performance and reference criteria for the Title design preparation. (b) Functional Design Criteria (FDC) Revision 1: This DOE-RL technical criteria document specified the overall operational criteria for the facility. The document was a Revision 0 at the beginning of the design and advanced to Revision 1 during the tenure of the Title design. (c) Supplemental Design Requirements Document (SDRD) Revision 3: This baseline criteria document prepared by WHC for DOE-RL augments the FDC by providing further definition of the process, operational safety, and facility requirements to the A/E for guidance in preparing the design. The document was at a very preliminary stage at the onset of Title design and was revised in concert with the results of the engineering studies that were performed to resolve the numerous technical issues that the project faced when Title I was initiated, as well as, by requirements established during the course of the Title II design

  17. Cholinergic modulation of cognitive processing: insights drawn from computational models

    Directory of Open Access Journals (Sweden)

    Ehren L Newman

    2012-06-01

    Full Text Available Acetylcholine plays an important role in cognitive function, as shown by pharmacological manipulations that impact working memory, attention, episodic memory and spatial memory function. Acetylcholine also shows striking modulatory influences on the cellular physiology of hippocampal and cortical neurons. Modeling of neural circuits provides a framework for understanding how the cognitive functions may arise from the influence of acetylcholine on neural and network dynamics. We review the influences of cholinergic manipulations on behavioral performance in working memory, attention, episodic memory and spatial memory tasks, the physiological effects of acetylcholine on neural and circuit dynamics, and the computational models that provide insight into the functional relationships between the physiology and behavior. Specifically, we discuss the important role of acetylcholine in governing mechanisms of active maintenance in working memory tasks and in regulating network dynamics important for effective processing of stimuli in attention and episodic memory tasks. We also propose that theta rhythm play a crucial role as an intermediary between the physiological influences of acetylcholine and behavior in episodic and spatial memory tasks. We conclude with a synthesis of the existing modeling work and highlight future directions that are likely to be rewarding given the existing state of the literature for both empiricists and modelers.

  18. Modulation of p25 and inflammatory pathways by fisetin maintains cognitive function in Alzheimer’s disease transgenic mice

    Science.gov (United States)

    Currais, Antonio; Prior, Marguerite; Dargusch, Richard; Armando, Aaron; Ehren, Jennifer; Schubert, David; Quehenberger, Oswald; Maher, Pamela

    2014-01-01

    Alzheimer’s disease (AD) is the most common type of dementia. It is the only one of the top ten causes of death in the USA for which prevention strategies have not been developed. Although AD has traditionally been associated with the deposition of amyloid β plaques and tau tangles, it is becoming increasingly clear that it involves disruptions in multiple cellular systems. Therefore, it is unlikely that hitting a single target will result in significant benefits to patients with AD. An alternative approach is to identify molecules that have multiple biological activities that are relevant to the disease. Fisetin is a small, orally active molecule which can act on many of the target pathways implicated in AD. We show here that oral administration of fisetin to APPswe/PS1dE9 double transgenic AD mice from 3 to 12 months of age prevents the development of learning and memory deficits. This correlates with an increase in ERK phosphorylation along with a decrease in protein carbonylation, a marker of oxidative stress. Importantly, fisetin also reduces the levels of the cyclin-dependent kinase 5 (Cdk5) activator p35 cleavage product, p25, in both control and AD brains. Elevated levels of p25 relative to p35 cause dysregulation of Cdk5 activity leading to neuroinflammation and neurodegeneration. These fisetin-dependent changes correlate with additional anti-inflammatory effects, including alterations in global eicosanoid synthesis, and the maintenance of markers of synaptic function in the AD mice. Together, these results suggest that fisetin may provide a new approach to the treatment of AD. PMID:24341874

  19. Restoration of dietary-fat induced blood–brain barrier dysfunction by anti-inflammatory lipid-modulating agents

    Directory of Open Access Journals (Sweden)

    Pallebage-Gamarallage Menuka

    2012-09-01

    Full Text Available Abstract Background Several studies have identified use of non-steroidal-anti-inflammatory drugs and statins for prevention of dementia, but their efficacy in slowing progression is not well understood. Cerebrovascular disturbances are common pathological feature of Alzheimer’s disease. We previously reported chronic ingestion of saturated fatty acids (SFA compromises blood–brain barrier (BBB integrity resulting in cerebral extravasation of plasma proteins and inflammation. However, the SFA-induced parenchymal accumulation of plasma proteins could be prevented by co-administration of some cholesterol lowering agents. Restoration of BBB dysfunction is clinically relevant, so the purpose of this study was to explore lipid-lowering agents could reverse BBB disturbances induced by chronic ingestion of SFA’s. Methods Wild-type mice were fed an SFA diet for 12 weeks to induce BBB dysfunction, and then randomised to receive atorvastatin, pravastatin or ibuprofen in combination with the SFA-rich diet for 2 or 8 weeks. Abundance of plasma-derived immunoglobulin-G (IgG and amyloid-β enriched apolipoprotein (apo-B lipoproteins within brain parenchyme were quantified utilising immunofluorescence microscopy. Results Atorvastatin treatment for 2 and 8 weeks restored BBB integrity, indicated by a substantial reduction of IgG and apo B, particularly within the hippocampus. Pravastatin, a water-soluble statin was less effective than atorvastatin (lipid-soluble. Statin effects were independent of changes in plasma lipid homeostasis. Ibuprofen, a lipid-soluble cyclooxygenase inhibitor attenuated cerebral accumulation of IgG and apo B as effectively as atorvastatin. Our findings are consistent with the drug effects being independent of plasma lipid homeostasis. Conclusion Our findings suggest that BBB dysfunction induced by chronic ingestion of SFA is reversible with timely introduction and sustained treatment with agents that suppress inflammation.

  20. Validity of Scientific Based Chemistry Android Module to Empower Science Process Skills (SPS) in Solubility Equilibrium

    Science.gov (United States)

    Antrakusuma, B.; Masykuri, M.; Ulfa, M.

    2018-04-01

    Evolution of Android technology can be applied to chemistry learning, one of the complex chemistry concept was solubility equilibrium. this concept required the science process skills (SPS). This study aims to: 1) Characteristic scientific based chemistry Android module to empowering SPS, and 2) Validity of the module based on content validity and feasibility test. This research uses a Research and Development approach (RnD). Research subjects were 135 s1tudents and three teachers at three high schools in Boyolali, Central of Java. Content validity of the module was tested by seven experts using Aiken’s V technique, and the module feasibility was tested to students and teachers in each school. Characteristics of chemistry module can be accessed using the Android device. The result of validation of the module contents got V = 0.89 (Valid), and the results of the feasibility test Obtained 81.63% (by the student) and 73.98% (by the teacher) indicates this module got good criteria.

  1. Towards large-scale production of solution-processed organic tandem modules based on ternary composites: Design of the intermediate layer, device optimization and laser based module processing

    DEFF Research Database (Denmark)

    Li, Ning; Kubis, Peter; Forberich, Karen

    2014-01-01

    on commercially available materials, which enhances the absorption of poly(3-hexylthiophene) (P3HT) and as a result increase the PCE of the P3HT-based large-scale OPV devices; 3. laser-based module processing, which provides an excellent processing resolution and as a result can bring the power conversion...... efficiency (PCE) of mass-produced organic photovoltaic (OPV) devices close to the highest PCE values achieved for lab-scale solar cells through a significant increase in the geometrical fill factor. We believe that the combination of the above mentioned concepts provides a clear roadmap to push OPV towards...

  2. Org 214007-0: a novel non-steroidal selective glucocorticoid receptor modulator with full anti-inflammatory properties and improved therapeutic index.

    Science.gov (United States)

    van Lierop, Marie-José C; Alkema, Wynand; Laskewitz, Anke J; Dijkema, Rein; van der Maaden, Hans M; Smit, Martin J; Plate, Ralf; Conti, Paolo G M; Jans, Christan G J M; Timmers, C Marco; van Boeckel, Constant A A; Lusher, Scott J; McGuire, Ross; van Schaik, Rene C; de Vlieg, Jacob; Smeets, Ruben L; Hofstra, Claudia L; Boots, Annemieke M H; van Duin, Marcel; Ingelse, Benno A; Schoonen, Willem G E J; Grefhorst, Aldo; van Dijk, Theo H; Kuipers, Folkert; Dokter, Wim H A

    2012-01-01

    Glucocorticoids (GCs) such as prednisolone are potent immunosuppressive drugs but suffer from severe adverse effects, including the induction of insulin resistance. Therefore, development of so-called Selective Glucocorticoid Receptor Modulators (SGRM) is highly desirable. Here we describe a non-steroidal Glucocorticoid Receptor (GR)-selective compound (Org 214007-0) with a binding affinity to GR similar to that of prednisolone. Structural modelling of the GR-Org 214007-0 binding site shows disturbance of the loop between helix 11 and helix 12 of GR, confirmed by partial recruitment of the TIF2-3 peptide. Using various cell lines and primary human cells, we show here that Org 214007-0 acts as a partial GC agonist, since it repressed inflammatory genes and was less effective in induction of metabolic genes. More importantly, in vivo studies in mice indicated that Org 214007-0 retained full efficacy in acute inflammation models as well as in a chronic collagen-induced arthritis (CIA) model. Gene expression profiling of muscle tissue derived from arthritic mice showed a partial activity of Org 214007-0 at an equi-efficacious dosage of prednisolone, with an increased ratio in repression versus induction of genes. Finally, in mice Org 214007-0 did not induce elevated fasting glucose nor the shift in glucose/glycogen balance in the liver seen with an equi-efficacious dose of prednisolone. All together, our data demonstrate that Org 214007-0 is a novel SGRMs with an improved therapeutic index compared to prednisolone. This class of SGRMs can contribute to effective anti-inflammatory therapy with a lower risk for metabolic side effects.

  3. P-glycoprotein Modulates Morphine Uptake into the CNS: A Role for the Non-steroidal Anti-inflammatory Drug Diclofenac

    Science.gov (United States)

    Sanchez-Covarrubias, Lucy; Slosky, Lauren M.; Thompson, Brandon J.; Zhang, Yifeng; Laracuente, Mei-Li; DeMarco, Kristin M.; Ronaldson, Patrick T.; Davis, Thomas P.

    2014-01-01

    Our laboratory has previously demonstrated that peripheral inflammatory pain (PIP), induced by subcutaneous plantar injection of λ-carrageenan, results in increased expression and activity of the ATP-dependent efflux transporter P-glycoprotein (P-gp) that is endogenously expressed at the blood-brain barrier (BBB). The result of increased P-gp functional expression was a significant reduction in CNS uptake of morphine and, subsequently, reduced morphine analgesic efficacy. A major concern in the treatment of acute pain/inflammation is the potential for drug-drug interactions resulting from P-gp induction by therapeutic agents co-administered with opioids. Such effects on P-gp activity can profoundly modulate CNS distribution of opioid analgesics and alter analgesic efficacy. In this study, we examined the ability of diclofenac, a non-steroidal anti-inflammatory drug (NSAID) that is commonly administered in conjunction with the opioids during pain therapy, to alter BBB transport of morphine via P-gp and whether such changes in P-gp morphine transport could alter morphine analgesic efficacy. Administration of diclofenac reduced paw edema and thermal hyperalgesia in rats subjected to PIP, which is consistent with the known mechanism of action of this NSAID. Western blot analysis demonstrated an increase in P-gp expression in rat brain microvessels not only following PIP induction but also after diclofenac treatment alone. Additionally, in situ brain perfusion studies showed that both PIP and diclofenac treatment alone increased P-gp efflux activity resulting in decreased morphine brain uptake. Critically, morphine analgesia was significantly reduced in animals pretreated with diclofenac (3 h), as compared to animals administered diclofenac and morphine concurrently. These novel findings suggest that administration of diclofenac and P-gp substrate opioids during pain pharmacotherapy may result in a clinically significant drug-drug interaction. PMID:24520393

  4. P-glycoprotein modulates morphine uptake into the CNS: a role for the non-steroidal anti-inflammatory drug diclofenac.

    Science.gov (United States)

    Sanchez-Covarrubias, Lucy; Slosky, Lauren M; Thompson, Brandon J; Zhang, Yifeng; Laracuente, Mei-Li; DeMarco, Kristin M; Ronaldson, Patrick T; Davis, Thomas P

    2014-01-01

    Our laboratory has previously demonstrated that peripheral inflammatory pain (PIP), induced by subcutaneous plantar injection of λ-carrageenan, results in increased expression and activity of the ATP-dependent efflux transporter P-glycoprotein (P-gp) that is endogenously expressed at the blood-brain barrier (BBB). The result of increased P-gp functional expression was a significant reduction in CNS uptake of morphine and, subsequently, reduced morphine analgesic efficacy. A major concern in the treatment of acute pain/inflammation is the potential for drug-drug interactions resulting from P-gp induction by therapeutic agents co-administered with opioids. Such effects on P-gp activity can profoundly modulate CNS distribution of opioid analgesics and alter analgesic efficacy. In this study, we examined the ability of diclofenac, a non-steroidal anti-inflammatory drug (NSAID) that is commonly administered in conjunction with the opioids during pain therapy, to alter BBB transport of morphine via P-gp and whether such changes in P-gp morphine transport could alter morphine analgesic efficacy. Administration of diclofenac reduced paw edema and thermal hyperalgesia in rats subjected to PIP, which is consistent with the known mechanism of action of this NSAID. Western blot analysis demonstrated an increase in P-gp expression in rat brain microvessels not only following PIP induction but also after diclofenac treatment alone. Additionally, in situ brain perfusion studies showed that both PIP and diclofenac treatment alone increased P-gp efflux activity resulting in decreased morphine brain uptake. Critically, morphine analgesia was significantly reduced in animals pretreated with diclofenac (3 h), as compared to animals administered diclofenac and morphine concurrently. These novel findings suggest that administration of diclofenac and P-gp substrate opioids during pain pharmacotherapy may result in a clinically significant drug-drug interaction.

  5. P-glycoprotein modulates morphine uptake into the CNS: a role for the non-steroidal anti-inflammatory drug diclofenac.

    Directory of Open Access Journals (Sweden)

    Lucy Sanchez-Covarrubias

    Full Text Available Our laboratory has previously demonstrated that peripheral inflammatory pain (PIP, induced by subcutaneous plantar injection of λ-carrageenan, results in increased expression and activity of the ATP-dependent efflux transporter P-glycoprotein (P-gp that is endogenously expressed at the blood-brain barrier (BBB. The result of increased P-gp functional expression was a significant reduction in CNS uptake of morphine and, subsequently, reduced morphine analgesic efficacy. A major concern in the treatment of acute pain/inflammation is the potential for drug-drug interactions resulting from P-gp induction by therapeutic agents co-administered with opioids. Such effects on P-gp activity can profoundly modulate CNS distribution of opioid analgesics and alter analgesic efficacy. In this study, we examined the ability of diclofenac, a non-steroidal anti-inflammatory drug (NSAID that is commonly administered in conjunction with the opioids during pain therapy, to alter BBB transport of morphine via P-gp and whether such changes in P-gp morphine transport could alter morphine analgesic efficacy. Administration of diclofenac reduced paw edema and thermal hyperalgesia in rats subjected to PIP, which is consistent with the known mechanism of action of this NSAID. Western blot analysis demonstrated an increase in P-gp expression in rat brain microvessels not only following PIP induction but also after diclofenac treatment alone. Additionally, in situ brain perfusion studies showed that both PIP and diclofenac treatment alone increased P-gp efflux activity resulting in decreased morphine brain uptake. Critically, morphine analgesia was significantly reduced in animals pretreated with diclofenac (3 h, as compared to animals administered diclofenac and morphine concurrently. These novel findings suggest that administration of diclofenac and P-gp substrate opioids during pain pharmacotherapy may result in a clinically significant drug-drug interaction.

  6. Deoxynivalenol as a new factor in the persistence of intestinal inflammatory diseases: an emerging hypothesis through possible modulation of Th17-mediated response.

    Directory of Open Access Journals (Sweden)

    Patricia M Cano

    Full Text Available BACKGROUND/AIMS: Deoxynivalenol (DON is a mycotoxin produced by Fusarium species which is commonly found in temperate regions worldwide as a natural contaminant of cereals. It is of great concern not only in terms of economic losses but also in terms of animal and public health. The digestive tract is the first and main target of this food contaminant and it represents a major site of immune tolerance. A finely tuned cross-talk between the innate and the adaptive immune systems ensures the homeostatic equilibrium between the mucosal immune system and commensal microorganisms. The aim of this study was to analyze the impact of DON on the intestinal immune response. METHODOLOGY: Non-transformed intestinal porcine epithelial cells IPEC-1 and porcine jejunal explants were used to investigate the effect of DON on the intestinal immune response and the modulation of naive T cells differentiation. Transcriptomic proteomic and flow cytometry analysis were performed. RESULTS: DON induced a pro-inflammatory response with a significant increase of expression of mRNA encoding for IL-8, IL-1α and IL-1β, TNF-α in all used models. Additionally, DON significantly induced the expression of genes involved in the differentiation of Th17 cells (STAT3, IL-17A, IL-6, IL-1β at the expenses of the pathway of regulatory T cells (Treg (FoxP3, RALDH1. DON also induced genes related to the pathogenic Th17 cells subset such as IL-23A, IL-22 and IL-21 and not genes related to the regulatory Th17 cells (rTh17 such as TGF-β and IL-10. CONCLUSION: DON triggered multiple immune modulatory effects which could be associated with an increased susceptibility to intestinal inflammatory diseases.

  7. Comprehensive two-dimensional gas chromatography: A perspective on processes of modulation.

    Science.gov (United States)

    Tranchida, Peter Q

    2018-02-09

    The first comprehensive two-dimensional gas chromatography (GC×GC) experiment was reported about 25 years ago [J. Chromatogr. Sci. 29 (1991) 227-231]; the GC×GC process was made possible by the development of a transfer device, defined as modulator. The process of modulation enables the isolation of effluent segments from the first column, and their re-injection onto the second column, in a continuous and sequential manner throughout the analysis. Over the years, many types of modulation systems have been introduced, each with specific advantages and disadvantages. Cryogenic systems are, at present, the most popular devices and represent the most effective form of modulation. The present contribution is focused on possible future scenarios, with respect to modulation, and as a consequence related to comprehensive GC, in general. The development of new forms of modulation may open the road to a more widespread use of GC×GC technologies. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. High power n-type metal-wrap-through cells and modules using industrial processes

    Energy Technology Data Exchange (ETDEWEB)

    Guillevin, N.; Heurtault, B.J.B.; Geerligs, L.J.; Van Aken, B.B.; Bennett, I.J.; Jansen, M.J.; Weeber, A.W.; Bultman, J.H. [ECN Solar Energy, P.O. Box 1, NL-1755 ZG Petten (Netherlands); Jianming, Wang; Ziqian, Wang; Jinye, Zhai; Zhiliang, Wan; Shuquan, Tian; Wenchao, Zhao; Zhiyan, Hu; Gaofei, Li; Bo, Yu; Jingfeng, Xiong [Yingli Green Energy Holding Co.,Ltd. 3399 North Chaoyang Avenue, Baoding (China)

    2013-10-15

    This paper reviews our recent progress in the development of metal wrap through (MWT) cells and modules, produced from n-type Czochralski silicon wafers. The use of n-type silicon as base material allows for high efficiencies: for front emitter-contacted industrial cells, efficiencies above 20% have been reported. N-type MWT (nMWT) cells produced by industrial process technologies allow even higher efficiency due to reduced front metal coverage. Based on the same industrial technology, the efficiency of the bifacial n-MWT cells exceeds the efficiency of the n-type front-and-rear contact and bifacial 'Pasha' technology (n-Pasha) by 0.1-0.2% absolute, with a maximum nMWT efficiency of 20.1% so far. Additionally, full back-contacting of the MWT cells in a module results in reduced cell to module (CTM) fill factor losses. In a direct 60-cell module performance comparison, the n-MWT module, based on integrated backfoil, produced 3% higher power output than the comparable tabbed front emitter-contacted n-Pasha module. Thanks to reduced resistive losses in copper circuitry on the backfoil compared to traditional tabs, the CTM FF loss of the MWT module was reduced by about 2.2%abs. compared to the tabbed front emitter contact module. A full-size module made using MWT cells of 19.6% average efficiency resulted in a power output close to 280W. Latest results of the development of the n-MWT technology at cell and module level are discussed in this paper, including a recent direct comparison run between n-MWT and n-Pasha cells and results of n-MWT cells from 140{mu}m thin mono-crystalline wafers, with only very slight loss (1% of Isc) for the thin cells. Also reverse characteristics and effects of reverse bias for extended time at cell and module level are reported, where we find a higher tolerance of MWT modules than tabbed front contact modules for hotspots.

  9. SCM-198 attenuates early atherosclerotic lesions in hypercholesterolemic rabbits via modulation of the inflammatory and oxidative stress pathways.

    Science.gov (United States)

    Zhang, Yanfei; Guo, Wei; Wen, Yadan; Xiong, Qinghui; Liu, Hongrui; Wu, Jian; Zou, Yunzeng; Zhu, Yizhun

    2012-09-01

    GPx in the aorta. In a rabbit atherosclerotic model, SCM-198 dose-dependently ameliorated the progression of atherosclerotic lesions and vascular dysfunction accompanied by the suppression of inflammatory factors and oxidative stress. These findings suggested that SCM-198 might be a potential agent for the treatment of atherosclerosis. Crown Copyright © 2012. Published by Elsevier Ireland Ltd. All rights reserved.

  10. Melatonin Receptor Agonists as the "Perioceutics" Agents for Periodontal Disease through Modulation of Porphyromonas gingivalis Virulence and Inflammatory Response.

    Science.gov (United States)

    Zhou, Wei; Zhang, Xuan; Zhu, Cai-Lian; He, Zhi-Yan; Liang, Jing-Ping; Song, Zhong-Chen

    2016-01-01

    A, and ragA), while increasing the mRNA expression of ferritin (ftn) or hemolysin (hem). They did not show obvious cytotoxicity toward HGFs. They inhibited Pg-LPS-induced IL-6 and IL-8 secretion, which was reversed by luzindole, the melatonin receptor antagonist. Melatonin receptor agonists can inhibit planktonic and biofilm growth of Porphyromonas gingivalis by affecting the virulent properties, as well as Pg-LPS-induced inflammatory response. Our study provides new evidence that melatonin receptor agonists might be useful as novel "perioceutics" agents to prevent and treat Porphyromonas gingivalis-associated periodontal diseases.

  11. Melatonin Receptor Agonists as the "Perioceutics" Agents for Periodontal Disease through Modulation of Porphyromonas gingivalis Virulence and Inflammatory Response.

    Directory of Open Access Journals (Sweden)

    Wei Zhou

    A, rgpB, hagA, and ragA, while increasing the mRNA expression of ferritin (ftn or hemolysin (hem. They did not show obvious cytotoxicity toward HGFs. They inhibited Pg-LPS-induced IL-6 and IL-8 secretion, which was reversed by luzindole, the melatonin receptor antagonist.Melatonin receptor agonists can inhibit planktonic and biofilm growth of Porphyromonas gingivalis by affecting the virulent properties, as well as Pg-LPS-induced inflammatory response. Our study provides new evidence that melatonin receptor agonists might be useful as novel "perioceutics" agents to prevent and treat Porphyromonas gingivalis-associated periodontal diseases.

  12. Modifications to the composition of the hyphal outer layer of Aspergillus fumigatus modulates HUVEC proteins related to inflammatory and stress responses.

    Science.gov (United States)

    Neves, Gabriela Westerlund Peixoto; Curty, Nathália de Andrade; Kubitschek-Barreira, Paula Helena; Fontaine, Thierry; Souza, Gustavo Henrique Martins Ferreira; Cunha, Marcel Lyra; Goldman, Gustavo H; Beauvais, Anne; Latgé, Jean-Paul; Lopes-Bezerra, Leila M

    2017-01-16

    Aspergillus fumigatus, the main etiologic agent causing invasive aspergillosis, can induce an inflammatory response and a prothrombotic phenotype upon contact with human umbilical vein endothelial cells (HUVECs). However, the fungal molecules involved in this endothelial response remain unknown. A. fumigatus hyphae produce an extracellular matrix composed of galactomannan, galactosaminogalactan and α-(1,3)-glucan. In this study, we investigated the consequences of UGM1 gene deletion in A. fumigatus, which produces a mutant with increased galactosaminogalactan production. The ∆ugm1 mutant exhibited an HUVEC-hyperadhesive phenotype and induced increased endothelial TNF-α secretion and tissue factor mRNA overexpression in this "semi-professional" immune host cell. Using a shotgun proteomics approach, we show that the A. fumigatus ∆ugm1 strain can modulate the levels of proteins in important endothelial pathways related to the inflammatory response mediated by TNF-α and to stress response pathways. Furthermore, a purified galactosaminogalactan fraction was also able to induce TNF-α secretion and the coincident HUVEC pathways regulated by the ∆ugm1 mutant, which overexpresses this component, as demonstrated by fluorescence microscopy. This work contributes new data regarding endothelial mechanisms in response to A. fumigatus infection. Invasive aspergillosis is the main opportunistic fungal infection described in neutropenic hematologic patients. One important clinical aspect of this invasive fungal infection is vascular thrombosis, which could be related, at least in part, to the activation of endothelial cells, as shown in previous reports from our group. It is known that direct contact between the A. fumigatus hyphal cell wall and the HUVEC cell surface is necessary to induce an endothelial prothrombotic phenotype and secretion of pro-inflammatory cytokines, though the cell surface components of this angioinvasive fungus that trigger this endothelial

  13. Modulation, resolution and signal processing in radar, sonar and related systems

    CERN Document Server

    Benjamin, R; Costrell, L

    1966-01-01

    Electronics and Instrumentation, Volume 35: Modulation, Resolution and Signal Processing in Radar, Sonar and Related Systems presents the practical limitations and potentialities of advanced modulation systems. This book discusses the concepts and techniques in the radar context, but they are equally essential to sonar and to a wide range of signaling and data-processing applications, including seismology, radio astronomy, and band-spread communications.Organized into 15 chapters, this volume begins with an overview of the principal developments sought in pulse radar. This text then provides a

  14. High throughput diffractive multi-beam femtosecond laser processing using a spatial light modulator

    Energy Technology Data Exchange (ETDEWEB)

    Kuang Zheng [Laser Group, Department of Engineering, University of Liverpool Brownlow Street, Liverpool L69 3GQ (United Kingdom)], E-mail: z.kuang@liv.ac.uk; Perrie, Walter [Laser Group, Department of Engineering, University of Liverpool Brownlow Street, Liverpool L69 3GQ (United Kingdom); Leach, Jonathan [Department of Physics and Astronomy, University of Glasgow, Glasgow G12 8QQ (United Kingdom); Sharp, Martin; Edwardson, Stuart P. [Laser Group, Department of Engineering, University of Liverpool Brownlow Street, Liverpool L69 3GQ (United Kingdom); Padgett, Miles [Department of Physics and Astronomy, University of Glasgow, Glasgow G12 8QQ (United Kingdom); Dearden, Geoff; Watkins, Ken G. [Laser Group, Department of Engineering, University of Liverpool Brownlow Street, Liverpool L69 3GQ (United Kingdom)

    2008-12-30

    High throughput femtosecond laser processing is demonstrated by creating multiple beams using a spatial light modulator (SLM). The diffractive multi-beam patterns are modulated in real time by computer generated holograms (CGHs), which can be calculated by appropriate algorithms. An interactive LabVIEW program is adopted to generate the relevant CGHs. Optical efficiency at this stage is shown to be {approx}50% into first order beams and real time processing has been carried out at 50 Hz refresh rate. Results obtained demonstrate high precision surface micro-structuring on silicon and Ti6Al4V with throughput gain >1 order of magnitude.

  15. Inflammatory process decrease by gallium-aluminium-arsenide (GaAlAs) low intensity laser irradiation on postoperative extraction of impacted lower third molar

    International Nuclear Information System (INIS)

    Atihe, Mauricio Martins

    2002-01-01

    This study aimed the observation of inflammatory process decrease by the use of GaAlAs Low Intensity Laser (λ=830 nm; 40 mW) irradiation. Five patients were selected and submitted to surgery of impacted lower third molars, both right and left sides at different occasions. On a first stage, a tooth of a random chosen side - right or left - was extracted by conventional surgery, without LILT. The inflammatory process was measured at postoperative on the first, third and seventh days. This side was then called 'control side'. After 21 days, period in which the inflammatory process of the first surgery was terminated, the other side surgery took place, this time using LILT (4 J at four spots) at postoperative, first and third days. As the previous surgery, the inflammatory process was also measured at postoperative on the first, third and seventh days. This side was called 'experimental or lased side'. The inflammatory process was evaluated by measuring its four characteristic signs: swelling, pain, color and temperature. It was clearly observed a decrease for swelling, pain and color on the lased side which presented significant inference and descriptive statistics. It can be concluded that GaAlAs Low Intensity Laser (λ=830 nm) can surely be used as an additional and important anti-inflammatory source on impacted lower third molar surgeries. (author)

  16. Electroabsorption modulators used for all-optical signal processing and labelling

    DEFF Research Database (Denmark)

    Xu, Lin

    2004-01-01

    This thesis concerns the applications of semiconductor components, primarily electroabsorption modulators (EAMs), in optical signal processing and labelling for future all optical communication networks. An introduction to electroabsorption modulators is given and several mechanisms that form...... function of an EAM is frequency dependent and the main improvement from an EAM-based regenerator is the enhancement of the ER and the suppression of the noise in a space bit. Applications of EAMs in optical label processing using various orthogonal labelling schemes are discussed. Through EAM...... encoding are –25.6/-28.1 dBm and –23.7/-21 dBm, respectively. Using an EAM for optical label insertion and a MZ-SOA for optical label erasure and payload regeneration in the ASK(10 Gb/s)/ Frequency Shift Keying (312 Mb/s) orthogonal modulation format, the complete functionality of a network node including...

  17. Category-selective attention modulates unconscious processes in the middle occipital gyrus.

    Science.gov (United States)

    Tu, Shen; Qiu, Jiang; Martens, Ulla; Zhang, Qinglin

    2013-06-01

    Many studies have revealed the top-down modulation (spatial attention, attentional load, etc.) on unconscious processing. However, there is little research about how category-selective attention could modulate the unconscious processing. In the present study, using functional magnetic resonance imaging (fMRI), the results showed that category-selective attention modulated unconscious face/tool processing in the middle occipital gyrus (MOG). Interestingly, MOG effects were of opposed direction for face and tool processes. During unconscious face processing, activation in MOG decreased under the face-selective attention compared with tool-selective attention. This result was in line with the predictive coding theory. During unconscious tool processing, however, activation in MOG increased under the tool-selective attention compared with face-selective attention. The different effects might be ascribed to an interaction between top-down category-selective processes and bottom-up processes in the partial awareness level as proposed by Kouider, De Gardelle, Sackur, and Dupoux (2010). Specifically, we suppose an "excessive activation" hypothesis. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Batching alternatives for Phase I retrieval wastes to be processed in WRAP Module 1

    International Nuclear Information System (INIS)

    Mayancsik, B.A.

    1994-01-01

    During the next two decades, the transuranic (TRU) waste now stored in the 200 Area burial trenches and storage buildings is to be retrieved, processed in the Waste Receiving and Processing (WRAP) Module 1 facility, and shipped to a final disposal facility. The purpose of this document is to identify the criteria that can be used to batch suspect TRU waste, currently in retrievable storage, for processing through the WRAP Module 1 facility. These criteria are then used to generate a batch plan for Phase 1 Retrieval operations, which will retrieve the waste located in Trench 4C-04 of the 200 West Area burial ground. The reasons for batching wastes for processing in WRAP Module 1 include reducing the exposure of workers and the environment to hazardous material and ionizing radiation; maximizing the efficiency of the retrieval, processing, and disposal processes by reducing costs, time, and space throughout the process; reducing analytical sampling and analysis; and reducing the amount of cleanup and decontamination between process runs. The criteria selected for batching the drums of retrieved waste entering WRAP Module 1 are based on the available records for the wastes sent to storage as well as knowledge of the processes that generated these wastes. The batching criteria identified in this document include the following: waste generator; type of process used to generate or package the waste; physical waste form; content of hazardous/dangerous chemicals in the waste; radiochemical type and quantity of waste; drum weight; and special waste types. These criteria were applied to the waste drums currently stored in Trench 4C-04. At least one batching scheme is shown for each of the criteria listed above

  19. Arrays of surface-normal electroabsorption modulators for the generation and signal processing of microwave photonics signals

    NARCIS (Netherlands)

    Noharet, Bertrand; Wang, Qin; Platt, Duncan; Junique, Stéphane; Marpaung, D.A.I.; Roeloffzen, C.G.H.

    2011-01-01

    The development of an array of 16 surface-normal electroabsorption modulators operating at 1550nm is presented. The modulator array is dedicated to the generation and processing of microwave photonics signals, targeting a modulation bandwidth in excess of 5GHz. The hybrid integration of the

  20. Sphingosine 1 Phosphate at the Blood Brain Barrier: Can the Modulation of S1P Receptor 1 Influence the Response of Endothelial Cells and Astrocytes to Inflammatory Stimuli?

    Directory of Open Access Journals (Sweden)

    Simona F Spampinato

    Full Text Available The ability of the Blood Brain Barrier (BBB to maintain proper barrier functions, keeping an optimal environment for central nervous system (CNS activity and regulating leukocytes' access, can be affected in CNS diseases. Endothelial cells and astrocytes are the principal BBB cellular constituents and their interaction is essential to maintain its function. Both endothelial cells and astrocytes express the receptors for the bioactive sphingolipid S1P. Fingolimod, an immune modulatory drug whose structure is similar to S1P, has been approved for treatment in multiple sclerosis (MS: fingolimod reduces the rate of MS relapses by preventing leukocyte egress from the lymph nodes. Here, we examined the ability of S1P and fingolimod to act on the BBB, using an in vitro co-culture model that allowed us to investigate the effects of S1P on endothelial cells, astrocytes, and interactions between the two. Acting selectively on endothelial cells, S1P receptor signaling reduced cell death induced by inflammatory cytokines. When acting on astrocytes, fingolimod treatment induced the release of a factor, granulocyte macrophage colony-stimulating factor (GM-CSF that reduced the effects of cytokines on endothelium. In an in vitro BBB model incorporating shear stress, S1P receptor modulation reduced leukocyte migration across the endothelial barrier, indicating a novel mechanism that might contribute to fingolimod efficacy in MS treatment.

  1. A Comparison of the 2/3/5 Selective Positive Allosteric Modulators L-838,417 and TPA023 in Preclinical Models of Inflammatory and Neuropathic Pain

    Directory of Open Access Journals (Sweden)

    Sarah Nickolls

    2011-01-01

    Full Text Available GABAA receptors containing α2/3 subunits are current targets in the battle to develop new pain medications, as they are expressed in the spinal cord where increasing inhibitory drive should result in analgesia. However, this approach is prone to a range of side effects including sedation, cognitive impairment, and abuse as a consequence of the widespread influence of GABA. The ability to make subtype selective low-efficacy benzodiazepine compounds, which potentiate the action of GABA at specific α subunits, has the potential to reduce this side effect profile. In this study, we have investigated the effects of the medium-efficacy positive allosteric modulator (PAM L-838,417 and the low-efficacy PAM TPA023 in a number of preclinical inflammatory and neuropathic pain models. We conclude that either the higher level of efficacy at α2/3 or efficacy at α5 is required for compounds to have a significant analgesic effect in a range of models, and, therefore, although the side-effect profile of compounds can be reduced compared to typical benzodiazepines, it is unlikely that it can be completely eliminated.

  2. Design of the 12-bit Delta-Sigma Modulator using SC Technique for Vibration Sensor Output Processing

    Directory of Open Access Journals (Sweden)

    M. Pavlik

    2012-04-01

    Full Text Available The work deals with the design of the 12-bit Delta-Sigma modulator using switched capacitors (SC technique. The modulator serves to vibration sensor output processing. The first part describes the Delta-Sigma modulator parameters definition. Results of the proposed topology ideal model were presented as well. Next, the Delta-Sigma modulator circuitry on the transistor level was done. The ONSemiconductor I2T100 0.7 um CMOS technology was used for design. Then, the Delta-Sigma modulator nonidealities were simulated and implemented into the MATLAB ideal model of the modulator. The model of real Delta-Sigma modulator was derived. Consequently, modulator coefficients were optimized. Finally, the corner analysis of the Delta-Sigma modulator with the optimized coefficients was simulated. The value of SNDR = 82.2 dB (ENOB = 13.4 bits was achieved.

  3. Modulation of Cartilage Degradation Biomarkers Reflect the Activation and Inhibition of Pro-Inflammatory Cytokine Signaling in an Ex Vivo Model of Bovine Cartilage

    DEFF Research Database (Denmark)

    Kjelgaard-Petersen, Cecilie Freja; Sharma, Neha; Kayed, Ashref

    2017-01-01

    -inflammatory treatments for inflammatory arthritis. The aim of this study was to investigate the effect of small molecule inhibitors targeting 4 main pro-inflammatory signaling pathways (p38, Syk, IκBα, and STAT) on Oncostatin M (OSM) and Tumor Necrosis Factor α (TNFα) stimulated cartilage....

  4. Project management plan, Waste Receiving and Processing Facility, Module 1, Project W-026

    Energy Technology Data Exchange (ETDEWEB)

    Starkey, J.G.

    1993-05-01

    The Hanford Waste Receiving and Processing Facility Module 1 Project (WRAP 1) has been established to support the retrieval and final disposal of approximately 400K grams of plutonium and quantities of hazardous components currently stored in drums at the Hanford Site.

  5. Conceptual design for the Waste Receiving and Processing facility Module 2A

    International Nuclear Information System (INIS)

    1992-07-01

    This is part of a Conceptual Design Report (CDR) for the Waste Receiving and Processing (WRAP) Module 2A facility at Hanford Reservation. The mission of the WRAP Module 2A facility is to receive, process, package, certify, and ship for permanent burial at the Hanford site disposal facilities those contact handled (CH) low-level radioactive mixed wastes (LLMW) that: (1) are currently in retrievable storage at the Hanford Central Waste Complex (HCWC) awaiting a treatment capability to permit permanent disposal compliant with the Land Disposal Restrictions and; (2) are forecasted to be generated over the next 30 years. The primary sources of waste to be treated at WRAP Module 2A include the currently stored waste from the 183-H solar basin evaporators, secondary solids from the future Hanford site liquid effluenttreatment facilities, thermal treatment facility ash, other WRAP modules, and other miscellaneous waste from storage and onsite/offsite waste generators consisting of compactible and non-compactible solids, contaminated soils, and metals. This volume, Volume V, provides a comprehensive conceptual design level narrative description of the process, utility, ventilation, and plant control systems. The feeds and throughputs, design requirements, and basis for process selection are provided, as appropriate. Key DOE/WHC criteria and reference drawings are delineated

  6. Understanding Reactions to Workplace Injustice through Process Theories of Motivation: A Teaching Module and Simulation

    Science.gov (United States)

    Stecher, Mary D.; Rosse, Joseph G.

    2007-01-01

    Management and organizational behavior students are often overwhelmed by the plethora of motivation theories they must master at the undergraduate level. This article offers a teaching module geared toward helping students understand how two major process theories of motivation, equity and expectancy theories and theories of organizational…

  7. NJOY nuclear data processing system. Volume IV. The ERRORR and COVR modules

    International Nuclear Information System (INIS)

    Muir, D.W.; MacFarlane, R.E.

    1985-12-01

    The NJOY nuclear data processing system is a comprehensive computer code package for producing cross sections and related nuclear parameters from ENDF/B evaluated nuclear data. This volume provides detailed descriptions of the NJOY modules ERRORR and COVR, which are concerned with the covariances (uncertainties and correlations) of multigroup cross sections and fission neutron yield (anti nu) values. 17 refs

  8. Project management plan, Waste Receiving and Processing Facility, Module 1, Project W-026

    International Nuclear Information System (INIS)

    Starkey, J.G.

    1993-05-01

    The Hanford Waste Receiving and Processing Facility Module 1 Project (WRAP 1) has been established to support the retrieval and final disposal of approximately 400K grams of plutonium and quantities of hazardous components currently stored in drums at the Hanford Site

  9. The hormonal Zeitgeber melatonin: Role as a circadian modulator in memory processing

    Directory of Open Access Journals (Sweden)

    Oliver eRawashdeh

    2012-03-01

    Full Text Available The neuroendocrine substance melatonin is a hormone synthesized rhythmically by the pineal gland under the influence of the circadian system and alternating light/dark cycles. Melatonin has been shown to have broad applications, and consequently becoming a molecule of great controversy. Undoubtedly, however, melatonin plays an important role as a time cue for the endogenous circadian system. This review focuses on melatonin as a regulator in the circadian modulation of memory processing. Memory processes (acquisition, consolidation and retrieval are modulated by the circadian system. However, the mechanism by which the biological clock is rhythmically influencing cognitive processes remains unknown. We also discuss, how the circadian system by generating cycling melatonin levels can implant information about daytime into memory processing, depicted as day and nighttime differences in acquisition, memory consolidation and/or retrieval.

  10. ADHESION MOLECULES IN INTESTINAL DESTRUCTIVE-INFLAMMATORY PROCESS IN THE CHILDREN WITH ULCERATIVE COLITIS

    Directory of Open Access Journals (Sweden)

    V. I. Ashkinazi

    2013-01-01

    Full Text Available Aim: to study the content of serum soluble cell adhesion molecules in children with ulcerative colitis that mediate the initial and final stages of the migration of leukocytes to the focus of inflammation: sP-selectin (soluble platelet selectin and Specam-1 (soluble platelet-endothelial cell adhesion molecule 1 as well some earlier unexplored factors associated with their level. Patients and methods: we examined 107 patients with ulcerative colitis aged from 6 up to 17 years. The diagnosis was set on the base of a comprehensive examination. The content of serum soluble adhesion molecules sP-selectin and sPECAM-1 as well cytokine status and neopterin were evaluated by ELISA. Respiratory metabolism was investigated by using chemiluminescent reactions. Results: it was shown that the content of sP-selectin and sPECAM-1 is significantly higher in patients than in the control group, which may influence on the migration of leukocytes into tissues for realization of their effector potential. It is confirmed by morphological analyses of the intestine biopsies, where it was observed the increasing of the number of leukocytes in vascular endothelium and epithelial layer. At the same time strengthening of the oxygen-dependent metabolism of neutrophils, the increase of the concentration of neopterin and tumor necrosis factor α were noted. Conclusions: the correlation of the studied adhesion molecules with a number of inflammatory markers (TNFα (tumor necrosis factor α, free radicals, neopterin was revealed, which indicates the diagnostic value of serum levels of the membrane antigens. The increase of the concentration of adhesion molecules sP-selectin and sPECAM-1 may be one of the links of the pathogenesis of ulcerative colitis. 

  11. Method for Signal Processing of Electric Field Modulation Sensor in a Conductive Environment

    Directory of Open Access Journals (Sweden)

    O. I. Miseyk

    2015-01-01

    Full Text Available In investigating the large waters and deep oceans the most promising are modulation sensors for measuring electric field in a conducting environment in a very low frequency range in devices of autonomous or non-autonomous vertical sounding. When using sensors of this type it is necessary to solve the problem of enhancement and measurement of the modulated signal from the baseband noise.The work analyses hydrodynamic and electromagnetic noise at the input of transducer with "rotating" sensitive axis. By virtue of matching the measuring electrodes with the signal processing circuit a conclusion has been drawn that the proposed basic model of a transducer with "rotating” sensitive axis is the most efficient in terms of enhancement and measurement of modulated signal from the baseband noise. It has been shown that it is undesirable for transducers to have the rotation of electrodes resulting, in this case, in arising noise to be synchronously changed with transducer rotation frequency (modulation frequency. This will complicate the further signal-noise enhancement later in their processing.The paper justifies the choice of demodulation output signal, called synchronous demodulation using a low-pass filter with a cutoff frequency much lower than the carrier frequency to provide an output signal in the range of very low frequency and dc electric fields.The paper offers an original circuit to process the signals taken from the modulation sensor with "rotating" measurement base. This circuit has advantages over the earlier known circuits for measuring electric fields in a conducting (marine environment in the ultralow frequency range of these fields in terms of sensitivity and measuring accuracy of modulation sensors.

  12. Emotion processing in the aging brain is modulated by semantic elaboration

    OpenAIRE

    Ritchey, Maureen; Bessette-Symons, Brandy; Hayes, Scott M.; Cabeza, Roberto

    2010-01-01

    The neural correlates of emotion processing have been shown to vary with age: older adults (OAs) exhibit increased frontal activations and, under some circumstances, decreased amygdala activations relative to young adults (YAs) during emotion processing. Some of these differences are additionally modulated by valence, with age-related biases toward positive versus negative stimuli, and are thought to depend on OAs’ capacity for controlled elaboration. However, the role of semantic elaboration...

  13. Waste receiving and processing facility module 1 data management system software project management plan

    International Nuclear Information System (INIS)

    Clark, R.E.

    1994-01-01

    This document provides the software development plan for the Waste Receiving and Processing (WRAP) Module 1 Data Management System (DMS). The DMS is one of the plant computer systems for the new WRAP 1 facility (Project W-026). The DMS will collect, store, and report data required to certify the low level waste (LLW) and transuranic (TRU) waste items processed at WRAP 1 as acceptable for shipment, storage, or disposal

  14. Waste Receiving and Processing Facility Module 1 Data Management System software requirements specification

    International Nuclear Information System (INIS)

    Rosnick, C.K.

    1996-01-01

    This document provides the software requirements for Waste Receiving and Processing (WRAP) Module 1 Data Management System (DMS). The DMS is one of the plant computer systems for the new WRAP 1 facility (Project W-0126). The DMS will collect, store and report data required to certify the low level waste (LLW) and transuranic (TRU) waste items processed at WRAP 1 as acceptable for shipment, storage, or disposal

  15. Waste Receiving and Processing Facility Module 1 Data Management System Software Requirements Specification

    International Nuclear Information System (INIS)

    Brann, E.C. II.

    1994-01-01

    This document provides the software requirements for Waste Receiving and Processing (WRAP) Module 1 Data Management System (DMS). The DMS is one of the plant computer systems for the new WRAP 1 facility (Project W-026). The DMS will collect, store and report data required to certify the low level waste (LLW) and transuranic (TRU) waste items processed at WRAP 1 as acceptable for shipment, storage, or disposal

  16. Waste Receiving and Processing Facility Module 1 Data Management System Software Requirements Specification

    Energy Technology Data Exchange (ETDEWEB)

    Brann, E.C. II

    1994-09-09

    This document provides the software requirements for Waste Receiving and Processing (WRAP) Module 1 Data Management System (DMS). The DMS is one of the plant computer systems for the new WRAP 1 facility (Project W-026). The DMS will collect, store and report data required to certify the low level waste (LLW) and transuranic (TRU) waste items processed at WRAP 1 as acceptable for shipment, storage, or disposal.

  17. All-optical microwave signal processing based on optical phase modulation

    Science.gov (United States)

    Zeng, Fei

    This thesis presents a theoretical and experimental study of optical phase modulation and its applications in all-optical microwave signal processing, which include all-optical microwave filtering, all-optical microwave mixing, optical code-division multiple-access (CDMA) coding, and ultrawideband (UWB) signal generation. All-optical microwave signal processing can be considered as the use of opto-electronic devices and systems to process microwave signals in the optical domain, which provides several significant advantages such as low loss, low dispersion, light weight, high time bandwidth products, and immunity to electromagnetic interference. In conventional approaches, the intensity of an optical carrier is modulated by a microwave signal based on direct modulation or external modulation. The intensity-modulated optical signal is then fed to a photonic circuit or system to achieve specific signal processing functionalities. The microwave signal being processed is usually obtained based on direct detection, i.e., an opto-electronic conversion by use of a photodiode. In this thesis, the research efforts are focused on the optical phase modulation and its applications in all-optical microwave signal processing. To avoid using coherent detection which is complicated and costly, simple and effective phase modulation to intensity modulation (PM-IM) conversion schemes are pursued. Based on a theoretical study of optical phase modulation, two approaches to achieving PM-IM conversions are proposed. In the first approach, the use of chromatic dispersion induced by a dispersive device to alter the phase relationships among the sidebands and the optical carrier of a phase-modulated optical signal to realize PM-IM conversion is investigated. In the second approach, instead of using a dispersive device, the PM-IM conversion is realized based on optical frequency discrimination implemented using an optical filter. We show that the proposed PM-IM conversion schemes can be

  18. Central vasopressin V1a receptors modulate neural processing in mothers facing intruder threat to pups

    OpenAIRE

    Caffrey, Martha K.; Nephew, Benjamin C.; Febo, Marcelo

    2009-01-01

    Vasopressin V1a receptors in the rat brain have been studied for their role in modulating aggression and anxiety. In the current study blood-oxygen-level-dependent (BOLD) functional MRI was used to test whether V1a receptors modulate neural processing in the maternal brain when dams are exposed to a male intruder. Primiparous females were given an intracerebroventricular (ICV) injection of vehicle or V1a receptor antagonist ([deamino-Pen1, O-Me-Try, Arg8]-Vasopressin, 125 ng/10 μL) 90-120 min...

  19. Work continues on Destiny, the U.S. Lab module, in the Space Station Processing Facility

    Science.gov (United States)

    1999-01-01

    In the Space Station Processing Facility (SSPF), work continues on the U.S. Lab module, Destiny, which is scheduled to be launched on Space Shuttle Endeavour in early 2000. It will become the centerpiece of scientific research on the International Space Station. Destiny shares space in the SSPF with the Shuttle Radar Topography Mission (SRTM) and Leonardo, the Multipurpose Logistics Module (MPLM) built by the Agenzia Spaziale Italiana (ASI). The SRTM is targeted for launch on mission STS-99 in September 1999. Leonardo is scheduled to launch on mission STS- 102 in June 2000.

  20. Conceptual design for the Waste Receiving and Processing facility Module 2A

    International Nuclear Information System (INIS)

    1992-07-01

    This is a Conceptual Design Report (CDR) for the Waste Receiving and Processing (WRAP) Module 2A facility at Hanford Reservation. The mission of the WRAP Module 2A facility is to receive, process, package, certify, and ship for permanent burial at the Hanford site disposal facilities those contact handled (CH) low-level radioactive mixed wastes (LLMW) that: (1) are currently in retrievable storage at the Hanford Central Waste Complex (HCWC) awaiting a treatment capability to permit permanent disposal compliant with the Land Disposal Restrictions and; (2) are forecasted to be generated over the next 30 years. The primary sources of waste to be treated at WRAP Module 2A include the currently stored waste from the 183-H solar basin evaporators, secondary solids from the future Hanford site liquid effluent treatment facilities, thermal treatment facility ash, other WRAP modules, and other, miscellaneous waste from storage and onsite/offsite waste generators consisting of compactible and non-compactible solids, contaminated soils, and metals. This volume, Volume 1 provides a narrative of the project background, objective and justification. A description of the WRAP 2A mission, operations and project scope is also included. Significant project requirements such as security, health, safety, decontamination and decomissioning, maintenance, data processing, and quality are outlined. Environmental compliance issues and regulatory permits are identified, and a preliminary safety evaluation is provided

  1. Corticofugal modulation of initial neural processing of sound information from the ipsilateral ear in the mouse.

    Directory of Open Access Journals (Sweden)

    Xiuping Liu

    2010-11-01

    Full Text Available Cortical neurons implement a high frequency-specific modulation of subcortical nuclei that includes the cochlear nucleus. Anatomical studies show that corticofugal fibers terminating in the auditory thalamus and midbrain are mostly ipsilateral. Differently, corticofugal fibers terminating in the cochlear nucleus are bilateral, which fits to the needs of binaural hearing that improves hearing quality. This leads to our hypothesis that corticofugal modulation of initial neural processing of sound information from the contralateral and ipsilateral ears could be equivalent or coordinated at the first sound processing level.With the focal electrical stimulation of the auditory cortex and single unit recording, this study examined corticofugal modulation of the ipsilateral cochlear nucleus. The same methods and procedures as described in our previous study of corticofugal modulation of contralateral cochlear nucleus were employed simply for comparison. We found that focal electrical stimulation of cortical neurons induced substantial changes in the response magnitude, response latency and receptive field of ipsilateral cochlear nucleus neurons. Cortical stimulation facilitated auditory response and shortened the response latency of physiologically matched neurons whereas it inhibited auditory response and lengthened the response latency of unmatched neurons. Finally, cortical stimulation shifted the best frequencies of cochlear neurons towards those of stimulated cortical neurons.Our data suggest that cortical neurons enable a high frequency-specific remodelling of sound information processing in the ipsilateral cochlear nucleus in the same manner as that in the contralateral cochlear nucleus.

  2. Toward Eco Product Development with Qualitative and CAE Design Process - Case Study of Flame Guiding Module

    Science.gov (United States)

    Chen, W. L.; Chao, F. L.

    2018-04-01

    Sustainable products become increasingly important for company in addressing eco-performance to satisfy global environmental regulations. Case study of flame guiding module reviewed design process and concerns related to the torch design. For enhancing flame height, the torch was embedded with an airflow guidance structure. The design process and design methodologies were investigated as an eco-design case study. Combine qualitative and CAE simulation were proposed to fulfil its main and auxiliary functions including reduction of impact during use. The design guidelines help prevent mistake arrangements, CAE helps understand combustion phenomenon. The flow field simulation enables fine tune of geometric design. Functional test and measurement are carried out to confirm the product features. On Eco-performance, we choose 5 items for evaluation the status of previous and redesign module, namely function need, low impact material, few manufacturing steps, low energy consumption, and safety. The radar diagram indicates that eco-performance of redesign module is better. Life cycle assessment calculated the carbon footprint of the manufacturing and processing stage with Eco-it. By using recycled steel in the flame module, it reduces raw material stage carbon footprint significantly.

  3. D-Aspartate Modulates Nociceptive-Specific Neuron Activity and Pain Threshold in Inflammatory and Neuropathic Pain Condition in Mice

    Directory of Open Access Journals (Sweden)

    Serena Boccella

    2015-01-01

    Full Text Available D-Aspartate (D-Asp is a free D-amino acid found in the mammalian brain with a temporal-dependent concentration based on the postnatal expression of its metabolizing enzyme D-aspartate oxidase (DDO. D-Asp acts as an agonist on NMDA receptors (NMDARs. Accordingly, high levels of D-Asp in knockout mice for Ddo gene (Ddo−/− or in mice treated with D-Asp increase NMDAR-dependent processes. We have here evaluated in Ddo−/− mice the effect of high levels of free D-Asp on the long-term plastic changes along the nociceptive pathway occurring in chronic and acute pain condition. We found that Ddo−/− mice show an increased evoked activity of the nociceptive specific (NS neurons of the dorsal horn of the spinal cord (L4–L6 and a significant decrease of mechanical and thermal thresholds, as compared to control mice. Moreover, Ddo gene deletion exacerbated the nocifensive responses in the formalin test and slightly reduced pain thresholds in neuropathic mice up to 7 days after chronic constriction injury. These findings suggest that the NMDAR agonist, D-Asp, may play a role in the regulation of NS neuron electrophysiological activity and behavioral responses in physiological and pathological pain conditions.

  4. Harm avoidance in adolescents modulates late positive potentials during affective picture processing.

    Science.gov (United States)

    Zhang, Wenhai; Lu, Jiamei; Ni, Ziyin; Liu, Xia; Wang, Dahua; Shen, Jiliang

    2013-08-01

    Research in adults has shown that individual differences in harm avoidance (HA) modulate electrophysiological responses to affective stimuli. To determine whether HA in adolescents modulates affective information processing, we collected event-related potentials from 70 adolescents while they viewed 90 pictures from the Chinese affective picture system. Multiple regressions revealed that HA negatively predicted late positive potential (LPP) for positive pictures and positively predicted for negative pictures; however, HA did not correlate with LPP for neutral pictures. The results suggest that at the late evaluative stage, high-HA adolescents display attentional bias to negative pictures while low-HA adolescents display attentional bias to negative pictures. Moreover, these dissociable attentional patterns imply that individual differences in adolescents' HA modulate the late selective attention mechanism of affective information. Copyright © 2013. Published by Elsevier Ltd.

  5. A Range Ambiguity Suppression Processing Method for Spaceborne SAR with Up and Down Chirp Modulation

    Directory of Open Access Journals (Sweden)

    Xuejiao Wen

    2018-05-01

    Full Text Available Range ambiguity is one of the factors which affect the SAR image quality. Alternately transmitting up and down chirp modulation pulses is one of the methods used to suppress the range ambiguity. However, the defocusing range ambiguous signal can still hold the stronger backscattering intensity than the mainlobe imaging area in some case, which has a severe impact on visual effects and subsequent applications. In this paper, a novel hybrid range ambiguity suppression method for up and down chirp modulation is proposed. The method can obtain the ambiguity area image and reduce the ambiguity signal power appropriately, by applying pulse compression using a contrary modulation rate and CFAR detecting method. The effectiveness and correctness of the approach is demonstrated by processing the archive images acquired by Chinese Gaofen-3 SAR sensor in full-polarization mode.

  6. A Range Ambiguity Suppression Processing Method for Spaceborne SAR with Up and Down Chirp Modulation.

    Science.gov (United States)

    Wen, Xuejiao; Qiu, Xiaolan; Han, Bing; Ding, Chibiao; Lei, Bin; Chen, Qi

    2018-05-07

    Range ambiguity is one of the factors which affect the SAR image quality. Alternately transmitting up and down chirp modulation pulses is one of the methods used to suppress the range ambiguity. However, the defocusing range ambiguous signal can still hold the stronger backscattering intensity than the mainlobe imaging area in some case, which has a severe impact on visual effects and subsequent applications. In this paper, a novel hybrid range ambiguity suppression method for up and down chirp modulation is proposed. The method can obtain the ambiguity area image and reduce the ambiguity signal power appropriately, by applying pulse compression using a contrary modulation rate and CFAR detecting method. The effectiveness and correctness of the approach is demonstrated by processing the archive images acquired by Chinese Gaofen-3 SAR sensor in full-polarization mode.

  7. Detection and processing of phase modulated optical signals at 40 Gbit/s and beyond

    DEFF Research Database (Denmark)

    Geng, Yan

    the amplitude regeneration capability based on FWM in a highly nonlinear fiber (HNLF). The first reported experimental demonstration of amplitude equalization of 40 Gbit/s RZ-DPSK signals using a 500 m long HNLF is presented. Using four possible phase levels to carry the information, DQPSK allows generation......This thesis addresses demodulation in direct detection systems and signal processing of high speed phase modulated signals in future all-optical wavelength division multiplexing (WDM) communication systems where differential phase shift keying (DPSK) or differential quadrature phase shift keying...... (DQPSK) are used to transport information. All-optical network functionalities -such as optical labeling, wavelength conversion and signal regeneration- are experimentally investigated. Direct detection of phase modulated signals requires phase-to-intensity modulation conversion in a demodulator...

  8. The NJOY Nuclear Data Processing System: Volume 3, The GROUPR, GAMINR, and MODER modules

    International Nuclear Information System (INIS)

    MacFarlane, R.E.; Muir, D.W.

    1987-10-01

    The NJOY Nuclear Data Processing System is a comprehensive computer code package for producing pointwise and multigroup cross sections and related quantities from ENDF/B-IV, V, or VI evaluated nuclear data. A concise description of the code system and references to the ancestors of NJOY are given in Vol. 1 of this report. This volume describes the GROUPR module, which produces multigroup neutron interaction cross sections and group-to-group production cross sections for neutrons and photons; the GAMINR module, which produces multigroup photon-interaction cross sections and group-to-group matrices; and the MODER module, which converts ENDF/B and NJOY interface files back and forth between formatted (i.e., BCD, ASCII) and binary modes and performs several associated editing functions. 34 refs., 13 figs

  9. MODULATION OF THE INFLAMMATORY CYTOKINES AND CYTOPROTECTIVE ENZYME BY BILIRUBIN TREATMENT TO ENHANCE CUTANEOUS WOUND HEALING IN RATS

    Directory of Open Access Journals (Sweden)

    Raju Prasad

    2017-06-01

    Full Text Available Inflammation is the main process of wound healing where expression of certain cytokines likes Interleukin-10 (IL-10 and Tumour necrosis factor ∝ (TNF ∝ plays an important role. In view of the antioxidant potential of bilirubin, the present study was aimed to evaluate time-dependent (day 3, 7, 14 wound healing effects of bilirubin ointment (0.3% in excisional wound model in rats. Thirty-six acclimatized healthy male Wistar rats (120-150g were divided into control and treated groups containing 18 rats each. Each group was further sub- divided into three sub-groups (day 3, 7 and 14 days, n= 6. The ointment base (soft paraffin 90%, lanolin 5% and hard paraffin 5% and bilirubin ointment (0.3% were applied topically once daily for 14 days in control and treated group respectively. The wound area was determined on days 3, 7, and 14. The mRNA expression of TNF ∝ gene and IL-10 gene were determined on days 3, 7 and 14 by Real Time PCR and their protein levels by ELISA method. The protein expression of cyto-protective enzyme HO-1 (Heme oxygenage-1 and growth factor VEGF (Vascular growth factor was determined by western blotting method. The mRNA expression and protein level of TNF ∝ was significantly reduced and IL-10 was significantly increased whereas the expression of HO-1 enzyme and VEGF was significantly increased in treated group on days 3, 7 and 14. It may be concluded that the bilirubin has pro-healing potential.

  10. CCS mRNA transcripts and serum CCS protein as copper marker in adults suffering inflammatory processes.

    Science.gov (United States)

    Araya, Magdalena; Gutiérrez, Ricardo; Arredondo, Miguel

    2014-08-01

    The chaperone to Zn-Cu superoxide dismutase (CCS) has been postulated as a candidate copper indicator, changing in a consistent manner in induced and recovered copper deficiency, in experimental cell and animal models. In real life people have various conditions that may modify molecules acting as acute phase proteins, such as serum ceruloplasmin and copper concentration and could alter CCS responses. With the hypothesis that CCS mRNA transcripts and protein would be different in individuals suffering inflammatory processes in comparison to healthy individuals, we assessed adult individuals who, although not ill had conditions known to induce variable degrees of inflammation. Screening of 600 adults resulted in two study groups, formed on the basis of their clinical history and levels of serum C reactive protein (CRP): Group 1 (n = 61, mean (range) CRP = 0.9 (0.3-2.0 mg/dL) and Group 2 (n = 150, mean (range) CRP = 6.1 (4.3-8.7 mg/dL). Results showed that mRNA transcripts relative abundance was not different for CCS, MTIIA, TNF-alpha and Cu-Zn-SOD by group (p > 0.05, one way Anova), nor between sexes (p > 0.05, one way Anova). Distribution of CCS mRNA transcripts and CCS protein in serum did not show any differences or trends. Results disproved our hypothesis that CCS abundance of transcripts and CCS protein would be different in individuals suffering inflammatory processes, adding further support to the idea that CCS may be a copper marker.

  11. Occurrence and fate of antibiotic, analgesic/anti-inflammatory, and antifungal compounds in five wastewater treatment processes.

    Science.gov (United States)

    Guerra, P; Kim, M; Shah, A; Alaee, M; Smyth, S A

    2014-03-01

    The presence of pharmaceuticals and personal care products (PPCPs) in the aquatic environment as a result of wastewater effluent discharge is a concern in many countries. In order to expand our understanding on the occurrence and fate of PPCPs during wastewater treatment processes, 62 antibiotic, analgesic/anti-inflammatory, and antifungal compounds were analyzed in 72 liquid and 24 biosolid samples from six wastewater treatment plants (WWTPs) during the summer and winter seasons of 2010-2012. This is the first scientific study to compare five different wastewater treatment processes: facultative and aerated lagoons, chemically-enhanced primary treatment, secondary activated sludge, and advanced biological nutrient removal. PPCPs were detected in all WWTP influents at median concentrations of 1.5 to 92,000 ng/L, with no seasonal differences. PPCPs were also found in all final effluents at median levels ranging from 3.6 to 4,200 ng/L with higher values during winter (pRemoval efficiencies ranged between -450% and 120%, depending on the compound, WWTP type, and season. Mass balance showed that the fate of analgesic/anti-inflammatory compounds was predominantly biodegradation during biological treatment, while antibiotics and antifungal compounds were more likely to sorb to sludge. However, some PPCPs remained soluble and were detected in effluent samples. Overall, this study highlighted the occurrence and behavior of a large set of PPCPs and determined how their removal is affected by environmental/operational factors in different WWTPs. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

  12. Optical signal processing techniques and applications of optical phase modulation in high-speed communication systems

    Science.gov (United States)

    Deng, Ning

    In recent years, optical phase modulation has attracted much research attention in the field of fiber optic communications. Compared with the traditional optical intensity-modulated signal, one of the main merits of the optical phase-modulated signal is the better transmission performance. For optical phase modulation, in spite of the comprehensive study of its transmission performance, only a little research has been carried out in terms of its functions, applications and signal processing for future optical networks. These issues are systematically investigated in this thesis. The research findings suggest that optical phase modulation and its signal processing can greatly facilitate flexible network functions and high bandwidth which can be enjoyed by end users. In the thesis, the most important physical-layer technology, signal processing and multiplexing, are investigated with optical phase-modulated signals. Novel and advantageous signal processing and multiplexing approaches are proposed and studied. Experimental investigations are also reported and discussed in the thesis. Optical time-division multiplexing and demultiplexing. With the ever-increasing demand on communication bandwidth, optical time division multiplexing (OTDM) is an effective approach to upgrade the capacity of each wavelength channel in current optical systems. OTDM multiplexing can be simply realized, however, the demultiplexing requires relatively complicated signal processing and stringent timing control, and thus hinders its practicability. To tackle this problem, in this thesis a new OTDM scheme with hybrid DPSK and OOK signals is proposed. Experimental investigation shows this scheme can greatly enhance the demultiplexing timing misalignment and improve the demultiplexing performance, and thus make OTDM more practical and cost effective. All-optical signal processing. In current and future optical communication systems and networks, the data rate per wavelength has been approaching

  13. A Signal Processing Module for the Analysis of Heart Sounds and Heart Murmurs

    International Nuclear Information System (INIS)

    Javed, Faizan; Venkatachalam, P A; H, Ahmad Fadzil M

    2006-01-01

    In this paper a Signal Processing Module (SPM) for the computer-aided analysis of heart sounds has been developed. The module reveals important information of cardiovascular disorders and can assist general physician to come up with more accurate and reliable diagnosis at early stages. It can overcome the deficiency of expert doctors in rural as well as urban clinics and hospitals. The module has five main blocks: Data Acquisition and Pre-processing, Segmentation, Feature Extraction, Murmur Detection and Murmur Classification. The heart sounds are first acquired using an electronic stethoscope which has the capability of transferring these signals to the near by workstation using wireless media. Then the signals are segmented into individual cycles as well as individual components using the spectral analysis of heart without using any reference signal like ECG. Then the features are extracted from the individual components using Spectrogram and are used as an input to a MLP (Multiple Layer Perceptron) Neural Network that is trained to detect the presence of heart murmurs. Once the murmur is detected they are classified into seven classes depending on their timing within the cardiac cycle using Smoothed Pseudo Wigner-Ville distribution. The module has been tested with real heart sounds from 40 patients and has proved to be quite efficient and robust while dealing with a large variety of pathological conditions

  14. A Signal Processing Module for the Analysis of Heart Sounds and Heart Murmurs

    Energy Technology Data Exchange (ETDEWEB)

    Javed, Faizan; Venkatachalam, P A; H, Ahmad Fadzil M [Signal and Imaging Processing and Tele-Medicine Technology Research Group, Department of Electrical and Electronics Engineering, Universiti Teknologi PETRONAS, 31750 Tronoh, Perak (Malaysia)

    2006-04-01

    In this paper a Signal Processing Module (SPM) for the computer-aided analysis of heart sounds has been developed. The module reveals important information of cardiovascular disorders and can assist general physician to come up with more accurate and reliable diagnosis at early stages. It can overcome the deficiency of expert doctors in rural as well as urban clinics and hospitals. The module has five main blocks: Data Acquisition and Pre-processing, Segmentation, Feature Extraction, Murmur Detection and Murmur Classification. The heart sounds are first acquired using an electronic stethoscope which has the capability of transferring these signals to the near by workstation using wireless media. Then the signals are segmented into individual cycles as well as individual components using the spectral analysis of heart without using any reference signal like ECG. Then the features are extracted from the individual components using Spectrogram and are used as an input to a MLP (Multiple Layer Perceptron) Neural Network that is trained to detect the presence of heart murmurs. Once the murmur is detected they are classified into seven classes depending on their timing within the cardiac cycle using Smoothed Pseudo Wigner-Ville distribution. The module has been tested with real heart sounds from 40 patients and has proved to be quite efficient and robust while dealing with a large variety of pathological conditions.

  15. A Module Experimental Process System Development Unit (MEPSDU). [flat plate solar arrays

    Science.gov (United States)

    1981-01-01

    The development of a cost effective process sequence that has the potential for the production of flat plate photovoltaic modules which meet the price goal in 1986 of 70 cents or less per Watt peak is described. The major accomplishments include (1) an improved AR coating technique; (2) the use of sand blast back clean-up to reduce clean up costs and to allow much of the Al paste to serve as a back conductor; and (3) the development of wave soldering for use with solar cells. Cells were processed to evaluate different process steps, a cell and minimodule test plan was prepared and data were collected for preliminary Samics cost analysis.

  16. Icariin and its derivative, ICT, exert anti-inflammatory, anti-tumor effects, and modulate myeloid derived suppressive cells (MDSCs) functions.

    Science.gov (United States)

    Zhou, Junmin; Wu, Jinfeng; Chen, Xianghong; Fortenbery, Nicole; Eksioglu, Erika; Kodumudi, Krithika N; Pk, Epling-Burnette; Dong, Jingcheng; Djeu, Julie Y; Wei, Sheng

    2011-07-01

    3, 5,7-trihydroxy-4'-methoxy-8-(3-hydroxy-3-methylbutyl)-flavone (ICT) is a novel derivative of Icariin (ICA), the major active ingredient of Herba Epimedii, a herb used in traditional Chinese and alternative medicine. We previously demonstrated its anti-inflammatory effect in murine innate immune cells and activated human PBMCs. We report herein that ICA or ICT treatment reduces the expression of MRP8/MRP14 and toll-like receptor 4 (TLR4) on human PBMCs. Administration of ICA or ICT inhibited tumor growth in 4T1-Neu tumor-bearing mice and considerably decreased MDSC numbers in the spleen of these mice. Further, we saw a restoration of IFN-γ production by CD8+ T cells in tumor bearing mice when treated with ICA or ICT. ICA and ICT significantly decreased the amounts of nitric oxide and reactive oxygen species in MDSC in vivo. When MDSC were treated in vitro with ICT, we saw a significant reduction in the percent of these cells with concomitant differentiation into dendritic cells and macrophages. Concomitant with this cell type conversion was a down-regulation of IL-10, IL-6 and TNF-α production. Decreased expression of S100A8/9 and inhibition of activation of STAT3 and AKT may in part be responsible for the observed results. In conclusion, our results showed that ICA, and more robustly, ICT, directly modulate MDSC signaling and therefore altered the phenotype and function of these cells, in vitro and in vivo. Copyright © 2010 Elsevier B.V. All rights reserved.

  17. Phosphatase and tensin homolog-β-catenin signaling modulates regulatory T cells and inflammatory responses in mouse liver ischemia/reperfusion injury.

    Science.gov (United States)

    Zhu, Qiang; Li, Changyong; Wang, Kunpeng; Yue, Shi; Jiang, Longfeng; Ke, Michael; Busuttil, Ronald W; Kupiec-Weglinski, Jerzy W; Zhang, Feng; Lu, Ling; Ke, Bibo

    2017-06-01

    The phosphatase and tensin homolog (PTEN) deleted on chromosome 10 plays an important role in regulating T cell activation during inflammatory response. Activation of β-catenin is crucial for maintaining immune homeostasis. This study investigates the functional roles and molecular mechanisms by which PTEN-β-catenin signaling promotes regulatory T cell (Treg) induction in a mouse model of liver ischemia/reperfusion injury (IRI). We found that mice with myeloid-specific phosphatase and tensin homolog knockout (PTEN M-KO ) exhibited reduced liver damage as evidenced by decreased levels of serum alanine aminotransferase, intrahepatic macrophage trafficking, and proinflammatory mediators compared with the PTEN-proficient (floxed phosphatase and tensin homolog [PTEN FL/FL ]) controls. Disruption of myeloid PTEN-activated b-catenin promoted peroxisome proliferator-activated receptor gamma (PPARγ)-mediated Jagged-1/Notch signaling and induced forkhead box P3 (FOXP3)1 Tregs while inhibiting T helper 17 cells. However, blocking of Notch signaling by inhibiting γ-secretase reversed myeloid PTEN deficiency-mediated protection in ischemia/reperfusion-triggered liver inflammation with reduced FOXP3 + and increased retinoid A receptor-related orphan receptor gamma t-mediated interleukin 17A expression in ischemic livers. Moreover, knockdown of β-catenin or PPARγ in PTEN-deficient macrophages inhibited Jagged-1/Notch activation and reduced FOXP3 + Treg induction, leading to increased proinflammatory mediators in macrophage/T cell cocultures. In conclusion, our findings demonstrate that PTEN-β-catenin signaling is a novel regulator involved in modulating Treg development and provides a potential therapeutic target in liver IRI. Liver Transplantation 23 813-825 2017 AASLD. © 2017 by the American Association for the Study of Liver Diseases.

  18. Transcranial alternating current stimulation: A review of the underlying mechanisms and modulation of cognitive processes

    Directory of Open Access Journals (Sweden)

    Christoph S Herrmann

    2013-06-01

    Full Text Available Brain oscillations of different frequencies have been associated with a variety of cognitive functions. Convincing evidence supporting those associations has been provided by studies using intracranial stimulation, pharmacological interventions and lesion studies. The emergence of novel non-invasive brain stimulation techniques like repetitive transcranial magnetic stimulation (rTMS and transcranial alternating current stimulation (tACS now allows to modulate brain oscillations directly. Particularly, tACS offers the unique opportunity to causally link brain oscillations of a specific frequency range to cognitive processes, because it uses sinusoidal currents that are bound to one frequency only. Using tACS allows to modulate brain oscillations and in turn to influence cognitive processes, thereby demonstrating the causal link between the two. Here, we review findings about the physiological mechanism of tACS and studies that have used tACS to modulate basic motor and sensory processes as well as higher cognitive processes like memory, ambiguous perception, and decision making.

  19. Apparel Research Network (ARN) Apparel Order Processing Module (AOPM). Application Program for Management of Special Measurement Clothing Orders

    Science.gov (United States)

    1997-09-30

    Screen, abandoning changes. APPAREL ORDER PROCESSING MODULE FIELD USER MANUAL Ordering Official Screens The Ordering Official Screens are provided for...currendy selected Ordering Official will appear on the Ordering Official Information Screen. APPAREL ORDER PROCESSING MODULE FIELD USER MANUAL Ordering Official

  20. Multi-session transcranial direct current stimulation (tDCS elicits inflammatory and regenerative processes in the rat brain.

    Directory of Open Access Journals (Sweden)

    Maria Adele Rueger

    Full Text Available Transcranial direct current stimulation (tDCS is increasingly being used in human studies as an adjuvant tool to promote recovery of function after stroke. However, its neurobiological effects are still largely unknown. Electric fields are known to influence the migration of various cell types in vitro, but effects in vivo remain to be shown. Hypothesizing that tDCS might elicit the recruitment of cells to the cortex, we here studied the effects of tDCS in the rat brain in vivo. Adult Wistar rats (n = 16 were randomized to either anodal or cathodal stimulation for either 5 or 10 consecutive days (500 µA, 15 min. Bromodeoxyuridine (BrdU was given systemically to label dividing cells throughout the experiment. Immunohistochemical analyses ex vivo included stainings for activated microglia and endogenous neural stem cells (NSC. Multi-session tDCS with the chosen parameters did not cause a cortical lesion. An innate immune response with early upregulation of Iba1-positive activated microglia occurred after both cathodal and anodal tDCS. The involvement of adaptive immunity as assessed by ICAM1-immunoreactivity was less pronounced. Most interestingly, only cathodal tDCS increased the number of endogenous NSC in the stimulated cortex. After 10 days of cathodal stimulation, proliferating NSC increased by ∼60%, with a significant effect of both polarity and number of tDCS sessions on the recruitment of NSC. We demonstrate a pro-inflammatory effect of both cathodal and anodal tDCS, and a polarity-specific migratory effect on endogenous NSC in vivo. Our data suggest that tDCS in human stroke patients might also elicit NSC activation and modulate neuroinflammation.

  1. Modulation of inflammatory mediators by Opuntia ficus-indica and Prunus avium bioproducts using an in vitro cell-based model of intestinal inflammation

    OpenAIRE

    Nunes, Sara Alexandra Luis

    2011-01-01

    Dissertation to obtain a Master Degree in Biotechnology Inflammatory Bowel Diseases, namely Ulcerative colitis and Crohn’s disease, are chronic intestinal inflammatory disorders characterized by an excessive release of pro-inflammatory mediators, intestinal barrier dysfunction and altered permeability and excessive activation of NF-κB cascade that can lead to development of colon cancer. IBD conventional therapy involves multiple medications and long-term up to life-long treatments. Furthe...

  2. Music reading expertise modulates hemispheric lateralization in English word processing but not in Chinese character processing.

    Science.gov (United States)

    Li, Sara Tze Kwan; Hsiao, Janet Hui-Wen

    2018-07-01

    Music notation and English word reading both involve mapping horizontally arranged visual components to components in sound, in contrast to reading in logographic languages such as Chinese. Accordingly, music-reading expertise may influence English word processing more than Chinese character processing. Here we showed that musicians named English words significantly faster than non-musicians when words were presented in the left visual field/right hemisphere (RH) or the center position, suggesting an advantage of RH processing due to music reading experience. This effect was not observed in Chinese character naming. A follow-up ERP study showed that in a sequential matching task, musicians had reduced RH N170 responses to English non-words under the processing of musical segments as compared with non-musicians, suggesting a shared visual processing mechanism in the RH between music notation and English non-word reading. This shared mechanism may be related to the letter-by-letter, serial visual processing that characterizes RH English word recognition (e.g., Lavidor & Ellis, 2001), which may consequently facilitate English word processing in the RH in musicians. Thus, music reading experience may have differential influences on the processing of different languages, depending on their similarities in the cognitive processes involved. Copyright © 2018 Elsevier B.V. All rights reserved.

  3. The α7 nicotinic ACh receptor agonist compound B and positive allosteric modulator PNU-120596 both alleviate inflammatory hyperalgesia and cytokine release in the rat

    DEFF Research Database (Denmark)

    Munro, G; Hansen, Rikke Rie; Erichsen, Hk

    2012-01-01

    BACKGROUND AND PURPOSE: Agonists selective for the α7 nicotinic acetylcholine (nACh) receptor produce anti-hyperalgesic effects in rodent models of inflammatory pain, via direct actions on spinal pain circuits and possibly via attenuated release of peripheral pro-inflammatory mediators. Increasin......BACKGROUND AND PURPOSE: Agonists selective for the α7 nicotinic acetylcholine (nACh) receptor produce anti-hyperalgesic effects in rodent models of inflammatory pain, via direct actions on spinal pain circuits and possibly via attenuated release of peripheral pro-inflammatory mediators...

  4. Ocular allergy modulation to hi-dose antigen sensitization is a Treg-dependent process.

    Science.gov (United States)

    Lee, Hyun Soo; Schlereth, Simona; Khandelwal, Payal; Saban, Daniel R

    2013-01-01

    A reproducible method to inhibit allergic immune responses is accomplished with hi-dose Ag sensitization, via intraperitoneal (IP) injection. However, the role of CD4+ CD25+ FoxP3+ T regulatory cells (Treg) in this process is unknown, as is whether such modulation extends to ocular allergy. We therefore determined herein whether hi-dose sensitization modulates ocular allergy, and whether CD4+ CD25+ FoxP3+ Treg are involved. C57BL/6 mice were IP sensitized via low-dose (100 µg) versus hi-dose (1000 µg) ovalbumin (OVA), in aluminum hydroxide (1 mg) and pertussis-toxin (300 ng). Other mice received anti-CD25 Ab (PC61) to ablate Treg during sensitization. In another experiment, Treg from hi-dose sensitized mice were adoptively transferred into low-dose sensitized mice. Once daily OVA challenges were administered. Clinical signs, IgE, T cell cytokines, and eosinophils were assessed. Data revealed that hi-dose, but not low-dose, sensitization led to allergy modulation, indicated by decreased clinical signs, serum IgE levels, Th2 recall responses, and eosinophil recruitment. T cells from hi-dose sensitized mice showed a robust increase in TGF-b production, and Treg from these mice were able to efficiently suppress effector T cell proliferation in vitro. In addition, in vivo Treg ablation in hi-dose sensitized mice revoked allergy modulation. Lastly, Treg from hi-dose sensitized mice were able to adoptively transfer allergy modulation to their low-dose sensitized counterparts. Collectively, these findings indicate that modulation to hi-dose sensitization, which is extended to ocular allergy, occurs in a Treg-dependent manner. In addition, our data suggest that hi-dose sensitization may henceforth facilitate the further examination of CD4+ CD25+ FoxP3+ Treg in allergic disease.

  5. Use of a Video Module to Improve Faculty Understanding of the Pharmacists’ Patient Care Process

    Directory of Open Access Journals (Sweden)

    Crystal Deas

    2018-05-01

    Full Text Available Objective: To evaluate change in faculty’s knowledge and perceptions after an online video module on the Pharmacists’ Patient Care Process (PPCP. Innovation: An educational video module on the PPCP was developed and disseminated to full-time faculty members at Samford University, McWhorter School of Pharmacy. Voluntary and anonymous pre- and post-test assessments were evaluated and analyzed. Critical Analysis: Thirty faculty completed the pre-assessment, and 31 completed the post-assessment (73% and 75% response rates, respectively. A significant improvement in faculty perceptions was indicated by an increase in agreement with the majority (80% of questions on attitudes toward the PPCP on the post-test. Faculty’s knowledge of the introduction and assessment of PPCP within the school’s curriculum was significantly increased after viewing the video module. After viewing the module, more faculty were also able to correctly identify the majority of the PPCP components and their corresponding practice activities. Next Steps: A short video module was effective at improving faculty knowledge and perceptions of the PPCP. Development of a similar faculty development module is feasible for implementation in other Schools of Pharmacy. Conflict of Interest We declare no conflicts of interest or financial interests that the authors or members of their immediate families have in any product or service discussed in the manuscript, including grants (pending or received, employment, gifts, stock holdings or options, honoraria, consultancies, expert testimony, patents and royalties. Treatment of Human Subjects: IRB exemption granted   Type: Note

  6. Choice of the parameters of the cusum algorithms for parameter estimation in the markov modulated poisson process

    OpenAIRE

    Burkatovskaya, Yuliya Borisovna; Kabanova, T.; Khaustov, Pavel Aleksandrovich

    2016-01-01

    CUSUM algorithm for controlling chain state switching in the Markov modulated Poissonprocess was investigated via simulation. Recommendations concerning the parameter choice were givensubject to characteristics of the process. Procedure of the process parameter estimation was described.

  7. Conceptual design for the Waste Receiving And Processing facility Module 2A

    International Nuclear Information System (INIS)

    1992-07-01

    This Conceptual Design Report (CDR) for the Waste Receiving and Processing (WRAP) Module 2A facility. The mission of the WRAP Module 2A facility is to receive, process, package, certify, and ship for permanent burial at the Hanford site disposal facilities those contact handled (CH) low-level radioactive mixed wastes (LLMW) that: (1) are currently in retrievable storage at the Hanford Central Waste Complex (HCWC) awaiting a treatment capability to permit permanent disposal compliant with the Land Disposal Restrictions and; (2) are forecasted to be generated over the next 30 years. This volume provides the detailed cost estimate for the WRAP 2A facility. Included in this volume is the project construction schedule

  8. Modulating Spatial Processes and Navigation via Transcranial Electrical Stimulation: A Mini Review

    Directory of Open Access Journals (Sweden)

    Tad T. Brunyé

    2018-01-01

    Full Text Available Transcranial electrical stimulation (tES uses low intensity current to alter neuronal activity in superficial cortical regions, and has gained popularity as a tool for modulating several aspects of perception and cognition. This mini-review article provides an overview of tES and its potential for modulating spatial processes underlying successful navigation, including spatial attention, spatial perception, mental rotation and visualization. Also considered are recent advances in empirical research and computational modeling elucidating several stable cortical-subcortical networks with dynamic involvement in spatial processing and navigation. Leveraging these advances may prove valuable for using tES, particularly transcranial direct and alternating current stimulation (tDCS/tACS, to indirectly target subcortical brain regions by altering neuronal activity in distant yet functionally connected cortical areas. We propose future research directions to leverage these advances in human neuroscience.

  9. Self-reflection modulates the outcome evaluation process: Evidence from an ERP study.

    Science.gov (United States)

    Zhu, Xiangru; Gu, Ruolei; Wu, Haiyan; Luo, Yuejia

    2015-12-01

    Recent research demonstrated structural overlap between reward and self processing, but the functional relationship that explains how self processing influences reward processing remains unclear. The present study used an experimentally constrained reflection task to investigate whether individuals' outcome evaluations in a gambling task are modulated by task-unrelated self- and other-reflection processes. The self- and other-reflection task contained descriptions of the self or others, and brain event-related potentials (ERPs) were recorded while 16 normal adults performed a gambling task. The ERP analysis focused on the feedback-related negativity (FRN) component. We found that the difference wave of FRN increased in the self-reflection condition compared with the other-reflection condition. The present findings provide direct evidence that self processing can influence reward processing. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. 17th Workshop on Crystalline Silicon Solar Cells and Modules: Materials and Processes; Workshop Proceedings

    Energy Technology Data Exchange (ETDEWEB)

    Sopori, B. L.

    2007-08-01

    The National Center for Photovoltaics sponsored the 17th Workshop on Crystalline Silicon Solar Cells & Modules: Materials and Processes, held in Vail, CO, August 5-8, 2007. This meeting provided a forum for an informal exchange of technical and scientific information between international researchers in the photovoltaic and relevant non-photovoltaic fields. The theme of this year's meeting was 'Expanding Technology for a Future Powered by Si Photovoltaics.'

  11. Refractive index modulation of SU-8 polymer optical waveguides by means of hybrid photothermal process

    OpenAIRE

    Salazar-Miranda, D.; Castillón, F. F.; Sánchez-Sánchez, J. J.; Angel-Valenzuela, J. L.; Márquez, H.

    2010-01-01

    This paper describes the fabrication and characterization of multimode polymer optical waveguides obtained using a SU-8-2005 polymer by means of photolithographic process. Critical information about refractive index modulation of polymer waveguides as function of fabrication parameters as pre-baked and ultraviolet exposure times is presented. Physical properties of the waveguides were determined by means prism-coupling technique, optical and SEM microscopy. Este trabajo describe la fabrica...

  12. Waste receiving and processing (WRAP) module 1 hazards assessment. Revision 1

    International Nuclear Information System (INIS)

    Sutton, L.N.

    1997-01-01

    This report documents the hazards assessment for the Waste Receiving and Processing Module I (WRAP 1) located on the U.S. Department of Energy (DOE) Hanford Site. Operation of the WRAP 1 is the responsibility of Rust Federal Services Hanford (RFSH). This hazards assessment was conducted to provide the emergency planning technical basis for the WRAP 1. DOE Orders require an emergency planning hazards assessment for each facility that has the potential to reach or exceed the lowest level emergency classification

  13. Close interpersonal proximity modulates visuomotor processing of object affordances in shared, social space.

    Science.gov (United States)

    Saccone, Elizabeth J; Szpak, Ancret; Churches, Owen; Nicholls, Michael E R

    2018-01-01

    Research suggests that the human brain codes manipulable objects as possibilities for action, or affordances, particularly objects close to the body. Near-body space is not only a zone for body-environment interaction but also is socially relevant, as we are driven to preserve our near-body, personal space from others. The current, novel study investigated how close proximity of a stranger modulates visuomotor processing of object affordances in shared, social space. Participants performed a behavioural object recognition task both alone and with a human confederate. All object images were in participants' reachable space but appeared relatively closer to the participant or the confederate. Results revealed when participants were alone, objects in both locations produced an affordance congruency effect but when the confederate was present, only objects nearer the participant elicited the effect. Findings suggest space is divided between strangers to preserve independent near-body space boundaries, and in turn this process influences motor coding for stimuli within that social space. To demonstrate that this visuomotor modulation represents a social phenomenon, rather than a general, attentional effect, two subsequent experiments employed nonhuman joint conditions. Neither a small, Japanese, waving cat statue (Experiment 2) nor a metronome (Experiment 3) modulated the affordance effect as in Experiment 1. These findings suggest a truly social explanation of the key interaction from Experiment 1. This study represents an important step toward understanding object affordance processing in real-world, social contexts and has implications broadly across fields of social action and cognition, and body space representation.

  14. Edge sealing for low cost stability enhancement of roll-to-roll processed flexible polymer solar cell modules

    DEFF Research Database (Denmark)

    Tanenbaum, David M.; Dam, Henrik Friis; Rösch, R.

    2012-01-01

    Fully roll-to-roll processed polymer solar cell modules were prepared, characterized, and laminated. Cell modules were cut from the roll and matched pairs were selected, one module with exposed cut edges, the other laminated again with the same materials and adhesive sealing fully around the cut...... edges. The edge sealing rim was 10 mm wide. Cell modules were characterized by periodic measurements of IV curves over extended periods in a variety of conditions, as well as by a variety of spatial imaging techniques. Data show significant stability benefits of the edge sealing process. The results...

  15. Prehospital resuscitation with hypertonic saline-dextran modulates inflammatory, coagulation and endothelial activation marker profiles in severe traumatic brain injured patients

    Directory of Open Access Journals (Sweden)

    Morrison Laurie J

    2010-01-01

    Full Text Available Abstract Background Traumatic brain injury (TBI initiates interrelated inflammatory and coagulation cascades characterized by wide-spread cellular activation, induction of leukocyte and endothelial cell adhesion molecules and release of soluble pro/antiinflammatory cytokines and thrombotic mediators. Resuscitative care is focused on optimizing cerebral perfusion and reducing secondary injury processes. Hypertonic saline is an effective osmotherapeutic agent for the treatment of intracranial hypertension and has immunomodulatory properties that may confer neuroprotection. This study examined the impact of hypertonic fluids on inflammatory/coagulation cascades in isolated head injury. Methods Using a prospective, randomized controlled trial we investigated the impact of prehospital resuscitation of severe TBI (GCS vs 0.9% normal saline (NS, on selected cellular and soluble inflammatory/coagulation markers. Serial blood samples were drawn from 65 patients (30 HSD, 35 NS at the time of hospital admission and at 12, 24, and 48-h post-resuscitation. Flow cytometry was used to analyze leukocyte cell-surface adhesion (CD62L, CD11b and degranulation (CD63, CD66b molecules. Circulating concentrations of soluble (sL- and sE-selectins (sL-, sE-selectins, vascular and intercellular adhesion molecules (sVCAM-1, sICAM-1, pro/antiinflammatory cytokines [tumor necrosis factor (TNF-α and interleukin (IL-10], tissue factor (sTF, thrombomodulin (sTM and D-dimers (D-D were assessed by enzyme immunoassay. Twenty-five healthy subjects were studied as a control group. Results TBI provoked marked alterations in a majority of the inflammatory/coagulation markers assessed in all patients. Relative to control, NS patients showed up to a 2-fold higher surface expression of CD62L, CD11b and CD66b on polymorphonuclear neutrophils (PMNs and monocytes that persisted for 48-h. HSD blunted the expression of these cell-surface activation/adhesion molecules at all time-points to

  16. Vacuumed gap membrane distillation (vagmed) module, multi-stage vagmed systems, and vagmed processes

    KAUST Repository

    Ghaffour, NorEddine; Alsaadi, Ahmad Salem; Francis, Lijo

    2016-01-01

    Vacuumed gap membrane distillation (VAGMED) modules, and multi-stage VAGMED systems and processes using the modules are provided. In an embodiment, the membrane distillation modules (10) can comprise: a) a condenser (12) including a condensation surface (15); b) a first passageway (13) having an inlet for receiving a first feed stream (14) and an outlet through which the first stream can pass out of the first passageway, the first passageway configured to bring the first feed stream into thermal communication with the condensation surface; c) an evaporator (17) including a permeable evaporation surface allowing condensable gas to pass there through; d) a second passageway (18) having an inlet for receiving a second feed stream (19) and an outlet through which the second feed stream can pass out of the second passageway, the second passageway configured to bring the second feed stream into communication with the permeable evaporation surface; and e) an enclosure (24) providing a vacuum compartment within which the condenser, the evaporator and the first and second passageways of the module are contained.

  17. Vacuumed gap membrane distillation (vagmed) module, multi-stage vagmed systems, and vagmed processes

    KAUST Repository

    Ghaffour, Noreddine

    2016-06-30

    Vacuumed gap membrane distillation (VAGMED) modules, and multi-stage VAGMED systems and processes using the modules are provided. In an embodiment, the membrane distillation modules (10) can comprise: a) a condenser (12) including a condensation surface (15); b) a first passageway (13) having an inlet for receiving a first feed stream (14) and an outlet through which the first stream can pass out of the first passageway, the first passageway configured to bring the first feed stream into thermal communication with the condensation surface; c) an evaporator (17) including a permeable evaporation surface allowing condensable gas to pass there through; d) a second passageway (18) having an inlet for receiving a second feed stream (19) and an outlet through which the second feed stream can pass out of the second passageway, the second passageway configured to bring the second feed stream into communication with the permeable evaporation surface; and e) an enclosure (24) providing a vacuum compartment within which the condenser, the evaporator and the first and second passageways of the module are contained.

  18. Electrophysiological correlates of learning-induced modulation of visual motion processing in humans

    Directory of Open Access Journals (Sweden)

    Viktor Gál

    2010-01-01

    Full Text Available Training on a visual task leads to increased perceptual and neural responses to visual features that were attended during training as well as decreased responses to neglected distractor features. However, the time course of these attention-based modulations of neural sensitivity for visual features has not been investigated before. Here we measured event related potentials (ERP in response to motion stimuli with different coherence levels before and after training on a speed discrimination task requiring object-based attentional selection of one of the two competing motion stimuli. We found that two peaks on the ERP waveform were modulated by the strength of the coherent motion signal; the response amplitude associated with motion directions that were neglected during training was smaller than the response amplitude associated with motion directions that were attended during training. The first peak of motion coherence-dependent modulation of the ERP responses was at 300 ms after stimulus onset and it was most pronounced over the occipitotemporal cortex. The second peak was around 500 ms and was focused over the parietal cortex. A control experiment suggests that the earlier motion coherence-related response modulation reflects the extraction of the coherent motion signal whereas the later peak might index accumulation and readout of motion signals by parietal decision mechanisms. These findings suggest that attention-based learning affects neural responses both at the sensory and decision processing stages.

  19. A High Density Low Cost Digital Signal Processing Module for Large Scale Radiation Detectors

    International Nuclear Information System (INIS)

    Tan, Hui; Hennig, Wolfgang; Walby, Mark D.; Breus, Dimitry; Harris, Jackson T.; Grudberg, Peter M.; Warburton, William K.

    2013-06-01

    A 32-channel digital spectrometer PIXIE-32 is being developed for nuclear physics or other radiation detection applications requiring digital signal processing with large number of channels at relatively low cost. A single PIXIE-32 provides spectrometry and waveform acquisition for 32 input signals per module whereas multiple modules can be combined into larger systems. It is based on the PCI Express standard which allows data transfer rates to the host computer of up to 800 MB/s. Each of the 32 channels in a PIXIE-32 module accepts signals directly from a detector preamplifier or photomultiplier. Digitally controlled offsets can be individually adjusted for each channel. Signals are digitized in 12-bit, 50 MHz multi-channel ADCs. Triggering, pile-up inspection and filtering of the data stream are performed in real time, and pulse heights and other event data are calculated on an event-by event basis. The hardware architecture, internal and external triggering features, and the spectrometry and waveform acquisition capability of the PIXIE- 32 as well as its capability to distribute clock and triggers among multiple modules, are presented. (authors)

  20. A synthetic NCAM-derived mimetic peptide, FGL, exerts anti-inflammatory properties via IGF-1 and interferon-gamma modulation

    DEFF Research Database (Denmark)

    Downer, Eric J; Cowley, Thelma R; Cox, Fionnuala

    2009-01-01

    activation and subsequent pro-inflammatory cytokine production. The aim of the current study was to determine if FGL corrects the age-related imbalance in hippocampal levels of insulin-like growth factor-1 (IGF-1) and pro-inflammatory interferon-gamma (IFNgamma), and subsequently attenuates the glial...

  1. Waste Receiving and Processing Facility, Module 1: Volume 7, Project design criteria

    International Nuclear Information System (INIS)

    1992-03-01

    This Project Design Criteria document for the WRAP facility at the Hanford Site is presented within a systems format. The WRAP Module 1 facility has been categorized into eight (8) engineering systems for design purposes. These systems include: receiving, shipping and storage, nondestructive assay/nondestructive examination (NDA/NDE), waste process, internal transportation, building, heating ventilation and air conditioning (HVAC), process control, and utilities. Within each system section of this document, the system-specific requirements are identified. The scope of the system is defined, the design goals are identified and the functional requirements are detailed

  2. Ground processing of the McDonnell Douglas Payload Assist Module (PAM)

    Science.gov (United States)

    Bryan, C. E.; Maclean, D. A.

    1985-01-01

    The payload assist module (PAM) ground processing operations which have evolved since they were started in 1982 are described. The objective of the changes was to reduce the prelaunch testing of the airborne support equipment to increase the throughput of PAM systems while not compromising the reliability of the system when functioned on-orbit. The changes that resulted from the initial cargo element ground processing, the on-orbit performance of the systems, plus the postflight refurbishment and recertification of the airborne support equipment resulted in significant reductions in labor expenditures and work shifts required to prepare a PAM system for flight.

  3. Markov-modulated infinite-server queues driven by a common background process

    OpenAIRE

    Mandjes , Michel; De Turck , Koen

    2016-01-01

    International audience; This paper studies a system with multiple infinite-server queues which are modulated by a common background process. If this background process, being modeled as a finite-state continuous-time Markov chain, is in state j, then the arrival rate into the i-th queue is λi,j, whereas the service times of customers present in this queue are exponentially distributed with mean µ −1 i,j ; at each of the individual queues all customers present are served in parallel (thus refl...

  4. 14th Workshop on Crystalline Silicon Solar Cells& Modules: Materials and Processes; Extended Abstracts and Papers

    Energy Technology Data Exchange (ETDEWEB)

    Sopori, B. L.

    2004-08-01

    The 14th Workshop will provide a forum for an informal exchange of technical and scientific information between international researchers in the photovoltaic and relevant non-photovoltaic fields. It will offer an excellent opportunity for researchers in private industry and at universities to prioritize mutual needs for future collaborative research. The workshop is intended to address the fundamental properties of PV silicon, new solar cell designs, advanced solar cell processing techniques, and cell-related module issues. A combination of oral presentations by invited speakers, poster sessions, and discussion sessions will review recent advances in crystal growth, new cell designs, new processes and process characterization techniques, cell fabrication approaches suitable for future manufacturing demands, and solar cell encapsulation. This year's theme, ''Crystalline Si Solar Cells: Leapfrogging the Barriers,'' reflects the continued success of crystalline Si PV in overcoming technological barriers to improve solar cell performance and lower the cost of Si PV. The workshop will consist of presentations by invited speakers, followed by discussion sessions. In addition, there will be two poster sessions presenting the latest research and development results. Some presentations will address recent technologies in the microelectronics field that may have a direct bearing on PV. The sessions will include: Advances in crystal growth and material issues; Impurities and defects; Dynamics during device processing; Passivation; High-efficiency Si solar cells; Advanced processing; Thin Si solar cells; and Solar cell reliability and module issues.

  5. Optical integrated circuit of a 40-channel electrooptical LiNbO/sub 3/ modulator for data-processing devices

    Energy Technology Data Exchange (ETDEWEB)

    Bukreev, I.N.; Venediktov, V.V.; Gorbatovskii, M.V.; Demina, T.P.; Kashintsev, M.A.

    1988-06-01

    An optical integrated circuit for a 40-channel electrooptical phase modulator has been developed. The channel waveguides are prepared through Ti thermal diffusion into a Y-cut LiNbO/sub 3/ substrate. The half-wave voltage for each channel is 1.6 V at a modulating frequency bandwidth of 0-290 MHz. Results are presented from an experiment concerning the use of the modulator as an input device for the optical processing of radio signals.

  6. Feeding State Modulates Behavioral Choice and Processing of Prey Stimuli in the Zebrafish Tectum.

    Science.gov (United States)

    Filosa, Alessandro; Barker, Alison J; Dal Maschio, Marco; Baier, Herwig

    2016-05-04

    Animals use the sense of vision to scan their environment, respond to threats, and locate food sources. The neural computations underlying the selection of a particular behavior, such as escape or approach, require flexibility to balance potential costs and benefits for survival. For example, avoiding novel visual objects reduces predation risk but negatively affects foraging success. Zebrafish larvae approach small, moving objects ("prey") and avoid large, looming objects ("predators"). We found that this binary classification of objects by size is strongly influenced by feeding state. Hunger shifts behavioral decisions from avoidance to approach and recruits additional prey-responsive neurons in the tectum, the main visual processing center. Both behavior and tectal function are modulated by signals from the hypothalamic-pituitary-interrenal axis and the serotonergic system. Our study has revealed a neuroendocrine mechanism that modulates the perception of food and the willingness to take risks in foraging decisions. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Multidisciplinary Team Meetings appear to be effective in Inflammatory Bowel Disease Management: An audit of process and outcomes.

    Science.gov (United States)

    Ferman, Mutaz; Lim, Amanda H; Hossain, Monowar; Siow, Glenn W; Andrews, Jane M

    2018-05-14

    Multidisciplinary team meetings (MDTMs) have proven efficacy in cancer management. Whilst widely implemented in inflammatory bowel disease (IBD) care, their value is yet to be investigated. We reviewed the performance of MDTMs for IBD patients. Retrospective review of MDTMs from March 2013 to July 2016. Each patient's first MDTM was considered. Data collected included: report production and location, disease factors, recommendation(s), implementation and barriers to implementation. The MDTM process was considered successful when at least top-level recommendations were implemented within 6 months. MDTM attendance included IBD gastroenterologist, surgeons, radiologist, nurses, dieticians, psychologists and clinical trial staff. Initial MDTM encounters for 166 patients were reviewed: 86 females; mean age 40 years; 140 (84.3%) with Crohn's disease; mean disease duration 10.8 years (interquartile range 15 years). Electronic reports were filed for all patients; hard copies in 84%. In 151/166 episodes, all (n=127) or top-line (n=24) recommendations were implemented, although there was a delay beyond 6 months in 5. Of 146 patients with a successful MDTM, 85 (58.2%) were in clinical remission at last review (median follow-up 27 months). Amongst patients with unsuccessful MDTMs (n=13), only 2 (15.4%) were in clinical remission at follow-up. Barriers to implementation included patients declining recommendations and loss to follow-up. The majority of MDTM encounters were successful from both a process and clinical outcome perspective. System opportunities to improve the process include ensuring 100% reports are available and addressing implementation delays. Patient factors to address include improved engagement and understanding reasons for declining recommendations. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  8. Intracellular Secretory Leukoprotease Inhibitor Modulates Inositol 1,4,5-Triphosphate Generation and Exerts an Anti-Inflammatory Effect on Neutrophils of Individuals with Cystic Fibrosis and Chronic Obstructive Pulmonary Disease

    Directory of Open Access Journals (Sweden)

    Emer P. Reeves

    2013-01-01

    Full Text Available Secretory leukoprotease inhibitor (SLPI is an anti-inflammatory protein present in respiratory secretions. Whilst epithelial cell SLPI is extensively studied, neutrophil associated SLPI is poorly characterised. Neutrophil function including chemotaxis and degranulation of proteolytic enzymes involves changes in cytosolic calcium (Ca2+ levels which is mediated by production of inositol 1,4,5-triphosphate (IP3 in response to G-protein-coupled receptor (GPCR stimuli. The aim of this study was to investigate the intracellular function of SLPI and the mechanism-based modulation of neutrophil function by this antiprotease. Neutrophils were isolated from healthy controls (n=10, individuals with cystic fibrosis (CF (n=5 or chronic obstructive pulmonary disease (COPD (n=5. Recombinant human SLPI significantly inhibited fMet-Leu-Phe (fMLP and interleukin(IL-8 induced neutrophil chemotaxis (P<0.05 and decreased degranulation of matrix metalloprotease-9 (MMP-9, hCAP-18, and myeloperoxidase (MPO (P<0.05. The mechanism of inhibition involved modulation of cytosolic IP3 production and downstream Ca2+ flux. The described attenuation of Ca2+ flux was overcome by inclusion of exogenous IP3 in electropermeabilized cells. Inhibition of IP3 generation and Ca2+ flux by SLPI may represent a novel anti-inflammatory mechanism, thus strengthening the attractiveness of SLPI as a potential therapeutic molecule in inflammatory airway disease associated with excessive neutrophil influx including CF, non-CF bronchiectasis, and COPD.

  9. Modulation of ROS levels in fibroblasts by altering mitochondria regulates the process of wound healing.

    Science.gov (United States)

    Janda, Jaroslav; Nfonsam, Valentine; Calienes, Fernanda; Sligh, James E; Jandova, Jana

    2016-05-01

    Mitochondria are the major source of reactive oxygen species (ROS) in fibroblasts which are thought to be crucial regulators of wound healing with a potential to affect the expression of nuclear genes involved in this process. ROS generated by mitochondria are involved in all stages of tissue repair process but the regulation of ROS-generating system in fibroblasts still remains poorly understood. The purpose of this study was to better understand molecular mechanisms of how the regulation of ROS levels generated by mitochondria may influence the process of wound repair. Cybrid model system of mtDNA variations was used to study the functional consequences of altered ROS levels on wound healing responses in a uniform nuclear background of cultured ρ(0) fibroblasts. Mitochondrial ROS in cybrids were modulated by antioxidants that quench ROS to examine their ability to close the wound. Real-time PCR arrays were used to investigate whether ROS generated by specific mtDNA variants have the ability to alter expression of some key nuclear-encoded genes central to the wound healing response and oxidative stress. Our data suggest levels of mitochondrial ROS affect expression of some nuclear encoded genes central to wound healing response and oxidative stress and modulation of mitochondrial ROS by antioxidants positively affects in vitro process of wound closure. Thus, regulation of mitochondrial ROS-generating system in fibroblasts can be used as effective natural redox-based strategy to help treat non-healing wounds.

  10. Hemispheric asymmetry: Looking for a novel signature of the modulation of spatial attention in multisensory processing.

    Science.gov (United States)

    Chen, Yi-Chuan; Spence, Charles

    2017-06-01

    The extent to which attention modulates multisensory processing in a top-down fashion is still a subject of debate among researchers. Typically, cognitive psychologists interested in this question have manipulated the participants' attention in terms of single/dual tasking or focal/divided attention between sensory modalities. We suggest an alternative approach, one that builds on the extensive older literature highlighting hemispheric asymmetries in the distribution of spatial attention. Specifically, spatial attention in vision, audition, and touch is typically biased preferentially toward the right hemispace, especially under conditions of high perceptual load. We review the evidence demonstrating such an attentional bias toward the right in extinction patients and healthy adults, along with the evidence of such rightward-biased attention in multisensory experimental settings. We then evaluate those studies that have demonstrated either a more pronounced multisensory effect in right than in left hemispace, or else similar effects in the two hemispaces. The results suggest that the influence of rightward-biased attention is more likely to be observed when the crossmodal signals interact at later stages of information processing and under conditions of higher perceptual load-that is, conditions under which attention is perhaps a compulsory enhancer of information processing. We therefore suggest that the spatial asymmetry in attention may provide a useful signature of top-down attentional modulation in multisensory processing.

  11. Effect of dental adhesives on the exudative phase of the inflammatory process in subcutaneous tissue of rats

    Directory of Open Access Journals (Sweden)

    Nagem-Filho Halim

    2003-01-01

    Full Text Available The vascular changes in the subcutaneous connective tissue of rats induced by dentin bonding systems (one step was studied and compared to those induced by saline solution (negative control and Furacin (positive control, during the exudative phase of the inflammatory process. Twenty mg/kg of Evan's blue were injected intravenously in the vein of the rats' penises; 0.1 ml of each substance tested was inoculated in the subcutaneous tissue. After a 3 hour period the animals were sacrificed and their skins were excised and punched out with a standard steel 2.5 cm in diameter. The specimens were immediately immersed in 8 ml of formamide and taken to a double boiler for 72 hours at 37ºC, to remove the dye. The liquid containing the overflowed dye was filtered, analyzed in the spectrophotometer (620 nm and classified according to the criteria established by Nagem-Filho, Pereira (1976. After statistical analysis, the irritative potential of the substances was ranked as follows: Furacin (severe > Single Bond and Bond 1 (moderate - no significant differences between the dentin bonding systems tested > saline solution (not significant as regards the irritation degree.

  12. Engineering structure design and fabrication process of small sized China helium-cooled solid breeder test blanket module

    International Nuclear Information System (INIS)

    Wang Zeming; Chen Lu; Hu Gang

    2014-01-01

    Preliminary design and analysis for china helium-cooled solid breeder (CHHC-SB) test blanket module (TBM) have been carried out recently. As partial verification that the original size module was reasonable and the development process was feasible, fabrication work of a small sized module was to be carried out targetedly. In this paper, detailed design and structure analysis of small sized TBM was carried out based on preliminary design work, fabrication process and integrated assembly process was proposed, so a fabrication for the trial engineering of TBM was layed successfully. (authors)

  13. Impact of red and processed meat and fibre intake on treatment outcomes among patients with chronic inflammatory diseases

    DEFF Research Database (Denmark)

    Christensen, Robin; Heitmann, Berit L; Andersen, Karina Winther

    2018-01-01

    INTRODUCTION: Chronic inflammatory diseases (CIDs) are frequently treated with biological medications, specifically tumour necrosis factor inhibitors (TNFi)). These medications inhibit the pro-inflammatory molecule TNF alpha, which has been strongly implicated in the aetiology of these diseases. Up...... with inflammatory bowel disease (Crohn's disease and ulcerative colitis), rheumatic disorders (rheumatoid arthritis, axial spondyloarthritis, psoriatic arthritis), inflammatory skin diseases (psoriasis, hidradenitis suppurativa) and non-infectious uveitis. At baseline (pretreatment), patient characteristics...... will be assessed using patient-reported outcome measures, clinical assessments of disease activity, quality of life and lifestyle, in addition to registry data on comorbidity and concomitant medication(s). In accordance with current Danish standards, follow-up will be conducted 14-16 weeks after treatment...

  14. Scintillators module for the detection of X or gamma rays, realization process, and detector set up incorporating such modules

    International Nuclear Information System (INIS)

    Colomb, Gilbert; Delattre, Dominique; Ricodeau, Jean; Roziere, Guy.

    1981-01-01

    The invention concerns a scintillator module (sodium iodide) for the detection of X and γ rays by light conversion into electrical signals. This conversion is made through optical elements associated to the scintillator and receiving the light generated by X and γ rays. This module is constituted of elementary scintillators separated by interstices, arranged on a transparent support exposed to incident radiations. These interstices constitute optical discontinuities at the surface between two elementary and successive scintillators. The interstices are blocked up by polymerisable and transparent resin to the light of the scintillator, and charged by magnesia powder reflecting this light [fr

  15. Scale-Up Design Analysis and Modelling of Cobalt Oxide Silica Membrane Module for Hydrogen Processing

    Directory of Open Access Journals (Sweden)

    Guozhao Ji

    2013-08-01

    Full Text Available This work shows the application of a validated mathematical model for gas permeation at high temperatures focusing on demonstrated scale-up design for H2 processing. The model considered the driving force variation with spatial coordinates and the mass transfer across the molecular sieve cobalt oxide silica membrane to predict the separation performance. The model was used to study the process of H2 separation at 500 °C in single and multi-tube membrane modules. Parameters of interest included the H2 purity in the permeate stream, H2 recovery and H2 yield as a function of the membrane length, number of tubes in a membrane module, space velocity and H2 feed molar fraction. For a single tubular membrane, increasing the length of a membrane tube led to higher H2 yield and H2 recovery, owing to the increase of the membrane area. However, the H2 purity decreased as H2 fraction was depleted, thus reducing the driving force for H2 permeation. By keeping the membrane length constant in a multi-tube arrangement, the H2 yield and H2 recovery increase was attributed to the higher membrane area, but the H2 purity was again compromised. Increasing the space velocity avoided the reduction of H2 purity and still delivered higher H2 yield and H2 recovery than in a single membrane arrangement. Essentially, if the membrane surface is too large, the driving force becomes lower at the expense of H2 purity. In this case, the membrane module is over designed. Hence, maintaining a driving force is of utmost importance to deliver the functionality of process separation.

  16. Motivation enhances visual working memory capacity through the modulation of central cognitive processes.

    Science.gov (United States)

    Sanada, Motoyuki; Ikeda, Koki; Kimura, Kenta; Hasegawa, Toshikazu

    2013-09-01

    Motivation is well known to enhance working memory (WM) capacity, but the mechanism underlying this effect remains unclear. The WM process can be divided into encoding, maintenance, and retrieval, and in a change detection visual WM paradigm, the encoding and retrieval processes can be subdivided into perceptual and central processing. To clarify which of these segments are most influenced by motivation, we measured ERPs in a change detection task with differential monetary rewards. The results showed that the enhancement of WM capacity under high motivation was accompanied by modulations of late central components but not those reflecting attentional control on perceptual inputs across all stages of WM. We conclude that the "state-dependent" shift of motivation impacted the central, rather than the perceptual functions in order to achieve better behavioral performances. Copyright © 2013 Society for Psychophysiological Research.

  17. Conceptual design for the Waste Receiving and Processing facility Module 2A

    International Nuclear Information System (INIS)

    1992-07-01

    This is part of a Conceptual Design Report (CDR) for the Waste Receiving and Processing (WRAP) Module 2A facility at the Hanford Reservation. The mission of the facility is to receive, process, package, certify, and ship for permanent burial at the Hanford site disposal facilities those contact handled (CH) low-level radioactive mixed wastes (LLMW) that: (1) are currently in retrievable storage at the Hanford Central Waste Complex (HCWC) awaiting a treatment capability to permit permanent disposal compliant with the Land Disposal Restrictions and; (2) are forecasted to be generated over the next 30 years. The primary sources of waste to be treated include the currently stored waste from the 183-H solar basin evaporators, secondary solids from the future Hanford site liquid effluent treatment facilities, thermal treatment facility ash, other WRAP modules, and other miscellaneous waste from storage and onsite/offsite waste generators consisting of compactible and non-compactible solids, contaminated soils, and metals. This volume, Volume III is a compilation of the outline specifications that will form the basis for development of the Title design construction specifications. This volume contains abbreviated CSI outline specifications for equipment as well as non-equipment related construction and material items. For process and mechanical equipment, data sheets are provided with the specifications which indicate the equipment overall design parameters. This volume also includes a major equipment list

  18. All-solution-processed PbS quantum dot solar modules

    Science.gov (United States)

    Jang, Jihoon; Shim, Hyung Cheoul; Ju, Yeonkyeong; Song, Jung Hoon; An, Hyejin; Yu, Jong-Su; Kwak, Sun-Woo; Lee, Taik-Min; Kim, Inyoung; Jeong, Sohee

    2015-05-01

    A rapid increase in power conversion efficiencies in colloidal quantum dot (QD) solar cells has been achieved recently with lead sulphide (PbS) QDs by adapting a heterojunction architecture, which consists of small-area devices associated with a vacuum-deposited buffer layer with metal electrodes. The preparation of QD solar modules by low-cost solution processes is required to further increase the power-to-cost ratio. Herein we demonstrate all-solution-processed flexible PbS QD solar modules with a layer-by-layer architecture comprising polyethylene terephthalate (PET) substrate/indium tin oxide (ITO)/titanium oxide (TiO2)/PbS QD/poly(3-hexylthiophene) (P3HT)/poly(3,4-ethylenedioxythiophene) : poly(styrene sulfonate) (PEDOT : PSS)/Ag, with an active area of up to 30 cm2, exhibiting a power conversion efficiency (PCE) of 1.3% under AM 1.5 conditions (PCE of 2.2% for a 1 cm2 unit cell). Our approach affords trade-offs between power and the active area of the photovoltaic devices, which results in a low-cost power source, and which is scalable to larger areas.A rapid increase in power conversion efficiencies in colloidal quantum dot (QD) solar cells has been achieved recently with lead sulphide (PbS) QDs by adapting a heterojunction architecture, which consists of small-area devices associated with a vacuum-deposited buffer layer with metal electrodes. The preparation of QD solar modules by low-cost solution processes is required to further increase the power-to-cost ratio. Herein we demonstrate all-solution-processed flexible PbS QD solar modules with a layer-by-layer architecture comprising polyethylene terephthalate (PET) substrate/indium tin oxide (ITO)/titanium oxide (TiO2)/PbS QD/poly(3-hexylthiophene) (P3HT)/poly(3,4-ethylenedioxythiophene) : poly(styrene sulfonate) (PEDOT : PSS)/Ag, with an active area of up to 30 cm2, exhibiting a power conversion efficiency (PCE) of 1.3% under AM 1.5 conditions (PCE of 2.2% for a 1 cm2 unit cell). Our approach affords trade

  19. Information transfer with rate-modulated Poisson processes: a simple model for nonstationary stochastic resonance.

    Science.gov (United States)

    Goychuk, I

    2001-08-01

    Stochastic resonance in a simple model of information transfer is studied for sensory neurons and ensembles of ion channels. An exact expression for the information gain is obtained for the Poisson process with the signal-modulated spiking rate. This result allows one to generalize the conventional stochastic resonance (SR) problem (with periodic input signal) to the arbitrary signals of finite duration (nonstationary SR). Moreover, in the case of a periodic signal, the rate of information gain is compared with the conventional signal-to-noise ratio. The paper establishes the general nonequivalence between both measures notwithstanding their apparent similarity in the limit of weak signals.

  20. Modelling and simulation of a pervaporation process using tubular module for production of anhydrous ethanol

    Science.gov (United States)

    Hieu, Nguyen Huu

    2017-09-01

    Pervaporation is a potential process for the final step of ethanol biofuel production. In this study, a mathematical model was developed based on the resistance-in-series model and a simulation was carried out using the specialized simulation software COMSOL Multiphysics to describe a tubular type pervaporation module with membranes for the dehydration of ethanol solution. The permeance of membranes, operating conditions, and feed conditions in the simulation were referred from experimental data reported previously in literature. Accordingly, the simulated temperature and density profiles of pure water and ethanol-water mixture were validated based on existing published data.

  1. Waste Receiving and Processing Facility, Module 1: Volume 6, Engineering assessments

    International Nuclear Information System (INIS)

    1992-03-01

    This report evaluates the ability of the WRAP Module 1 Facility to achieve the required material throughput by developing a time and motion simulation model of the facility using the WITNESS Simulation Program. Analysis of the simulation model indicated that the required throughput of 6825 drums per year based on working 5.5 hours in the Shipping ampersand Receiving and Waste Process areas and 7 hours in the NDA/NDE area for 175 days a year, as stated in the Functional Design Criteria (FDC) Rev. 1 and Supplemental Design Requirements Document (SDRD) Rev. 1, can be achieved

  2. Emotion processing in the aging brain is modulated by semantic elaboration

    Science.gov (United States)

    Ritchey, Maureen; Bessette-Symons, Brandy; Hayes, Scott M.; Cabeza, Roberto

    2010-01-01

    The neural correlates of emotion processing have been shown to vary with age: older adults (OAs) exhibit increased frontal activations and, under some circumstances, decreased amygdala activations relative to young adults (YAs) during emotion processing. Some of these differences are additionally modulated by valence, with age-related biases toward positive versus negative stimuli, and are thought to depend on OAs’ capacity for controlled elaboration. However, the role of semantic elaboration in mediating valence effects in the aging brain has not yet been explicitly tested. In the present study, YAs and OAs were scanned while they viewed negative, neutral, and positive pictures during either a deep, elaborative task or a shallow, perceptual task. FMRI results reveal that emotion-related activity in the amygdala is preserved in aging and insensitive to elaboration demands. This study provides novel evidence that differences in valence processing are modulated by elaboration: relative to YAs, OAs show enhanced activity in the medial prefrontal cortex (PFC) and ventrolateral PFC in response to positive versus negative stimuli, but only during elaborative processing. These positive valence effects are predicted by individual differences in executive function in OAs for the deep but not shallow task. Finally, psychophysiological interaction analyses reveal age effects on valence-dependent functional connectivity between medial PFC and ventral striatum, as well as age and task effects on medial PFC-retrosplenial cortex interactions. Altogether, these findings provide support for the hypothesis that valence shifts in the aging brain are mediated by controlled processes such as semantic elaboration, self-referential processing, and emotion regulation. PMID:20869375

  3. Emotion processing in the aging brain is modulated by semantic elaboration.

    Science.gov (United States)

    Ritchey, Maureen; Bessette-Symons, Brandy; Hayes, Scott M; Cabeza, Roberto

    2011-03-01

    The neural correlates of emotion processing have been shown to vary with age: older adults (OAs) exhibit increased frontal activations and, under some circumstances, decreased amygdala activations relative to young adults (YAs) during emotion processing. Some of these differences are additionally modulated by valence, with age-related biases toward positive versus negative stimuli, and are thought to depend on OAs' capacity for controlled elaboration. However, the role of semantic elaboration in mediating valence effects in the aging brain has not yet been explicitly tested. In the present study, YAs and OAs were scanned while they viewed negative, neutral, and positive pictures during either a deep, elaborative task or a shallow, perceptual task. fMRI results reveal that emotion-related activity in the amygdala is preserved in aging and insensitive to elaboration demands. This study provides novel evidence that differences in valence processing are modulated by elaboration: relative to YAs, OAs show enhanced activity in the medial prefrontal cortex (PFC) and ventrolateral PFC in response to positive versus negative stimuli, but only during elaborative processing. These positive valence effects are predicted by individual differences in executive function in OAs for the deep but not shallow task. Finally, psychophysiological interaction analyses reveal age effects on valence-dependent functional connectivity between medial PFC and ventral striatum, as well as age and task effects on medial PFC-retrosplenial cortex interactions. Altogether, these findings provide support for the hypothesis that valence shifts in the aging brain are mediated by controlled processes such as semantic elaboration, self-referential processing, and emotion regulation. Copyright © 2010 Elsevier Ltd. All rights reserved.

  4. Apparel Research Network (ARN) Apparel Order Processing Module (AOPM). Application Program for Management of Special Measurement Clothing Orders

    National Research Council Canada - National Science Library

    Brekhus, Dennis

    1997-01-01

    ..., to the defense apparel manufacturers. The Apparel Order Processing Module (AOPM) is designed to respond to the critical need for an ability to order clothing expeditiously for military recruits and for other military personnel...

  5. Performance evaluation of the DCMD desalination process under bench scale and large scale module operating conditions

    KAUST Repository

    Francis, Lijo; Ghaffour, NorEddine; Alsaadi, Ahmad Salem; Nunes, Suzana Pereira; Amy, Gary L.

    2014-01-01

    The flux performance of different hydrophobic microporous flat sheet commercial membranes made of poly tetrafluoroethylene (PTFE) and poly propylene (PP) was tested for Red Sea water desalination using the direct contact membrane distillation (DCMD) process, under bench scale (high δT) and large scale module (low δT) operating conditions. Membranes were characterized for their surface morphology, water contact angle, thickness, porosity, pore size and pore size distribution. The DCMD process performance was optimized using a locally designed and fabricated module aiming to maximize the flux at different levels of operating parameters, mainly feed water and coolant inlet temperatures at different temperature differences across the membrane (δT). Water vapor flux of 88.8kg/m2h was obtained using a PTFE membrane at high δT (60°C). In addition, the flux performance was compared to the first generation of a new locally synthesized and fabricated membrane made of a different class of polymer under the same conditions. A total salt rejection of 99.99% and boron rejection of 99.41% were achieved under extreme operating conditions. On the other hand, a detailed water characterization revealed that low molecular weight non-ionic molecules (ppb level) were transported with the water vapor molecules through the membrane structure. The membrane which provided the highest flux was then tested under large scale module operating conditions. The average flux of the latter study (low δT) was found to be eight times lower than that of the bench scale (high δT) operating conditions.

  6. Performance evaluation of the DCMD desalination process under bench scale and large scale module operating conditions

    KAUST Repository

    Francis, Lijo

    2014-04-01

    The flux performance of different hydrophobic microporous flat sheet commercial membranes made of poly tetrafluoroethylene (PTFE) and poly propylene (PP) was tested for Red Sea water desalination using the direct contact membrane distillation (DCMD) process, under bench scale (high δT) and large scale module (low δT) operating conditions. Membranes were characterized for their surface morphology, water contact angle, thickness, porosity, pore size and pore size distribution. The DCMD process performance was optimized using a locally designed and fabricated module aiming to maximize the flux at different levels of operating parameters, mainly feed water and coolant inlet temperatures at different temperature differences across the membrane (δT). Water vapor flux of 88.8kg/m2h was obtained using a PTFE membrane at high δT (60°C). In addition, the flux performance was compared to the first generation of a new locally synthesized and fabricated membrane made of a different class of polymer under the same conditions. A total salt rejection of 99.99% and boron rejection of 99.41% were achieved under extreme operating conditions. On the other hand, a detailed water characterization revealed that low molecular weight non-ionic molecules (ppb level) were transported with the water vapor molecules through the membrane structure. The membrane which provided the highest flux was then tested under large scale module operating conditions. The average flux of the latter study (low δT) was found to be eight times lower than that of the bench scale (high δT) operating conditions.

  7. Development of CAD-Based Geometry Processing Module for a Monte Carlo Particle Transport Analysis Code

    International Nuclear Information System (INIS)

    Choi, Sung Hoon; Kwark, Min Su; Shim, Hyung Jin

    2012-01-01

    As The Monte Carlo (MC) particle transport analysis for a complex system such as research reactor, accelerator, and fusion facility may require accurate modeling of the complicated geometry. Its manual modeling by using the text interface of a MC code to define the geometrical objects is tedious, lengthy and error-prone. This problem can be overcome by taking advantage of modeling capability of the computer aided design (CAD) system. There have been two kinds of approaches to develop MC code systems utilizing the CAD data: the external format conversion and the CAD kernel imbedded MC simulation. The first approach includes several interfacing programs such as McCAD, MCAM, GEOMIT etc. which were developed to automatically convert the CAD data into the MCNP geometry input data. This approach makes the most of the existing MC codes without any modifications, but implies latent data inconsistency due to the difference of the geometry modeling system. In the second approach, a MC code utilizes the CAD data for the direct particle tracking or the conversion to an internal data structure of the constructive solid geometry (CSG) and/or boundary representation (B-rep) modeling with help of a CAD kernel. MCNP-BRL and OiNC have demonstrated their capabilities of the CAD-based MC simulations. Recently we have developed a CAD-based geometry processing module for the MC particle simulation by using the OpenCASCADE (OCC) library. In the developed module, CAD data can be used for the particle tracking through primitive CAD surfaces (hereafter the CAD-based tracking) or the internal conversion to the CSG data structure. In this paper, the performances of the text-based model, the CAD-based tracking, and the internal CSG conversion are compared by using an in-house MC code, McSIM, equipped with the developed CAD-based geometry processing module

  8. Specification and development of the sharing memory data management module for a nuclear processes simulator

    International Nuclear Information System (INIS)

    Telesforo R, D.

    2003-01-01

    Actually it is developed in the Engineering Faculty of UNAM a simulator of nuclear processes with research and teaching purposes. It consists of diverse modules, included the one that is described in the present work that is the shared memory module. It uses the IPC mechanisms of the UNIX System V operative system, and it was codified with C language. To model the diverse components of the simulator the RELAP code is used. The function of the module is to generate locations of shared memory for to deposit in these the necessary variables for the interaction among the diverse ones processes of the simulator. In its it will be able read and to write the information that generate the running of the simulation program, besides being able to interact with the internal variables of the code in execution time. The graphic unfolding (mimic, pictorials, tendency graphics, virtual instrumentation, etc.) they also obtain information of the shared memory. In turn, actions of the user in interactive unfolding, they modify the segments of shared memory, and the information is sent to the RELAP code to modify the simulation course. The program has two beginning modes: automatic and manual. In automatic mode taking an enter file of RELAP (indta) and it joins in shared memory, the control variables that in this appear. In manual mode the user joins, he reads and he writes the wanted control variables, whenever they exist in the enter file (indta). This is a dynamic mode of interacting with the simulator in a direct way and of even altering the values as when its don't exist in the board elements associated to the variables. (Author)

  9. Offspring of parents with Balkan Endemic Nephropathy have higher C-reactive protein levels suggestive of inflammatory processes: a longitudinal study

    Directory of Open Access Journals (Sweden)

    Tsolova Svetla

    2009-04-01

    Full Text Available Abstract Background Despite the characteristic extensive tubulointerstitial fibrosis, Balkan Endemic Nephropathy (BEN is usually considered a non-inflammatory disease. Methods We examined a marker of inflammation, C-reactive protein (CRP, in the offspring of patients with BEN, a population at risk for BEN, prior to development of established disease to determine if an inflammatory process could be identified in the early stages of the disease. In 2003/04, 102 adult offspring whose parents had BEN and a control group of 99 adult offspring of non-BEN patients were enrolled in this prospective study. This cohort was re-examined yearly for four consecutive years. Levels of serum CRP were measured in years 3 and 4 and compared between groups. The data were analyzed with mixed models. Results Compared to controls, offspring of BEN parents had statistically higher CRP levels in two consecutive years, suggestive of early inflammatory reactivity. Whenever the mother was affected by BEN (both parents, or mother only, serum CRP was significantly increased, but not if only the father had BEN. CRP was inversely related to kidney cortex width but not to markers or renal function. Conclusion Early stages of BEN may involve inflammatory processes. The observation of a maternal involvement supports the concept of fetal programming, which has been implicated in the pathogenesis of other chronic kidney diseases.

  10. Toll-Like Receptor 2 mediates in vivo pro- and anti-inflammatory effects of Mycobacterium tuberculosis and modulates autoimmune encephalomyelitis

    Directory of Open Access Journals (Sweden)

    Alessia ePiermattei

    2016-05-01

    Full Text Available Mycobacteria display pro- and anti-inflammatory effects in human and experimental pathology. We show here that both effects are mediated by Toll like receptor 2 (Tlr2, by exploiting a previously characterized Tlr2 variant (Met82Ile. Tlr2 82ile promoted self-specific pro-inflammatory polarization as well as expansion of ag-specific FoxP3+ Tregs, while Tlr2 82met impairs the expansion of Tregs and reduces the production of IFN-γ and IL-17 pro-inflammatory cytokines. Preferential dimerization with Tlr1 or Tlr6 could not explain these differences. In silico, we showed that Tlr2 variant Met82Ile modified the binding pocket for peptidoglycans and participate directly to a putative binding pocket for sugars and Cadherins. The distinct pro- and anti-inflammatory actions impacted on severity, extent of remission and distribution of the lesions within the Central Nervous System of Experimental Autoimmune Encephalomyelitis. Thus, Tlr2 has a janus function in vivo as mediator of the role of bacterial products in balancing pro- and anti-inflammatory immune responses.

  11. Cholinergic enhancement modulates neural correlates of selective attention and emotional processing.

    Science.gov (United States)

    Bentley, Paul; Vuilleumier, Patrik; Thiel, Christiane M; Driver, Jon; Dolan, Raymond J

    2003-09-01

    Neocortical cholinergic afferents are proposed to influence both selective attention and emotional processing. In a study of healthy adults we used event-related fMRI while orthogonally manipulating attention and emotionality to examine regions showing effects of cholinergic modulation by the anticholinesterase physostigmine. Either face or house pictures appeared at task-relevant locations, with the alternative picture type at irrelevant locations. Faces had either neutral or fearful expressions. Physostigmine increased relative activity within the anterior fusiform gyrus for faces at attended, versus unattended, locations, but decreased relative activity within the posterolateral occipital cortex for houses in attended, versus unattended, locations. A similar pattern of regional differences in the effect of physostigmine on cue-evoked responses was also present in the absence of stimuli. Cholinergic enhancement augmented the relative neuronal response within the middle fusiform gyrus to fearful faces, whether at attended or unattended locations. By contrast, physostigmine influenced responses in the orbitofrontal, intraparietal and cingulate cortices to fearful faces when faces occupied task-irrelevant locations. These findings suggest that acetylcholine may modulate both selective attention and emotional processes through independent, region-specific effects within the extrastriate cortex. Furthermore, cholinergic inputs to the frontoparietal cortex may influence the allocation of attention to emotional information.

  12. Modulations of the processing of line discontinuities under selective attention conditions?

    Science.gov (United States)

    Giersch, Anne; Fahle, Manfred

    2002-01-01

    We examined whether the processing of discontinuities involved in figure-ground segmentation, like line ends, can be modulated under selective attention conditions. Subjects decided whether a gap in collinear or parallel lines was located to the right or left. Two stimuli were displayed in immediate succession. When the gaps were on the same side, reaction times (RTs) for the second stimulus increased when collinear lines followed parallel lines, or the reverse, but only when the two stimuli shared the same orientation and location. The effect did not depend on the global form of the stimuli or on the relative orientation of the gaps. A frame drawn around collinear elements affected the results, suggesting a crucial role of the "amodal" orthogonal lines produced when line ends are aligned. Including several gaps in the first stimulus also eliminated RT variations. By contrast, RT variations remained stable across several experimental blocks and were significant for interstimulus intervals from 50 to 600 msec between the two stimuli. These results are interpreted in terms of a modulation of the processing of line ends or the production of amodal lines, arising when attention is selectively drawn to a gap.

  13. Experimentally Investigating the Effect of Temperature Differences in the Particle Deposition Process on Solar Photovoltaic (PV Modules

    Directory of Open Access Journals (Sweden)

    Yu Jiang

    2016-10-01

    Full Text Available This paper reports an experimental investigation of the dust particle deposition process on solar photovoltaic (PV modules with different surface temperatures by a heating plate to illustrate the effect of the temperature difference (thermophoresis between the module surface and the surrounding air on the dust accumulation process under different operating temperatures. In general, if the temperature of PV modules is increased, the energy conversion efficiency of the modules is decreased. However, in this study, it is firstly found that higher PV module surface temperature differences result in a higher energy output compared with those modules with lower temperature differences because of a reduced accumulation of dust particles. The measured deposition densities of dust particles were found to range from 0.54 g/m2 to 0.85 g/m2 under the range of experimental conditions and the output power ratios were found to increase from 0.861 to 0.965 with the increase in the temperature difference from 0 to 50 °C. The PV module with a higher temperature difference experiences a lower dust density because of the effect of the thermophoresis force arising from the temperature gradient between the module surface and its surrounding air. In addition, dust particles have a significant impact on the short circuit current, as well as the output power. However, the influence of particles on open circuit voltage can be negligible.

  14. Waste Receiving and Processing Facility Module 2A: Advanced Conceptual Design Report. Volume 1

    Energy Technology Data Exchange (ETDEWEB)

    1994-03-01

    This ACDR was performed following completed of the Conceptual Design Report in July 1992; the work encompassed August 1992 to January 1994. Mission of the WRAP Module 2A facility is to receive, process, package, certify, and ship for permanent burial at the Hanford site disposal facilities the Category 1 and 3 contact handled low-level radioactive mixed wastes that are currently in retrievable storage at Hanford and are forecast to be generated over the next 30 years by Hanford, and waste to be shipped to Hanford from about DOE sites. This volume provides an introduction to the ACDR process and the scope of the task along with a project summary of the facility, treatment technologies, cost, and schedule. Major areas of departure from the CDR are highlighted. Descriptions of the facility layout and operations are included.

  15. Modulation of Inhibitory Processing by Posttraumatic Stress Symptoms and Anxiety in a Subclinical Sample of Children.

    Science.gov (United States)

    Gindt, Morgane; Chanquoy, Lucile; Garcia, René

    2016-12-01

    In adults, pathologies of anxiety such as posttraumatic stress symptoms (PTSS) involve deficits in information processing that may reflect hypervigilance and deficient inhibitory control, specifically for negative information. However, little is known about inhibitory processing in children, particularly regarding the inhibition of emotional information. This study investigated whether children with PTSS or anxiety show impairments in executive control in an inhibition task. A total of 45 children (M age = 9.2 year, SD = 0.7, range: 8-11) completed an inhibition task involving emotional-happy, angry, and fearful-and neutral stimuli and clinical scales for PTSS and anxiety. The results indicated that the percentage of correct answers was modulated by PTSS status, particularly in the happiness task. PTSS and anxiety altered the inhibition of fearful information in children. These data suggest different types of inhibitory deficits depending on clinical symptoms, and implications are discussed. © The Author(s) 2016.

  16. Waste Receiving and Processing Facility, Module 1: Volume 5, Engineering studies

    International Nuclear Information System (INIS)

    1992-03-01

    The WRAP facility at Hanford will retrieve, process, certify transuranic, mixed, and low level radioactive wastes for disposal/either on-site or at the WIPP. The Conceptual Design Report for the Waste Receiving And Processing Facility, Module 1 (WRAP 1), established the technical benchmark. The UE ampersand C Engineering Proposal/Work Plan proposed twenty Evaluation/Optimization Engineering Studies to evaluate design alternatives and critically examine functional performance requirements prior to commencement of Preliminary Design. Of these twenty studies, one has been eliminated as unnecessary (The Use of Scintered Metal Filters) due mainly to the lack of National Standards and to the fact that standard HEPA type filters are totally adequate for WRAP application. This report presents an executive summary of the remaining nineteen studies

  17. Verification of the cross-section and depletion chain processing module of DRAGON 3.06

    International Nuclear Information System (INIS)

    Chambon, R.; Marleau, G.; Zkiek, A.

    2008-01-01

    In this paper we present a verification of the module of the lattice code DRAGON 3.06 used for processing microscopic cross-section libraries, including their associated depletion chain. This verification is performed by reprogramming the capabilities of DRAGON in another language (MATLAB) and testing them on different problems typical of the CANDU reactor. The verification procedure consists in first programming MATLAB m-files to read the different cross section libraries in ASCII format and to compute the reference cross-sections and depletion chains. The same information is also recovered from the output files of DRAGON (using different m-files) and the resulting cross sections and depletion chain are compared with the reference library, the differences being evaluated and tabulated. The results show that the cross-section calculations and the depletion chains are correctly processed in version 3.06 of DRAGON. (author)

  18. Anti-inflammatory and Antinociceptive Activity of Ouabain in Mice

    Directory of Open Access Journals (Sweden)

    Danielle Ingrid Bezerra de Vasconcelos

    2011-01-01

    Full Text Available Ouabain, an inhibitor of the Na+/K+-ATPase pump, was identified as an endogenous substance of human plasma. Ouabain has been studied for its ability to interfere with various regulatory mechanisms. Despite the studies portraying the ability of ouabain to modulate the immune response, little is known about the effect of this substance on the inflammatory process. The aim of this work was to study the effects triggered by ouabain on inflammation and nociceptive models. Ouabain produced a reduction in the mouse paw edema induced by carrageenan, compound 48/80 and zymosan. This anti-inflammatory potential might be related to the inhibition of prostaglandin E2, bradykinin, and mast-cell degranulation but not to histamine. Ouabain also modulated the inflammation induced by concanavalin A by inhibiting cell migration. Besides that, ouabain presented antinociceptive activity. Taken these data together, this work demonstrated, for the first time, that ouabain presented in vivo analgesic and anti-inflammatory effects.

  19. Modulation of the immune response by Fonsecaea pedrosoi morphotypes in the course of experimental chromoblastomycosis and their role on inflammatory response chronicity.

    Directory of Open Access Journals (Sweden)

    Isaque Medeiros Siqueira

    2017-03-01

    Full Text Available A common theme across multiple fungal pathogens is their ability to impair the establishment of a protective immune response. Although early inflammation is beneficial in containing the infection, an uncontrolled inflammatory response is detrimental and may eventually oppose disease eradication. Chromoblastomycosis (CBM, a cutaneous and subcutaneous mycosis, caused by dematiaceous fungi, is capable of inducing a chronic inflammatory response. Muriform cells, the parasitic form of Fonsecaea pedrosoi, are highly prevalent in infected tissues, especially in long-standing lesions. In this study we show that hyphae and muriform cells are able to establish a murine CBM with skin lesions and histopathological aspects similar to that found in humans, with muriform cells being the most persistent fungal form, whereas mice infected with conidia do not reach the chronic phase of the disease. Moreover, in injured tissue the presence of hyphae and especially muriform cells, but not conidia, is correlated with intense production of pro-inflammatory cytokines in vivo. High-throughput RNA sequencing analysis (RNA-Seq performed at early time points showed a strong up-regulation of genes related to fungal recognition, cell migration, inflammation, apoptosis and phagocytosis in macrophages exposed in vitro to muriform cells, but not conidia. We also demonstrate that only muriform cells required FcγR and Dectin-1 recognition to be internalized in vitro, and this is the main fungal form responsible for the intense inflammatory pattern observed in CBM, clarifying the chronic inflammatory reaction observed in most patients. Furthermore, our findings reveal two different fungal-host interaction strategies according to fungal morphotype, highlighting fungal dimorphism as an important key in understanding the bipolar nature of inflammatory response in fungal infections.

  20. The Manufacturing Process for the NASA Composite Crew Module Demonstration Structure

    Science.gov (United States)

    Pelham, Larry; Higgins, John E.

    2008-01-01

    This paper will describe the approaches and methods selected in fabrication of a carbon composite demonstration structure for the Composite Crew Module (CCM) Program. The program is managed by the NASA Safety and Engineering Center with participants from ten NASA Centers and AFRL. Multiple aerospace contractors are participating in the design development, tooling and fabrication effort as well. The goal of the program is to develop an agency wide design team for composite habitable spacecraft. The specific goals for this development project are: a).To gain hands on experience in design, building and testing a composite crew module. b) To validate key assumptions by resolving composite spacecraft design details through fabrication and testing of hardware. This abstract is based on Preliminary Design data..The final design will continue to evolve through the fall of 2007 with fabrication mostly completed by conference date. From a structures perspective, the.CCM can be viewed as a pressure module with variable pressure time histories and a series of both impact and quasi-static, high intensity point, line, and area distributed loads. The portion of the overall space vehicle being designed and. fabricated by the CCM team is just the pressure module and primary loading points. The heaviest point loads are applied and distributed to the pressure module at.an aluminum Service Module/Alternate Launch Abort System (SM/ALAS) fittings and at Main and Drogue Chute fittings. Significant line loads with metal to metal impact is applied at.the Lids ring. These major external point and line loads as well as pressure impact loads (blast and water landing) are applied to the lobed floor though the reentry shield and crushable materials. The pressure module is divided into upper and lower. shells that mate together with a bonded belly band splice joint to create the completed structural assembly. The benefits of a split CCM far outweigh the risks of a joint. These benefits include

  1. An application of modulated poisson processes to the reliability analysis of repairable systems

    Energy Technology Data Exchange (ETDEWEB)

    Saldanha, Pedro L.C. [Comissao Nacional de Energia Nuclear (CNEN), Rio de Janeiro, RJ (Brazil). Coordenacao de Reatores]. E-mail: saldanha@cnen.gov.br; Melo, P.F. Frutuoso e [Universidade Federal, Rio de Janeiro, RJ (Brazil). Coordenacao dos Programas de Pos-graduacao de Engenharia. Programa de Engenharia Nuclear]. E-mail: frutuoso@con.ufrj.br; Noriega, Hector C. [Universidad Austral de Chile (UACh), Valdivia (Chile). Faculdad de Ciencias de la Ingeniaria]. E-mail: hnoriega@uach.cl

    2005-07-01

    This paper discusses the application of the modulated power law process (MPLP) model to the rate of occurrence of failures of active repairable systems in reliability engineering. Traditionally, two ways of modeling repairable systems, in what concerns maintenance policies, are: a pessimistic approach (non-homogeneous process - NHPP), and a very optimistic approach (renewal processes - RP). It is important to build a generalized model that might consider characteristics and properties both of the NHPP and of the RP models as particular cases. In practice, by considering the pattern of times between failures, the MPLP appears to be more realistic to represent the occurrence of failures of repairable systems in order to define whether they can be modeled by a homogeneous or a non-homogeneous process. The study has shown that the model can be used to make decisions concerning the evaluation of the qualified life of plant equipment. By controlling and monitoring two of the three parameters of the MPLP model during the equipment operation, it is possible to check whether and how the equipment is following the basis of its qualification process, and so identify how the effects of time, degradation and operation modes are influencing the equipment performance. The discussion is illustrated by an application to the service water pumps of a typical PWR plant. (author)

  2. Fermented non-digestible fraction from combined nixtamalized corn (Zea mays L.)/cooked common bean (Phaseolus vulgaris L.) chips modulate anti-inflammatory markers on RAW 264.7 macrophages.

    Science.gov (United States)

    Luzardo-Ocampo, I; Campos-Vega, R; Cuellar-Nuñez, M L; Vázquez-Landaverde, P A; Mojica, L; Acosta-Gallegos, J A; Loarca-Piña, G

    2018-09-01

    Chronic non-communicable diseases (NCDs) are low-level inflammation processes affected by several factors including diet. It has been reported that mixed whole grain and legume consumption, e.g. corn and common bean, might be a beneficial combination due to its content of bioactive compounds. A considerable amount would be retained in the non-digestible fraction (NDF), reaching the colon, where microbiota produce short-chain fatty acids (SCFAs) and phenolic compounds (PC) with known anti-inflammatory effect. The aim of this study was to estimate the anti-inflammatory potential of fermented-NDF of corn-bean chips (FNDFC) in RAW 264.7 macrophages. After 24 h, FNDFC produced SCFAs (0.156-0.222 mmol/l), inhibited nitric oxide production > 80% and H 2 O 2  > 30%, up-regulated anti-inflammatory cytokines (I-TAC, TIMP-1) > 2-fold, and produced angiostatic and protective factors against vascular/tissue damage, and amelioration of tumor necrosis factor signalling and inflammatory bowel disease. These results confirm the anti-inflammatory potential derived from healthy corn-bean chips. Copyright © 2018. Published by Elsevier Ltd.

  3. Involvement of α2-adrenoceptors in inhibitory and facilitatory pain modulation processes.

    Science.gov (United States)

    Vo, L; Drummond, P D

    2016-03-01

    In healthy humans, high-frequency electrical stimulation (HFS) of the forearm not only produces hyperalgesia at the site of stimulation but also reduces sensitivity to pressure-pain on the ipsilateral side of the forehead. In addition, HFS augments the ipsilateral trigeminal nociceptive blink reflex and intensifies the ipsilateral component of conditioned pain modulation. The aim of this study was to determine whether α2-adrenoceptors mediate these ipsilateral nociceptive influences. The α2-adrenoceptor antagonist yohimbine was administered to 22 participants in a double-blind, placebo-controlled crossover study. In each session, thermal and mechanical sensitivity in the forearms and forehead was assessed before and after HFS. In addition, the combined effect of HFS and yohimbine on the nociceptive blink reflex and on conditioned pain modulation was explored. In this paradigm, the conditioning stimulus was cold pain in the ipsilateral or contralateral temple, and the test stimulus was electrically evoked pain in the forearm. Blood pressure and electrodermal activity increased for several hours after yohimbine administration, consistent with blockade of central α2-adrenoceptors. Yohimbine not only augmented the nociceptive blink reflex ipsilateral to HFS but also intensified the inhibitory influence of ipsilateral temple cooling on electrically evoked pain at the HFS-treated site in the forearm. Yohimbine had no consistent effect on primary or secondary hyperalgesia in the forearm or on pressure-pain in the ipsilateral forehead. These findings imply involvement of α2-adrenoceptors both in ipsilateral antinociceptive and pronociceptive pain modulation processes. However, a mechanism not involving α2-adrenoceptors appears to mediate analgesia in the ipsilateral forehead after HFS. © 2015 European Pain Federation - EFIC®

  4. Validity of High School Physic Module With Character Values Using Process Skill Approach In STKIP PGRI West Sumatera

    Science.gov (United States)

    Anaperta, M.; Helendra, H.; Zulva, R.

    2018-04-01

    This study aims to describe the validity of physics module with Character Oriented Values Using Process Approach Skills at Dynamic Electrical Material in high school physics / MA and SMK. The type of research is development research. The module development model uses the development model proposed by Plomp which consists of (1) preliminary research phase, (2) the prototyping phase, and (3) assessment phase. In this research is done is initial investigation phase and designing. Data collecting technique to know validation is observation and questionnaire. In the initial investigative phase, curriculum analysis, student analysis, and concept analysis were conducted. In the design phase and the realization of module design for SMA / MA and SMK subjects in dynamic electrical materials. After that, the formative evaluation which include self evaluation, prototyping (expert reviews, one-to-one, and small group. At this stage validity is performed. This research data is obtained through the module validation sheet, which then generates a valid module.

  5. Cholinergic and serotonergic modulation of visual information processing in monkey V1.

    Science.gov (United States)

    Shimegi, Satoshi; Kimura, Akihiro; Sato, Akinori; Aoyama, Chisa; Mizuyama, Ryo; Tsunoda, Keisuke; Ueda, Fuyuki; Araki, Sera; Goya, Ryoma; Sato, Hiromichi

    2016-09-01

    The brain dynamically changes its input-output relationship depending on the behavioral state and context in order to optimize information processing. At the molecular level, cholinergic/monoaminergic transmitters have been extensively studied as key players for the state/context-dependent modulation of brain function. In this paper, we review how cortical visual information processing in the primary visual cortex (V1) of macaque monkey, which has a highly differentiated laminar structure, is optimized by serotonergic and cholinergic systems by examining anatomical and in vivo electrophysiological aspects to highlight their similarities and distinctions. We show that these two systems have a similar layer bias for axonal fiber innervation and receptor distribution. The common target sites are the geniculorecipient layers and geniculocortical fibers, where the appropriate gain control is established through a geniculocortical signal transformation. Both systems exert activity-dependent response gain control across layers, but in a manner consistent with the receptor subtype. The serotonergic receptors 5-HT1B and 5HT2A modulate the contrast-response curve in a manner consistent with bi-directional response gain control, where the sign (facilitation/suppression) is switched according to the firing rate and is complementary to the other. On the other hand, cholinergic nicotinic/muscarinic receptors exert mono-directional response gain control without a sign reversal. Nicotinic receptors increase the response magnitude in a multiplicative manner, while muscarinic receptors exert both suppressive and facilitative effects. We discuss the implications of the two neuromodulator systems in hierarchical visual signal processing in V1 on the basis of the developed laminar structure. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  6. Short-term alpha-tocopherol treatment during neonatal period modulates pro-inflammatory response to endotoxin (LPS) challenge in the same calves several months later

    Science.gov (United States)

    Vitamin E, a major natural antioxidant, has been previously shown to attenuate pro-inflammatory response to immune challenge in cattle. Our objective was to evaluate the effect of short-term treatment with alpha-tocopherol in newborn calves on selected elements of the pro-inflamatory response to LPS...

  7. Modulation of Invading and Resident Inflammatory Cell Activation as a Novel Way to Mitigate Spinal Cord Injury-Associated Neuropathic Pain

    Science.gov (United States)

    2017-09-01

    7-9]. Several of the chemical constituents of Cannabis sativa (aka marijuana ) have been shown to possess potent anti-inflammatory and...its synthetic analogues: effect on vanilloid VR1 receptors and on the cellular uptake and enzymatic hydrolysis of anandamide. Br J Pharmacol, 2001

  8. Spatiotemporal brain dynamics of emotional face processing modulations induced by the serotonin 1A/2A receptor agonist psilocybin.

    Science.gov (United States)

    Bernasconi, Fosco; Schmidt, André; Pokorny, Thomas; Kometer, Michael; Seifritz, Erich; Vollenweider, Franz X

    2014-12-01

    Emotional face processing is critically modulated by the serotonergic system. For instance, emotional face processing is impaired by acute psilocybin administration, a serotonin (5-HT) 1A and 2A receptor agonist. However, the spatiotemporal brain mechanisms underlying these modulations are poorly understood. Here, we investigated the spatiotemporal brain dynamics underlying psilocybin-induced modulations during emotional face processing. Electrical neuroimaging analyses were applied to visual evoked potentials in response to emotional faces, following psilocybin and placebo administration. Our results indicate a first time period of strength (i.e., Global Field Power) modulation over the 168-189 ms poststimulus interval, induced by psilocybin. A second time period of strength modulation was identified over the 211-242 ms poststimulus interval. Source estimations over these 2 time periods further revealed decreased activity in response to both neutral and fearful faces within limbic areas, including amygdala and parahippocampal gyrus, and the right temporal cortex over the 168-189 ms interval, and reduced activity in response to happy faces within limbic and right temporo-occipital brain areas over the 211-242 ms interval. Our results indicate a selective and temporally dissociable effect of psilocybin on the neuronal correlates of emotional face processing, consistent with a modulation of the top-down control. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  9. The Modulation of Error Processing in the Medial Frontal Cortex by Transcranial Direct Current Stimulation

    Directory of Open Access Journals (Sweden)

    Lisa Bellaïche

    2013-01-01

    Full Text Available Background. In order to prevent future errors, we constantly control our behavior for discrepancies between the expected (i.e., intended and the real action outcome and continuously adjust our behavior accordingly. Neurophysiological correlates of this action-monitoring process can be studied with event-related potentials (error-related negativity (ERN and error positivity (Pe originating from the medial prefrontal cortex (mPFC. Patients with neuropsychiatric diseases often show performance monitoring dysfunctions potentially caused by pathological changes of cortical excitability; therefore, a modulation of the underlying neuronal activity might be a valuable therapeutic tool. One technique which allows us to explore cortical modulation of neural networks is transcranial direct current stimulation (tDCS. Therefore, we tested the effect of medial-prefrontal tDCS on error-monitoring potentials in 48 healthy subjects randomly assigned to anodal, cathodal, or sham stimulation. Results. We found that cathodal stimulation attenuated Pe amplitudes compared to both anodal and sham stimulation, but no effect for the ERN. Conclusions. Our results indicate that cathodal tDCS over the mPFC results in an attenuated cortical excitability leading to decreased Pe amplitudes. We therefore conclude that tDCS has a neuromodulatory effect on error-monitoring systems suggesting a future approach to modify the sensitivity of corresponding neural networks in patients with action-monitoring deficits.

  10. Thyroid hormone’s role in regulating brain glucose metabolism and potentially modulating hippocampal cognitive processes

    Science.gov (United States)

    Jahagirdar, V; McNay, EC

    2012-01-01

    Cognitive performance is dependent on adequate glucose supply to the brain. Insulin, which regulates systemic glucose metabolism, has been recently shown both to regulate hippocampal metabolism and to be a mandatory component of hippocampally-mediated cognitive performance. Thyroid hormones (TH) regulate systemic glucose metabolism and may also be involved in regulation of brain glucose metabolism. Here we review potential mechanisms for such regulation. Importantly, TH imbalance is often encountered in combination with metabolic disorders, such as diabetes, and may cause additional metabolic dysregulation and hence worsening of disease states. TH’s potential as a regulator of brain glucose metabolism is heightened by interactions with insulin signaling, but there have been relatively few studies on this topic or on the actions of TH in a mature brain. This review discusses evidence for mechanistic links between TH, insulin, cognitive function, and brain glucose metabolism, and suggests that TH is a good candidate to be a modulator of memory processes, likely at least in part by modulation of central insulin signaling and glucose metabolism. PMID:22437199

  11. Modulation of early cortical processing during divided attention to non-contiguous locations.

    Science.gov (United States)

    Frey, Hans-Peter; Schmid, Anita M; Murphy, Jeremy W; Molholm, Sophie; Lalor, Edmund C; Foxe, John J

    2014-05-01

    We often face the challenge of simultaneously attending to multiple non-contiguous regions of space. There is ongoing debate as to how spatial attention is divided under these situations. Whereas, for several years, the predominant view was that humans could divide the attentional spotlight, several recent studies argue in favor of a unitary spotlight that rhythmically samples relevant locations. Here, this issue was addressed by the use of high-density electrophysiology in concert with the multifocal m-sequence technique to examine visual evoked responses to multiple simultaneous streams of stimulation. Concurrently, we assayed the topographic distribution of alpha-band oscillatory mechanisms, a measure of attentional suppression. Participants performed a difficult detection task that required simultaneous attention to two stimuli in contiguous (undivided) or non-contiguous parts of space. In the undivided condition, the classic pattern of attentional modulation was observed, with increased amplitude of the early visual evoked response and increased alpha amplitude ipsilateral to the attended hemifield. For the divided condition, early visual responses to attended stimuli were also enhanced, and the observed multifocal topographic distribution of alpha suppression was in line with the divided attention hypothesis. These results support the existence of divided attentional spotlights, providing evidence that the corresponding modulation occurs during initial sensory processing time-frames in hierarchically early visual regions, and that suppressive mechanisms of visual attention selectively target distracter locations during divided spatial attention. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  12. Significant Modules and Biological Processes between Active Components of Salvia miltiorrhiza Depside Salt and Aspirin

    Directory of Open Access Journals (Sweden)

    Yuan Li

    2016-01-01

    Full Text Available The aim of this study is to examine and compare the similarities and differences between active components of S. miltiorrhiza depside salt and aspirin using perspective of pharmacological molecular networks. Active components of S. miltiorrhiza depside salt and aspirin’s related genes were identified via the STITCH4.0 and GeneCards Database. A text search engine (Agilent Literature Search 2.71 and MCODE software were applied to construct network and divide modules, respectively. Finally, 32, 2, and 28 overlapping genes, modules, and pathways were identified between active components of S. miltiorrhiza depside salt and aspirin. A multidimensional framework of drug network showed that two networks reflected commonly in human aortic endothelial cells and atherosclerosis process. Aspirin plays a more important role in metabolism, such as the well-known AA metabolism pathway and other lipid or carbohydrate metabolism pathways. S. miltiorrhiza depside salt still plays a regulatory role in type II diabetes mellitus, insulin resistance, and adipocytokine signaling pathway. Therefore, this study suggests that aspirin combined with S. miltiorrhiza depside salt may be more efficient in treatment of CHD patients, especially those with diabetes mellitus or hyperlipidemia. Further clinical trials to confirm this hypothesis are still needed.

  13. NMDA receptor modulation by dextromethorphan and acute stress selectively alters electroencephalographic indicators of partial report processing.

    Science.gov (United States)

    Weckesser, Lisa J; Enge, Sören; Riedel, Philipp; Kirschbaum, Clemens; Miller, Robert

    2017-10-01

    Proceeding from a biophysical network model, the present study hypothesized that glutamatergic neurotransmission across the NMDA receptor (NMDAR) plays a key role in visual perception and its modulation by acute stress. To investigate these hypotheses, behavioral and electroencephalographic (EEG) indicators of partial report task processing were assessed in twenty-four healthy young men who randomly received a non-competitive NMDAR antagonist (0.8 mg/kg dextromethorphan, DXM) or a placebo, and concurrently accomplished a stress-induction (MAST) or control protocol in three consecutive sessions. Saliva samples served to quantify cortisol responses to the MAST, whereas a passive auditory oddball paradigm was implemented to verify the impact of DXM on the EEG-derived mismatch negativity component (MMN). DXM administration significantly increased MMN amplitudes but not salivary cortisol concentrations. By contrast, concurrent MAST exposure significantly reduced MMN latencies but also increased cortisol concentrations. With regard to EEG indicators, DXM administration reduced visually "evoked" (30Hz to 50Hz) and "induced" occipital gamma-band activity (70Hz to 100Hz), which was partly compensated by additional MAST exposure. However, neither the interventions nor EEG activity were significantly associated with behavioral partial report sensitivities. In summary, the present data suggest that glutamatergic neurotransmission across the NMDAR is only one among many determinants of intact visual perception. Accordingly, therapeutic doses of DXM and their inhibitory modulation by stress probably yield more pronounced electroencephalographic as compared with behavioural effects. Copyright © 2017 Elsevier B.V. and ECNP. All rights reserved.

  14. Zn/Ga−DFO iron–chelating complex attenuates the inflammatory process in a mouse model of asthma

    Directory of Open Access Journals (Sweden)

    Haim Bibi

    2014-01-01

    Conclusion: In this mouse model of allergic asthma, Zn/Ga−DFO attenuated allergic airway inflammation. The beneficial effects of treatment were in accord with iron overload abatement in asthmatic lungs by Zn/Ga−DFO. The findings in both cellular and tissue levels supported the existence of a significant anti-inflammatory effect of Zn/Ga−DFO.

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

    NARCIS (Netherlands)

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

    2018-01-01

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

  16. Cerebrospinal fluid neopterin analysis in neuropediatric patients: establishment of a new cut off-value for the identification of inflammatory-immune mediated processes.

    Directory of Open Access Journals (Sweden)

    Marta Molero-Luis

    Full Text Available OBJECTIVE: A high level of cerebrospinal fluid (CSF neopterin is a marker of central nervous system inflammatory-immune mediated processes. We aimed to assess data from 606 neuropediatric patients, describing the clinical and biochemical features of those neurological disorders presenting CSF neopterin values above a new cut-off value that was defined in our laboratory. METHODS: To establish the new CSF neopterin cut-off value, we studied two groups of patients: Group 1 comprised 68 patients with meningoencephalitis, and Group 2 comprised 52 children with a confirmed peripheral infection and no central nervous system involvement. We studied 606 CSF samples from neuropediatric patients who were classified into 3 groups: genetic diagnosis (A, acquired/unknown etiologic neurologic diseases (B and inflammatory-immune mediated processes (C. RESULTS: The CSF neopterin cut-off value was 61 nmol/L. Out of 606 cases, 56 presented a CSF neopterin level above this value. Group C had significantly higher CSF neopterin, protein and leukocyte values than the other groups. Sixteen of twenty-three patients in this group had a CSF neopterin level above the cut-off, whereas three and seven patients presented increased leukocyte and protein values, respectively. A significant association was found among CSF neopterin, proteins and leukocytes in the 606 patients. White matter disturbances were associated with high CSF neopterin concentrations. CONCLUSIONS: Although children with inflammatory-immune mediated processes presented higher CSF neopterin values, patients with other neurological disorders also showed increased CSF neopterin concentrations. These results stress the importance of CSF neopterin analysis for the identification of inflammatory-immune mediated processes.

  17. Development of Automated Production Line Processes for Solar Brightfield Modules: Annual Technical Progress Report, 1 January 2003 -- 30 June 2004

    Energy Technology Data Exchange (ETDEWEB)

    Nowlan, M. J.; Murach, J. M.; Sutherland, S. F.; Miller, D. C.; Moore, S. B.; Hogan, S. J.

    2005-06-01

    This report describes how Spire Corporation is addressing the PV Manufacturing R&D project goals of improving photovoltaic (PV) manufacturing processes and products while reducing costs and providing a technology foundation that supports significant manufacturing scale-up. To accomplish this, we are focusing our efforts on the design of a large-area utility-scale module and the development of the necessary manufacturing techniques and equipment to manufacture such a module in a high-volume production environment. A three-phase program is under way for developing and demonstrating new automated systems for fabricating very large PV modules ideal for use in multi-megawatt grid-connected applications. We designed a large-area 800 W module and we are developing associated module production equipment that will minimize the total installed system cost for utility-scale PV arrays. Unique features of the module design include a cantilevered glass superstrate to reduce the glass thickness a nd internally laminated bypass diodes that simplify internal busing and junction-box designs. Other program activities include the development of automation for solar cell string inspections, string busing, materials lay-up, and lamination; enhancements to the lamination process; and performance testing of large-area modules.

  18. Implementation of thermoelectric module for cooling process of microscale experimental room

    Science.gov (United States)

    Gołebiowska, Justyna; Żelazna, Agnieszka; Zioło, Paweł

    2017-08-01

    Thermoelectric modules, also known as Peltier modules, are used for cooling small devices and also, according to literature, in refrigeration. They can be an alternative to conventional refrigeration systems based on the use of compressors chillers powered by AC power. Peltier modules are powered by direct current (DC), which allows to power them directly supply by photovoltaic modules. In this paper operation of thermoelectric module used for cooling experimental room of cubature 0.125 m3 is presented. The study involves investigation of temperatures achieved on the cold and hot sides of module and inside the experimental room depending on the values of module supplying current. These studies provide an introduction to the assessment of the influence of different methods of heat removal on the hot side of thermoelectric module on cooling efficiency of whole system.

  19. Proton Induced Modulation of ICT and PET Processes in an Imidazo-phenanthroline Based BODIPY Fluorophores.

    Science.gov (United States)

    Thakare, Shrikant S; Chakraborty, Goutam; Kothavale, Shantaram; Mula, Soumyaditya; Ray, Alok K; Sekar, Nagaiyan

    2017-11-01

    BODIPY fluorophores linked with an imidazo-phenanthroline donor at α and β positions have been synthesized. Intriguing intramolecular charge transfer phenomenon is observed in both the dyes which has been extensively investigated using UV-vis absorption, steady-state and time-resolved fluorescence measurements. H-bonding and intrinsic polarity of the solvents has modulated the absorption and emission bands of these fluorophores strongly causing significant increase in the Stokes shifts. In spite of having difference only in terms of the position of donor subunit, the photophysics of these dyes are not only significantly different from each other, but contradictory too. Interestingly, acidochromic studies revealed the shuttling mechanism between ICT and PET processes for BDP 2. Quantum chemical calculations have been employed further to support experimental findings. DFT and TD-DFT method of analysis have been used to optimize ground and excited state geometries of the synthesized dyes.

  20. Lobster eye X-ray optics: Data processing from two 1D modules

    Science.gov (United States)

    Nentvich, O.; Urban, M.; Stehlikova, V.; Sieger, L.; Hudec, R.

    2017-07-01

    The X-ray imaging is usually done by Wolter I telescopes. They are suitable for imaging of a small part of the sky, not for all-sky monitoring. This monitoring could be done by a Lobster eye optics which can theoretically have a field of view up to 360 deg. All sky monitoring system enables a quick identification of source and its direction. This paper describes the possibility of using two independent one-dimensional Lobster Eye modules for this purpose instead of Wolter I and their post-processing into an 2D image. This arrangement allows scanning with less energy loss compared to Wolter I or two-dimensional Lobster Eye optics. It is most suitable especially for very weak sources.

  1. Top3 processes recombination intermediates and modulates checkpoint activity after DNA damage

    DEFF Research Database (Denmark)

    Mankouri, Hocine W; Hickson, Ian D

    2006-01-01

    Mutation of TOP3 in Saccharomyces cerevisiae causes poor growth, hyperrecombination, and a failure to fully activate DNA damage checkpoints in S phase. Here, we report that overexpression of a dominant-negative allele of TOP3, TOP3(Y356F), which lacks the catalytic (decatenation) activity of Top3......, the catalytic activity of Top3 is not required for DNA damage checkpoint activation, but it is required for normal S-phase progression after DNA damage. We also present evidence that the checkpoint-mediated cell cycle delay and persistence of X-shaped DNA molecules resulting from overexpression of TOP3(Y356F......) are downstream of Rad51 function. We propose that Top3 functions in S phase to both process homologous recombination intermediates and modulate checkpoint activity....

  2. Chitosan drives anti-inflammatory macrophage polarisation and pro-inflammatory dendritic cell stimulation

    Directory of Open Access Journals (Sweden)

    MI Oliveira

    2012-07-01

    Full Text Available Macrophages and dendritic cells (DC share the same precursor and play key roles in immunity. Modulation of their behaviour to achieve an optimal host response towards an implanted device is still a challenge. Here we compare the differentiation process and polarisation of these related cell populations and show that they exhibit different responses to chitosan (Ch, with human monocyte-derived macrophages polarising towards an anti-inflammatory phenotype while their DC counterparts display pro-inflammatory features. Macrophages and DC, whose interactions with biomaterials are frequently analysed using fully differentiated cells, were cultured directly on Ch films, rather than exposed to the polymer after complete differentiation. Ch was the sole stimulating factor and activated both macrophages and DC, without leading to significant T cell proliferation. After 10 d on Ch, macrophages significantly down-regulated expression of pro-inflammatory markers, CD86 and MHCII. Production of pro-inflammatory cytokines, particularly TNF-α, decreased with time for cells cultured on Ch, while anti-inflammatory IL-10 and TGF-β1, significantly increased. Altogether, these results suggest an M2c polarisation. Also, macrophage matrix metalloproteinase activity was augmented and cell motility was stimulated by Ch. Conversely, DC significantly enhanced CD86 expression, reduced IL-10 secretion and increased TNF-α and IL-1β levels. Our findings indicate that cells with a common precursor may display different responses, when challenged by the same biomaterial. Moreover, they help to further comprehend macrophage/DC interactions with Ch and the balance between pro- and anti-inflammatory signals associated with implant biomaterials. We propose that an overall pro-inflammatory reaction may hide the expression of anti-inflammatory cytokines, likely relevant for tissue repair/regeneration.

  3. Module generator of plans for dynamic processes; Modulo generdor de planes para procesos dinamicos

    Energy Technology Data Exchange (ETDEWEB)

    Reyes B, Alberto; Fernandez J, Jose L [Instituto de Investigaciones Electricas, Cuernavaca, Morelos (Mexico)

    2002-07-01

    This work describes the generating module of plans (Geplan) as a part of the project: Development of Techniques of Intelligent Planning for Dynamic Processes, based on techniques of artificial intelligence, and that is being developed in the Gerencia de Control e Instrumentacion the Instituto de Investigaciones Electricas (IIE). The study case corresponds to the elaboration of a plan to help the plant operators in the task of taking a combined cycle central (CCC) to a stable state of operation given a specific load level. The architecture of the module generator of plans is presented and the codification of the actions allowed (ACT) is illustrated by means of rules, in addition the challenges that are due to face so that the system operates in line with the process. Also the technical aspects of the generator of plans, as well as the benefits and expectations of their use in any CCC are mentioned. [Spanish] En este trabajo se describe el modulo generador de planes (Geplan) como parte del proyecto Desarrollo de Tecnicas de Planificacion Inteligente para Procesos Dinamicos, basado en tecnicas de inteligencia Artificial, y que estan desarrollandose en la Gerencia de Control e Instrumentacion del Instituto de Investigaciones Electrica (IIE). El caso de estudio corresponde a la elaboracion de un plan para asistir a los operadores de planta en la tarea de llevar una central de ciclo combinado (CCC) a un estado estable de operacion dedo un nivel de carga especifico. Se presenta la arquitectura del modulo generador de planes y se ilustra la codificacion de las acciones permitidas (ACT) mediante reglas, ademas los retos que se deben enfrentar para que el sistema opere en linea con el proceso. Tambien se mencionan los aspectos tecnicos del generador de planes, asi como los beneficios y expectativas de su uso en cualquier CCC.

  4. Task and spatial frequency modulations of object processing: an EEG study.

    Directory of Open Access Journals (Sweden)

    Matt Craddock

    Full Text Available Visual object processing may follow a coarse-to-fine sequence imposed by fast processing of low spatial frequencies (LSF and slow processing of high spatial frequencies (HSF. Objects can be categorized at varying levels of specificity: the superordinate (e.g. animal, the basic (e.g. dog, or the subordinate (e.g. Border Collie. We tested whether superordinate and more specific categorization depend on different spatial frequency ranges, and whether any such dependencies might be revealed by or influence signals recorded using EEG. We used event-related potentials (ERPs and time-frequency (TF analysis to examine the time course of object processing while participants performed either a grammatical gender-classification task (which generally forces basic-level categorization or a living/non-living judgement (superordinate categorization on everyday, real-life objects. Objects were filtered to contain only HSF or LSF. We found a greater positivity and greater negativity for HSF than for LSF pictures in the P1 and N1 respectively, but no effects of task on either component. A later, fronto-central negativity (N350 was more negative in the gender-classification task than the superordinate categorization task, which may indicate that this component relates to semantic or syntactic processing. We found no significant effects of task or spatial frequency on evoked or total gamma band responses. Our results demonstrate early differences in processing of HSF and LSF content that were not modulated by categorization task, with later responses reflecting such higher-level cognitive factors.

  5. Task and spatial frequency modulations of object processing: an EEG study.

    Science.gov (United States)

    Craddock, Matt; Martinovic, Jasna; Müller, Matthias M

    2013-01-01

    Visual object processing may follow a coarse-to-fine sequence imposed by fast processing of low spatial frequencies (LSF) and slow processing of high spatial frequencies (HSF). Objects can be categorized at varying levels of specificity: the superordinate (e.g. animal), the basic (e.g. dog), or the subordinate (e.g. Border Collie). We tested whether superordinate and more specific categorization depend on different spatial frequency ranges, and whether any such dependencies might be revealed by or influence signals recorded using EEG. We used event-related potentials (ERPs) and time-frequency (TF) analysis to examine the time course of object processing while participants performed either a grammatical gender-classification task (which generally forces basic-level categorization) or a living/non-living judgement (superordinate categorization) on everyday, real-life objects. Objects were filtered to contain only HSF or LSF. We found a greater positivity and greater negativity for HSF than for LSF pictures in the P1 and N1 respectively, but no effects of task on either component. A later, fronto-central negativity (N350) was more negative in the gender-classification task than the superordinate categorization task, which may indicate that this component relates to semantic or syntactic processing. We found no significant effects of task or spatial frequency on evoked or total gamma band responses. Our results demonstrate early differences in processing of HSF and LSF content that were not modulated by categorization task, with later responses reflecting such higher-level cognitive factors.

  6. Operational applications of a process-based runoff generation module on the Swiss Plateau and Prealps

    Science.gov (United States)

    Horat, Christoph; Antonetti, Manuel; Wernli, Heini; Zappa, Massimiliano

    2017-04-01

    Flash floods evolve rapidly during and after heavy precipitation events and represent a risk for society, especially in mountainous areas. Knowledge on meteorological variables and their temporal development is often not sufficient to predict their occurrence. Therefore, information about the state of the hydrological system derived from hydrological models is used. These models rely however on strong simplifying assumptions and need therefore to be calibrated. This prevents their application on catchments, where no runoff data is available. Here we present a flash-flood forecasting chain including: (i) a nowcasting product which combines radar and rain gauge rainfall data (CombiPrecip), (ii) meteorological data from numerical weather prediction models at currently finest available resolution (COSMO-1, COSMO-E), (iii) operationally available soil moisture estimations from the PREVAH hydrological model, and (iv) a process-based runoff generation module with no need for calibration (RGM-PRO). This last component uses information on the spatial distribution of dominant runoff processes (DRPs) which can be derived with different mapping approaches, and is parameterised a priori based on expert knowledge. First, we compared the performance of RGM-PRO with the one of a traditional conceptual runoff generation module for several events on Swiss Emme catchment, as well as on their nested catchments. Different DRP-maps are furthermore tested to evaluate the sensitivity of the forecasting chain to the mapping approaches. Then, we benchmarked the new forecasting chain with the traditional chain used on the Swiss Verzasca catchment. The results show that RGM-PRO performs similarly or even better than the traditional calibrated conceptual module on the investigated catchments. The use of strongly simplified DRP mapping approaches still leads to satisfying results, due mainly to the fact that the largest uncertainty source is represented by the meteorological input data. On the

  7. The anti-inflammatory effects of the tellurium redox modulating compound, AS101, are associated with regulation of NFκB signaling pathway and nitric oxide induction in macrophages

    Directory of Open Access Journals (Sweden)

    Sredni Benjamin

    2010-01-01

    Full Text Available Abstract Background LPS-activated macrophages produce mediators which are involved in inflammation and tissue injury, and especially those associated with endotoxic shock. The non toxic tellurium compound ammonium tri-chloro(dioxoethylene-O,O'-tellurate, AS101, has been recently shown to exert profound anti-inflammatory properties in animal models, associated with its Te(IV redox chemistry. This study explores the anti-inflammatory properties of AS101 with respect to modulation of inflammatory cytokines production and regulation of iNOS transcription and expression in activated macrophages via targeting the NFkB complex. Results AS101 decreased production of IL-6 and in parallel down-regulated LPS-induced iNOS expression and NO secretion by macrophages. AS101 reduced IkB phosphorylation and degradation, and reduced NFkB nuclear translocalization, albeit these effects were exerted at different kinetics. Chromatin immunoprecipitation assays showed that AS101 treatment attenuated p50-subunit ability to bind DNA at the NFkB consensus site in the iNOS promotor following LPS induction. Conclusions Besides AS101, the investigation of therapeutic activities of other tellurium(IV compounds is scarce in the literature, although tellurium is the fourth most abundant trace element in the human body. Since IKK and NFkB may be regulated by thiol modifications, we may thus envisage, inview of our integrated results, that Te(IV compounds, may have important roles in thiol redox biological activity in the human body and represent a new class of anti-inflammatory compounds.

  8. Flexible organic tandem solar modules with 6% efficiency: combining roll-to-roll compatible processing with high geometric fill factors

    DEFF Research Database (Denmark)

    Spyropoulos, G. D.; Kubis, P.; Li, Na

    2014-01-01

    Organic solar cell technology bears the potential for high photovoltaic performance combined with truly low-cost, high-volume processing. Here we demonstrate organic tandem solar modules on flexible substrates fabricated by fully roll-to-roll compatible processing at temperatures...

  9. Modulation of human extrastriate visual processing by selective attention to colours and words.

    Science.gov (United States)

    Nobre, A C; Allison, T; McCarthy, G

    1998-07-01

    The present study investigated the effect of visual selective attention upon neural processing within functionally specialized regions of the human extrastriate visual cortex. Field potentials were recorded directly from the inferior surface of the temporal lobes in subjects with epilepsy. The experimental task required subjects to focus attention on words from one of two competing texts. Words were presented individually and foveally. Texts were interleaved randomly and were distinguishable on the basis of word colour. Focal field potentials were evoked by words in the posterior part of the fusiform gyrus. Selective attention strongly modulated long-latency potentials evoked by words. The attention effect co-localized with word-related potentials in the posterior fusiform gyrus, and was independent of stimulus colour. The results demonstrated that stimuli receive differential processing within specialized regions of the extrastriate cortex as a function of attention. The late onset of the attention effect and its co-localization with letter string-related potentials but not with colour-related potentials recorded from nearby regions of the fusiform gyrus suggest that the attention effect is due to top-down influences from downstream regions involved in word processing.

  10. Waste Receiving and Processing Facility Module 1: Volume 1, Preliminary Design report

    International Nuclear Information System (INIS)

    1992-03-01

    The Preliminary Design Report (Title 1) for the Waste Receiving and Processing (WRAP) Module 1 provides a comprehensive narrative description of the proposed facility and process systems, the basis for each of the systems design, and the engineering assessments that were performed to support the technical basis of the Title 1 design. The primary mission of the WRAP 1 Facility is to characterize and certify contact-handled (CH) waste in 55-gallon drums for disposal. Its secondary function is to certify CH waste in Standard Waste Boxes (SWBs) for disposal. The preferred plan consist of retrieving the waste and repackaging as necessary in the Waste Receiving and Processing (WRAP) facility to certify TRU waste for shipment to the Waste Isolation Pilot Plant (WIPP) in New Mexico. WIPP is a research and development facility designed to demonstrate the safe and environmentally acceptable disposal of TRU waste from National Defense programs. Retrieved waste found to be Low-Level Waste (LLW) after examination in the WRAP facility will be disposed of on the Hanford site in the low-level waste burial ground. The Hanford Site TRU waste will be shipped to the WIPP for disposal between 1999 and 2013

  11. How does experience modulate auditory spatial processing in individuals with blindness?

    Science.gov (United States)

    Tao, Qian; Chan, Chetwyn C H; Luo, Yue-jia; Li, Jian-jun; Ting, Kin-hung; Wang, Jun; Lee, Tatia M C

    2015-05-01

    Comparing early- and late-onset blindness in individuals offers a unique model for studying the influence of visual experience on neural processing. This study investigated how prior visual experience would modulate auditory spatial processing among blind individuals. BOLD responses of early- and late-onset blind participants were captured while performing a sound localization task. The task required participants to listen to novel "Bat-ears" sounds, analyze the spatial information embedded in the sounds, and specify out of 15 locations where the sound would have been emitted. In addition to sound localization, participants were assessed on visuospatial working memory and general intellectual abilities. The results revealed common increases in BOLD responses in the middle occipital gyrus, superior frontal gyrus, precuneus, and precentral gyrus during sound localization for both groups. Between-group dissociations, however, were found in the right middle occipital gyrus and left superior frontal gyrus. The BOLD responses in the left superior frontal gyrus were significantly correlated with accuracy on sound localization and visuospatial working memory abilities among the late-onset blind participants. In contrast, the accuracy on sound localization only correlated with BOLD responses in the right middle occipital gyrus among the early-onset counterpart. The findings support the notion that early-onset blind individuals rely more on the occipital areas as a result of cross-modal plasticity for auditory spatial processing, while late-onset blind individuals rely more on the prefrontal areas which subserve visuospatial working memory.

  12. Metallothionein as an Anti-Inflammatory Mediator

    Directory of Open Access Journals (Sweden)

    Ken-ichiro Inoue

    2009-01-01

    Full Text Available The integration of knowledge concerning the regulation of MT, a highly conserved, low molecular weight, cystein-rich metalloprotein, on its proposed functions is necessary to clarify how MT affects cellular processes. MT expression is induced/enhanced in various tissues by a number of physiological mediators. The cellular accumulation of MT depends on the availability of cellular zinc derived from the diet. MT modulates the binding and exchange/transport of heavy metals such as zinc, cadmium, or copper under physiological conditions and cytoprotection from their toxicities, and the release of gaseous mediators such as hydroxyl radicals or nitric oxide. In addition, MT reportedly affects a number of cellular processes, such as gene expression, apoptosis, proliferation, and differentiation. Given the genetic approach, the apparently healthy status of MT-deficient mice argues against an essential biological role for MT; however, this molecule may be critical in cells/tissues/organs in times of stress, since MT expression is also evoked/enhanced by various stresses. In particular, because metallothionein (MT is induced by inflammatory stress, its roles in inflammation are implied. Also, MT expression in various organs/tissues can be enhanced by inflammatory stimuli, implicating in inflammatory diseases. In this paper, we review the role of MT of various inflammatory conditions.

  13. Therapeutic effects of date fruits (Phoenix dactylifera) in the prevention of diseases via modulation of anti-inflammatory, anti-oxidant and anti-tumour activity.

    Science.gov (United States)

    Rahmani, Arshad H; Aly, Salah M; Ali, Habeeb; Babiker, Ali Y; Srikar, Sauda; Khan, Amjad A

    2014-01-01

    The current mode of treatment of various diseases based on synthetic drugs is expensive, alters genetic and metabolic pathways and also shows adverse side effects. Thus, safe and effective approach is needed to prevent the diseases development and progression. In this vista, Natural products are good remedy in the treatment/management of diseases and they are affordable and effective without any adverse effects. Dates are main fruit in the Arabian Peninsula and are considered to be one of the most significant commercial crops and also have been documented in Holy Quran and modern scientific literatures. Earlier studies have shown that constituents of dates act as potent antioxidant, anti-tumour as well as anti-inflammatory, provide a suitable alternative therapy in various diseases cure. In this review, dates fruits has medicinal value are summarized in terms of therapeutic implications in the diseases control through anti-oxidant, anti-inflammatory, anti-tumour and ant-diabetic effect.

  14. Triterpenoid herbal saponins enhance beneficial bacteria, decrease sulfate-reducing bacteria, modulate inflammatory intestinal microenvironment and exert cancer preventive effects in ApcMin/+ mice

    Science.gov (United States)

    Chen, Lei; Brar, Manreetpal S.; Leung, Frederick C. C.; Hsiao, W. L. Wendy

    2016-01-01

    Saponins derived from medicinal plants have raised considerable interest for their preventive roles in various diseases. Here, we investigated the impacts of triterpenoid saponins isolated from Gynostemma pentaphyllum (GpS) on gut microbiome, mucosal environment, and the preventive effect on tumor growth. Six-week old ApcMin/+ mice and their wild-type littermates were fed either with vehicle or GpS daily for the duration of 8 weeks. The fecal microbiome was analyzed by enterobacterial repetitive intergenic consensus (ERIC)-PCR and 16S rRNA gene pyrosequencing. Study showed that GpS treatment significantly reduced the number of intestinal polyps in a preventive mode. More importantly, GpS feeding strikingly reduced the sulfate-reducing bacteria lineage, which are known to produce hydrogen sulfide and contribute to damage the intestinal epithelium or even promote cancer progression. Meanwhile, GpS also boosted the beneficial microbes. In the gut barrier of the ApcMin/+ mice, GpS treatment increased Paneth and goblet cells, up-regulated E-cadherin and down-regulated N-cadherin. In addition, GpS decreased the pro-oncogenic β-catenin, p-Src and the p-STAT3. Furthermore, GpS might also improve the inflamed gut epithelium of the ApcMin/+ mice by upregulating the anti-inflammatory cytokine IL-4, while downregulating pro-inflammatory cytokines TNF-β, IL-1β and IL-18. Intriguingly, GpS markedly stimulated M2 and suppressed M1 macrophage markers, indicating that GpS altered mucosal cytokine profile in favor of the M1 to M2 macrophages switching, facilitating intestinal tissue repair. In conclusion, GpS might reverse the host's inflammatory phenotype by increasing beneficial bacteria, decreasing sulfate-reducing bacteria, and alleviating intestinal inflammatory gut environment, which might contribute to its cancer preventive effects. PMID:27121311

  15. The influence of vitamin D analogs on calcification modulators, N-terminal pro-B-type natriuretic peptide and inflammatory markers in hemodialysis patients

    DEFF Research Database (Denmark)

    Hansen, Ditte; Rasmussen, Knud; Rasmussen, Lars M

    2014-01-01

    BACKGROUND: The risk of cardiovascular disease is tremendously high in dialysis patients. Dialysis patients treated with vitamin D analogs show decreased cardiovascular morbidity and mortality compared with untreated patients. We examined the influence of two common vitamin D analogs, alfacalcidol...... and paricalcitol, on important cardiovascular biomarkers in hemodialysis patients. Anti-inflammatory effects and the influence on regulators of vascular calcification as well as markers of heart failure were examined. METHODS: In 57 chronic hemodialysis patients enrolled in a randomized crossover trial comparing...

  16. Interhemispheric connectivity influences the degree of modulation of TMS-induced effects during auditory processing

    Directory of Open Access Journals (Sweden)

    Jamila eAndoh

    2011-07-01

    Full Text Available Repetitive TMS (rTMS has been shown to interfere with many components of language processing, including semantic, syntactic and phonologic. However, not much is known about its effects on primary auditory processing, especially its action on Heschl’s gyrus (HG. We aimed to investigate the behavioural and neural basis of rTMS during a melody processing task, while targeting the left HG, the right HG and the Vertex as a control site. Response Times (RT were normalized relative to the baseline-rTMS (Vertex and expressed as percentage change from baseline (%RT change. We also looked at sex differences in rTMS-induced response as well as in functional connectivity during melody processing using rTMS and functional Magnetic Resonance Imaging (fMRI.Functional MRI results showed an increase in the right HG compared with the left HG during the melody task, as well as sex differences in functional connectivity indicating a greater interhemispheric connectivity between left and right HG in females compared with males. TMS results showed that 10Hz-rTMS targeting the right HG induced differential effects according to sex, with a facilitation of performance in females and an impairment of performance in males. We also found a differential correlation between the %RT change after 10Hz-rTMS targeting the right HG and the interhemispheric functional connectivity between right and left HG, indicating that an increase in interhemispheric functional connectivity was associated with a facilitation of performance. This is the first study to report a differential rTMS-induced interference with melody processing depending on sex. In addition, we showed a relationship between the interference induced by rTMS on behavioral performance and the neural activity in the network connecting left and right HG, suggesting that the interhemispheric functional connectivity could determine the degree of modulation of behavioral performance.

  17. [Statistical process control applied to intensity modulated radiotherapy pretreatment controls with portal dosimetry].

    Science.gov (United States)

    Villani, N; Gérard, K; Marchesi, V; Huger, S; François, P; Noël, A

    2010-06-01

    The first purpose of this study was to illustrate the contribution of statistical process control for a better security in intensity modulated radiotherapy (IMRT) treatments. This improvement is possible by controlling the dose delivery process, characterized by pretreatment quality control results. So, it is necessary to put under control portal dosimetry measurements (currently, the ionisation chamber measurements were already monitored by statistical process control thanks to statistical process control tools). The second objective was to state whether it is possible to substitute ionisation chamber with portal dosimetry in order to optimize time devoted to pretreatment quality control. At Alexis-Vautrin center, pretreatment quality controls in IMRT for prostate and head and neck treatments were performed for each beam of each patient. These controls were made with an ionisation chamber, which is the reference detector for the absolute dose measurement, and with portal dosimetry for the verification of dose distribution. Statistical process control is a statistical analysis method, coming from industry, used to control and improve the studied process quality. It uses graphic tools as control maps to follow-up process, warning the operator in case of failure, and quantitative tools to evaluate the process toward its ability to respect guidelines: this is the capability study. The study was performed on 450 head and neck beams and on 100 prostate beams. Control charts, showing drifts, both slow and weak, and also both strong and fast, of mean and standard deviation have been established and have shown special cause introduced (manual shift of the leaf gap of the multileaf collimator). Correlation between dose measured at one point, given with the EPID and the ionisation chamber has been evaluated at more than 97% and disagreement cases between the two measurements were identified. The study allowed to demonstrate the feasibility to reduce the time devoted to

  18. Statistical process control applied to intensity modulated radiotherapy pretreatment controls with portal dosimetry

    International Nuclear Information System (INIS)

    Villani, N.; Noel, A.; Villani, N.; Gerard, K.; Marchesi, V.; Huger, S.; Noel, A.; Francois, P.

    2010-01-01

    Purpose The first purpose of this study was to illustrate the contribution of statistical process control for a better security in intensity modulated radiotherapy (I.M.R.T.) treatments. This improvement is possible by controlling the dose delivery process, characterized by pretreatment quality control results. So, it is necessary to put under control portal dosimetry measurements (currently, the ionisation chamber measurements were already monitored by statistical process control thanks to statistical process control tools). The second objective was to state whether it is possible to substitute ionisation chamber with portal dosimetry in order to optimize time devoted to pretreatment quality control. Patients and methods At Alexis-Vautrin center, pretreatment quality controls in I.M.R.T. for prostate and head and neck treatments were performed for each beam of each patient. These controls were made with an ionisation chamber, which is the reference detector for the absolute dose measurement, and with portal dosimetry for the verification of dose distribution. Statistical process control is a statistical analysis method, coming from industry, used to control and improve the studied process quality. It uses graphic tools as control maps to follow-up process, warning the operator in case of failure, and quantitative tools to evaluate the process toward its ability to respect guidelines: this is the capability study. The study was performed on 450 head and neck beams and on 100 prostate beams. Results Control charts, showing drifts, both slow and weak, and also both strong and fast, of mean and standard deviation have been established and have shown special cause introduced (manual shift of the leaf gap of the multi-leaf collimator). Correlation between dose measured at one point, given with the E.P.I.D. and the ionisation chamber has been evaluated at more than 97% and disagreement cases between the two measurements were identified. Conclusion The study allowed to

  19. Anti-inflammatory properties of clovamide and Theobroma cacao phenolic extracts in human monocytes: evaluation of respiratory burst, cytokine release, NF-κB activation, and PPARγ modulation.

    Science.gov (United States)

    Zeng, Huawu; Locatelli, Monica; Bardelli, Claudio; Amoruso, Angela; Coisson, Jean Daniel; Travaglia, Fabiano; Arlorio, Marco; Brunelleschi, Sandra

    2011-05-25

    There is a great interest in the potential health benefits of biologically active phenolic compounds in cocoa (Theobroma cacao) and dark chocolate. We investigated the anti-inflammatory potential of clovamide (a N-phenylpropenoyl-L-amino acid amide present in cocoa beans) and two phenolic extracts from unroasted and roasted cocoa beans, by evaluating superoxide anion (O(2)(-)) production, cytokine release, and NF-κB activation in human monocytes stimulated by phorbol 12-myristate 13-acetate (PMA). The effects of rosmarinic acid are shown for comparison. Clovamide and rosmarinic acid inhibited PMA-induced O(2)(-) production and cytokine release (with a bell-shaped curve and maximal inhibition at 10-100 nM), as well as PMA-induced NF-κB activation; the two cocoa extracts were less effective. In all tests, clovamide was the most potent compound and also enhanced peroxisome proliferator-activated receptor-γ (PPARγ) activity, which may exert anti-inflammatory effects. These findings indicate clovamide as a possible bioactive compound with anti-inflammatory activity in human cells.

  20. BUILING THE INFLAMMATORY PROCESS IN BRONCHES AT THE PHASE OF PATIENTS REHABILITATION WITH PROFESSIONAL CHRONIC OBSTRUCTIVE LUNG DISEASE

    Directory of Open Access Journals (Sweden)

    Раиса Васильевна Гордеева

    2017-10-01

    Conclusions. In case of exacerbation of occupational COPD at the stage of rehabilitation for rapid relief of inflammation of the mucosa of respiratory tract, it is advisable to prescribe Miramistin inhalation, laser therapy and SMC- phoresis of Miramistin. The proposed sequence of the application of physical factors contributes to the recovery of the protection of the mucosa of the respiratory tract and as a result an anti-inflammatory effect is manifested.

  1. Multi-Gigahertz radar range processing of baseband and RF carrier modulated signals in Tm:YAG

    International Nuclear Information System (INIS)

    Merkel, K.D.; Krishna Mohan, R.; Cole, Z.; Chang, T.; Olson, A.; Babbitt, W.R.

    2004-01-01

    An optical device is described and demonstrated that uses a spatial-spectral holographic material to perform coherent signal processing operations on analog, high-bandwidth optical signals with large time-bandwidth-products. Signal processing is performed as the material records the coherent spectral interference (or cross-power spectrum) of modulated optical signals as a spatial-spectral population grating between electronic transition states. Multiple exposures of processing pulse sequences are integrated with increasing grating strength. The device, coined as the Spatial-Spectral Coherent Holographic Integrating Processor (or S 2 -CHIP), is described as currently envisioned for a broadband, mid-to-high pulse repetition frequency range-Doppler radar signal processing system. Experiments were performed in Tm:YAG (0.1 at% at 5 K) to demonstrate time delay variation, integration dynamics, and effects of coding as applied to a radar range processor. These demonstrations used baseband modulation with a 1 gigabit per second (GPBS) bit rate and code length of 512 bits (512 ns), where delays up to 1.0 μs were resolved with greater than a 40 dB peak to RMS sidelobe ratio after 800 processing shots. Multi-GHz processing was demonstrated using a bit rate of 2.5 GBPS (baseband modulation) and code length of 2048 bits (819.2 ns). Processing of double-sideband modulated signals on a radio frequency (RF) carrier was demonstrated, where 512 bit, 1.0 GBPS codes were modulated on a 1.75 GHz carrier and then modulated on the optical carrier

  2. Modelling of processes occurring in deep geological repository - development of new modules in the GoldSim environment

    International Nuclear Information System (INIS)

    Vopalka, D.; Lukin, D.; Vokal, A.

    2006-01-01

    Three new modules modelling the processes that occur in a deep geological repository have been prepared in the GoldSim computer code environment (using its Transport Module). These modules help to understand the role of selected parameters in the near-field region of the final repository and to prepare an own complex model of the repository behaviour. The source term module includes radioactive decay and ingrowth in the canister, first order degradation of fuel matrix, solubility limitation of the concentration of the studied nuclides, and diffusive migration through the surrounding bentonite layer controlled by the output boundary condition formulated with respect to the rate of water flow in the rock. The corrosion module describes corrosion of canisters made of carbon steel and transport of corrosion products in the near-field region. This module computes balance equations between dissolving species and species transported by diffusion and/or advection from the surface of a solid material. The diffusion module that includes also non-linear form of the interaction isotherm can be used for an evaluation of small-scale diffusion experiments. (author)

  3. Modelling of processes occurring in deep geological repository - Development of new modules in the GoldSim environment

    Science.gov (United States)

    Vopálka, D.; Lukin, D.; Vokál, A.

    2006-01-01

    Three new modules modelling the processes that occur in a deep geological repository have been prepared in the GoldSim computer code environment (using its Transport Module). These modules help to understand the role of selected parameters in the near-field region of the final repository and to prepare an own complex model of the repository behaviour. The source term module includes radioactive decay and ingrowth in the canister, first order degradation of fuel matrix, solubility limitation of the concentration of the studied nuclides, and diffusive migration through the surrounding bentonite layer controlled by the output boundary condition formulated with respect to the rate of water flow in the rock. The corrosion module describes corrosion of canisters made of carbon steel and transport of corrosion products in the near-field region. This module computes balance equations between dissolving species and species transported by diffusion and/or advection from the surface of a solid material. The diffusion module that includes also non-linear form of the interaction isotherm can be used for an evaluation of small-scale diffusion experiments.

  4. Long chain polyunsaturated fatty acids (LCPUFAs) and nordihydroguaiaretic acid (NDGA) modulate metabolic and inflammatory markers in a spontaneous type 2 diabetes mellitus model (Stillman Salgado rats).

    Science.gov (United States)

    Dain, Alejandro; Repossi, Gaston; Diaz-Gerevini, Gustavo T; Vanamala, Jairam; Das, Undurti N; Eynard, Aldo R

    2016-11-25

    Diabetes mellitus (DM) is a complex disease with alterations in metabolic and inflammatory markers. Stillman Salgado rats (eSS) spontaneously develop type 2 DM by middle age showing progressive impairment of glucose tolerance with hyperglycemia, hypertriglyceridemia and hyperinsulinemia. We analyzed the effects of supplementation of ω-3 and ω-6 polyunsaturated fatty acids (PUFAs) with or without nordihydroguaiaretic acid (NDGA) added, an antioxidant and lipoxygenase inhibitor, on metabolic and inflammatory parameters in eSS rats to evaluate whether they can delay development and/or prevent progression of DM. After weaning, eSS rats received, intraperitoneally, once a month ω-3 (EPA 35% and DHA 40%-6.25 mg/Kg) or ω-6 (90% arachidonic acid- 6. 25 mg/Kg) for twelve months. Two additional groups of rats received 1.9 mg/kg NDGA added to ω-3 and ω-6 fatty acids. Blood samples were collected at day 40, and at the end of the 6th month and 12th month of age to determine plasma triglycerides (TGs), total plasma fatty acids (FA), A1C hemoglobin (HbA1C), C-reactive protein (CRP), gamma glutamyl transpeptidase (GGT), lipo and hydro peroxides, nitrites and IL-6 (in plasma and liver, kidney, and pancreas) and underwent oral glucose tolerance test (OGTT) as well. Wistar and eSS rats that received saline solution were used as controls. Plasma lipids profile, TG, fasting and post-prandial blood glucose levels, and glycosylated HbA1C showed significant improvements in ω-3 and ω-3 + NDGA treated animals compared to eSS control group. ω-3 and ω-3 + NDGA groups showed an inverse correlation with fasting blood glucose and showed lower plasma levels of GGT, TG, and CRP. eSS rats treated with ω-3 LCPUFAs showed reduced level of inflammatory and oxidative indices in plasma and liver, kidney and pancreas tissues in comparison with eSS control (non-treated) and ω-6 treated groups. eSS rats are a useful model to study type 2 DM pathophysiology and related inflammatory

  5. Amygdala modulation of memory-related processes in the hippocampus: potential relevance to PTSD.

    Science.gov (United States)

    Tsoory, M M; Vouimba, R M; Akirav, I; Kavushansky, A; Avital, A; Richter-Levin, G

    2008-01-01

    A key assumption in the study of stress-induced cognitive and neurobiological modifications is that alterations in hippocampal functioning after stress are due to an excessive activity exerted by the amygdala on the hippocampus. Research so far focused on stress-induced impairment of hippocampal plasticity and memory but an exposure to stress may simultaneously also result in strong emotional memories. In fact, under normal conditions emotionally charged events are better remembered compared with neutral ones. Results indicate that under these conditions there is an increase in activity within the amygdala that may lead to memory of a different quality. Studying the way emotionality activates the amygdala and the functional impact of this activation we found that the amygdala modulates memory-related processes in other brain areas, such as the hippocampus. However, this modulation is complex, involving both enhancing and suppressing effects, depending on the way the amygdala is activated and the hippocampal subregion examined. The current review summarizes our findings and attempts to put them in context with the impact of an exposure to a traumatic experience, in which there is a mixture of a strong memory of some aspects of the experience but impaired memory of other aspects of that experience. Toward that end, we have recently developed an animal model for the induction of predisposition to stress-related disorders, focusing on the consequences of exposure to stressors during juvenility on the ability to cope with stress in adulthood. Exposing juvenile-stressed rats to an additional stressful challenge in adulthood revealed their impairment to cope with stress and resulted in significant elevation of the amygdala. Interestingly, and similar to our electrophysiological findings, differential effects were observed between the impact of the emotional challenge on CA1 and dentate gyrus subregions of the hippocampus. Taken together, the results indicate that long

  6. Predicting speech intelligibility based on the signal-to-noise envelope power ratio after modulation-frequency selective processing

    DEFF Research Database (Denmark)

    Jørgensen, Søren; Dau, Torsten

    2011-01-01

    A model for predicting the intelligibility of processed noisy speech is proposed. The speech-based envelope power spectrum model has a similar structure as the model of Ewert and Dau [(2000). J. Acoust. Soc. Am. 108, 1181-1196], developed to account for modulation detection and masking data. The ...... process provides a key measure of speech intelligibility. © 2011 Acoustical Society of America.......A model for predicting the intelligibility of processed noisy speech is proposed. The speech-based envelope power spectrum model has a similar structure as the model of Ewert and Dau [(2000). J. Acoust. Soc. Am. 108, 1181-1196], developed to account for modulation detection and masking data....... The model estimates the speech-to-noise envelope power ratio, SNR env, at the output of a modulation filterbank and relates this metric to speech intelligibility using the concept of an ideal observer. Predictions were compared to data on the intelligibility of speech presented in stationary speech...

  7. Transcranial Electrical Stimulation over Dorsolateral Prefrontal Cortex Modulates Processing of Social Cognitive and Affective Information.

    Directory of Open Access Journals (Sweden)

    Massimiliano Conson

    Full Text Available Recent neurofunctional studies suggested that lateral prefrontal cortex is a domain-general cognitive control area modulating computation of social information. Neuropsychological evidence reported dissociations between cognitive and affective components of social cognition. Here, we tested whether performance on social cognitive and affective tasks can be modulated by transcranial direct current stimulation (tDCS over dorsolateral prefrontal cortex (DLPFC. To this aim, we compared the effects of tDCS on explicit recognition of emotional facial expressions (affective task, and on one cognitive task assessing the ability to adopt another person's visual perspective. In a randomized, cross-over design, male and female healthy participants performed the two experimental tasks after bi-hemispheric tDCS (sham, left anodal/right cathodal, and right anodal/left cathodal applied over DLPFC. Results showed that only in male participants explicit recognition of fearful facial expressions was significantly faster after anodal right/cathodal left stimulation with respect to anodal left/cathodal right and sham stimulations. In the visual perspective taking task, instead, anodal right/cathodal left stimulation negatively affected both male and female participants' tendency to adopt another's point of view. These findings demonstrated that concurrent facilitation of right and inhibition of left lateral prefrontal cortex can speed-up males' responses to threatening faces whereas it interferes with the ability to adopt another's viewpoint independently from gender. Thus, stimulation of cognitive control areas can lead to different effects on social cognitive skills depending on the affective vs. cognitive nature of the task, and on the gender-related differences in neural organization of emotion processing.

  8. Evidence of functional connectivity between auditory cortical areas revealed by amplitude modulation sound processing.

    Science.gov (United States)

    Guéguin, Marie; Le Bouquin-Jeannès, Régine; Faucon, Gérard; Chauvel, Patrick; Liégeois-Chauvel, Catherine

    2007-02-01

    The human auditory cortex includes several interconnected areas. A better understanding of the mechanisms involved in auditory cortical functions requires a detailed knowledge of neuronal connectivity between functional cortical regions. In human, it is difficult to track in vivo neuronal connectivity. We investigated the interarea connection in vivo in the auditory cortex using a method of directed coherence (DCOH) applied to depth auditory evoked potentials (AEPs). This paper presents simultaneous AEPs recordings from insular gyrus (IG), primary and secondary cortices (Heschl's gyrus and planum temporale), and associative areas (Brodmann area [BA] 22) with multilead intracerebral electrodes in response to sinusoidal modulated white noises in 4 epileptic patients who underwent invasive monitoring with depth electrodes for epilepsy surgery. DCOH allowed estimation of the causality between 2 signals recorded from different cortical sites. The results showed 1) a predominant auditory stream within the primary auditory cortex from the most medial region to the most lateral one whatever the modulation frequency, 2) unidirectional functional connection from the primary to secondary auditory cortex, 3) a major auditory propagation from the posterior areas to the anterior ones, particularly at 8, 16, and 32 Hz, and 4) a particular role of Heschl's sulcus dispatching information to the different auditory areas. These findings suggest that cortical processing of auditory information is performed in serial and parallel streams. Our data showed that the auditory propagation could not be associated to a unidirectional traveling wave but to a constant interaction between these areas that could reflect the large adaptive and plastic capacities of auditory cortex. The role of the IG is discussed.

  9. Multi-channel logical circuit module used for high-speed, low amplitude signals processing and QDC gate signals generation

    International Nuclear Information System (INIS)

    Su Hong; Li Xiaogang; Zhu Haidong; Ma Xiaoli; Yin Weiwei; Li Zhuyu; Jin Genming; Wu Heyu

    2001-01-01

    A new kind of logical circuit will be introduced in brief. There are 16 independent channels in the module. The module receives low amplitude signals(≥40 mV), and processes them to amplify, shape, delay, sum and etc. After the processing each channel produces 2 pairs of ECL logical signal to feed the gate of QDC as the gate signal of QDC. The module consists of high-speed preamplifier unit, high-speed discriminate unit, delaying and shaping unit, summing unit and trigger display unit. The module is developed for 64 CH. 12 BIT Multi-event QDC. The impedance of QDC is 110 Ω. Each gate signal of QDC requires a pair of differential ECL level, Min. Gate width 30 ns and Max. Gate width 1 μs. It has showed that the outputs of logical circuit module satisfy the QDC requirements in experiment. The module can be used on data acquisition system to acquire thousands of data at high-speed ,high-density and multi-parameter, in heavy particle nuclear physics experiment. It also can be used to discriminate multi-coincidence events

  10. A negative feedback modulator of antigen processing evolved from a frameshift in the cowpox virus genome.

    Directory of Open Access Journals (Sweden)

    Jiacheng Lin

    2014-12-01

    Full Text Available Coevolution of viruses and their hosts represents a dynamic molecular battle between the immune system and viral factors that mediate immune evasion. After the abandonment of smallpox vaccination, cowpox virus infections are an emerging zoonotic health threat, especially for immunocompromised patients. Here we delineate the mechanistic basis of how cowpox viral CPXV012 interferes with MHC class I antigen processing. This type II membrane protein inhibits the coreTAP complex at the step after peptide binding and peptide-induced conformational change, in blocking ATP binding and hydrolysis. Distinct from other immune evasion mechanisms, TAP inhibition is mediated by a short ER-lumenal fragment of CPXV012, which results from a frameshift in the cowpox virus genome. Tethered to the ER membrane, this fragment mimics a high ER-lumenal peptide concentration, thus provoking a trans-inhibition of antigen translocation as supply for MHC I loading. These findings illuminate the evolution of viral immune modulators and the basis of a fine-balanced regulation of antigen processing.

  11. Dopamine modulates reward system activity during subconscious processing of sexual stimuli.

    Science.gov (United States)

    Oei, Nicole Y L; Rombouts, Serge Arb; Soeter, Roelof P; van Gerven, Joop M; Both, Stephanie

    2012-06-01

    Dopaminergic medication influences conscious processing of rewarding stimuli, and is associated with impulsive-compulsive behaviors, such as hypersexuality. Previous studies have shown that subconscious subliminal presentation of sexual stimuli activates brain areas known to be part of the 'reward system'. In this study, it was hypothesized that dopamine modulates activation in key areas of the reward system, such as the nucleus accumbens, during subconscious processing of sexual stimuli. Young healthy males (n=53) were randomly assigned to two experimental groups or a control group, and were administered a dopamine antagonist (haloperidol), a dopamine agonist (levodopa), or placebo. Brain activation was assessed during a backward-masking task with subliminally presented sexual stimuli. Results showed that levodopa significantly enhanced the activation in the nucleus accumbens and dorsal anterior cingulate when subliminal sexual stimuli were shown, whereas haloperidol decreased activations in those areas. Dopamine thus enhances activations in regions thought to regulate 'wanting' in response to potentially rewarding sexual stimuli that are not consciously perceived. This running start of the reward system might explain the pull of rewards in individuals with compulsive reward-seeking behaviors such as hypersexuality and patients who receive dopaminergic medication.

  12. Level of processing modulates the neural correlates of emotional memory formation

    Science.gov (United States)

    Ritchey, Maureen; LaBar, Kevin S.; Cabeza, Roberto

    2010-01-01

    Emotion is known to influence multiple aspects of memory formation, including the initial encoding of the memory trace and its consolidation over time. However, the neural mechanisms whereby emotion impacts memory encoding remain largely unexplored. The present study employed a levels-of-processing manipulation to characterize the impact of emotion on encoding with and without the influence of elaborative processes. Participants viewed emotionally negative, neutral, and positive scenes under two conditions: a shallow condition focused on the perceptual features of the scenes and a deep condition that queried their semantic meaning. Recognition memory was tested 2 days later. Results showed that emotional memory enhancements were greatest in the shallow condition. FMRI analyses revealed that the right amygdala predicted subsequent emotional memory in the shallow more than deep condition, whereas the right ventrolateral prefrontal cortex demonstrated the reverse pattern. Furthermore, the association of these regions with the hippocampus was modulated by valence: the amygdala-hippocampal link was strongest for negative stimuli, whereas the prefrontal-hippocampal link was strongest for positive stimuli. Taken together, these results suggest two distinct activation patterns underlying emotional memory formation: an amygdala component that promotes memory during shallow encoding, especially for negative information, and a prefrontal component that provides extra benefits during deep encoding, especially for positive information. PMID:20350176

  13. Modulation of induced gamma band activity in the human EEG by attention and visual information processing.

    Science.gov (United States)

    Müller, M M; Gruber, T; Keil, A

    2000-12-01

    Here we present a series of four studies aimed to investigate the link between induced gamma band activity in the human EEG and visual information processing. We demonstrated and validated the modulation of spectral gamma band power by spatial selective visual attention. When subjects attended to a certain stimulus, spectral power was increased as compared to when the same stimulus was ignored. In addition, we showed a shift in spectral gamma band power increase to the contralateral hemisphere when subjects shifted their attention to one visual hemifield. The following study investigated induced gamma band activity and the perception of a Gestalt. Ambiguous rotating figures were used to operationalize the law of good figure (gute Gestalt). We found increased gamma band power at posterior electrode sites when subjects perceived an object. In the last experiment we demonstrated a differential hemispheric gamma band activation when subjects were confronted with emotional pictures. Results of the present experiments in combination with other studies presented in this volume are supportive for the notion that induced gamma band activity in the human EEG is closely related to visual information processing and attentional perceptual mechanisms.

  14. Atmosphere Processing Module Automation and Catalyst Durability Analysis for Mars ISRU Pathfinder

    Science.gov (United States)

    Petersen, Elspeth M.

    2016-01-01

    The Mars In-Situ Resource Utilization Pathfinder was designed to create fuel using components found in the planet’s atmosphere and regolith for an ascension vehicle to return a potential sample return or crew return vehicle from Mars. The Atmosphere Processing Module (APM), a subunit of the pathfinder, uses cryocoolers to isolate and collect carbon dioxide from Mars simulant gas. The carbon dioxide is fed with hydrogen into a Sabatier reactor where methane is produced. The APM is currently undergoing the final stages of testing at Kennedy Space Center prior to process integration testing with the other subunits of the pathfinder. The automation software for the APM cryocoolers was tested and found to perform nominally. The catalyst used for the Sabatier reactor was investigated to determine the factors contributing to catalyst failure. The results from the catalyst testing require further analysis, but it appears that the rapid change in temperature during reactor start up or the elevated operating temperature is responsible for the changes observed in the catalyst.

  15. Level of processing modulates the neural correlates of emotional memory formation.

    Science.gov (United States)

    Ritchey, Maureen; LaBar, Kevin S; Cabeza, Roberto

    2011-04-01

    Emotion is known to influence multiple aspects of memory formation, including the initial encoding of the memory trace and its consolidation over time. However, the neural mechanisms whereby emotion impacts memory encoding remain largely unexplored. The present study used a levels-of-processing manipulation to characterize the impact of emotion on encoding with and without the influence of elaborative processes. Participants viewed emotionally negative, neutral, and positive scenes under two conditions: a shallow condition focused on the perceptual features of the scenes and a deep condition that queried their semantic meaning. Recognition memory was tested 2 days later. Results showed that emotional memory enhancements were greatest in the shallow condition. fMRI analyses revealed that the right amygdala predicted subsequent emotional memory in the shallow more than deep condition, whereas the right ventrolateral PFC demonstrated the reverse pattern. Furthermore, the association of these regions with the hippocampus was modulated by valence: the amygdala-hippocampal link was strongest for negative stimuli, whereas the prefrontal-hippocampal link was strongest for positive stimuli. Taken together, these results suggest two distinct activation patterns underlying emotional memory formation: an amygdala component that promotes memory during shallow encoding, especially for negative information, and a prefrontal component that provides extra benefits during deep encoding, especially for positive information.

  16. Statistical process control analysis for patient quality assurance of intensity modulated radiation therapy

    Science.gov (United States)

    Lee, Rena; Kim, Kyubo; Cho, Samju; Lim, Sangwook; Lee, Suk; Shim, Jang Bo; Huh, Hyun Do; Lee, Sang Hoon; Ahn, Sohyun

    2017-11-01

    This study applied statistical process control to set and verify the quality assurances (QA) tolerance standard for our hospital's characteristics with the criteria standards that are applied to all the treatment sites with this analysis. Gamma test factor of delivery quality assurances (DQA) was based on 3%/3 mm. Head and neck, breast, prostate cases of intensity modulated radiation therapy (IMRT) or volumetric arc radiation therapy (VMAT) were selected for the analysis of the QA treatment sites. The numbers of data used in the analysis were 73 and 68 for head and neck patients. Prostate and breast were 49 and 152 by MapCHECK and ArcCHECK respectively. C p value of head and neck and prostate QA were above 1.0, C pml is 1.53 and 1.71 respectively, which is close to the target value of 100%. C pml value of breast (IMRT) was 1.67, data values are close to the target value of 95%. But value of was 0.90, which means that the data values are widely distributed. C p and C pml of breast VMAT QA were respectively 1.07 and 2.10. This suggests that the VMAT QA has better process capability than the IMRT QA. Consequently, we should pay more attention to planning and QA before treatment for breast Radiotherapy.

  17. Social eye gaze modulates processing of speech and co-speech gesture.

    Science.gov (United States)

    Holler, Judith; Schubotz, Louise; Kelly, Spencer; Hagoort, Peter; Schuetze, Manuela; Özyürek, Aslı

    2014-12-01

    In human face-to-face communication, language comprehension is a multi-modal, situated activity. However, little is known about how we combine information from different modalities during comprehension, and how perceived communicative intentions, often signaled through visual signals, influence this process. We explored this question by simulating a multi-party communication context in which a speaker alternated her gaze between two recipients. Participants viewed speech-only or speech+gesture object-related messages when being addressed (direct gaze) or unaddressed (gaze averted to other participant). They were then asked to choose which of two object images matched the speaker's preceding message. Unaddressed recipients responded significantly more slowly than addressees for speech-only utterances. However, perceiving the same speech accompanied by gestures sped unaddressed recipients up to a level identical to that of addressees. That is, when unaddressed recipients' speech processing suffers, gestures can enhance the comprehension of a speaker's message. We discuss our findings with respect to two hypotheses attempting to account for how social eye gaze may modulate multi-modal language comprehension. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Differential preparation intervals modulate repetition processes in task switching: an ERP study

    Directory of Open Access Journals (Sweden)

    Min eWang

    2016-02-01

    Full Text Available In task-switching paradigms, reaction times (RTs switch cost (SC and the neural correlates underlying the SC are affected by different preparation intervals. However, little is known about the effect of the preparation interval on the repetition processes in task-switching. To examine this effect we utilized a cued task-switching paradigm with long sequences of repeated trials. Response-stimulus intervals (RSI and cue-stimulus intervals (CSI were manipulated in short and long conditions. Electroencephalography (EEG and behavioral data were recorded. We found that with increasing repetitions, RTs were faster in the short CSI conditions, while P3 amplitudes decreased in the LS (long RSI and short CSI conditions. Positive correlations between RT benefit and P3 activation decrease (repeat 1 minus repeat 5, and between the slope of the RT and P3 regression lines were observed only in the LS condition. Our findings suggest that differential preparation intervals modulate repetition processes in task switching.

  19. Emotion processing fails to modulate putative mirror neuron response to trained visuomotor associations.

    Science.gov (United States)

    Fitzgibbon, Bernadette M; Kirkovski, Melissa; Fornito, Alex; Paton, Bryan; Fitzgerald, Paul B; Enticott, Peter G

    2016-04-01

    Recent neuroimaging studies have demonstrated that activation of the putative human mirror neuron system (MNS) can be elicited via visuomotor training. This is generally interpreted as supporting an associative learning account of the mirror neuron system (MNS) that argues against the ontogeny of the MNS to be an evolutionary adaptation for social cognition. The current study assessed whether a central component of social cognition, emotion processing, would influence the MNS activity to trained visuomotor associations, which could support a broader role of the MNS in social cognition. Using functional magnetic resonance imaging (fMRI), we assessed repetition suppression to the presentation of stimulus pairs involving a simple hand action and a geometric shape that was either congruent or incongruent with earlier association training. Each pair was preceded by an image of positive, negative, or neutral emotionality. In support of an associative learning account of the MNS, repetition suppression was greater for trained pairs compared with untrained pairs in several regions, primarily supplementary motor area (SMA) and right inferior frontal gyrus (rIFG). This response, however, was not modulated by the valence of the emotional images. These findings argue against a fundamental role of emotion processing in the mirror neuron response, and are inconsistent with theoretical accounts linking mirror neurons to social cognition. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Shielding voices: The modulation of binding processes between voice features and response features by task representations.

    Science.gov (United States)

    Bogon, Johanna; Eisenbarth, Hedwig; Landgraf, Steffen; Dreisbach, Gesine

    2017-09-01

    Vocal events offer not only semantic-linguistic content but also information about the identity and the emotional-motivational state of the speaker. Furthermore, most vocal events have implications for our actions and therefore include action-related features. But the relevance and irrelevance of vocal features varies from task to task. The present study investigates binding processes for perceptual and action-related features of spoken words and their modulation by the task representation of the listener. Participants reacted with two response keys to eight different words spoken by a male or a female voice (Experiment 1) or spoken by an angry or neutral male voice (Experiment 2). There were two instruction conditions: half of participants learned eight stimulus-response mappings by rote (SR), and half of participants applied a binary task rule (TR). In both experiments, SR instructed participants showed clear evidence for binding processes between voice and response features indicated by an interaction between the irrelevant voice feature and the response. By contrast, as indicated by a three-way interaction with instruction, no such binding was found in the TR instructed group. These results are suggestive of binding and shielding as two adaptive mechanisms that ensure successful communication and action in a dynamic social environment.

  1. Seeing music: The perception of melodic 'ups and downs' modulates the spatial processing of visual stimuli.

    Science.gov (United States)

    Romero-Rivas, Carlos; Vera-Constán, Fátima; Rodríguez-Cuadrado, Sara; Puigcerver, Laura; Fernández-Prieto, Irune; Navarra, Jordi

    2018-05-10

    Musical melodies have "peaks" and "valleys". Although the vertical component of pitch and music is well-known, the mechanisms underlying its mental representation still remain elusive. We show evidence regarding the importance of previous experience with melodies for crossmodal interactions to emerge. The impact of these crossmodal interactions on other perceptual and attentional processes was also studied. Melodies including two tones with different frequency (e.g., E4 and D3) were repeatedly presented during the study. These melodies could either generate strong predictions (e.g., E4-D3-E4-D3-E4-[D3]) or not (e.g., E4-D3-E4-E4-D3-[?]). After the presentation of each melody, the participants had to judge the colour of a visual stimulus that appeared in a position that was, according to the traditional vertical connotations of pitch, either congruent (e.g., high-low-high-low-[up]), incongruent (high-low-high-low-[down]) or unpredicted with respect to the melody. Behavioural and electroencephalographic responses to the visual stimuli were obtained. Congruent visual stimuli elicited faster responses at the end of the experiment than at the beginning. Additionally, incongruent visual stimuli that broke the spatial prediction generated by the melody elicited larger P3b amplitudes (reflecting 'surprise' responses). Our results suggest that the passive (but repeated) exposure to melodies elicits spatial predictions that modulate the processing of other sensory events. Copyright © 2018 Elsevier Ltd. All rights reserved.

  2. Modulation of Female Genital Tract-Derived Dendritic Cell Migration and Activation in Response to Inflammatory Cytokines and Toll-Like Receptor Agonists.

    Science.gov (United States)

    Shey, Muki S; Maharaj, Niren; Archary, Derseree; Ngcapu, Sinaye; Garrett, Nigel; Abdool Karim, Salim; Passmore, Jo-Ann S

    2016-01-01

    HIV transmission across the genital mucosa is a major mode of new HIV infections in women. The probability of infection may be influenced by several factors including recruitment and activation of HIV target cells, such as dendritic cells (DCs) and cytokine production, associated with genital inflammation. We evaluated the role of inflammatory cytokines and TLR signaling in migration and activation of genital tract DCs in the human cervical explant model. Hysterectomy tissues from 10 HIV-negative and 7 HIV-positive donor women were separated into ecto- and endocervical explants, and incubated with inflammatory cytokines (TNF-α, IL-1β, IL-8, MIP-1β) or agonists for TLR4 (LPS), TLR2/1 (PAM3) and TLR7/8 (R848). Migration (frequency) and activation (HLA-DR expression) of myeloid and plasmacytoid DCs and Langerhans cells were measured by flow cytometry. We observed that cytokines, LPS and PAM3 induced activation of migrating myeloid and plasmacytoid DCs. LPS induced a 3.6 fold lower levels of migration of plasmacytoid DCs from HIV-infected women compared with HIV-uninfected women (median activation indices of 2.932 vs 0.833). There was however a 4.5 fold increase in migration of Langerhans cells in HIV-infected compared with HIV-uninfected women in response to cytokines (median activation indices of 3.539 vs 0.77). Only TLR agonists induced migration and activation of DCs from endocervical explants. Hormonal contraception use was associated with an increase in activation of DC subsets in the endo and ectocervical explants. We conclude that inflammatory signals in the female genital tract induced DC migration and activation, with possible important implications for HIV susceptibility of cervical tissues.

  3. Modulation of Female Genital Tract-Derived Dendritic Cell Migration and Activation in Response to Inflammatory Cytokines and Toll-Like Receptor Agonists.

    Directory of Open Access Journals (Sweden)

    Muki S Shey

    Full Text Available HIV transmission across the genital mucosa is a major mode of new HIV infections in women. The probability of infection may be influenced by several factors including recruitment and activation of HIV target cells, such as dendritic cells (DCs and cytokine production, associated with genital inflammation. We evaluated the role of inflammatory cytokines and TLR signaling in migration and activation of genital tract DCs in the human cervical explant model. Hysterectomy tissues from 10 HIV-negative and 7 HIV-positive donor women were separated into ecto- and endocervical explants, and incubated with inflammatory cytokines (TNF-α, IL-1β, IL-8, MIP-1β or agonists for TLR4 (LPS, TLR2/1 (PAM3 and TLR7/8 (R848. Migration (frequency and activation (HLA-DR expression of myeloid and plasmacytoid DCs and Langerhans cells were measured by flow cytometry. We observed that cytokines, LPS and PAM3 induced activation of migrating myeloid and plasmacytoid DCs. LPS induced a 3.6 fold lower levels of migration of plasmacytoid DCs from HIV-infected women compared with HIV-uninfected women (median activation indices of 2.932 vs 0.833. There was however a 4.5 fold increase in migration of Langerhans cells in HIV-infected compared with HIV-uninfected women in response to cytokines (median activation indices of 3.539 vs 0.77. Only TLR agonists induced migration and activation of DCs from endocervical explants. Hormonal contraception use was associated with an increase in activation of DC subsets in the endo and ectocervical explants. We conclude that inflammatory signals in the female genital tract induced DC migration and activation, with possible important implications for HIV susceptibility of cervical tissues.

  4. Silicon dioxide etching process for fabrication of micro-optics employing pulse-modulated electron-beam-excited plasma

    International Nuclear Information System (INIS)

    Takeda, Keigo; Ohta, Takayuki; Ito, Masafumi; Hori, Masaru

    2006-01-01

    Silicon dioxide etching process employing a pulse-modulated electron-beam-excited plasma (EBEP) has been developed for a fabrication process of optical micro-electro-mechanical systems (MEMSs). Nonplanar dielectric materials were etched by using self-bias induced by the electron beam generating the plasma. In order to investigate the effect of pulse modulation on electron beam, plasma diagnostics were carried out in the EBEP employing C 4 F 8 gas diluted with Ar gas by using a Langmuir single probe and time resolved optical emission spectroscopy. It was found that the pulse-modulated EBEP has an excellent potential to reduce the plasma-induced thermal damage on a photoresist film on a substrate to get the uniform etching and the anisotropic SiO 2 etching in comparison with the conventional EBEP. The pulse-modulated EBEP enabled us to get the high etch rate of SiO 2 of 375 nm/min without any additional bias power supply. Furthermore, the microfabrication on the core area of optical fiber was realized. These results indicate that the pulse-modulated EBEP will be a powerful tool for the application to optical MEMS process

  5. Lactobacillus rhamnosus GG and its SpaC pilus adhesin modulate inflammatory responsiveness and TLR-related gene expression in the fetal human gut

    NARCIS (Netherlands)

    Ganguli, K.; Collado, M.C.; Rautava, J.; Lu, L.; Satokari, R.M.; Ossowski, von I.; Reunanen, J.; Vos, de W.M.; Palva, A.; Isolauri, E.; Salminen, S.; Walker, W.A.; Rautava, S.

    2015-01-01

    BACKGROUND: Bacterial contact in utero modulates fetal and neonatal immune responses. Maternal probiotic supplementation reduces the risk of immune-mediated disease in the infant. We investigated the immunomodulatory properties of live Lactobacillus rhamnosus GG and its SpaC pilus adhesin in human

  6. Development and Validation of Web-based Training Modules for Systematic Evaluation of Active Inflammatory Lesions in the Spine and Sacroiliac Joints in Spondyloarthritis

    DEFF Research Database (Denmark)

    Maksymowych, Walter P; Dhillon, Suhkvinder S; Chiowchanwisawakit, Praveena

    2009-01-01

    no prior experience scoring inflammation by MRI and 2 experienced SPARCC readers. The first readings by the inexperienced readers were conducted after verbal instructions on the scoring method. The second readings were conducted after formal training using the Web-based training modules. Interreader...

  7. Antimicrobial, Cytotoxic, Anti-Inflammatory, and Antioxidant Activity of Culinary Processed Shiitake Medicinal Mushroom (Lentinus edodes, Agaricomycetes) and Its Major Sulfur Sensory-Active Compound-Lenthionine.

    Science.gov (United States)

    Kupcova, Kristyna; Stefanova, Iveta; Plavcova, Zuzana; Hosek, Jan; Hrouzek, Pavel; Kubec, Roman

    2018-01-01

    The antimicrobial, cytotoxic, anti-inflammatory, and antioxidant properties of aqueous extracts of raw and culinary processed shiitake mushrooms were evaluated and compared with those of lenthionine (1,2,3,5,6-penta-thiepane), the principal aroma-bearing substance of the shiitake medicinal mushroom (Lentinus edodes). Antimicrobial activity was tested using a panel of 4 strains of bacteria, 2 yeasts, and 2 fungi. Cytotoxic properties were evaluated against 3 cell lines (HepG2, HeLa, PaTu), whereas the anti-inflammatory activity of tested samples was assayed based on their ability to attenuate the secretion of the cytokine tumor necrosis factor-α. Antioxidant activity was measured using in vitro DPPH and ABTS assays. It was found that lenthionine possesses significant antimicrobial properties; it is remarkably effective in inhibiting the growth of yeasts and fungi (minimum inhibitory concentration, 2-8 μg/mL) and thus is comparable to standard antifungal agents. Lenthionine is also able to decrease significantly the production of tumor necrosis factor-a and thus could be at least partly responsible for the observed anti-inflammatory effect of shiitake. On the other hand, lenthionine does not seem to contribute significantly to the well-known anticancer and antioxidant effects of the mushroom.

  8. The protective arm of the renin-angiotensin system may counteract the intense inflammatory process in fetuses with posterior urethral valves.

    Science.gov (United States)

    Rocha, Natalia P; Bastos, Fernando M; Vieira, Érica L M; Prestes, Thiago R R; Silveira, Katia D da; Teixeira, Mauro M; Simões E Silva, Ana Cristina

    2018-03-11

    Posterior urethral valve is the most common lower urinary tract obstruction in male children. A high percentage of patients with posterior urethral valve evolve to end-stage renal disease. Previous studies showed that cytokines, chemokines, and components of the renin-angiotensin system contribute to the renal damage in obstructive uropathies. The authors recently found that urine samples from fetuses with posterior urethral valve have increased levels of inflammatory molecules. The aim of this study was to measure renin-angiotensin system molecules and to investigate their correlation with previously detected inflammatory markers in the same urine samples of fetuses with posterior urethral valve. Urine samples from 24 fetuses with posterior urethral valve were collected and compared to those from 22 healthy male newborns at the same gestational age (controls). Renin-angiotensin system components levels were measured by enzyme-linked immunosorbent assay. Fetuses with posterior urethral valve presented increased urinary levels of angiotensin (Ang) I, Ang-(1-7) and angiotensin-converting enzyme 2 in comparison with controls. ACE levels were significantly reduced and Ang II levels were similar in fetuses with posterior urethral valve in comparison with controls. Increased urinary levels of angiotensin-converting enzyme 2 and of Ang-(1-7) in fetuses with posterior urethral valve could represent a regulatory response to the intense inflammatory process triggered by posterior urethral valve. Copyright © 2018 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  9. Intake of Red Wine in Different Meals Modulates Oxidized LDL Level, Oxidative and Inflammatory Gene Expression in Healthy People: A Randomized Crossover Trial

    Directory of Open Access Journals (Sweden)

    Laura Di Renzo

    2014-01-01

    Full Text Available Several studies have found that adherence to the Mediterranean Diet, including consumption of red wine, is associated with beneficial effects on oxidative and inflammatory conditions. We evaluate the outcome of consumption of a McDonald’s Meal (McD and a Mediterranean Meal (MM, with and without the additive effect of red wine, in order to ascertain whether the addition of the latter has a positive impact on oxidized (ox- LDL and on expression of oxidative and inflammatory genes. A total of 24 subjects were analyzed for ox-LDL, CAT, GPX1, SOD2, SIRT2, and CCL5 gene expression levels, before and after consumption of the 4 different meal combinations with washout intervals between each meal. When red wine is associated with McD or MM, values of ox-LDL are lowered (P<0.05 and expression of antioxidant genes is increased, while CCL5 expression is decreased (P<0.05. SIRT2 expression after MM and fasting with red wine is significantly correlated with downregulation of CCL5 and upregulation of CAT (P<0.001. GPX1 increased significantly in the comparison between baseline and all conditions with red wine. We highlighted for the first time the positive effect of red wine intake combined with different but widely consumed meal types on ox-LDL and gene expression. Trial Registration. This trial is registered with ClinicalTrials.gov NCT01890070.

  10. Intake of Red Wine in Different Meals Modulates Oxidized LDL Level, Oxidative and Inflammatory Gene Expression in Healthy People: A Randomized Crossover Trial

    Science.gov (United States)

    Di Renzo, Laura; Valente, Roberto; Colica, Carmen

    2014-01-01

    Several studies have found that adherence to the Mediterranean Diet, including consumption of red wine, is associated with beneficial effects on oxidative and inflammatory conditions. We evaluate the outcome of consumption of a McDonald's Meal (McD) and a Mediterranean Meal (MM), with and without the additive effect of red wine, in order to ascertain whether the addition of the latter has a positive impact on oxidized (ox-) LDL and on expression of oxidative and inflammatory genes. A total of 24 subjects were analyzed for ox-LDL, CAT, GPX1, SOD2, SIRT2, and CCL5 gene expression levels, before and after consumption of the 4 different meal combinations with washout intervals between each meal. When red wine is associated with McD or MM, values of ox-LDL are lowered (P < 0.05) and expression of antioxidant genes is increased, while CCL5 expression is decreased (P < 0.05). SIRT2 expression after MM and fasting with red wine is significantly correlated with downregulation of CCL5 and upregulation of CAT (P < 0.001). GPX1 increased significantly in the comparison between baseline and all conditions with red wine. We highlighted for the first time the positive effect of red wine intake combined with different but widely consumed meal types on ox-LDL and gene expression. Trial Registration. This trial is registered with ClinicalTrials.gov NCT01890070. PMID:24876915

  11. Secretome of Aggregated Embryonic Stem Cell-Derived Mesenchymal Stem Cell Modulates the Release of Inflammatory Factors in Lipopolysaccharide-Induced Peripheral Blood Mononuclear Cells

    Science.gov (United States)

    Mohammadi Ghahhari, Nastaran; Maghsood, Faezeh; Jahandideh, Saeed; Lotfinia, Majid; Lak, Shirin; Johari, Behrooz; Azarnezhad, Asaad; Kadivar, Mehdi

    2018-07-01

    Bone marrow mesenchymal stem cells (BM-MSCs) have emerged as a potential therapy for various inflammatory diseases. Because of some limitations, several recent studies have suggested the use of embryonic stem cell-derived MSCs (ESC-MSCs) as an alternative for BM-MSCs. Some of the therapeutic effects of the ESC-MSCs are related to the secretion of a broad array of cytokines and growth factors, known as secretome. Harnessing this secretome for therapeutic applications requires the optimization of production of secretary molecules. It has been shown that aggregation of MSCs into 3D spheroids, as a preconditioning strategy, can enhance immunomodulatory potential of such cells. In this study, we investigated the effect of secretome derived from human ESC-MSCs (hESC-MSCs) spheroids on secretion of IL-1β, IL-10, and tumor necrosis factor α (TNF-α) from lipopolysaccharide (LPS)-induced peripheral blood mononuclear cells (PBMCs). In the present study, after immunophenotyping and considering mesodermal differentiation of hESC-MSCs, the cells were non-adherently grown to prepare 3D aggregates, and then conditioned medium or secretome was extracted from the cultures. Afterwards, the anti-inflammatory effects of the secretome were assessed in an in vitro model of inflammation. Results from this study showed that aggregate-prepared secretome from hESC-MSCs was able to significantly decrease the secretion of TNF-α (301.7 ± 5.906, p strategy to increase immunomodulatory characteristics of hESC-MSCs.

  12. Chronic Ethanol Feeding Modulates Inflammatory Mediators, Activation of Nuclear Factor-κB, and Responsiveness to Endotoxin in Murine Kupffer Cells and Circulating Leukocytes

    Directory of Open Access Journals (Sweden)

    Miriam Maraslioglu

    2014-01-01

    Full Text Available Chronic ethanol abuse is known to increase susceptibility to infections after injury, in part, by modification of macrophage function. Several intracellular signalling mechanisms are involved in the initiation of inflammatory responses, including the nuclear factor-κB (NF-κB pathway. In this study, we investigated the systemic and hepatic effect of chronic ethanol feeding on in vivo activation of NF-κB in NF-κBEGFP reporter gene mice. Specifically, the study focused on Kupffer cell proinflammatory cytokines IL-6 and TNF-α and activation of NF-κB after chronic ethanol feeding followed by in vitro stimulation with lipopolysaccharide (LPS. We found that chronic ethanol upregulated NF-κB activation and increased hepatic and systemic proinflammatory cytokine levels. Similarly, LPS-stimulated IL-1β release from whole blood was significantly enhanced in ethanol-fed mice. However, LPS significantly increased IL-6 and TNF-α levels. These results demonstrate that chronic ethanol feeding can improve the responsiveness of macrophage LPS-stimulated IL-6 and TNF-α production and indicate that this effect may result from ethanol-induced alterations in intracellular signalling through NF-κB. Furthermore, LPS and TNF-α stimulated the gene expression of different inflammatory mediators, in part, in a NF-κB-dependent manner.

  13. Differential modulation of apoptotic processes by proanthocyanidins as a dietary strategy for delaying chronic pathologies.

    Science.gov (United States)

    Puiggròs, Francesc; Salvadó, Maria-Josepa; Bladé, Cinta; Arola, Lluís

    2014-01-01

    Apoptosis is a biological process necessary for maintaining cellular homeostasis. Several diseases can result if it is deregulated. For example, inhibition of apoptotic signaling pathways is linked to the survival of pathological cells, which contributes to cancer, whereas excessive apoptosis is linked to neurodegenerative diseases, partially via oxidative stress. The activation or restoration of apoptosis via extrinsic or intrinsic pathways combined with cell signaling pathways triggered by reactive oxygen specises (ROS) formation is considered a key strategy by which bioactive foods can exert their health effects. Proanthocyanidins, a class of flavonoids naturally found in fruits, vegetables, and beverages, have attracted a great deal of attention not only because they are strong antioxidants but also because they appear to exert a different modulation of apoptosis, stimulating apoptosis in damaged cells, thus preventing cancer or reducing apoptosis in healthy cells, and as a result, preserving the integrity of normal cells and protecting against neurodegenerative diseases. Therefore, proanthocyanidins could provide a defense against apoptosis induced by oxidative stress or directly inhibit apoptosis, and they could also provide a promising treatment for a variety of diseases. Emerging data suggest that proanthocyanidins, especially those that humans can be persuaded to consume, may be used to prevent and manage cancer and mental disorders.

  14. Social provocation modulates decision making and feedback processing: Examining the trajectory of development in adolescent participants

    Directory of Open Access Journals (Sweden)

    Hannah L. Pincham

    2015-10-01

    Full Text Available Increasingly, research is turning to the ways in which social context impacts decision making and feedback processing in adolescents. The current study recorded electroencephalography to examine the trajectory of development across adolescence, with a focus on how social context impacts cognition and behaviour. To that end, younger (10–12 years and older (14–16 years adolescents played a modified Taylor Aggression Paradigm against two virtual opponents: a low-provoker and a high-provoker. During the task's decision phase (where participants select punishment for their opponent, we examined two event-related potentials: the N2 and the late positive potential (LPP. During the outcome phase (where participants experience win or loss feedback, we measured the feedback related negativity (FRN. Although N2 amplitudes did not vary with provocation, LPP amplitudes were enhanced under high provocation for the younger group, suggesting that emotional reactivity during the decision phase was heightened for early adolescents. During the outcome phase, the FRN was reduced following win outcomes under high provocation for both groups, suggesting that a highly provocative social opponent may influence the reward response. Collectively, the data argue that social context is an important factor modulating neural responses in adolescent behavioural and brain development.

  15. Semantics and the multisensory brain: how meaning modulates processes of audio-visual integration.

    Science.gov (United States)

    Doehrmann, Oliver; Naumer, Marcus J

    2008-11-25

    By using meaningful stimuli, multisensory research has recently started to investigate the impact of stimulus content on crossmodal integration. Variations in this respect have often been termed as "semantic". In this paper we will review work related to the question for which tasks the influence of semantic factors has been found and which cortical networks are most likely to mediate these effects. More specifically, the focus of this paper will be on processing of object stimuli presented in the auditory and visual sensory modalities. Furthermore, we will investigate which cortical regions are particularly responsive to experimental variations of content by comparing semantically matching ("congruent") and mismatching ("incongruent") experimental conditions. In this context, recent neuroimaging studies point toward a possible functional differentiation of temporal and frontal cortical regions, with the former being more responsive to semantically congruent and the latter to semantically incongruent audio-visual (AV) stimulation. To account for these differential effects, we will suggest in the final section of this paper a possible synthesis of these data on semantic modulation of AV integration with findings from neuroimaging studies and theoretical accounts of semantic memory.

  16. Modulation-Doped In2O3/ZnO Heterojunction Transistors Processed from Solution

    KAUST Repository

    Khim, Dongyoon

    2017-03-15

    This paper reports the controlled growth of atomically sharp In2 O3 /ZnO and In2 O3 /Li-doped ZnO (In2 O3 /Li-ZnO) heterojunctions via spin-coating at 200 °C and assesses their application in n-channel thin-film transistors (TFTs). It is shown that addition of Li in ZnO leads to n-type doping and allows for the accurate tuning of its Fermi energy. In the case of In2 O3 /ZnO heterojunctions, presence of the n-doped ZnO layer results in an increased amount of electrons being transferred from its conduction band minimum to that of In2 O3 over the interface, in a process similar to modulation doping. Electrical characterization reveals the profound impact of the presence of the n-doped ZnO layer on the charge transport properties of the isotype In2 O3 /Li-ZnO heterojunctions as well as on the operating characteristics of the resulting TFTs. By judicious optimization of the In2 O3 /Li-ZnO interface microstructure, and Li concentration, significant enhancement in both the electron mobility and TFT bias stability is demonstrated.

  17. Modulation-Doped In2O3/ZnO Heterojunction Transistors Processed from Solution

    KAUST Repository

    Khim, Dongyoon; Lin, Yen-Hung; Nam, Sungho; Faber, Hendrik; Tetzner, Kornelius; Li, Ruipeng; Zhang, Qiang; Li, Jun; Zhang, Xixiang; Anthopoulos, Thomas D.

    2017-01-01

    This paper reports the controlled growth of atomically sharp In2 O3 /ZnO and In2 O3 /Li-doped ZnO (In2 O3 /Li-ZnO) heterojunctions via spin-coating at 200 °C and assesses their application in n-channel thin-film transistors (TFTs). It is shown that addition of Li in ZnO leads to n-type doping and allows for the accurate tuning of its Fermi energy. In the case of In2 O3 /ZnO heterojunctions, presence of the n-doped ZnO layer results in an increased amount of electrons being transferred from its conduction band minimum to that of In2 O3 over the interface, in a process similar to modulation doping. Electrical characterization reveals the profound impact of the presence of the n-doped ZnO layer on the charge transport properties of the isotype In2 O3 /Li-ZnO heterojunctions as well as on the operating characteristics of the resulting TFTs. By judicious optimization of the In2 O3 /Li-ZnO interface microstructure, and Li concentration, significant enhancement in both the electron mobility and TFT bias stability is demonstrated.

  18. Does caffeine modulate verbal working memory processes? An fMRI study.

    Science.gov (United States)

    Koppelstaetter, F; Poeppel, T D; Siedentopf, C M; Ischebeck, A; Verius, M; Haala, I; Mottaghy, F M; Rhomberg, P; Golaszewski, S; Gotwald, T; Lorenz, I H; Kolbitsch, C; Felber, S; Krause, B J

    2008-01-01

    To assess the effect of caffeine on the functional MRI signal during a 2-back verbal working memory task, we examined blood oxygenation level-dependent regional brain activity in 15 healthy right-handed males. The subjects, all moderate caffeine consumers, underwent two scanning sessions on a 1.5-T MR-Scanner separated by a 24- to 48-h interval. Each participant received either placebo or 100 mg caffeine 20 min prior to the performance of the working memory task in blinded crossover fashion. The study was implemented as a blocked-design. Analysis was performed using SPM2. In both conditions, the characteristic working memory network of frontoparietal cortical activation including the precuneus and the anterior cingulate could be shown. In comparison to placebo, caffeine caused an increased response in the bilateral medial frontopolar cortex (BA 10), extending to the right anterior cingulate cortex (BA 32). These results suggest that caffeine modulates neuronal activity as evidenced by fMRI signal changes in a network of brain areas associated with executive and attentional functions during working memory processes.

  19. Morphological features of kidneys in fetuses and newborns from mothers with subacute infectious-inflammatory process in the abdominal cavity caused by Escherichia coli (experimental study

    Directory of Open Access Journals (Sweden)

    I.V. Sorokina

    2018-02-01

    Full Text Available Background. In Ukraine, every year the number of women whose pregnancy occurs on the background of chronic infectious diseases increases. Escherichia coli is a frequent causative agent of bacterial infections in women. The purpose of the study was to identify the morphological features of fetuses and newborns kidneys from mothers with an experimental abdominal subacute infectious-inflammatory process caused by Esche­richia coli. Materials and methods. The authors conduc­ted an experiment on WAG rats, during which two groups were formed: group I — 7 fetuses and 11 newborns from 3 healthy females; group II — 10 fetuses and 13 newborns from 4 females with an abdominal infectious-inflammatory process in the abdominal cavity caused by Escherichia coli. The material of the study was the kidneys of fetuses and newborns. The authors used histological, histochemical, morphometric and statistical methods of investigation. Results. The abdominal subacute infectious-inflammatory process in the mother’s body caused by Escherichia coli leads to structural changes in the parenchymal and stromal components of the kidneys that have been growing from the fetus to the newborn. The glomerular apparatus of the kidneys is characterized by uneven distribution in the cortical layer, developmental delay, shape change, hemodynamic disorders, expansion of the urinary space, absence of capillaries, a decrease in the number and localization compactness of capillaries in some young and mature renal corpuscles; the tubular apparatus — developmental delay, shape change and focal thickening of the basal membranes of some tubules, focal dystrophic, necrotic and desquamative changes in the epithelium; stromal component — sclerotic changes, hemodynamic disorders, which were more pronounced in the medulla layer, cellular infiltration, characterized by the presence of fibroblastic cells and immune cells. Conclusions. Histological and morphometric changes in the fetuses