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Sample records for ep1 ep2 ep3

  1. Vacuolar Localization of Endoproteinases EP(1) and EP(2) in Barley Mesophyll Cells.

    Science.gov (United States)

    Thayer, S S; Huffaker, R C

    1984-05-01

    The localization of two previously characterized endoproteinases (EP(1) and EP(2)) that comprise more than 95% of the protease activity in primary Hordeum vulgare L. var Numar leaves was determined. Intact vacuoles released from washed mesophyll protoplasts by gentle osmotic shock and increase in pH, were purified by flotation through a four-step Ficoll gradient. These vacuoles contained endoproteinases that rapidly degraded purified barley ribulose-1,5-bisphosphate carboxylase (RuBPCase) substrate. Breakdown products and extent of digestion of RuBPCase were determined using 12% polyacrylamide-sodium dodecyl sulfate gels. Coomassie brilliant blue- or silver-stained gels were scanned, and the peaks were integrated to provide quantitative information. The characteristics of the vacuolar endoproteinases (e.g. sensitivity to various inhibitors and activators, and the molecular weights of the breakdown products, i.e. peptide maps) closely resembled those of purified EP(1) and partially purified EP(2). It is therefore concluded that EP(1) and EP(2) are localized in the vacuoles of mesophyll cells.

  2. PGE2 maintains the tone of the guinea pig trachea through a balance between activation of contractile EP1 receptors and relaxant EP2 receptors

    Science.gov (United States)

    Säfholm, J; Dahlén, S-E; Delin, I; Maxey, K; Stark, K; Cardell, L-O; Adner, M

    2013-01-01

    Background and Purpose The guinea pig trachea (GPT) is commonly used in airway pharmacology. The aim of this study was to define the expression and function of EP receptors for PGE2 in GPT as there has been ambiguity concerning their role. Experimental Approach Expression of mRNA for EP receptors and key enzymes in the PGE2 pathway were assessed by real-time PCR using species-specific primers. Functional studies of GPT were performed in tissue organ baths. Key Results Expression of mRNA for the four EP receptors was found in airway smooth muscle. PGE2 displayed a bell-shaped concentration–response curve, where the initial contraction was inhibited by the EP1 receptor antagonist ONO-8130 and the subsequent relaxation by the EP2 receptor antagonist PF-04418948. Neither EP3 (ONO-AE5-599) nor EP4 (ONO-AE3-208) selective receptor antagonists affected the response to PGE2. Expression of COX-2 was greater than COX-1 in GPT, and the spontaneous tone was most effectively abolished by selective COX-2 inhibitors. Furthermore, ONO-8130 and a specific PGE2 antibody eliminated the spontaneous tone, whereas the EP2 antagonist PF-04418948 increased it. Antagonists of other prostanoid receptors had no effect on basal tension. The relaxant EP2 response to PGE2 was maintained after long-term culture, whereas the contractile EP1 response showed homologous desensitization to PGE2, which was prevented by COX-inhibitors. Conclusions and Implications Endogenous PGE2, synthesized predominantly by COX-2, maintains the spontaneous tone of GPT by a balance between contractile EP1 receptors and relaxant EP2 receptors. The model may be used to study interactions between EP receptors. PMID:22934927

  3. IL-6 Overexpression in ERG-Positive Prostate Cancer Is Mediated by Prostaglandin Receptor EP2.

    Science.gov (United States)

    Merz, Constanze; von Mässenhausen, Anne; Queisser, Angela; Vogel, Wenzel; Andrén, Ove; Kirfel, Jutta; Duensing, Stefan; Perner, Sven; Nowak, Michael

    2016-04-01

    Prostate cancer is the most diagnosed cancer in men and multiple risk factors and genetic alterations have been described. The TMPRSS2-ERG fusion event and the overexpression of the transcription factor ERG are present in approximately 50% of all prostate cancer patients, however, the clinical outcome is still controversial. Prostate tumors produce various soluble factors, including the pleiotropic cytokine IL-6, regulating cellular processes such as proliferation and metastatic segregation. Here, we used prostatectomy samples in a tissue microarray format and analyzed the co-expression and the clinicopathologic data of ERG and IL-6 using immunohistochemical double staining and correlated the read-out with clinicopathologic data. Expression of ERG and IL-6 correlated strongly in prostate tissue samples. Forced expression of ERG in prostate tumor cell lines resulted in significantly increased secretion of IL-6, whereas the down-regulation of ERG decreased IL-6 secretion. By dissecting the underlying mechanism in prostate tumor cell lines we show the ERG-mediated up-regulation of the prostanoid receptors EP2 and EP3. The prostanoid receptor EP2 was overexpressed in human prostate cancer tissue. Furthermore, the proliferation rate and IL-6 secretion in DU145 cells was reduced after treatment with EP2-receptor antagonist. Collectively, our study shows that the expression of ERG in prostate cancer is linked to the expression of IL-6 mediated by the prostanoid receptor EP2. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  4. Separate individual control systems come together at EP2

    International Nuclear Information System (INIS)

    Podmore, A.

    1991-01-01

    At BNFL's EP2 radioactive waste encapsulation plant in the UK, eight area supervisory control and data acquisition systems (SCADAs) and one central SCADA are being installed to provide computer-controlled processing of waste drums. The individual systems are all autonomous, minimizing the effect they have on other areas of the process. At the same time, they are part of an integrated system which provides effective communication between the various areas. (author)

  5. Prostanoid receptor EP2 as a therapeutic target.

    Science.gov (United States)

    Ganesh, Thota

    2014-06-12

    Cycoloxygenase-2 (COX-2) induction is prevalent in a variety of (brain and peripheral) injury models where COX-2 levels correlate with disease progression. Thus, COX-2 has been widely explored for anti-inflammatory therapy with COX-2 inhibitors, which proved to be effective in reducing the pain and inflammation in patients with arthritis and menstrual cramps, but they have not provided any benefit to patients with chronic inflammatory neurodegenerative disease. Recently, two COX-2 drugs, rofecoxib and valdecoxib, were withdrawn from the United States market due to cardiovascular side effects. Thus, future anti-inflammatory therapy could be targeted through a specific prostanoid receptor downstream of COX-2. The PGE2 receptor EP2 is emerging as a pro-inflammatory target in a variety of CNS and peripheral diseases. Here we highlight the latest developments on the role of EP2 in diseases, mechanism of activation, and small molecule discovery targeted either to enhance or to block the function of this receptor.

  6. Prostaglandin E2 Prevents Hyperosmolar-Induced Human Mast Cell Activation through Prostanoid Receptors EP2 and EP4

    Science.gov (United States)

    Torres-Atencio, Ivonne; Ainsua-Enrich, Erola; de Mora, Fernando; Picado, César; Martín, Margarita

    2014-01-01

    Background Mast cells play a critical role in allergic and inflammatory diseases, including exercise-induced bronchoconstriction (EIB) in asthma. The mechanism underlying EIB is probably related to increased airway fluid osmolarity that activates mast cells to the release inflammatory mediators. These mediators then act on bronchial smooth muscle to cause bronchoconstriction. In parallel, protective substances such as prostaglandin E2 (PGE2) are probably also released and could explain the refractory period observed in patients with EIB. Objective This study aimed to evaluate the protective effect of PGE2 on osmotically activated mast cells, as a model of exercise-induced bronchoconstriction. Methods We used LAD2, HMC-1, CD34-positive, and human lung mast cell lines. Cells underwent a mannitol challenge, and the effects of PGE2 and prostanoid receptor (EP) antagonists for EP1–4 were assayed on the activated mast cells. Beta-hexosaminidase release, protein phosphorylation, and calcium mobilization were assessed. Results Mannitol both induced mast cell degranulation and activated phosphatidyl inositide 3-kinase and mitogen-activated protein kinase (MAPK) pathways, thereby causing de novo eicosanoid and cytokine synthesis. The addition of PGE2 significantly reduced mannitol-induced degranulation through EP2 and EP4 receptors, as measured by beta-hexosaminidase release, and consequently calcium influx. Extracellular-signal-regulated kinase 1/2, c-Jun N-terminal kinase, and p38 phosphorylation were diminished when compared with mannitol activation alone. Conclusions Our data show a protective role for the PGE2 receptors EP2 and EP4 following osmotic changes, through the reduction of human mast cell activity caused by calcium influx impairment and MAP kinase inhibition. PMID:25329458

  7. Pathophysiological role of prostaglandin E2-induced up-regulation of the EP2 receptor in motor neuron-like NSC-34 cells and lumbar motor neurons in ALS model mice.

    Science.gov (United States)

    Kosuge, Yasuhiro; Miyagishi, Hiroko; Yoneoka, Yuki; Yoneda, Keiko; Nango, Hiroshi; Ishige, Kumiko; Ito, Yoshihisa

    2017-07-04

    Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by selective degeneration of motor neurons. The primary triggers for motor neuronal death are still unknown, but inflammation is considered to be an important factor contributing to the pathophysiology of ALS both clinically and in ALS models. Prostaglandin E2 (PGE2) and its corresponding four E-prostanoid receptors play a pivotal role in the degeneration of motor neurons in human and transgenic models of ALS. It has also been shown that PGE2-EP2 signaling in glial cells (astrocytes or microglia) promotes motor neuronal death in G93A mice. The present study was designed to investigate the levels of expression of EP receptors in the spinal motor neurons of ALS model mice and to examine whether PGE2 alters the expression of EP receptors in differentiated NSC-34 cells, a motor neuron-like cell line. Immunohistochemical staining demonstrated that EP2 and EP3 immunoreactivity was localized in NeuN-positive large cells showing the typical morphology of motor neurons in mice. Semi-quantitative analysis showed that the immunoreactivity of EP2 in motor neurons was significantly increased in the early symptomatic stage in ALS model mice. In contrast, the level of EP3 expression remained constant, irrespective of age. In differentiated NSC-34 cells, bath application of PGE2 resulted in a concentration-dependent decrease of MTT reduction. Although PGE2 had no effect on cell survival at concentrations of less than 10 μM, pretreatment with 10 μM PGE2 significantly up-regulated EP2 and concomitantly potentiated cell death induced by 30 μM PGE2. These results suggest that PGE2 is an important effector for induction of the EP2 subtype in differentiated NSC-34 cells, and that not only EP2 up-regulation in glial cells but also EP2 up-regulation in motor neurons plays a pivotal role in the vulnerability of motor neurons in ALS model mice. Copyright © 2017 Elsevier Ltd. All rights

  8. Castor oil induces laxation and uterus contraction via ricinoleic acid activating prostaglandin EP3 receptors.

    Science.gov (United States)

    Tunaru, Sorin; Althoff, Till F; Nüsing, Rolf M; Diener, Martin; Offermanns, Stefan

    2012-06-05

    Castor oil is one of the oldest drugs. When given orally, it has a laxative effect and induces labor in pregnant females. The effects of castor oil are mediated by ricinoleic acid, a hydroxylated fatty acid released from castor oil by intestinal lipases. Despite the wide-spread use of castor oil in conventional and folk medicine, the molecular mechanism by which ricinoleic acid acts remains unknown. Here we show that the EP(3) prostanoid receptor is specifically activated by ricinoleic acid and that it mediates the pharmacological effects of castor oil. In mice lacking EP(3) receptors, the laxative effect and the uterus contraction induced via ricinoleic acid are absent. Although a conditional deletion of the EP(3) receptor gene in intestinal epithelial cells did not affect castor oil-induced diarrhea, mice lacking EP(3) receptors only in smooth-muscle cells were unresponsive to this drug. Thus, the castor oil metabolite ricinoleic acid activates intestinal and uterine smooth-muscle cells via EP(3) prostanoid receptors. These findings identify the cellular and molecular mechanism underlying the pharmacological effects of castor oil and indicate a role of the EP(3) receptor as a target to induce laxative effects.

  9. Prostaglandin receptor EP3 regulates cell proliferation and migration with impact on survival of endometrial cancer patients.

    Science.gov (United States)

    Zhu, Junyan; Trillsch, Fabian; Mayr, Doris; Kuhn, Christina; Rahmeh, Martina; Hofmann, Simone; Vogel, Marianne; Mahner, Sven; Jeschke, Udo; von Schönfeldt, Viktoria

    2018-01-02

    Prostaglandin E2 (PGE2) receptor 3 (EP3) regulates tumor cell proliferation, migration, and invasion in numerous cancers. The role of EP3 as a prognostic biomarker in endometrial cancer remains unclear. The primary aim of this study was to analyze the prognostic significance of EP3 expression in endometrial cancer. We analyzed the EP3 expression of 140 endometrial carcinoma patients by immunohistochemistry. RL95-2 endometrial cancer cell line was chosen from four endometrial cancer cell lines (RL95-2, Ishikawa, HEC-1-A, and HEC-1-B) according to EP3 expression level. Treated with PGE2 and EP3 antagonist, RL95-2 cells were investigated by MTT, BrdU, and wound healing assay for functional assessment of EP3. EP3 staining differed significantly according to WHO tumor grading in both whole cohort (p = 0.01) and the subgroup of endometrioid carcinoma (p = 0.01). Patients with high EP3 expression in their respective tumors had impaired progression-free survival as well as overall survival in both cohorts above. EP3 expression in the overall cohort was identified as an independent prognostic marker for progression-free survival (HR 1.014, 95%CI 1.003-1.024, p = 0.01) when adjusted for age, stage, grading, and recurrence. Treatment with EP3 antagonists induced upregulation of estrogen receptor β and decreased activity of Ras and led to attenuated proliferation and migration of RL95-2 cells. EP3 seems to play a crucial role in endometrial cancer progression. In the context of limited systemic treatment options for endometrial cancer, this explorative analysis identifies EP3 as a potential target for diagnostic workup and therapy.

  10. Role of the Prostaglandin E2 EP1 Receptor in Traumatic Brain Injury

    Science.gov (United States)

    Glushakov, Alexander V.; Fazal, Jawad A.; Narumiya, Shuh; Doré, Sylvain

    2014-01-01

    Brain injuries promote upregulation of so-called proinflammatory prostaglandins, notably prostaglandin E2 (PGE2), leading to overactivation of a class of its cognate G-protein-coupled receptors, including EP1, which is considered a promising target for treatment of ischemic stroke. However, the role of the EP1 receptor is complex and depends on the type of brain injury. This study is focused on the investigation of the role of the EP1 receptor in a controlled cortical impact (CCI) model, a preclinical model of traumatic brain injury (TBI). The therapeutic effects of post-treatments with a widely studied EP1 receptor antagonist, SC-51089, were examined in wildtype and EP1 receptor knockout C57BL/6 mice. Neurological deficit scores (NDS) were assessed 24 and 48 h following CCI or sham surgery, and brain immunohistochemical pathology was assessed 48 h after surgery. In wildtype mice, CCI resulted in an obvious cortical lesion and localized hippocampal edema with an associated significant increase in NDS compared to sham-operated animals. Post-treatments with the selective EP1 receptor antagonist SC-51089 or genetic knockout of EP1 receptor had no significant effects on cortical lesions and hippocampal swelling or on the NDS 24 and 48 h after CCI. Immunohistochemistry studies revealed CCI-induced gliosis and microglial activation in selected ipsilateral brain regions that were not affected by SC-51089 or in the EP1 receptor-deleted mice. This study provides further clarification on the respective contribution of the EP1 receptor in TBI and suggests that, under this experimental paradigm, the EP1 receptor would have limited effects in modulating acute neurological and anatomical pathologies following contusive brain trauma. Findings from this protocol, in combination with previous studies demonstrating differential roles of EP1 receptor in ischemic, neurotoxic, and hemorrhagic conditions, provide scientific background and further clarification of potential therapeutic

  11. Evolving the JET virtual reality system for delivering the JET EP2 shutdown remote handling tasks

    Energy Technology Data Exchange (ETDEWEB)

    Williams, Adrian, E-mail: adrian.williams@oxfordtechnologies.co.uk [Oxford Technologies Ltd., 7 Nuffield Way, Abingdon, Oxon, OX14 1RJ (United Kingdom); JET-EFDA, Culham Science Centre, Abingdon, OX14 3DB (United Kingdom); Sanders, Stephen [Oxford Technologies Ltd., 7 Nuffield Way, Abingdon, Oxon, OX14 1RJ (United Kingdom); JET-EFDA, Culham Science Centre, Abingdon, OX14 3DB (United Kingdom); Weder, Gerard [Tree-C Technology BV, Buys Ballotstraat 8, 6716 BL Ede (Netherlands); JET-EFDA, Culham Science Centre, Abingdon, OX14 3DB (United Kingdom); Bastow, Roger; Allan, Peter; Hazel, Stuart [CCFE, Culham Science Centre, Abingdon, OX14 3DB (United Kingdom); JET-EFDA, Culham Science Centre, Abingdon, OX14 3DB (United Kingdom)

    2011-10-15

    The quality, functionality and performance of the virtual reality (VR) system used at JET for preparation and implementation of remote handling (RH) operations has been progressively enhanced since its first use in the original JET remote handling shutdown in 1998. As preparation began for the JET EP2 (Enhanced Performance 2) shutdown it was recognised that the VR system being used was unable to cope with the increased functionality and the large number of 3D models needed to fully represent the JET in-vessel components and tooling planned for EP2. A bespoke VR software application was developed in collaboration with the OEM, which allowed enhancements to be made to the VR system to meet the requirements of JET remote handling in preparation for EP2. Performance improvements required to meet the challenges of EP2 could not be obtained from the development of the new VR software alone. New methodologies were also required to prepare source, CATIA models for use in the VR using a collection of 3D software packages. In collaboration with the JET drawing office, techniques were developed within CATIA using polygon reduction tools to reduce model size, while retaining surface detail at required user limits. This paper will discuss how these developments have played an essential part in facilitating EP2 remote handling task development and examine their impact during the EP2 shutdown.

  12. Evolving the JET virtual reality system for delivering the JET EP2 shutdown remote handling tasks

    International Nuclear Information System (INIS)

    Williams, Adrian; Sanders, Stephen; Weder, Gerard; Bastow, Roger; Allan, Peter; Hazel, Stuart

    2011-01-01

    The quality, functionality and performance of the virtual reality (VR) system used at JET for preparation and implementation of remote handling (RH) operations has been progressively enhanced since its first use in the original JET remote handling shutdown in 1998. As preparation began for the JET EP2 (Enhanced Performance 2) shutdown it was recognised that the VR system being used was unable to cope with the increased functionality and the large number of 3D models needed to fully represent the JET in-vessel components and tooling planned for EP2. A bespoke VR software application was developed in collaboration with the OEM, which allowed enhancements to be made to the VR system to meet the requirements of JET remote handling in preparation for EP2. Performance improvements required to meet the challenges of EP2 could not be obtained from the development of the new VR software alone. New methodologies were also required to prepare source, CATIA models for use in the VR using a collection of 3D software packages. In collaboration with the JET drawing office, techniques were developed within CATIA using polygon reduction tools to reduce model size, while retaining surface detail at required user limits. This paper will discuss how these developments have played an essential part in facilitating EP2 remote handling task development and examine their impact during the EP2 shutdown.

  13. Castor oil induces laxation and uterus contraction via ricinoleic acid activating prostaglandin EP3 receptors

    OpenAIRE

    Tunaru, Sorin; Althoff, Till F.; Nüsing, Rolf M.; Diener, Martin; Offermanns, Stefan

    2012-01-01

    Castor oil is one of the oldest drugs. When given orally, it has a laxative effect and induces labor in pregnant females. The effects of castor oil are mediated by ricinoleic acid, a hydroxylated fatty acid released from castor oil by intestinal lipases. Despite the wide-spread use of castor oil in conventional and folk medicine, the molecular mechanism by which ricinoleic acid acts remains unknown. Here we show that the EP3 prostanoid receptor is specifically activated by ricinoleic acid and...

  14. Different populations of prostaglandin EP3 receptor-expressing preoptic neurons project to two fever-mediating sympathoexcitatory brain regions.

    Science.gov (United States)

    Nakamura, Y; Nakamura, K; Morrison, S F

    2009-06-30

    The central mechanism of fever induction is triggered by an action of prostaglandin E(2) (PGE(2)) on neurons in the preoptic area (POA) through the EP3 subtype of prostaglandin E receptor. EP3 receptor (EP3R)-expressing POA neurons project directly to the dorsomedial hypothalamus (DMH) and to the rostral raphe pallidus nucleus (rRPa), key sites for the control of thermoregulatory effectors. Based on physiological findings, we hypothesize that the febrile responses in brown adipose tissue (BAT) and those in cutaneous vasoconstrictors are controlled independently by separate neuronal pathways: PGE(2) pyrogenic signaling is transmitted from EP3R-expressing POA neurons via a projection to the DMH to activate BAT thermogenesis and via another projection to the rRPa to increase cutaneous vasoconstriction. In this case, DMH-projecting and rRPa-projecting neurons would constitute segregated populations within the EP3R-expressing neuronal group in the POA. Here, we sought direct anatomical evidence to test this hypothesis with a double-tracing experiment in which two types of the retrograde tracer, cholera toxin b-subunit (CTb), conjugated with different fluorophores were injected into the DMH and the rRPa of rats and the resulting retrogradely labeled populations of EP3R-immunoreactive neurons in the POA were identified with confocal microscopy. We found substantial numbers of EP3R-immunoreactive neurons in both the DMH-projecting and the rRPa-projecting populations. However, very few EP3R-immunoreactive POA neurons were labeled with both the CTb from the DMH and that from the rRPa, although a substantial number of neurons that were not immunoreactive for EP3R were double-labeled with both CTbs. The paucity of the EP3R-expressing neurons that send collaterals to both the DMH and the rRPa suggests that pyrogenic signals are sent independently to these caudal brain regions from the POA and that such pyrogenic outputs from the POA reflect different control mechanisms for BAT

  15. Product Plan of New Generation System Camera "OLYMPUS PEN E-P1"

    Science.gov (United States)

    Ogawa, Haruo

    "OLYMPUS PEN E-P1", which is new generation system camera, is the first product of Olympus which is new standard "Micro Four-thirds System" for high-resolution mirror-less cameras. It continues good sales by the concept of "small and stylish design, easy operation and SLR image quality" since release on July 3, 2009. On the other hand, the half-size film camera "OLYMPUS PEN" was popular by the concept "small and stylish design and original mechanism" since the first product in 1959 and recorded sale number more than 17 million with 17 models. By the 50th anniversary topic and emotional value of the Olympus pen, Olympus pen E-P1 became big sales. I would like to explain the way of thinking of the product plan that included not only the simple functional value but also emotional value on planning the first product of "Micro Four-thirds System".

  16. The prostaglandin EP1 receptor potentiates kainate receptor activation via a protein kinase C pathway and exacerbates status epilepticus

    Science.gov (United States)

    Rojas, Asheebo; Gueorguieva, Paoula; Lelutiu, Nadia; Quan, Yi; Shaw, Renee; Dingledine, Raymond

    2014-01-01

    Prostaglandin E2 (PGE2) regulates membrane excitability, synaptic transmission, plasticity, and neuronal survival. The consequences of PGE2 release following seizures has been the subject of much study. Here we demonstrate that the prostaglandin E2 receptor 1 (EP1, or Ptger1) modulates native kainate receptors, a family of ionotropic glutamate receptors widely expressed throughout the central nervous system. Global ablation of the EP1 gene in mice (EP1-KO) had no effect on seizure threshold after kainate injection but reduced the likelihood to enter status epilepticus. EP1-KO mice that did experience typical status epilepticus had reduced hippocampal neurodegeneration and a blunted inflammatory response. Further studies with native prostanoid and kainate receptors in cultured cortical neurons, as well as with recombinant prostanoid and kainate receptors expressed in Xenopus oocytes, demonstrated that EP1 receptor activation potentiates heteromeric but not homomeric kainate receptors via a second messenger cascade involving phospholipase C, calcium and protein kinase C. Three critical GluK5 C-terminal serines underlie the potentiation of the GluK2/GluK5 receptor by EP1 activation. Taken together, these results indicate that EP1 receptor activation during seizures, through a protein kinase C pathway, increases the probability of kainic acid induced status epilepticus, and independently promotes hippocampal neurodegeneration and a broad inflammatory response. PMID:24952362

  17. Prostaglandin E2 EP2 Receptor Deletion Attenuates Intracerebral Hemorrhage-Induced Brain Injury and Improves Functional Recovery

    Directory of Open Access Journals (Sweden)

    Jenna L. Leclerc

    2015-04-01

    Full Text Available Intracerebral hemorrhage (ICH is a devastating type of stroke characterized by bleeding into the brain parenchyma and secondary brain injury resulting from strong neuroinflammatory responses to blood components. Production of prostaglandin E2 (PGE2 is significantly upregulated following ICH and contributes to this inflammatory response in part through its E prostanoid receptor subtype 2 (EP2. Signaling through the EP2 receptor has been shown to affect outcomes of many acute and chronic neurological disorders; although, not yet explored in the context of ICH. Wildtype (WT and EP2 receptor knockout (EP2−/− mice were subjected to ICH, and various anatomical and functional outcomes were assessed by histology and neurobehavioral testing, respectively. When compared with age-matched WT controls, EP2−/− mice had 41.9 ± 4.7% smaller ICH-induced brain lesions and displayed significantly less ipsilateral hemispheric enlargement and incidence of intraventricular hemorrhage. Anatomical outcomes correlated with improved functional recovery as identified by neurological deficit scoring. Histological staining was performed to begin investigating the mechanisms involved in EP2-mediated neurotoxicity after ICH. EP2−/− mice exhibited 45.5 ± 5.8% and 41.4 ± 8.1% less blood and ferric iron accumulation, respectively. Furthermore, significantly less striatal and cortical microgliosis, striatal and cortical astrogliosis, blood–brain barrier breakdown, and peripheral neutrophil infiltration were seen in EP2−/− mice. This study is the first to suggest a deleterious role for the PGE2-EP2 signaling axis in modulating brain injury, inflammation, and functional recovery following ICH. Targeting the EP2 G protein-coupled receptor may represent a new therapeutic avenue for the treatment of hemorrhagic stroke.

  18. Obligatory Role of EP1 Receptors in the Increase in Cerebral Blood Flow Produced by Hypercapnia in the Mice.

    Directory of Open Access Journals (Sweden)

    Ken Uekawa

    Full Text Available Hypercapnia induces potent vasodilation in the cerebral circulation. Although it has long been known that prostanoids participate in the cerebrovascular effects of hypercapnia, the role of prostaglandin E2 (PGE2 and PGE2 receptors have not been fully investigated. In this study, we sought to determine whether cyclooxygenase-1 (COX-1-derived PGE2 and EP1 receptors are involved in the cerebrovascular response induced by hypercapnia. Cerebral blood flow (CBF was recorded by laser-Doppler flowmetry in the somatosenasory cortex of anesthetized male EP1-/- mice and wild type (WT littermates. In WT mice, neocortical application of the EP1 receptor antagonist SC-51089 attenuated the increase in CBF elicited by systemic hypercapnia (pCO2 = 50-60 mmHg. SC-51089 also attenuated the increase in CBF produced by neocortical treatment of arachidonic acid or PGE2. These CBF responses were also attenuated in EP1-/- mice. In WT mice, the COX-1 inhibitor SC-560, but not the COX-2 inhibitor NS-398, attenuated the hypercapnic CBF increase. Neocortical application of exogenous PGE2 restored the attenuation in resting CBF and the hypercapnic response induced by SC-560. In contrast, exogenous PGE2 failed to rescue the attenuation both in WT mice induced by SC-51089 and EP1-/- mice, attesting to the obligatory role of EP1 receptors in the response. These findings indicate that the hypercapnic vasodilatation depends on COX-1-derived PGE2 acting on EP1 receptors and highlight the critical role that COX-1-derived PGE2 and EP1 receptors play in the hypercapnic regulation of the cerebral circulation.

  19. Prostaglandin E2 stimulates Fas ligand expression via the EP1 receptor in colon cancer cells.

    LENUS (Irish Health Repository)

    O'Callaghan, G

    2012-02-03

    Fas ligand (FasL\\/CD95L) is a member of the tumour necrosis factor superfamily that triggers apoptosis following crosslinking of the Fas receptor. Despite studies strongly implicating tumour-expressed FasL as a major inhibitor of the anti-tumour immune response, little is known about the mechanisms that regulate FasL expression in tumours. In this study, we show that the cyclooxygenase (COX) signalling pathway, and in particular prostaglandin E(2) (PGE(2)), plays a role in the upregulation of FasL expression in colon cancer. Suppression of either COX-2 or COX-1 by RNA interference in HCA-7 and HT29 colon tumour cells reduced FasL expression at both the mRNA and protein level. Conversely, stimulation with PGE(2) increased FasL expression and these cells showed increased cytotoxicity against Fas-sensitive Jurkat T cells. Prostaglandin E(2)-induced FasL expression was mediated by signalling via the EP1 receptor. Moreover, immunohistochemical analysis using serial sections of human colon adenocarcinomas revealed a strong positive correlation between COX-2 and FasL (r=0.722; P<0.0001) expression, and between EP1 receptor and FasL (r=0.740; P<0.0001) expression, in the tumour cells. Thus, these findings indicate that PGE(2) positively regulates FasL expression in colon tumour cells, adding another pro-neoplastic activity to PGE(2).

  20. PGE2 receptor EP3 inhibits water reabsorption and contributes to polyuria and kidney injury in a streptozotocin-induced mouse model of diabetes.

    Science.gov (United States)

    Hassouneh, Ramzi; Nasrallah, Rania; Zimpelmann, Joe; Gutsol, Alex; Eckert, David; Ghossein, Jamie; Burns, Kevin D; Hébert, Richard L

    2016-06-01

    The first clinical manifestation of diabetes is polyuria. The prostaglandin E2 (PGE2) receptor EP3 antagonises arginine vasopressin (AVP)-mediated water reabsorption and its expression is increased in the diabetic kidney. The purpose of this work was to study the contribution of EP3 to diabetic polyuria and renal injury. Male Ep 3 (-/-) (also known as Ptger3 (-/-)) mice were treated with streptozotocin (STZ) to generate a mouse model of diabetes and renal function was evaluated after 12 weeks. Isolated collecting ducts (CDs) were microperfused to study the contribution of EP3 to AVP-mediated fluid reabsorption. Ep 3 (-/-)-STZ mice exhibited attenuated polyuria and increased urine osmolality compared with wild-type STZ (WT-STZ) mice, suggesting enhanced water reabsorption. Compared with WT-STZ mice, Ep 3 (-/-)-STZ mice also had increased protein expression of aquaporin-1, aquaporin-2, and urea transporter A1, and reduced urinary AVP excretion, but increased medullary V2 receptors. In vitro microperfusion studies indicated that Ep 3 (-/-) and WT-STZ CDs responded to AVP stimulation similarly to those of wild-type mice, with a 60% increase in fluid reabsorption. In WT non-injected and WT-STZ mice, EP3 activation with sulprostone (PGE2 analogue) abrogated AVP-mediated water reabsorption; this effect was absent in mice lacking EP3. A major finding of this work is that Ep 3 (-/-)-STZ mice showed blunted renal cyclooxygenase-2 protein expression, reduced renal hypertrophy, reduced hyperfiltration and reduced albuminuria, as well as diminished tubular dilation and nuclear cysts. Taken together, the data suggest that EP3 contributes to diabetic polyuria by inhibiting expression of aquaporins and that it promotes renal injury during diabetes. EP3 may prove to be a promising target for more selective management of diabetic kidney disease.

  1. The Prostaglandin E2-EP3 Receptor Axis Regulates Anaplasma phagocytophilum-Mediated NLRC4 Inflammasome Activation

    Czech Academy of Sciences Publication Activity Database

    Wang, X.; Shaw, D.K.; Hammond, H.L.; Sutterwala, F.S.; Rayamajhi, M.; Shirey, K.A.; Perkins, D.J.; Bonventre, J.V.; Velayutham, T.S.; Evans, S.M.; Rodino, K.G.; VieBrock, L.; Scanlon, K.M.; Carbonetti, N.H.; Carlyon, J.A.; Miao, E.A.; McBride, J.W.; Kotsyfakis, Michalis; Pedra, J. H. F.

    2016-01-01

    Roč. 12, č. 8 (2016), č. článku e1005803. E-ISSN 1553-7374 Institutional support: RVO:60077344 Keywords : Rickettsial agents * Anaplasma phagocytophilum * prostaglandin E2-EP3 Receptor Axis Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 7.003, year: 2015

  2. Quantification of the number of EP3 receptors on a living CHO cell surface by the AFM

    International Nuclear Information System (INIS)

    Kim, Hyonchol; Arakawa, Hideo; Hatae, Noriyuki; Sugimoto, Yukihiko; Matsumoto, Osamu; Osada, Toshiya; Ichikawa, Atsushi; Ikai, Atsushi

    2006-01-01

    The distribution of EP3 receptors on a living cell surface was quantitatively studied by atomic force microscopy (AFM). Green fluorescent protein (GFP) was introduced to the extracellular region of the EP3 receptor on a CHO cell. A microbead was used as a probe to ensure certain contact area, whose surface was coated with anti-GFP antibody. The interactions between the antibodies and GFP molecules on the cell surface were recorded to observe the distribution of the receptors. The result indicated that EP3 receptors were distributed on the CHO cell surface not uniformly but in small patches coincident with immunohistochemical observation. Repeated measurements on the same area of cell surface gave confirmation that it was unlikely that the receptors were extracted from the cell membrane during the experiments. The measurement of single molecular interaction between GFP and the anti-GFP antibody was succeeded on the cell surface using compression-free force spectroscopy. The value of separation work required to break a single molecular pair was estimated to be about 1.5x10 -18 J. The number of EP3 receptor on the CHO cell surface was estimated using this value to be about 1x10 4 under the assumption that the area of the cell surface was about 5000 μm 2 . These results indicated that the number of receptors on a living cell surface could be quantified through the force measurement by the AFM

  3. Prostaglandin E2 activates the mTORC1 pathway through an EP4/cAMP/PKA- and EP1/Ca2+-mediated mechanism in the human pancreatic carcinoma cell line PANC-1.

    Science.gov (United States)

    Chang, Hui-Hua; Young, Steven H; Sinnett-Smith, James; Chou, Caroline Ei Ne; Moro, Aune; Hertzer, Kathleen M; Hines, Oscar Joe; Rozengurt, Enrique; Eibl, Guido

    2015-11-15

    Obesity, a known risk factor for pancreatic cancer, is associated with inflammation and insulin resistance. Proinflammatory prostaglandin E2 (PGE2) and elevated insulin-like growth factor type 1 (IGF-1), related to insulin resistance, are shown to play critical roles in pancreatic cancer progression. We aimed to explore a potential cross talk between PGE2 signaling and the IGF-1/Akt/mammalian target of rapamycin complex 1 (mTORC1) pathway in pancreatic cancer, which may be a key to unraveling the obesity-cancer link. In PANC-1 human pancreatic cancer cells, we showed that PGE2 stimulated mTORC1 activity independently of Akt, as evaluated by downstream signaling events. Subsequently, using pharmacological and genetic approaches, we demonstrated that PGE2-induced mTORC1 activation is mediated by the EP4/cAMP/PKA pathway, as well as an EP1/Ca(2+)-dependent pathway. The cooperative roles of the two pathways were supported by the maximal inhibition achieved with the combined pharmacological blockade, and the coexistence of highly expressed EP1 (mediating the Ca(2+) response) and EP2 or EP4 (mediating the cAMP/PKA pathway) in PANC-1 cells and in the prostate cancer line PC-3, which also robustly exhibited PGE2-induced mTORC1 activation, as identified from a screen in various cancer cell lines. Importantly, we showed a reinforcing interaction between PGE2 and IGF-1 on mTORC1 signaling, with an increase in IL-23 production as a cellular outcome. Our data reveal a previously unrecognized mechanism of PGE2-stimulated mTORC1 activation mediated by EP4/cAMP/PKA and EP1/Ca(2+) signaling, which may be of great importance in elucidating the promoting effects of obesity in pancreatic cancer. Ultimately, a precise understanding of these molecular links may provide novel targets for efficacious interventions devoid of adverse effects. Copyright © 2015 the American Physiological Society.

  4. Human microdose evaluation of the novel EP1 receptor antagonist GSK269984A.

    Science.gov (United States)

    Ostenfeld, Thor; Beaumont, Claire; Bullman, Jonathan; Beaumont, Maria; Jeffrey, Phillip

    2012-12-01

    The primary objective was to evaluate the pharmacokinetics (PK) of the novel EP(1) antagonist GSK269984A in human volunteers after a single oral and intravenous (i.v.) microdose (100 µg). GSK269984A was administered to two groups of healthy human volunteers as a single oral (n= 5) or i.v. (n= 5) microdose (100 µg). Blood samples were collected for up to 24 h and the parent drug concentrations were measured in separated plasma using a validated high pressure liquid chromatography-tandem mass spectrometry method following solid phase extraction. Following the i.v. microdose, the geometric mean values for clearance (CL), steady-state volume of distribution (V(ss) ) and terminal elimination half-life (t(1/2) ) of GSK269984A were 9.8 l h(-1) , 62.8 l and 8.2 h. C(max) and AUC(0,∞) were 3.2 ng ml(-1) and 10.2 ng ml(-1)  h, respectively; the corresponding oral parameters were 1.8 ng ml(-1) and 9.8 ng ml(-1)  h, respectively. Absolute oral bioavailability was estimated to be 95%. These data were inconsistent with predictions of human PK based on allometric scaling of in vivo PK data from three pre-clinical species (rat, dog and monkey). For drug development programmes characterized by inconsistencies between pre-clinical in vitro metabolic and in vivo PK data, and where uncertainty exists with respect to allometric predictions of the human PK profile, these data support the early application of a human microdose study to facilitate the selection of compounds for further clinical development. © 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

  5. Promotion of adipogenesis by an EP2 receptor agonist via stimulation of angiogenesis in pulmonary emphysema.

    Science.gov (United States)

    Tsuji, Takao; Yamaguchi, Kazuhiro; Kikuchi, Ryota; Itoh, Masayuki; Nakamura, Hiroyuki; Nagai, Atsushi; Aoshiba, Kazutetsu

    2014-08-01

    Body weight loss is a common manifestation in patients with chronic obstructive pulmonary disease (COPD), particularly those with severe emphysema. Adipose angiogenesis is a key mediator of adipogenesis and use of pro-angiogenic agents may serve as a therapeutic option for lean COPD patients. Since angiogenesis is stimulated by PGE2, we examined whether ONO-AE1-259, a selective E-prostanoid (EP) 2 receptor agonist, might promote adipose angiogenesis and adipogenesis in a murine model of elastase-induced pulmonary emphysema (EIE mice). Mice were intratracheally instilled with elastase or saline, followed after 4 weeks by intraperitoneal administration of ONO-AE1-259 for 4 weeks. The subcutaneous adipose tissue (SAT) weight decreased in the EIE mice, whereas in the EIE mice treated with ONO-AE1-259, the SAT weight was largely restored, which was associated with significant increases in SAT adipogenesis, angiogenesis, and VEGF protein production. In contrast, ONO-AE1-259 administration induced no alteration in the weight of the visceral adipose tissue. These results suggest that in EIE mice, ONO-AE1-259 stimulated adipose angiogenesis possibly via VEGF production, and thence, adipogenesis. Our data pave the way for the development of therapeutic interventions for weight loss in emphysema patients, e.g., use of pro-angiogenic agents targeting the adipose tissue vascular component. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. The Prostaglandin E2-EP3 Receptor Axis Regulates Anaplasma phagocytophilum-Mediated NLRC4 Inflammasome Activation.

    Directory of Open Access Journals (Sweden)

    Xiaowei Wang

    2016-08-01

    Full Text Available Rickettsial agents are sensed by pattern recognition receptors but lack pathogen-associated molecular patterns commonly observed in facultative intracellular bacteria. Due to these molecular features, the order Rickettsiales can be used to uncover broader principles of bacterial immunity. Here, we used the bacterium Anaplasma phagocytophilum, the agent of human granulocytic anaplasmosis, to reveal a novel microbial surveillance system. Mechanistically, we discovered that upon A. phagocytophilum infection, cytosolic phospholipase A2 cleaves arachidonic acid from phospholipids, which is converted to the eicosanoid prostaglandin E2 (PGE2 via cyclooxygenase 2 (COX2 and the membrane associated prostaglandin E synthase-1 (mPGES-1. PGE2-EP3 receptor signaling leads to activation of the NLRC4 inflammasome and secretion of interleukin (IL-1β and IL-18. Importantly, the receptor-interacting serine/threonine-protein kinase 2 (RIPK2 was identified as a major regulator of the immune response against A. phagocytophilum. Accordingly, mice lacking COX2 were more susceptible to A. phagocytophilum, had a defect in IL-18 secretion and exhibited splenomegaly and damage to the splenic architecture. Remarkably, Salmonella-induced NLRC4 inflammasome activation was not affected by either chemical inhibition or genetic ablation of genes associated with PGE2 biosynthesis and signaling. This divergence in immune circuitry was due to reduced levels of the PGE2-EP3 receptor during Salmonella infection when compared to A. phagocytophilum. Collectively, we reveal the existence of a functionally distinct NLRC4 inflammasome illustrated by the rickettsial agent A. phagocytophilum.

  7. Prostanoid Receptors Involved in Regulation of the Beating Rate of Neonatal Rat Cardiomyocytes

    Science.gov (United States)

    Mechiche, Hakima; Grassin-Delyle, Stanislas; Robinet, Arnaud; Nazeyrollas, Pierre; Devillier, Philippe

    2012-01-01

    Although prostanoids are known to be involved in regulation of the spontaneous beating rate of cultured neonatal rat cardiomyocytes, the various subtypes of prostanoid receptors have not been investigated in detail. In our experiments, prostaglandin (PG)F2α and prostanoid FP receptor agonists (fluprostenol, latanoprost and cloprostenol) produced a decrease in the beating rate. Two prostanoid IP receptor agonists (iloprost and beraprost) induced first a marked drop in the beating rate and then definitive abrogation of beating. In contrast, the prostanoid DP receptor agonists (PGD2 and BW245C) and TP receptor agonists (U-46619) produced increases in the beating rate. Sulprostone (a prostanoid EP1 and EP3 receptor agonist) induced marked increases in the beating rate, which were suppressed by SC-19220 (a selective prostanoid EP1 antagonist). Butaprost (a selective prostanoid EP2 receptor agonist), misoprostol (a prostanoid EP2 and EP3 receptor agonist), 11-deoxy-PGE1 (a prostanoid EP2, EP3 and EP4 receptor agonist) did not alter the beating rate. Our results strongly suggest that prostanoid EP1 receptors are involved in positive regulation of the beating rate. Prostanoid EP1 receptor expression was confirmed by western blotting with a selective antibody. Hence, neonatal rat cardiomyocytes express both prostanoid IP and FP receptors (which negatively regulate the spontaneous beating rate) and prostanoid TP, DP1 and EP1 receptors (which positively regulate the spontaneous beating rate). PMID:22984630

  8. Reliability of EP3OS symptom criteria and nasal endoscopy in the assessment of chronic rhinosinusitis--a GA² LEN study

    NARCIS (Netherlands)

    Tomassen, P.; Newson, R. B.; Hoffmans, R.; Lötvall, J.; Cardell, L. O.; Gunnbjörnsdóttir, M.; Thilsing, T.; Matricardi, P.; Krämer, U.; Makowska, J. S.; Brozek, G.; Gjomarkaj, M.; Howarth, P.; Loureiro, C.; Toskala, E.; Fokkens, W.; Bachert, C.; Burney, P.; Jarvis, D.

    2011-01-01

    The European Position Paper on Rhinosinusitis and Nasal Polyps (EP3OS) incorporates symptomatic, endoscopic, and radiologic criteria in the clinical diagnosis of chronic rhinosinusitis (CRS), while in epidemiological studies, the definition is based on symptoms only. We aimed to assess the

  9. Reliability of EP3OS symptom criteria and nasal endoscopy in the assessment of chronic rhinosinusitis - a GA(2) LEN study

    DEFF Research Database (Denmark)

    Tomassen, P; Newson, R B; Hoffmans, R

    2011-01-01

    To cite this article: Tomassen P, Newson RB, Hoffmans R, Lötvall J, Cardell LO, Gunnbjörnsdóttir M, Thilsing T, Matricardi P, Krämer U, Makowska JS, Brozek G, Gjomarkaj M, Howarth P, Loureiro C, Toskala E, Fokkens W, Bachert C, Burney P, Jarvis D. Reliability of EP3OS symptom criteria and nasal...

  10. Effect of pretreatment with epoxy compounds on the mechanical properties of bovine pericardial bioprosthetic materials.

    Science.gov (United States)

    Xi, T; Liu, F; Xi, B

    1992-07-01

    Early failures of bovine pericardial heart valves are due to leaflet perforation, tearing and calcification. Since glutaraldehyde fixation has been shown to produce marked changes in leaflet mechanics and has been linked to development of calcification, bovine pericardium fixed with the four hydrophilic epoxy formulations and their mechanical properties are studied in this paper. We measured the thicknesses, shrinkage temperatures, stress relaxations and stress-strain curves of bovine pericardiums after different treatments with (1) non-treatment (fresh), (2) glutaraldehyde (GA), (3) epoxy compounds followed by the posttreatment with GA (EP 1#, EP 2#), and (4) epoxy compounds (EP 3# and EP 4#). Results of this study showed that the hydrophilic epoxy compounds are good crosslinking agents. There are no significant differences of shrinkage temperature and ultimate tensile stress among all tissue samples pretreated with GA, EP 1# and EP 2#. However, the stress relaxations of tissue-samples pretreated with epoxy compounds followed by the posttreatment with GA (EP 1# and EP 2#) are significantly slower than that pretreated with GA, and the strains at fracture of EP 1# and EP 2# are also significantly larger than that of GA or epoxy compounds. These facts show that the bovine pericardium pretreated with the epoxy compound followed by the posttreatment with GA (EP 1# and EP 2#) possesses greater tenacity and potential durability in dynamic stress.

  11. Structural optimization and structure-functional selectivity relationship studies of G protein-biased EP2 receptor agonists.

    Science.gov (United States)

    Ogawa, Seiji; Watanabe, Toshihide; Moriyuki, Kazumi; Goto, Yoshikazu; Yamane, Shinsaku; Watanabe, Akio; Tsuboi, Kazuma; Kinoshita, Atsushi; Okada, Takuya; Takeda, Hiroyuki; Tani, Kousuke; Maruyama, Toru

    2016-05-15

    The modification of the novel G protein-biased EP2 agonist 1 has been investigated to improve its G protein activity and develop a better understanding of its structure-functional selectivity relationship (SFSR). The optimization of the substituents on the phenyl ring of 1, followed by the inversion of the hydroxyl group on the cyclopentane moiety led to compound 9, which showed a 100-fold increase in its G protein activity compared with 1 without any increase in β-arrestin recruitment. Furthermore, SFSR studies revealed that the combination of meta and para substituents on the phenyl moiety was crucial to the functional selectivity. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. COX-2 and Prostaglandin EP3/EP4 Signaling Regulate the Tumor Stromal Proangiogenic Microenvironment via CXCL12-CXCR4 Chemokine Systems

    Science.gov (United States)

    Katoh, Hiroshi; Hosono, Kanako; Ito, Yoshiya; Suzuki, Tatsunori; Ogawa, Yasufumi; Kubo, Hidefumi; Kamata, Hiroki; Mishima, Toshiaki; Tamaki, Hideaki; Sakagami, Hiroyuki; Sugimoto, Yukihiko; Narumiya, Shuh; Watanabe, Masahiko; Majima, Masataka

    2010-01-01

    Bone marrow (BM)–derived hematopoietic cells, which are major components of tumor stroma, determine the tumor microenvironment and regulate tumor phenotypes. Cyclooxygenase (COX)−2 and endogenous prostaglandins are important determinants for tumor growth and tumor-associated angiogenesis; however, their contributions to stromal formation and angiogenesis remain unclear. In this study, we observed that Lewis lung carcinoma cells implanted in wild-type mice formed a tumor mass with extensive stromal formation that was markedly suppressed by COX-2 inhibition, which reduced the recruitment of BM cells. Notably, COX-2 inhibition attenuated CXCL12/CXCR4 expression as well as expression of several other chemokines. Indeed, in a Matrigel model, prostaglandin (PG) E2 enhanced stromal formation and CXCL12/CXCR4 expression. In addition, a COX-2 inhibitor suppressed stromal formation and reduced expression of CXCL12/CXCR4 and a fibroblast marker (S100A4) in a micropore chamber model. Moreover, stromal formation after tumor implantation was suppressed in EP3−/− mice and EP4−/− mice, in which stromal expression of CXCL12/CXCR4 and S100A4 was reduced. The EP3 or EP4 knockout suppressed S100A4+ fibroblasts, CXCL12+, and/or CXCR4+ stromal cells as well. Immunofluorescent analyses revealed that CXCL12+CXCR4+S100A4+ fibroblasts mainly comprised stromal cells and most of these were recruited from the BM. Additionally, either EP3- or EP4-specific agonists stimulated CXCL12 expression by fibroblasts in vitro. The present results address the novel activities of COX-2/PGE2-EP3/EP4 signaling that modulate tumor biology and show that CXCL12/CXCR4 axis may play a crucial role in tumor stromal formation and angiogenesis under the control of prostaglandins. PMID:20110411

  13. Inhibition of the prostaglandin EP2 receptor is neuroprotective and accelerates functional recovery in a rat model of organophosphorus induced status epilepticus

    Science.gov (United States)

    Rojas, Asheebo; Ganesh, Thota; Lelutiu, Nadia; Gueorguieva, Paoula; Dingledine, Raymond

    2015-01-01

    Exposure to high levels of organophosphorus compounds (OP) can induce status epilepticus (SE) in humans and rodents via acute cholinergic toxicity, leading to neurodegeneration and brain inflammation. Currently there is no treatment to combat the neuropathologies associated with OP exposure. We recently demonstrated that inhibition of the EP2 receptor for PGE2 reduces neuronal injury in mice following pilocarpine-induced SE. Here, we investigated the therapeutic effects of an EP2 inhibitor (TG6-10-1) in a rat model of SE using diisopropyl fluorophosphate (DFP). We tested the hypothesis that EP2 receptor inhibition initiated well after the onset of DFP-induced SE reduces the associated neuropathologies. Adult male Sprague-Dawley rats were injected with pyridostigmine bromide (0.1 mg/kg, sc) and atropine methylbromide (20 mg/kg, sc) followed by DFP (9.5 mg/kg, ip) to induce SE. DFP administration resulted in prolonged upregulation of COX-2. The rats were administered TG6-10-1 or vehicle (ip) at various time points relative to DFP exposure. Treatment with TG6-10-1 or vehicle did not alter the observed behavioral seizures, however six doses of TG6-10-1 starting 80-150 min after the onset of DFP-induced SE significantly reduced neurodegeneration in the hippocampus, blunted the inflammatory cytokine burst, reduced microglial activation and decreased weight loss in the days after status epilepticus. By contrast, astrogliosis was unaffected by EP2 inhibition 4 d after DFP. Transient treatments with the EP2 antagonist 1 h before DFP, or beginning 4 h after DFP, were ineffective. Delayed mortality, which was low (10%) after DFP, was unaffected by TG6-10-1. Thus, selective inhibition of the EP2 receptor within a time window that coincides with the induction of cyclooxygenase-2 by DFP is neuroprotective and accelerates functional recovery of rats. PMID:25656476

  14. The Vasopressin Type-2 Receptor and Prostaglandin Receptors EP2 and EP4 can Increase Aquaporin-2 Plasma Membrane Targeting Through a cAMP Independent Pathway

    DEFF Research Database (Denmark)

    Olesen, Emma Tina Bisgaard; Moeller, Hanne Bjerregaard; Assentoft, Mette

    2016-01-01

    Apical membrane targeting of the collecting duct water channel aquaporin-2 (AQP2) is essential for body water balance. As this event is regulated by Gs coupled 7-transmembrane receptors such as the vasopressin type 2 receptor (V2R) and the prostanoid receptors EP2 and EP4, it is believed to be c...

  15. Improvement of metabolic disorders by an EP2 receptor agonist via restoration of the subcutaneous adipose tissue in pulmonary emphysema.

    Science.gov (United States)

    Tsuji, Takao; Yamaguchi, Kazuhiro; Kikuchi, Ryota; Nakamura, Hiroyuki; Misaka, Ryoichi; Nagai, Atsushi; Aoshiba, Kazutetsu

    2017-05-01

    Chronic obstructive pulmonary disease (COPD) is often associated with co-morbidities. Metabolic disorders like hyperlipidemia and diabetes occur also in underweight COPD patients, although the mechanism is uncertain. Subcutaneous adipose tissue (SAT) plays an important role in energy homeostasis, since restricted capacity to increase fat cell number with increase in fat cell size occurring instead, is associated with lipotoxicity and metabolic disorders. The aim of this study is to show the protective role of SAT for the metabolic disorders in pulmonary emphysema of a murine model. We found ectopic fat accumulation and impaired glucose homeostasis with wasting of SAT in a murine model of elastase-induced pulmonary emphysema (EIE mice) reared on a high-fat diet. ONO-AE1-259, a selective E-prostanoid (EP) 2 receptor agonist, improved angiogenesis and subsequently adipogenesis, and finally improved ectopic fat accumulation and glucose homeostasis with restoration of the capacity for storage of surplus energy in SAT. These results suggest that metabolic disorders like hyperlipidemia and diabetes occured in underweight COPD is partially due to the less capacity for storage of surplus energy in SAT, though the precise mechanism is uncertained. Our data pave the way for the development of therapeutic interventions for metabolic disorders in emphysema patients, e.g., use of pro-angiogenic agents targeting the capacity for storage of surplus energy in the subcutaneous adipose tissue. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Reliability of EP3OS symptom criteria and nasal endoscopy in the assessment of chronic rhinosinusitis--a GA² LEN study.

    Science.gov (United States)

    Tomassen, P; Newson, R B; Hoffmans, R; Lötvall, J; Cardell, L O; Gunnbjörnsdóttir, M; Thilsing, T; Matricardi, P; Krämer, U; Makowska, J S; Brozek, G; Gjomarkaj, M; Howarth, P; Loureiro, C; Toskala, E; Fokkens, W; Bachert, C; Burney, P; Jarvis, D

    2011-04-01

    The European Position Paper on Rhinosinusitis and Nasal Polyps (EP3OS) incorporates symptomatic, endoscopic, and radiologic criteria in the clinical diagnosis of chronic rhinosinusitis (CRS), while in epidemiological studies, the definition is based on symptoms only. We aimed to assess the reliability and validity of a symptom-based definition of CRS using data from the GA(2) LEN European survey. On two separate occasions, 1700 subjects from 11 centers provided information on symptoms of CRS, allergic rhinitis, and asthma. CRS was defined by the epidemiological EP3OS symptom criteria. The difference in prevalence of CRS between two study points, the standardized absolute repeatability, and the chance-corrected repeatability (kappa) were determined. In two centers, 342 participants underwent nasal endoscopy. The association of symptom-based CRS with endoscopy and self-reported doctor-diagnosed CRS was assessed. There was a decrease in prevalence of CRS between the two study phases, and this was consistent across all centers (-3.0%, 95% CI: -5.0 to -1.0%, I(2) = 0). There was fair to moderate agreement between the two occasions (kappa = 39.6). Symptom-based CRS was significantly associated with positive endoscopy in nonallergic subjects, and with self-reported doctor-diagnosed CRS in all subjects, irrespective of the presence of allergic rhinitis. Our findings suggest that a symptom-based definition of CRS, according to the epidemiological part of the EP3OS criteria, has a moderate reliability over time, is stable between study centers, is not influenced by the presence of allergic rhinitis, and is suitable for the assessment of geographic variation in prevalence of CRS. © 2010 John Wiley & Sons A/S.

  17. Retinoic acid morpholine amide (RAMA) inhibits expression of Fas ligand through EP1 receptor in colon cancer cells.

    Science.gov (United States)

    Chen, Shao-Xuan; Du, Shi-Yu; Wang, Yun-Ting; Zhao, Hong-Chuan; Zhang, Yan-Li; Yao, Li

    2016-01-01

    Among the members of tumour necrosis factor family Fas ligand on binding to its receptor strongly induces apoptosis of tumour-infiltrating lymphocytes (TIL). Thus, FasL acts as an inhibitor of anti-tumour immune response. The present study demonstrates that retinoic acid morpholine amide (RAMA) significantly suppresses FasL expression in colon cancer cells in a dose- and time-dependent manner. The suppression of FasL mRNA and proteins was significant at a concentration of 30 μM after 48 h in CLT85 and HT26 colon cancer cells. There was around 2.6- and 3.2-fold decrease in FasL mRNA after incubation with 30 μM of RAMA in CLT85 cells and HT26 cells, respectively. The results from Western blot showed a decrease in FasL mRNA and protein expression in both CLT85 and HT26 cells after suppression of cyclooxygenase (COX)-2 and COX-1 by RNAi. However, when COX-2-specific silencer RNA (siCOX-2)- and siCOX-1-treated CLT85 and HT26 cells were exposed to RAMA, inhibition of FasL expression was further suppressed. The siCOX-2-treated CLT85 and HT26 cells on exposure to RAMA showed ∼87 and ∼54 % reduction in FasL mRNA, respectively. Co-culture of Jurkat T cells with RAMA-treated HT26 and CLT85 cells decreased the viability of Jurkat T cells by only 2 and 4.3 %, respectively, compared to 19.5 and 37.3 % in control HT26 and CLT85 cells. The results from real-time reverse transcription polymerase chain reaction (RT-PCR) and immunoblotting showed that suppression of EP1 prevented RAMA-induced FasL suppression in CLT85 cells at both the mRNA and protein levels. Thus, RAMA can be a potent therapeutic agent for the treatment of colon tumours.

  18. Prostaglandin E2-Induced COX-2 Expressions via EP2 and EP4 Signaling Pathways in Human LoVo Colon Cancer Cells

    Directory of Open Access Journals (Sweden)

    Hsi-Hsien Hsu

    2017-05-01

    Full Text Available Metastasis is the most dangerous risk faced by patients with hereditary non-polyposis colon cancer (HNPCC. The expression of matrix metalloproteinases (MMPs has been observed in several types of human cancers and regulates the efficacy of many therapies. Here, we show that treatment with various concentrations of prostaglandin E2 (PGE2; 0, 1, 5 or 10 μM promotes the migration ability of the human LoVo colon cancer cell line. As demonstrated by mRNA and protein expression analyses, EP2 and EP4 are the major PGE2 receptors expressed on the LoVo cell membrane. The Phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K/Akt cell survival pathway was upregulated by EP2 and EP4 activation. Following the activation of the PI3K/Akt pathway, β-catenin translocated into the nucleus and triggered COX2 transcription via LEF-1 and TCF-4 and its subsequent translation. COX2 expression correlated with the elevation in the migration ability of LoVo cells. The experimental evidence shows a possible mechanism by which PGE2 induces cancer cell migration and further suggests PGE2 to be a potential therapeutic target in colon cancer metastasis. On inhibition of PGE2, in order to determine the downstream pathway, the levels of PI3K/Akt pathway were suppressed and the β-catenin expression was also modulated. Inhibition of EP2 and EP4 shows that PGE2 induces protein expression of COX-2 through EP2 and EP4 receptors in LoVo colon cancer cells.

  19. Inhibition of the prostaglandin E2 receptor EP2 prevents status epilepticus-induced deficits in the novel object recognition task in rats

    Science.gov (United States)

    Rojas, Asheebo; Ganesh, Thota; Manji, Zahra; O’neill, Theon; Dingledine, Raymond

    2016-01-01

    Survivors of exposure to an organophosphorus nerve agent may develop a number of complications including long-term cognitive deficits (Miyaki et al., 2005; Nishiwaki et al., 2001). We recently demonstrated that inhibition of the prostaglandin E2 receptor, EP2, attenuates neuroinflammation and neurodegeneration caused by status epilepticus (SE) induced by the soman analog, diisopropylfluorophosphate (DFP), which manifest within hours to days of the initial insult. Here, we tested the hypothesis that DFP exposure leads to a loss of cognitive function in rats that is blocked by early, transient EP2 inhibition. Adult male Sprague-Dawley rats were administered vehicle or the competitive EP2 antagonist, TG6-10-1, (ip) at various times relative to DFP-induced SE. DFP administration resulted in prolonged seizure activity as demonstrated by cortical electroencephalography (EEG). A single intraperitoneal injection of TG6-10-1 or vehicle 1 h prior to DFP did not alter the development of seizures, the latency to SE or the duration of SE. Rats administered six injections of TG6-10-1 starting 90 min after the onset of DFP-induced SE could discriminate between a novel and familiar object 6–12 weeks after SE, unlike vehicle treated rats which showed no preference for the novel object. By contrast, behavioral changes in the light-dark box and open field assays were not affected by TG6-10-1. Delayed mortality after DFP was also unaffected by TG6-10-1. Thus, selective inhibition of the EP2 receptor may prevent SE-induced memory impairment in rats caused by exposure to a high dose of DFP. PMID:27477533

  20. Prostaglandin E2 EP2 activation reduces memory decline in R6/1 mouse model of Huntington's disease by the induction of BDNF-dependent synaptic plasticity.

    Science.gov (United States)

    Anglada-Huguet, Marta; Vidal-Sancho, Laura; Giralt, Albert; García-Díaz Barriga, Gerardo; Xifró, Xavier; Alberch, Jordi

    2016-11-01

    Huntington's disease (HD) patients and mouse models show learning and memory impairment even before the onset of motor symptoms. Deficits in hippocampal synaptic plasticity have been involved in the HD memory impairment. Several studies show that prostaglandin E2 (PGE2) EP2 receptor stimulates synaptic plasticity and memory formation. However, this role was not explored in neurodegenerative diseases. Here, we investigated the capacity of PGE2 EP2 receptor to promote synaptic plasticity and memory improvements in a model of HD, the R6/1 mice, by administration of the agonist misoprostol. We found that misoprostol increases dendritic branching in cultured hippocampal neurons in a brain-derived neurotrophic factor (BDNF)-dependent manner. Then, we implanted an osmotic mini-pump system to chronically administrate misoprostol to R6/1 mice from 14 to 18weeks of age. We observed that misoprostol treatment ameliorates the R6/1 long-term memory deficits as analyzed by the T-maze spontaneous alternation task and the novel object recognition test. Importantly, administration of misoprostol promoted the expression of hippocampal BDNF. Moreover, the treatment with misoprostol in R6/1 mice blocked the reduction in the number of PSD-95 and VGluT-1 positive particles observed in hippocampus of vehicle-R6/1 mice. In addition, we observed an increase of cAMP levels in the dentate ` of WT and R6/1 mice treated with misoprostol. Accordingly, we showed a reduction in the number of mutant huntingtin nuclear inclusions in the dentate gyrus of R6/1 mice. Altogether, these results suggest a putative therapeutic effect of PGE2 EP2 receptor in reducing cognitive deficits in HD. Copyright © 2016. Published by Elsevier Inc.

  1. Prostaglandin E2 EP2 and EP4 receptor activation mediates cAMP-dependent hyperpolarization and exocytosis of renin in juxtaglomerular cells

    DEFF Research Database (Denmark)

    Friis, Ulla Glenert; Stubbe, Jane; Uhrenholt, Torben Rene

    2005-01-01

    /l), AE1-259-01 (1 nmol/l), EP4-selective agonist AE1-329 (1 nmol/l), and IP agonist iloprost (1 micromol/l) significantly increased C(m) mediated by PKA. The EP4 antagonist AE3-208 (10 nmol/l) blocked the effect of EP4 agonist but did not alter the response to PGE(2). Application of both EP4 antagonist....... The membrane potential hyperpolarized significantly after PGE(2), butaprost, AE1-329 and AE1-259 and outward current was augmented in a PKA-dependent fashion. PGE(2)-stimulated outward current, but not C(m) change, was abolished by the BK(Ca) channel inhibitor iberiotoxin (300 nmol/l). EP2 and EP4 m......RNA was detected in sampled JG cells, and the preglomerular and glomerular vasculature was immunopositive for EP4. Thus IP, EP2, and EP4 receptors are associated with JG cells, and their activation leads to rapid PKA-mediated exocytotic fusion and release of renin granules....

  2. PGE2 maintains self-renewal of human adult stem cells via EP2-mediated autocrine signaling and its production is regulated by cell-to-cell contact.

    Science.gov (United States)

    Lee, Byung-Chul; Kim, Hyung-Sik; Shin, Tae-Hoon; Kang, Insung; Lee, Jin Young; Kim, Jae-Jun; Kang, Hyun Kyoung; Seo, Yoojin; Lee, Seunghee; Yu, Kyung-Rok; Choi, Soon Won; Kang, Kyung-Sun

    2016-05-27

    Mesenchymal stem cells (MSCs) possess unique immunomodulatory abilities. Many studies have elucidated the clinical efficacy and underlying mechanisms of MSCs in immune disorders. Although immunoregulatory factors, such as Prostaglandin E2 (PGE2), and their mechanisms of action on immune cells have been revealed, their effects on MSCs and regulation of their production by the culture environment are less clear. Therefore, we investigated the autocrine effect of PGE2 on human adult stem cells from cord blood or adipose tissue, and the regulation of its production by cell-to-cell contact, followed by the determination of its immunomodulatory properties. MSCs were treated with specific inhibitors to suppress PGE2 secretion, and proliferation was assessed. PGE2 exerted an autocrine regulatory function in MSCs by triggering E-Prostanoid (EP) 2 receptor. Inhibiting PGE2 production led to growth arrest, whereas addition of MSC-derived PGE2 restored proliferation. The level of PGE2 production from an equivalent number of MSCs was down-regulated via gap junctional intercellular communication. This cell contact-mediated decrease in PGE2 secretion down-regulated the suppressive effect of MSCs on immune cells. In conclusion, PGE2 produced by MSCs contributes to maintenance of self-renewal capacity through EP2 in an autocrine manner, and PGE2 secretion is down-regulated by cell-to-cell contact, attenuating its immunomodulatory potency.

  3. EP3/FP dual receptor agonist ONO-9054 administered morning or evening to patients with open-angle glaucoma or ocular hypertension: results of a randomised crossover study

    Science.gov (United States)

    Berlin, Michael S; Rowe-Rendleman, Cheryl; Ahmed, Ike; Ross, Douglas T; Fujii, Akifumi; Ouchi, Takafumi; Quach, Christine; Wood, Andrew; Ward, Caroline L

    2016-01-01

    Background/aims The novel prostaglandin E (EP) 3 and prostaglandin F (FP) receptor agonist ONO-9054 is effective in lowering intraocular pressure (IOP) in patients with ocular hypertension and open-angle glaucoma when administered once daily. This study compares the effects of morning (AM) versus evening (PM) dosing of ONO-9054 on tolerability and IOP lowering. Methods This was a single-centre, randomised, double-masked, two-sequence, placebo-controlled crossover study in 12 subjects with bilateral primary open-angle glaucoma or ocular hypertension. Two 14-day crossover regimens were separated by a 2-week washout: ONO-9054 (1 drop to each eye) in the morning (07:00) and vehicle in the evening (19:00) and vice versa. IOP was measured multiple times during select days. Ocular examinations also evaluated safety and tolerability. Results Mild ocular hyperaemia, reported by six subjects with PM dosing, was the most frequent adverse event. Mild to moderate dryness was also slightly more frequent after PM dosing. Maximum IOP reduction from baseline occurred on day 2 with decreases from baseline of −7.4 mm Hg (−30.8%) for AM dosing and −9.1 mm Hg, (−38.0%) for PM dosing; after 14 days, mean reduction in IOP was −6.8 mm Hg (−28.6%) for AM dosing and −7.5 mm Hg (−31.0%) for PM dosing. Conclusions PM dosing of ONO-0954 was associated with a slightly increased frequency of mild hyperaemia and mild to moderate dryness. Both dosing schedules provided sustained reduction in IOP. Trial registration number NCT01670266. PMID:26453641

  4. Effect of Selective Prostaglandin E2 EP2 Receptor Agonist CP-533,536 on Voiding Efficiency in Rats with Midodrine-Induced Functional Urethral Obstruction.

    Science.gov (United States)

    Kurihara, Ryoko; Imazumi, Katsunori; Takamatsu, Hajime; Ishizu, Kenichiro; Yoshino, Taiji; Masuda, Noriyuki

    2016-05-01

    We investigated the effect of the selective prostaglandin E2 EP2 receptor agonist CP-533,536 on voiding efficiency in rats with midodrine-induced functional urethral obstruction. The effect of CP-533,536 (0.03-0.3 mg/kg, intravenous [i.v.]) on urethral perfusion pressure (UPP) was investigated in anesthetized rats pre-treated with midodrine (1 mg/kg, i.v.), which forms an active metabolite that acts as an α1 -adrenoceptor agonist. The effect of CP-533,536 (0.03-0.3 mg/kg, i.v.) on cystometric parameters was also investigated in anesthetized rats. In addition, the effect of CP-533,536 (0.03-0.3 mg/kg, i.v.) on residual urine volume (RV) and voiding efficiency (VE) was investigated in conscious rats treated with midodrine (1 mg/kg, i.v.). CP-533,536 dose-dependently decreased UPP elevated by midodrine in anesthetized rats. In contrast, CP-533,536 did not affect maximum voiding pressure, intercontraction interval, or intravesical threshold pressure. In conscious rats, midodrine (1 mg/kg, i.v.) markedly increased RV and reduced VE. CP-533,536 dose-dependently ameliorated increases in RV and decreases in VE induced by midodrine. These results suggest that a selective EP2 receptor agonist could ameliorate the elevation of RV and improve the reduction of VE in rats with functional urethral obstruction caused by stimulation of α1 -adrenoceptors. The mechanism of action might be not potentiation of bladder contraction but rather preferential relief of urethral constriction. © 2014 Wiley Publishing Asia Pty Ltd.

  5. Molecular and preclinical basis to inhibit PGE2 receptors EP2 and EP4 as a novel nonsteroidal therapy for endometriosis

    Science.gov (United States)

    Arosh, Joe A.; Lee, JeHoon; Balasubbramanian, Dakshnapriya; Stanley, Jone A.; Long, Charles R.; Meagher, Mary W.; Osteen, Kevin G.; Bruner-Tran, Kaylon L.; Burghardt, Robert C.; Starzinski-Powitz, Anna; Banu, Sakhila K.

    2015-01-01

    Endometriosis is a debilitating, estrogen-dependent, progesterone-resistant, inflammatory gynecological disease of reproductive age women. Two major clinical symptoms of endometriosis are chronic intolerable pelvic pain and subfertility or infertility, which profoundly affect the quality of life in women. Current hormonal therapies to induce a hypoestrogenic state are unsuccessful because of undesirable side effects, reproductive health concerns, and failure to prevent recurrence of disease. There is a fundamental need to identify nonestrogen or nonsteroidal targets for the treatment of endometriosis. Peritoneal fluid concentrations of prostaglandin E2 (PGE2) are higher in women with endometriosis, and this increased PGE2 plays important role in survival and growth of endometriosis lesions. The objective of the present study was to determine the effects of pharmacological inhibition of PGE2 receptors, EP2 and EP4, on molecular and cellular aspects of the pathogenesis of endometriosis and associated clinical symptoms. Using human fluorescent endometriotic cell lines and chimeric mouse model as preclinical testing platform, our results, to our knowledge for the first time, indicate that selective inhibition of EP2/EP4: (i) decreases growth and survival of endometriosis lesions; (ii) decreases angiogenesis and innervation of endometriosis lesions; (iii) suppresses proinflammatory state of dorsal root ganglia neurons to decrease pelvic pain; (iv) decreases proinflammatory, estrogen-dominant, and progesterone-resistant molecular environment of the endometrium and endometriosis lesions; and (v) restores endometrial functional receptivity through multiple mechanisms. Our novel findings provide a molecular and preclinical basis to formulate long-term nonestrogen or nonsteroidal therapy for endometriosis. PMID:26199416

  6. Structural characterization and antioxidant property of released exopolysaccharides from Lactobacillus delbrueckii ssp. bulgaricus SRFM-1.

    Science.gov (United States)

    Tang, Weizhi; Dong, Mingsheng; Wang, Weilu; Han, Shuo; Rui, Xin; Chen, Xiaohong; Jiang, Mei; Zhang, Qiuqin; Wu, Junjun; Li, Wei

    2017-10-01

    Three released exopolysaccharide fractions (r-EPS1, r-EPS2 and r-EPS3) were isolated from the fermented milk of Lactobacillus delbrueckii ssp. bulgaricus SRFM-1 and purified by anion exchange chromatography, and characterizations of the structures were conducted. The r-EPS1 and r-EPS2 were homogenous with the average molecular weights of 3.97×10 5 Da and 3.86×10 5 Da, respectively. Three r-EPS fractions were composed of galactose and glucose with a molar ratio of 1.23: 1.00, 1.33: 1.00 and 1.00: 1.34, respectively. Structural characterization indicated that the r-EPS1 contained a backbone of →6-β-d-Galp-(1→4)-β-d-Glcp-(1→4)-α-d-Galp-(1→4)-β-d-Galp-(1→6)-β-d-Galp-(1→4)-β-d-Glcp-(1→4)-α-d-Galp-(1→4)-β-d-Galp-(1→4)-α-d-Glcp-(1→, and had three branching points which existed in terminal with D-Glcp residues with α/β-d-(1→6) linkages. The r-EPS2 was composed of →6-β-d-Galp-(1→4)-β-d-Glcp-(1→6)-α-d-Galp-(1→ as the backbone chain with a branching point which also existed in terminal D-Glcp residue with β-(1→6) linkage. In addition, three r-EPS fractions exhibited strong scavenging activities on superoxide radical, hydroxyl radical, DPPH radical and chelating activity on ferrous ion, and their antioxidant activities decreased in the order of r-EPS1>r-EPS2>r-EPS3. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. The Influence Of Hydrothermal Alteration And Weathering On Rock Magnetic Properties Of Granites From The Eps-1 Drilling (soultz-sous-forÊts / France)

    Science.gov (United States)

    Just, J.; Schleicher, A.; Kontny, A.; de Wall, H.

    The EPS-1 drilling in Soultz-sous-Forêts (Rhinegraben, France) recovered a core pro- file of Tertiary to Permo-Mesozoic sediments deposited on a Variscan granitic base- ment. Magnetic susceptibility (k) measurements on the core material revealed a con- tinous increase from the basement/cover boundary (kmean 0.4 x 10-3 SI) into the magnetite-bearing granite (kmean 13 x 10-3 SI) over a depth range of 1417 U 1555 m. Rock magnetic and mineralogic studies were performed for the fresh granite, the hydrothermally altered granite near a fault zone and the altered granite from the fossil land surface near the basement/cover boundary. The decrease in susceptibility can be correlated with a gradual decomposition of magnetite to hematite and an alteration of the matrix minerals feldspars, biotite and hornblende to clay minerals and carbon- ates. Along with this transition, characteristic rock magnetic signatures can be dis- criminated for different degrees of alteration. While temperature-dependent magnetic susceptibility k(T)-curves in fresh granites indicate a typical multidomain magnetite course with good reversibility, different types of irreversible courses are observed for the altered granite. However, hematite could not be identified in the k(T)-curves. Al- tered granite shows relatively weak magnetic behaviour in AF-demagnetisation exper- iments, untypical for hematite. The alteration of the fresh granite also causes a change in magnetic fabric parameter, especially of the anisotropy factor. The magnetic min- eralogy from the altered granite in respect to the changes in rock magnetic properties will be discussed.

  8. Selective inhibition of prostaglandin E2 receptors EP2 and EP4 induces apoptosis of human endometriotic cells through suppression of ERK1/2, AKT, NFkappaB, and beta-catenin pathways and activation of intrinsic apoptotic mechanisms.

    Science.gov (United States)

    Banu, Sakhila K; Lee, JeHoon; Speights, V O; Starzinski-Powitz, Anna; Arosh, Joe A

    2009-08-01

    Endometriosis is a benign chronic gynecological disease of reproductive-age women characterized by the presence of functional endometrial tissues outside the uterine cavity. It is an estrogen-dependent disease. Current treatment modalities to inhibit biosynthesis and actions of estrogen compromise menstruation, pregnancy, and the reproductive health of women and fail to prevent reoccurrence of disease. There is a critical need to identify new specific signaling modules for non-estrogen-targeted therapies for endometriosis. In our previous study, we reported that selective inhibition of cyclooxygenase-2 prevented survival, migration, and invasion of human endometriotic epithelial and stromal cells, which was due to decreased prostaglandin E(2) (PGE(2)) production. In this study, we determined mechanisms through which PGE(2) promoted survival of human endometriotic cells. Results of the present study indicate that 1) PGE(2) promotes survival of human endometriotic cells through EP2 and EP4 receptors by activating ERK1/2, AKT, nuclear factor-kappaB, and beta-catenin signaling pathways; 2) selective inhibition of EP2 and EP4 suppresses these cell survival pathways and augments interactions between proapoptotic proteins (Bax and Bad) and antiapoptotic proteins (Bcl-2/Bcl-XL), facilitates the release of cytochrome c, and thus activates caspase-3/poly (ADP-ribose) polymerase-mediated intrinsic apoptotic pathways; and 3) these PGE(2) signaling components are more abundantly expressed in ectopic endometriosis tissues compared with eutopic endometrial tissues during the menstrual cycle in women. These novel findings may provide an important molecular framework for further evaluation of selective inhibition of EP2 and EP4 as potential therapy, including nonestrogen target, to expand the spectrum of currently available treatment options for endometriosis in women.

  9. 10 CFR Appendix A1 to Subpart B of... - Uniform Test Method for Measuring the Energy Consumption of Electric Refrigerators and Electric...

    Science.gov (United States)

    2010-01-01

    ... equivalent to: ET=(1440 × EP1/T1) + (EP2F − (EPF × T2/T1)) × 12/CTF + (EP2R − (EPR × T3/T1)) × 12/CTR Where 1440, EP1, T1, EP2, 12, and CT are defined in 5.2.1.2 EPF = energy expended in kilowatt-hours during...

  10. Differential trypanosome surface coat regulation by a CCCH protein that co-associates with procyclin mRNA cis-elements.

    Directory of Open Access Journals (Sweden)

    Pegine Walrad

    2009-02-01

    Full Text Available The genome of Trypanosoma brucei is unusual in being regulated almost entirely at the post-transcriptional level. In terms of regulation, the best-studied genes are procyclins, which encode a family of major surface GPI-anchored glycoproteins (EP1, EP2, EP3, GPEET that show differential expression in the parasite's tsetse-fly vector. Although procyclin mRNA cis-regulatory sequences have provided the paradigm for post-transcriptional control in kinetoplastid parasites, trans-acting regulators of procyclin mRNAs are unidentified, despite intensive effort over 15 years. Here we identify the developmental regulator, TbZFP3, a CCCH-class predicted RNA binding protein, as an isoform-specific regulator of Procyclin surface coat expression in trypanosomes. We demonstrate (i that endogenous TbZFP3 shows sequence-specific co-precipitation of EP1 and GPEET, but not EP2 and EP3, procyclin mRNA isoforms, (ii that ectopic overexpression of TbZFP3 does not perturb the mRNA abundance of procyclin transcripts, but rather that (iii their protein expression is regulated in an isoform-specific manner, as evidenced by mass spectrometric analysis of the Procyclin expression signature in the transgenic cell lines. The TbZFP3 mRNA-protein complex (TbZFP3mRNP is identified as a trans-regulator of differential surface protein expression in trypanosomes. Moreover, its sequence-specific interactions with procyclin mRNAs are compatible with long-established predictions for Procyclin regulation. Combined with the known association of TbZFP3 with the translational apparatus, this study provides a long-sought missing link between surface protein cis-regulatory signals and the gene expression machinery in trypanosomes.

  11. Expression of prostanoid receptors in human ductus arteriosus

    Science.gov (United States)

    Leonhardt, Andreas; Glaser, Alexander; Wegmann, Markus; Schranz, Dietmar; Seyberth, Hannsjörg; Nüsing, Rolf

    2003-01-01

    Prostaglandins play a major role in maintaining ductal patency in utero. Ductal tone is regulated by both locally released and circulating vasodilatory prostaglandins. In infants with ductus arteriosus-dependent congenital heart disease, ductal patency is maintained by intravenous administration of prostaglandin (PG) E1. Little information is available regarding the expression of prostaglandin receptors in man. By means of RT–PCR and immunohistochemistry we studied the expression of the PGI2 receptor (IP), the four different PGE2 receptors (EP1, EP2, EP3 and EP4), and the receptors for thromboxane (Tx) A2 (TP), PGD2 (DP) and PGF2α (FP) in the ductus arteriosus of three newborn infants with ductus arteriosus-dependent congenital heart disease and intravenous infusion of PGE1 and of one 8 month old child with a patent ductus arteriosus. The EP3, EP4, FP, IP and TP receptor were markedly expressed at the mRNA and protein level, whereas the EP2 receptor was weakly expressed and the EP1 receptor was detected in two out of four tissue specimens only. The DP receptor was not detected in any of the samples. The most pronounced expression, which was located in the media of the ductus arteriosus, was observed for the EP4 and TP receptors followed by IP and FP receptor protein. These data indicate that ductal patency during the infusion of PGE1 in infants with ductus arteriosus-dependent congenital heart disease might be mediated by the EP4 and IP receptor. The data further suggest that a heterogeneous population of prostanoid receptors may contribute to the regulation of ductus arteriosus tone in humans. PMID:12598419

  12. Reaction /sup 140/Ce (e, e'p), (2)

    Energy Technology Data Exchange (ETDEWEB)

    Saito, T; Shoda, K [Tohoku Univ., Sendai (Japan). Lab. of Nuclear Science

    1975-06-01

    An experiment was carried out to study the character of the resonance observed at 24.4 MeV in the /sup 140/Ce (..gamma.., p) /sup 139/La reaction. The (..gamma.., p/sub 0/ + p/sub 1/) cross section was measured at the angles of 54.7/sup 0/ and 125.3/sup 0/, at which the angle-dependent term of E1 becomes zero, for the energy range between 19 and 26 MeV. Existence of a peak due to the E2 resonance around 24.4 MeV was examined. The energy of incident electrons from a linear accelerator was changed between 20 and 26.7 MeV. The target was a Ce foil of 7.3 mg/cm/sup 2/ thick. The proton spectra due to the /sup 140/Ce (e, e' p) /sup 139/La reaction were measured with a broad range magnetic spectrometer. In the determined spectra of /sup 140/Ce (..gamma.., p/sub 0/+p/sub 1/) /sup 139/La, any remarkable peak, except one at 20.5 MeV, was not seen. From the observed spectra, the total cross section and the asymmetry factor due to interference were obtained as functions of energy. The values of the asymmetry factor were almost flat in the energy range between 19 and 26 MeV. The resonance at 24.4 MeV in the total cross section may be due to the E1 resonance, and is not due to the E2.

  13. Prostaglandin Receptor Signaling in Disease

    Directory of Open Access Journals (Sweden)

    Toshiyuki Matsuoka

    2007-01-01

    Full Text Available Prostanoids, consisting of the prostaglandins (PGs and the thromboxanes (TXs, are a group of lipid mediators formed in response to various stimuli. They include PGD2, PGE2, PGF2α, PGI2, and TXA2. They are released outside of the cells immediately after synthesis, and exert their actions by binding to a G-protein coupled rhodopsin-type receptor on the surface of target cells. There are eight types of the prostanoid receptors conserved in mammals from mouse to human. They are the PGD receptor (DP, four subtypes of the PGE receptor (EP1, EP2, EP3, and EP4, the PGF receptor (FP, PGI receptor (IP, and TXA receptor (TP. Recently, mice deficient in each of these prostanoid receptors were generated and subjected to various experimental models of disease. These studies have revealed the roles of PG receptor signaling in various pathological conditions, and suggest that selective manipulation of the prostanoid receptors may be beneficial in treatment of the pathological conditions. Here we review these recent findings of roles of prostanoid receptor signaling and their therapeutic implications.

  14. Misoprostol, an anti-ulcer agent and PGE2 receptor agonist, protects against cerebral ischemia.

    Science.gov (United States)

    Li, Jun; Liang, Xibin; Wang, Qian; Breyer, Richard M; McCullough, Louise; Andreasson, Katrin

    2008-06-20

    Induction of COX-2 activity in cerebral ischemia results in increased neuronal injury and infarct size. Recent studies investigating neurotoxic mechanisms of COX-2 demonstrate both toxic and paradoxically protective effects of downstream prostaglandin receptor signaling pathways. We tested whether misoprostol, a PGE(2) receptor agonist that is utilized clinically as an anti-ulcer agent and signals through the protective PGE(2) EP2, EP3, and EP4 receptors, would reduce brain injury in the murine middle cerebral artery occlusion-reperfusion (MCAO-RP) model. Administration of misoprostol, at the time of MCAO or 2h after MCAO, resulted in significant rescue of infarct volume at 24 and 72h. Immunocytochemistry demonstrated dynamic regulation of the EP2 and EP4 receptors during reperfusion in neurons and endothelial cells of cerebral cortex and striatum, with limited expression of EP3 receptor. EP3-/- mice had no significant changes in infarct volume compared to control littermates. Moreover, administration of misoprostol to EP3+/+ and EP3-/- mice showed similar levels of infarct rescue, indicating that misoprostol protection was not mediated through the EP3 receptor. Taken together, these findings suggest a novel function for misoprostol as a protective agent in cerebral ischemia acting via the PGE(2) EP2 and/or EP4 receptors.

  15. FOXC1 Regulates Expression of Prostaglandin Receptors Leading to an Attenuated Response to Latanoprost.

    Science.gov (United States)

    Doucette, Lance P; Footz, Tim; Walter, Michael A

    2018-05-01

    This study examines the effect of FOXC1 on the prostaglandin pathway in order to explore FOXC1's role in the prostaglandin-resistant glaucoma phenotype commonly seen in Axenfeld-Rieger syndrome. Binding and transcriptional activity of FOXC1 to the gene coding for the EP3 prostaglandin receptor (PTGER3) were evaluated through ChIP-qPCR and luciferase-based assays. Immortalized trabecular meshwork cells (TM1) and HeLa cells had FOXC1 mRNA reduced via siRNA interference. qPCR and Western blot experiments were conducted to examine the changes in prostaglandin receptor expression brought about by lowered FOXC1. TM1 cells were then treated with 10 μM latanoprost acid and/or an siRNA for FOXC1. The expression of fibronectin and matrix metalloproteinase 9 were evaluated via qPCR in each treatment condition. ChIP-qPCR and luciferase experiments confirmed that FOXC1 binds to and activates transcription of the EP3 gene prostaglandin receptor. qPCR and Western experiments in HeLa and TM1 cells showed that FOXC1 siRNA knockdown results in significantly lowered EP3 levels (protein and RNA). In addition, RNA levels of the other prostaglandin receptor genes EP1 (PTGER1), EP2 (PTGER2), EP4 (PTGER4), and FP (PTGFR) were altered when FOXC1 was knocked down in TM1 and HeLa cells. Analysis of fibronectin expression in TM1 cells after treatment with 10 μM latanoprost acid showed a statistically significant increase in expression; this increase was abrogated by cotreatment with a siRNA for FOXC1. We show the abrogation of latanoprost signalling when FOXC1 is knocked down via siRNA in a trabecular meshwork cell line. We propose that the lower levels of active FOXC1 in Axenfeld-Rieger syndrome patients with glaucoma account for the lack of response to prostaglandin-based medications.

  16. EP3 receptors inhibit antidiuretic-hormone-dependent sodium transport across frog skin epithelium

    DEFF Research Database (Denmark)

    Rytved, Klaus A.; Nielsen, Robert

    1999-01-01

    Antidiuretic hormone; tight epithelium; prostaglandin receptors; sulprostone; misoprostol; cAMP; cellular Ca2+......Antidiuretic hormone; tight epithelium; prostaglandin receptors; sulprostone; misoprostol; cAMP; cellular Ca2+...

  17. 40 CFR 158.2120 - Microbial pesticides product analysis data requirements table.

    Science.gov (United States)

    2010-07-01

    ... Certification of limits R MP EP -- Physical and Chemical Characteristics 830.6302 Color R TGAI TGAI -- 830.6303....6319 Miscibility R MP EP 2 830.6320 Corrosion Characteristics R MP EP 3 830.7000 pH R TGAI TGAI -- 830... pesticides are packaged in metal, plastic, or paper containers. 4. Only required for liquid forms of...

  18. A gender perspective on gambling clusters in Sweden using longitudinal data

    Directory of Open Access Journals (Sweden)

    Romild Ulla

    2016-02-01

    Full Text Available AIMS - This study describes five groups of gamblers and changes in their gambling involvement and gambling problems over four years with a particular focus on whether gambling problems among men and women develop differently within the five groups. DESIGN - The study sample is a subset of participants from the Swedish Longitudinal Gambling Study (Swelogs. Six different clusters of past-year gambling, based on frequency of participation in the nine most common forms of gambling in Sweden (lotteries, horses, number games, sports games, bingo, poker, slot machines, casino games or TV contests were identified in Two-Way Cluster Analysis after the first wave of data collection in 2008/09. There were 2,508 individuals identified in EP1 (n=5,012 who then also participated in waves EP2 and EP3 and were selected for the present analysis. METHODS - Statistical analysis was done in SPSS 22.0 using Pearson’s Chi-Square test of Independence (or Fisher’s Exact test when the requirements or expected frequency were not met for Pearson’s Test, Mann-Whitney U-test and logistic regression. P-values below 0.05 were regarded as significant. RESULTS - Gambling remains gendered in Sweden. Even though the clusters are based on gambling activities, there are differences between men and women within the clusters as regards the gambling participation patterns. CONCLUSIONS - Men and women gamble differently, but they may still be equals in their total experience of gambling and in relation to how their gambling problems develop. All differences need to be taken into consideration when preventive actions or messages are created.

  19. Regulation of rat intrapulmonary arterial tone by arachidonic acid and prostaglandin E2 during hypoxia.

    Directory of Open Access Journals (Sweden)

    Gaoliang Yan

    Full Text Available Arachidonic acid (AA and its metabolites, prostaglandins (PG are known to be involved in regulation of vascular homeostasis including vascular tone and vessel wall tension, but their potential role in Hypoxic pulmonary vasoconstriction (HPV remains unclear. In this study, we examined the effects of AA and PGE2 on the hypoxic response in isolated rat intrapulmonary arteries (IPAs.We carried out the investigation on IPAs by vessel tension measurement. Isotetrandrine (20 µM significantly inhibited phase I, phase IIb and phase IIc of hypoxic vasoconstriction. Both indomethacin (100 µM and NS398 attenuated KPSS-induced vessel contraction and phase I, phase IIb and phase IIc of HPV, implying that COX-2 plays a primary role in the hypoxic response of rat IPAs. PGE2 alone caused a significant vasoconstriction in isolated rat IPAs. This constriction is mediated by EP4. Blockage of EP4 by L-161982 (1 µM significantly inhibited phase I, phase IIb and phase IIc of hypoxic vasoconstriction. However, AH6809 (3 µM, an antagonist of EP1, EP2, EP3 and DP1 receptors, exerted no effect on KPSS or hypoxia induced vessel contraction. Increase of cellular cAMP by forskolin could significantly reduce KPSS-induced vessel contraction and abolish phase I, phase II b and phase II c of HPV.Our results demonstrated a vasoconstrictive effect of PGE2 on rat IPAs and this effect is via activation of EP4. Furthermore, our results suggest that intracellular cAMP plays dual roles in regulation of vascular tone, depending on the spatial distribution of cAMP and its coupling with EP receptor and Ca(2+ channels.

  20. The EP4 receptor antagonist, L-161,982, blocks prostaglandin E2-induced signal transduction and cell proliferation in HCA-7 colon cancer cells

    International Nuclear Information System (INIS)

    Cherukuri, Durga Prasad; Chen, Xiao B.O.; Goulet, Anne-Christine; Young, Robert N.; Han, Yongxin; Heimark, Ronald L.; Regan, John W.; Meuillet, Emmanuelle; Nelson, Mark A.

    2007-01-01

    Accumulating evidence indicates that elevated levels of prostaglandin E 2 (PGE 2 ) can increase intestinal epithelial cell proliferation, and thus play a role in colorectal tumorigenesis. PGE 2 exerts its effects through four G-protein-coupled PGE receptor (EP) subtypes, named the EP1, EP2, EP3, and EP4. Increased phosphorylation of extracellular regulated kinases (ERK1/2) is required for PGE 2 to stimulate cell proliferation of human colon cancer cells. However, the EP receptor(s) that are involved in this process remain unknown. We provide evidence that L-161,982, a selective EP4 receptor antagonist, completely blocks PGE 2 -induced ERK phosphorylation and cell proliferation of HCA-7 cells. In order to identify downstream target genes of ERK1/2 signaling, we found that PGE 2 induces expression of early growth response gene-1 (EGR-1) downstream of ERK1/2 and regulates its expression at the level of transcription. PGE 2 treatment induces phosphorylation of cyclic AMP response element binding protein (CREB) at Ser133 residue and CRE-mediated luciferase activity in HCA-7 cells. Studies with dominant-negative CREB mutant (ACREB) provide clear evidence for the involvement of CREB in PGE 2 driven egr-1 transcription in HCA-7 cells. In conclusion, this study reveals that egr-1 is a target gene of PGE 2 in HCA-7 cells and is regulated via the newly identified EP4/ERK/CREB pathway. Finally our results support the notion that antagonizing EP4 receptors may provide a novel therapeutic approach to the treatment of colon cancer

  1. 40 CFR 158.2081 - Experimental use permit biochemical pesticides product chemistry data requirements table.

    Science.gov (United States)

    2010-07-01

    ... composition R TGAI, MP TGAI, EP 1, 2 880.1200 Description of starting materials, production and formulation process R TGAI, MP TGAI, EP 2, 3 880.1400 Discussion of formation of impurities R TGAI and MP TGAI and EP... TGAI TGAI 8 830.6313 Stability to normal and elevated temperatures, metals and metal ions R TGAI TGAI 8...

  2. Structure and biosynthesis of two exopolysaccharides produced by Lactobacillus johnsonii FI9785.

    Science.gov (United States)

    Dertli, Enes; Colquhoun, Ian J; Gunning, A Patrick; Bongaerts, Roy J; Le Gall, Gwénaëlle; Bonev, Boyan B; Mayer, Melinda J; Narbad, Arjan

    2013-11-01

    Exopolysaccharides were isolated and purified from Lactobacillus johnsonii FI9785, which has previously been shown to act as a competitive exclusion agent to control Clostridium perfringens in poultry. Structural analysis by NMR spectroscopy revealed that L. johnsonii FI9785 can produce two types of exopolysaccharide: EPS-1 is a branched dextran with the unusual feature that every backbone residue is substituted with a 2-linked glucose unit, and EPS-2 was shown to have a repeating unit with the following structure: -6)-α-Glcp-(1-3)-β-Glcp-(1-5)-β-Galf-(1-6)-α-Glcp-(1-4)-β-Galp-(1-4)-β-Glcp-(1-. Sites on both polysaccharides were partially occupied by substituent groups: 1-phosphoglycerol and O-acetyl groups in EPS-1 and a single O-acetyl group in EPS-2. Analysis of a deletion mutant (ΔepsE) lacking the putative priming glycosyltransferase gene located within a predicted eps gene cluster revealed that the mutant could produce EPS-1 but not EPS-2, indicating that epsE is essential for the biosynthesis of EPS-2. Atomic force microscopy confirmed the localization of galactose residues on the exterior of wild type cells and their absence in the ΔepsE mutant. EPS2 was found to adopt a random coil structural conformation. Deletion of the entire 14-kb eps cluster resulted in an acapsular mutant phenotype that was not able to produce either EPS-2 or EPS-1. Alterations in the cell surface properties of the EPS-specific mutants were demonstrated by differences in binding of an anti-wild type L. johnsonii antibody. These findings provide insights into the biosynthesis and structures of novel exopolysaccharides produced by L. johnsonii FI9785, which are likely to play an important role in biofilm formation, protection against harsh environment of the gut, and colonization of the host.

  3. Synthesis of the IRSN report related to severe accidents and to the probabilistic level-2 safety study for the Flamanville EPR reactor. Referral of the Permanent Group of Experts for nuclear reactors (GPR), examination of probabilistic level-2 safety studies (EPS 2) and severe accidents (AG) of the Flamanville reactor nr 3. Opinion related to severe accidents and to the probabilistic level-2 safety study for the Flamanville EPR reactor (FA3). Electronuclear reactors - EDF - Flamanville 3 EPR reactor. Severe accidents and probabilistic level 2 studies

    International Nuclear Information System (INIS)

    2015-01-01

    This document gathers several documents. The first one recalls the main arrangements implemented on the FA3 EPR reactor regarding accidents with core fusion, reports the analysis made by the IRSN about the sizing of these arrangements to reach a controlled status of the installation after a severe accident, regarding the probabilistic level-2 safety assessment, regarding the radiological impact of a severe accident on the population and on the environment, regarding those aimed at facing a total and long duration loss of electric power sources and cold sources, and about the situation of the reactor with respect to WENRA positions on severe accidents for new reactors. The second document is a letter sent by the ASN to the Permanent Group of Experts for nuclear reactors (GPR) to address probabilistic level-2 safety studies (EPS2) and severe accidents for the Flamanville 3 reactor. The third one reports the opinion of the GPR on these both issues and proposes a set of recommendations. The next document is a letter sent by the ASN to the Flamanville 3 project manager at EDF which recalls the related objectives, the ASN opinion on the implemented arrangements for severe accidents (de-pressurization of the primary circuit, management of hydrogen-related risks, corium recovery and cooling outside the vessel, limitation of vapour explosion risks outside the vessel, heat evacuation system, containment enclosure, management of the risk of a return to criticality), to face a total and long duration loss of electricity sources and cold sources, and other aspects addressed in the IRSN analysis. Requests and remarks formulated by the ASN are provided in an appendix to this last document

  4. Misoprostol, an anti-ulcer agent and PGE2 receptor agonist, protects against cerebral ischemia

    OpenAIRE

    Li, Jun; Liang, Xibin; Wang, Qian; Breyer, Richard M.; McCullough, Louise; Andreasson, Katrin

    2008-01-01

    Induction of COX-2 activity in cerebral ischemia results in increased neuronal injury and infarct size. Recent studies investigating neurotoxic mechanisms of COX-2 demonstrate both toxic and paradoxically protective effects of downstream prostaglandin receptor signaling pathways. We tested whether misoprostol, a PGE2 receptor agonist that is utilized clinically as an anti-ulcer agent and signals through the protective PGE2 EP2, EP3, and EP4 receptors, would reduce brain injury in the murine m...

  5. Production and properties of two novel exopolysaccharides synthesized by a thermophilic bacterium Aeribacillus pallidus 418.

    Science.gov (United States)

    Radchenkova, Nadja; Vassilev, Spasen; Panchev, Ivan; Anzelmo, Gianluca; Tomova, Iva; Nicolaus, Barbara; Kuncheva, Margarita; Petrov, Kaloyan; Kambourova, Margarita

    2013-09-01

    Synthesis of innovative exocellular polysaccharides (EPSs) was reported for few thermophilic microorganisms as one of the mechanisms for surviving at high temperature. Thermophilic aerobic spore-forming bacteria able to produce exopolysaccharides were isolated from hydrothermal springs in Bulgaria. They were referred to four species, such as Aeribacillus pallidus, Geobacillus toebii, Brevibacillus thermoruber, and Anoxybacillus kestanbolensis. The highest production was established for the strain 418, whose phylogenetic and phenotypic properties referred it to the species A. pallidus. Maltose and NH4Cl were observed to be correspondingly the best carbon and nitrogen sources and production yield was increased more than twofold in the process of culture condition optimization. After purification of the polymer fraction, a presence of two different EPSs, electroneutral EPS 1 and negatively charged EPS 2, in a relative weight ratio 3:2.2 was established. They were heteropolysaccharides consisting of unusual high variety of sugars (six for EPS 1 and seven for EPS 2). Six of the sugars were common for both EPSs. The main sugar in EPS 1 was mannose (69.3 %); smaller quantities of glucose (11.2 %), galactosamine (6.3 %), glucosamine (5.4 %), galactose (4.7 %), and ribose (2.9 %) were also identified. The main sugar in EPS 2 was also mannose (33.9 %), followed by galactose (17.9 %), glucose (15.5 %), galactosamine (11.7 %), glucosamine (8.1 %), ribose (5.3 %), and arabinose (4.9 %). Both polymers showed high molecular weight and high thermostability.

  6. Functional and molecular characterization of hyposensitive underactive bladder tissue and urine in streptozotocin-induced diabetic rat.

    Directory of Open Access Journals (Sweden)

    Jayabalan Nirmal

    Full Text Available The functional and molecular alterations of nerve growth factor (NGF and Prostaglandin E2 (PGE2 and its receptors were studied in bladder and urine in streptozotocin (STZ-induced diabetic rats.Diabetes mellitus was induced with a single dose of 45 mg/kg STZ Intraperitoneally (i.p in female Sprague-Dawley rats. Continuous cystometrogram were performed on control rats and STZ treated rats at week 4 or 12 under urethane anesthesia. Bladder was then harvested for histology, expression of EP receptors and NGF by western blotting, PGE2 levels by ELISA, and detection of apoptosis by TUNEL staining. In addition, 4-hr urine was collected from all groups for urine levels of PGE2, and NGF assay. DM induced progressive increase of bladder weight, urine production, intercontraction interval (ICI and residual urine in a time dependent fashion. Upregulation of Prostaglandin E receptor (EP1 and EP3 receptors and downregulation of NGF expression, increase in urine NGF and decrease levels of urine PGE2 at week 12 was observed. The decrease in ICI by intravesical instillation of PGE2 was by 51% in control rats and 31.4% in DM group at week 12.DM induced hyposensitive underactive bladder which is characterized by increased inflammatory reaction, apoptosis, urine NGF levels, upregulation of EP1 and EP3 receptors and decreased bladder NGF and urine PGE2. The data suggest that EP3 receptor are potential targets in the treatment of diabetes induced underactive bladder.

  7. EpsA is an essential gene in exopolysaccharide production in Lactobacillus johnsonii FI9785.

    Science.gov (United States)

    Dertli, Enes; Mayer, Melinda J; Colquhoun, Ian J; Narbad, Arjan

    2016-07-01

    Lactobacillus johnsonii FI9785 has an eps gene cluster which is required for the biosynthesis of homopolymeric exopolysaccharides (EPS)-1 and heteropolymeric EPS-2 as a capsular layer. The first gene of the cluster, epsA, is the putative transcriptional regulator. In this study we showed the crucial role of epsA in EPS biosynthesis by demonstrating that deletion of epsA resulted in complete loss of both EPS-1 and EPS-2 on the cell surface. Plasmid complementation of the epsA gene fully restored EPS production, as confirmed by transmission electron microscopy and nuclear magnetic resonance (NMR) analysis. Furthermore, this complementation resulted in a twofold increase in the expression levels of this gene, which almost doubled amounts of EPS production in comparison with the wild-type strain. Analysis of EPS by NMR showed an increased ratio of the heteropolysaccharide to homopolysaccharide in the complemented strain and allowed identification of the acetylated residue in EPS-2 as the (1,4)-linked βGlcp unit, with the acetyl group located at O-6. These findings indicate that epsA is a positive regulator of EPS production and that EPS production can be manipulated by altering its expression. © 2015 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

  8. Differential regulation of renal prostaglandin receptor mRNAs by dietary salt intake in the rat

    DEFF Research Database (Denmark)

    Jensen, B L; Mann, Birgitte; Skøtt, O

    1999-01-01

    and cells by ribonuclease protection assay and reverse transcription-polymerase chain reaction analysis. Functional correlates were studied by measurement of PGE2-induced cAMP formation and renin secretion in juxtaglomerular (JG) cells isolated from animals on various salt intakes. RESULTS: EP1 and EP3......BACKGROUND: In this study, we tested the hypothesis that prostaglandin (PG) receptor expression in the rat kidney is subject to physiological regulation by dietary salt intake. METHODS: Rats were fed diets with 0.02 or 4% NaCl for two weeks. PG receptor expression was assayed in kidney regions...... did not affect the expression of EP1 or IP receptors, whereas EP4 transcripts in glomeruli were increased twofold by salt deprivation. Consistent with this, we found that PGE2-evoked cAMP production and renin secretion by JG cells from salt-deprived animals were significantly higher compared...

  9. Control of flowering time and spike development in cereals: the earliness per se Eps-1 region in wheat, rice, and Brachypodium

    Czech Academy of Sciences Publication Activity Database

    Faricelli, M. E.; Valárik, Miroslav; Dubcovsky, J.

    2010-01-01

    Roč. 10, č. 2 (2010), s. 293-306 ISSN 1438-793X Institutional research plan: CEZ:AV0Z50380511 Keywords : Comparative genomics * Earliness per se * Flowering Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.397, year: 2010

  10. Extended Holomorphic Anomaly in Gauge Theory

    CERN Document Server

    Krefl, Daniel

    2011-01-01

    The partition function of an N=2 gauge theory in the Omega-background satisfies, for generic value of the parameter beta=-eps_1/eps_2, the, in general extended, but otherwise beta-independent, holomorphic anomaly equation of special geometry. Modularity together with the (beta-dependent) gap structure at the various singular loci in the moduli space completely fixes the holomorphic ambiguity, also when the extension is non-trivial. In some cases, the theory at the orbifold radius, corresponding to beta=2, can be identified with an "orientifold" of the theory at beta=1. The various connections give hints for embedding the structure into the topological string.

  11. Selective inhibition of prostaglandin E2 receptors EP2 and EP4 inhibits adhesion of human endometriotic epithelial and stromal cells through suppression of integrin-mediated mechanisms.

    Science.gov (United States)

    Lee, JeHoon; Banu, Sakhila K; Burghardt, Robert C; Starzinski-Powitz, Anna; Arosh, Joe A

    2013-03-01

    Endometriosis is a chronic gynecological disease of reproductive age women characterized by the presence of functional endometrial tissues outside the uterine cavity. Interactions between the endometriotic cells and the peritoneal extracellular matrix proteins (ECM) are crucial mechanisms that allow adhesion of the endometriotic cells into peritoneal mesothelia. Prostaglandin E2 (PGE2) plays an important role in the pathogenesis of endometriosis. In previous studies, we have reported that selective inhibition of PGE2 receptors PTGER2 and PTGER4 decreases survival and invasion of human endometriotic epithelial and stromal cells through multiple mechanisms. Results of the present study indicates that selective inhibition of PTGER2- and PTGER4-mediated PGE2 signaling 1) decreases the expression and/or activity of specific integrin receptor subunits Itgb1 (beta1) and Itgb3 (beta3) but not Itgb5 (beta5), Itga1 (alpha1), Itga2 (alpha2), Itga5 (alpha5), and Itgav (alphav); 2) decreases integrin-signaling components focal adhesion kinase or protein kinase 2 (PTK2) and talin proteins; 3) inhibits interactions between Itgb1/Itgb3 subunits, PTK2, and talin and PTGER2/PTGER4 proteins through beta-arrestin-1 and Src kinase protein complex in human endometriotic epithelial cells 12Z and stromal cells 22B; and 4) decreases adhesion of 12Z and 22B cells to ECM collagen I, collagen IV, fibronectin, and vitronectin in a substrate-specific manner. These novel findings provide an important molecular framework for further evaluation of selective inhibition of PTGER2 and PTGER4 as potential nonsteroidal therapy to expand the spectrum of currently available treatment options for endometriosis in child-bearing age women.

  12. Estudio de factibilidad para el desarrollo de un proyecto de inteligencia de negocios para una empresa pública de servicios, caso Etapa EP2

    OpenAIRE

    Mejía Freire, José Xavier

    2010-01-01

    La presente investigación analizó la situación actual de la Gerencia Comercial de la empresa ETAPA EP en función al desarrollo de proyectos de Inteligencia de Negocio.Para esto se evalúa diferentes aspectos como son: las Tecnologías de información para la Toma de Decisiones, Repositorio de Almacenamiento Corporativo, y Monitoreo para la Toma de decisiones.Esta evaluación se realizó por medio de entrevistas al personal del área de negocio así como al personal técnico del departamento inform...

  13. Molecular modeling and in-silico engineering of Cardamom mosaic virus coat protein for the presentation of immunogenic epitopes of Leptospira LipL32.

    Science.gov (United States)

    Kumar, Vikram; Damodharan, S; Pandaranayaka, Eswari P J; Madathiparambil, Madanan G; Tennyson, Jebasingh

    2016-01-01

    Expression of Cardamom mosaic virus (CdMV) coat protein (CP) in E. coli forms virus-like particles. In this study, the structure of CdMV CP was predicted and used as a platform to display epitopes of the most abundant surface-associated protein, LipL32 of Leptospira at C, N, and both the termini of CdMV CP. In silico, we have mapped sequential and conformational B-cell epitopes from the crystal structure of LipL32 of Leptospira interrogans serovar Copenhageni str. Fiocruz L1-130 using IEDB Elipro, ABCpred, BCPRED, and VaxiJen servers. Our results show that the epitopes displayed at the N-terminus of CdMV CP are promising vaccine candidates as compared to those displayed at the C-terminus or at both the termini. LipL32 epitopes, EP2, EP3, EP4, and EP6 are found to be promising B-cell epitopes for vaccine development. Based on the type of amino acids, length, surface accessibility, and docking energy with CdMV CP model, the order of antigenicity of the LipL32 epitopes was found to be EP4 > EP3 > EP2 > EP6.

  14. Polysaccharides from Extremophilic Microorganisms

    Science.gov (United States)

    Nicolaus, B.; Moriello, V. Schiano; Lama, L.; Poli, A.; Gambacorta, A.

    2004-02-01

    Several marine thermophilic strains were analyzed for exopolysaccharide production. The screening process revealed that a significant number of thermophilic microorganisms were able to produce biopolymers, and some of them also revealed interesting chemical compositions. We have identified four new polysaccharides from thermophilic marine bacteria, with complex primary structures and with different repetitive units: a galacto-mannane type from strain number 4004 and mannane type for the other strains. The thermophilic Bacillus thermantarcticus produces two exocellular polysaccharides (EPS 1, EPS 2) that give the colonies a typical mucous character. The exopolysaccharide fraction was produced with all substrates assayed, although a higher yield 400 mg liter-1 was obtained with mannose as carbon and energy source. NMR spectra confirmed that EPS 1 was a heteropolysaccharide of which the repeating unit was constituted by four different α-D-mannoses and three different β-D-glucoses. It seems to be close to some xantan polymers. EPS 2 was a mannan. Four different α-D-mannoses were found as the repeating unit. Production and chemical studies of biopolymers produced by halophilic archaea, Haloarcula species were also reported.

  15. Ultrastructural and cellular damage to rat lung with x-rays: a search for target cell in lung tissue

    Energy Technology Data Exchange (ETDEWEB)

    Furuta, I

    1975-03-01

    Radiation effects on the peripheral alveoli of conventional rats were examined by means of electron microscopy. The right hemithorax alone was exposed to various single doses of x rays. The initial cellular lesions selectively involved the cytoplasms of alveolar capillary endothelial (Ed) and type 1 epithelial (Ep 1) cells in a dose-dependent fashion, where the major alterations were multifocal vacuolations and swellings. These lesions became visible as early as 1 hr after 1000 R (the assumed mean lethal dose for Ed cells) and more. However, progenitor Ep 2 cells exhibited no obvious cytoplasmic lesions by the doses below 2000 R, indicating that Ep 2 cells are more resistant to x rays. With time following 1000 R, the capillary Ed blebbing abruptly developed in various forms from the sites presumably other than the Ed junctions. The Ed blebs and interstitial edema progressed until about 2 weeks without recovery, while some signs of cellular recovery were recognized in Ep 1 cells during this period. The observations after a long period of 6 months following 1000 R showed that the typical pulmonary fibrotic changes were initiated in the interstitium perhaps around unrepaired capillaries. Further, inflammatory reaction characterized by massive cellular infiltations was superimposed on developing pulmonary fibrosis. Considering the current knowledge about the cell sensitivity and renewal in stable tissues, the present results imply that capillary Ed cell is the primary target for the radiation lesion leading to the secondary pulmonary alterations.

  16. Effects of extruded pellet and moist pellet on growth performance, body composition, and hematology of juvenile olive flounder, Paralichthys olivaceus

    Directory of Open Access Journals (Sweden)

    Seunghan Lee

    2016-10-01

    Full Text Available Abstract A feeding trial was conducted to evaluate the effects of two different sizes of extruded pellets (EP (EP1 - 3 mm or EP2 - 5 mm and a moist pellet (MP in olive flounder, Paralichthys olivaceus, reared in semi-recirculation system. A total of 450 fish with an average initial weight of 5.0 ± 0.2 g (mean ± SD were fed one of the three experimental diets in triplicate groups. At the end of a 6-week feeding trial, weight gain, specific growth rate, and feed efficiency of fish fed EP diets were significantly higher than those of fish fed MP (P < 0.05. Water quality parameters like turbidity, total ammonia nitrogen, and total phosphorous from tanks of fish fed EP1 and EP2 were significantly lower than those from tanks of fish fed MP. Blood plasma glutamic oxaloacetic transaminase and glucose concentration were significantly higher in fish fed MP diet compared to fish fed EP diets (P < 0.05. Whole body crude protein contents in fish fed EP diets were higher than those from the fish fed MP diet. Whole body amino acid content like threonine, aspartic acid, serine, tyrosine, and cystine were found to be significantly higher in fish fed EP diets than those in fish fed MP diet. In considering overall performance of olive flounder, EP2 diet could be recommended for the successful aquaculture of this important fish species.

  17. Prostaglandin E2 facilitates neurite outgrowth in a motor neuron-like cell line, NSC-34

    Directory of Open Access Journals (Sweden)

    Hiroshi Nango

    2017-10-01

    Full Text Available Prostaglandin E2 (PGE2 exerts various biological effects by binding to E-prostanoid receptors (EP1-4. Although recent studies have shown that PGE2 induces cell differentiation in some neuronal cells such as mouse DRG neurons and sensory neuron-like ND7/23 cells, it is unclear whether PGE2 plays a role in differentiation of motor neurons. In the present study, we investigated the mechanism of PGE2-induced differentiation of motor neurons using NSC-34, a mouse motor neuron-like cell line. Exposure of undifferentiated NSC-34 cells to PGE2 and butaprost, an EP2-selective agonist, resulted in a reduction of MTT reduction activity without increase the number of propidium iodide-positive cells and in an increase in the number of neurite-bearing cells. Sulprostone, an EP1/3 agonist, also significantly lowered MTT reduction activity by 20%; however, no increase in the number of neurite-bearing cells was observed within the concentration range tested. PGE2-induced neurite outgrowth was attenuated significantly in the presence of PF-0441848, an EP2-selective antagonist. Treatment of these cells with dibutyryl-cAMP increased the number of neurite-bearing cells with no effect on cell proliferation. These results suggest that PGE2 promotes neurite outgrowth and suppresses cell proliferation by activating the EP2 subtype, and that the cAMP-signaling pathway is involved in PGE2-induced differentiation of NSC-34 cells. Keywords: Prostaglandin E2, E-prostanoid receptors, Motor neuron, Neurite outgrowth, cAMP

  18. Involvement of Cox-2 in the metastatic potential of chemotherapy-resistant breast cancer cells

    International Nuclear Information System (INIS)

    Kang, Ju-Hee; Song, Ki-Hoon; Jeong, Kyung-Chae; Kim, Sunshin; Choi, Changsun; Lee, Chang Hoon; Oh, Seung Hyun

    2011-01-01

    A major problem with the use of current chemotherapy regimens for several cancers, including breast cancer, is development of intrinsic or acquired drug resistance, which results in disease recurrence and metastasis. However, the mechanisms underlying this drug resistance are unknown. To study the molecular mechanisms underlying the invasive and metastatic activities of drug-resistant cancer cells, we generated a doxorubicin-resistant MCF-7 breast cancer cell line (MCF-7/DOX). We used MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays, flow cytometry assays, DNA fragmentation assays, Western blot analysis, cell invasion assays, small interfering RNA (siRNA) transfection, reverse transcription-polymerase chain reaction, experimental lung metastasis models, and gelatin and fibrinogen/plasminogen zymography to study the molecular mechanism of metastatic activities in MCF-7/DOX cells. We found that MCF-7/DOX acquired invasive activities. In addition, Western blot analysis showed increased expression of epidermal growth factor receptor (EGFR) and Cox-2 in MCF-7/DOX cells. Inhibition of Cox-2, phosphoinositide 3-kinase (PI3K)/Akt, or mitogen-activated protein kinase (MAPK) pathways effectively inhibited the invasive activities of MCF-7/DOX cells. Gelatin and fibrinogen/plasminogen zymography analysis showed that the enzymatic activities of matrix metalloproteinase-2 (MMP-2), MMP-9, and urokinase-type plasminogen activator were markedly higher in MCF-7/DOX cells than in the MCF-7 cells. In vitro invasion assays and mouse models of lung metastasis demonstrated that MCF-7/DOX cells acquired invasive abilities. Using siRNAs and agonists specific for prostaglandin E (EP) receptors, we found that EP1 and EP3 played important roles in the invasiveness of MCF-7/DOX cells. We found that the invasive activity of MCF-7/DOX cells is mediated by Cox-2, which is induced by the EGFR-activated PI3K/Akt and MAPK pathways. In addition, EP1 and EP3 are important in

  19. Determinação da escala de coloração da casca e do rendimento em suco do maracujá-amarelo em diferentes épocas de colheita Determination of the peel color scale and juice yield of yellow passion fruits in different harvest seasons

    Directory of Open Access Journals (Sweden)

    Thais Vianna Silva

    2008-12-01

    Full Text Available Este trabalho teve como objetivo determinar uma escala de coloração da casca para identificar o estádio de maturação do maracujá-amarelo e avaliar o rendimento em suco, em diferentes épocas de colheita. Os experimentos foram constituídos de 2 épocas de colheita, contemplando a estação de menor temperatura e menor precipitação de chuvas (EP1-Maio/Setembro, a estação de maior temperatura e precipitação de chuvas (EP2-Outubro/Dezembro e 7 estádios de maturação, com 10 repetições. Os resultados foram avaliados pelo teste de Tukey, a 5% de significância. O parâmetro b de Hunter foi utilizado como o indexador da mudança da coloração amarela. Verificou-se que a mudança de coloração ocorreu no sentido da base para o pedúnculo do fruto. Os frutos da época EP2 apresentaram a maior espessura de casca e o menor rendimento em suco, nos estádios iniciais de amadurecimento. Nos frutos com mais de 65,9% da casca amarelada, a época de colheita não influenciou na espessura da casca e no rendimento em suco, apresentando níveis máximos de suco. Frutos da época EP1 apresentaram o máximo rendimento a partir do estádio com 21,3% de cor amarela.This work had the aim to determinate the peel color scale intended to identify the ripening stage of the yellow passion fruit and evaluate its juice yield in different harvest seasons. The experiments were constituted of 2 harvest seasons and they were accomplished during the period of low temperatures and less precipitation (EP1 - May/September and high temperatures and more precipitation (EP2 - October/December, and seven ripening stages using ten replications. The results were compared by applying the Tukey test at the level of 5% of probability. Hunter b parameter was used as the yellowing index. It was verified that the yellow color progressed from the base to the fruit peduncle. Fruits from the EP2 season presented the lowest juice yield and the highest peel thickness in the early

  20. Pacing-induced chronic atrial fibrillation impairs sinus node function in dogs. Electrophysiological remodeling.

    Science.gov (United States)

    Elvan, A; Wylie, K; Zipes, D P

    1996-12-01

    We assessed the effects of pacing-induced chronic atrial fibrillation (AF) on sinus node function, intra-atrial conduction, and atrial refractoriness. In 15 mongrel dogs (20 to 30 kg), AV nodal block was produced by radiofrequency catheter ablation, and a ventricular-inhibited (VVI) pacemaker (Minix 8330, Medtronic) was implanted and programmed to pace at 80 pulses per minute. In 11 of these dogs, right atrial endocardial pacing leads were connected to a pulse generator (Itrel 7432, Medtronic) and set at a rate of 20 Hz to induce AF. Corrected sinus node recovery time, P-wave duration, 24-hour Holter ECG to assess AF duration, maximal heart rate in response to isoproterenol (10 micrograms/min), intrinsic heart rate after administration of atropine (0.04 mg/kg) and propranolol (0.1 mg/kg), and atrial effective refractory periods (ERPs) were obtained at baseline (EPS-1) and after 2 to 6 weeks (EPS-2) of VVI pacing alone (n = 4) or VVI pacing and rapid atrial pacing (n = 11). At EPS-2, corrected sinus node recovery time and P-wave duration were prolonged, maximal heart rate and intrinsic heart rate were decreased, atrial ERPs were shortened, and the duration of AF was increased significantly compared with EPS-1. These changes partially reversed toward baseline 1 week after conversion to sinus rhythm. Sinus node function and AF inducibility observed in the control dogs that underwent ventricular pacing alone (n = 4) did not change. Pacing-induced chronic AF induces sinus node dysfunction, prolongs intra-atrial conduction time, shortens atrial refractoriness, and perpetuates AF, changes that reverse gradually after termination of AF.

  1. The protection of meloxicam against chronic aluminium overload-induced liver injury in rats.

    Science.gov (United States)

    Yang, Yang; He, Qin; Wang, Hong; Hu, Xinyue; Luo, Ying; Liang, Guojuan; Kuang, Shengnan; Mai, Shaoshan; Ma, Jie; Tian, Xiaoyan; Chen, Qi; Yang, Junqing

    2017-04-04

    The present study was designed to observe the protective effect and mechanisms of meloxicam on liver injury caused by chronic aluminium exposure in rats. The histopathology was detected by hematoxylin-eosin staining. The levels of prostaglandin E2, cyclic adenosine monophosphate and inflammatory cytokines were detected by enzyme linked immunosorbent assay. The expressions of cyclooxygenases-2, prostaglandin E2 receptors and protein kinase A were measured by western blotting and immunohistochemistry. Our experimental results showed that aluminium overload significantly damaged the liver. Aluminium also significantly increased the expressions of cyclooxygenases-2, prostaglandin E2, cyclic adenosine monophosphate, protein kinase A and the prostaglandin E2 receptors (EP1,2,4) and the levels of inflammation and oxidative stress, while significantly decreased the EP3 expression in liver. The administration of meloxicam significantly improved the impairment of liver. The contents of prostaglandin E2 and cyclic adenosine monophosphate were significantly decreased by administration of meloxicam. The administration of meloxicam also significantly decreased the expressions of cyclooxygenases-2 and protein kinase A and the levels of inflammation and oxidative stress, while significantly increased the EP1,2,3,4 expressions in rat liver. Our results suggested that the imbalance of cyclooxygenases-2 and downstream prostaglandin E2 signaling pathway is involved in the injury of chronic aluminium-overload rat liver. The protective mechanism of meloxicam on aluminium-overload liver injury is attributed to reconstruct the balance of cyclooxygenases-2 and downstream prostaglandin E2 signaling pathway.

  2. Prostaglandin E2 and the protein kinase A pathway mediate arachidonic acid induction of c-fos in human prostate cancer cells

    Science.gov (United States)

    Chen, Y.; Hughes-Fulford, M.

    2000-01-01

    Arachidonic acid (AA) is the precursor for prostaglandin E2 (PGE2) synthesis and increases growth of prostate cancer cells. To further elucidate the mechanisms involved in AA-induced prostate cell growth, induction of c-fos expression by AA was investigated in a human prostate cancer cell line, PC-3. c-fos mRNA was induced shortly after addition of AA, along with a remarkable increase in PGE2 production. c-fos expression and PGE2 production induced by AA was blocked by a cyclo-oxygenase inhibitor, flurbiprofen, suggesting that PGE2 mediated c-fos induction. Protein kinase A (PKA) inhibitor H-89 abolished induction of c-fos expression by AA, and partially inhibited PGE2 production. Protein kinase C (PKC) inhibitor GF109203X had no significant effect on c-fos expression or PGE2 production. Expression of prostaglandin (EP) receptors, which mediate signal transduction from PGE2 to the cells, was examined by reverse transcription polymerase chain reaction in several human prostate cell lines. EP4 and EP2, which are coupled to the PKA signalling pathway, were expressed in all cells tested. Expression of EP1, which activates the PKC pathway, was not detected. The current study showed that induction of the immediate early gene c-fos by AA is mediated by PGE2, which activates the PKA pathway via the EP2/4 receptor in the PC-3 cells.

  3. Adaptive selection on bracovirus genomes drives the specialization of Cotesia parasitoid wasps.

    Directory of Open Access Journals (Sweden)

    Séverine Jancek

    Full Text Available The geographic mosaic of coevolution predicts parasite virulence should be locally adapted to the host community. Cotesia parasitoid wasps adapt to local lepidopteran species possibly through their symbiotic bracovirus. The virus, essential for the parasitism success, is at the heart of the complex coevolutionary relationship linking the wasps and their hosts. The large segmented genome contained in the virus particles encodes virulence genes involved in host immune and developmental suppression. Coevolutionary arms race should result in the positive selection of particular beneficial alleles. To understand the global role of bracoviruses in the local adaptation or specialization of parasitoid wasps to their hosts, we studied the molecular evolution of four bracoviruses associated with wasps of the genus Cotesia, including C congregata, C vestalis and new data and annotation on two ecologically differentiated populations of C sesamie, Kitale and Mombasa. Paired orthologs analyses revealed more genes under positive selection when comparing the two C sesamiae bracoviruses belonging to the same species, and more genes under strong evolutionary constraint between species. Furthermore branch-site evolutionary models showed that 17 genes, out of the 54 currently available shared by the four bracoviruses, harboured sites under positive selection including: the histone H4-like, a C-type lectin, two ep1-like, ep2, a viral ankyrin, CrV1, a ben-domain, a Serine-rich, and eight unknown genes. Lastly the phylogenetic analyses of the histone, ep2 and CrV1 genes in different African C sesamiae populations showed that each gene described differently the individual relationships. In particular we found recombination had happened between the ep2 and CrV1 genes, which are localized 37.5 kb apart on the wasp chromosomes. Involved in multidirectional coevolutionary interactions, C sesamiae wasps rely on different bracovirus mediated molecular pathways to overcome

  4. Characteristics of long-lasting haze episodes observed in Seoul, South Korea, for 2009-2014

    Science.gov (United States)

    Lee, Hae-Jung; Kim, Jeong Eun; Cha, Joo Wan; Song, Seungjoo; Ryoo, Sang-Boom; Kim, Yong Pyo

    2018-03-01

    The meteorological, physical, chemical, and optical characteristics of long-lasting haze in Seoul were studied. Four episodes were observed between 2009 and 2014, all in winter. PM10 mass concentration (PM10), chemical species, and aerosol optical depth (AOD) were analyzed along with the synoptic meteorological conditions. During the episodes, the temporal variations of the PM10 generally proceeded from the west along the Yellow Sea. The ground-based AOD was also high in Seoul and other sites. High AOD (MODIS) distributions were observed to move from China to Korea. The high sulfate concentration, along with the high sulfur oxidation ratio value of the third and fourth episodes (Eps. 3 and 4), respectively, corroborated the possible long-range transport of air pollutants. Stagnant meteorological conditions were a reason for the occurrence of long-lasting hazes. An anticyclone system had a dominant influence on the Korean peninsula during all episodes. The air mass over China was able to rise, and that over Korea was more stagnant in terms of climatology except Ep. 2. In addition to transport from outside, locally emitted air pollutants contributed to the PM10 partly due to the stagnant conditions, during which diurnal variations in NO2 and nitrates showed similar peak times during Eps. 3 and 4. Analysis of the episodes consistently showed that the long-lasting haze episodes were influenced by both the long-range transport of air pollutants from outside Seoul, mostly from China, and the accumulation of air pollutants that were locally emitted and transformed.

  5. Atividade antiviral do extrato de própolis contra o calicivírus felino, adenovírus canino 2 e vírus da diarréia viral bovina Antiviral activity of propolis extracts against feline calicivirus, canine adenovirus 2, and bovine viral diarrhea virus

    Directory of Open Access Journals (Sweden)

    Ana Paula Cueto

    2011-10-01

    Full Text Available Dentre as propriedades biológicas da própolis, a atividade antimicrobiana tem merecido destacada atenção. Neste artigo, descreve-se a atividade antiviral de dois extratos etanólicos de própolis (EP1 e EP2 frente aos vírus: calicivírus felino (FCV, adenovírus canino tipo 2 (CAV-2 e vírus da diarréia viral bovina (BVDV. Um dos extratos (EP1 foi obtido por extração etanólica de própolis obtida da região central do Estado do Rio Grande do Sul e o segundo (EP2, obtido comercialmente de uma empresa de Minas Gerais. A análise dos extratos de própolis através da cromatografia líquida de alta eficiência (CLAE identificou a presença de flavonóides como: rutina, quercetina e ácido gálico. A atividade antiviral bem como a citotoxicidade dos extratos aos cultivos celulares foram avaliadas através do MTT [3- (4,5 dimetiltiazol-2yl-2-5-difenil-2H tetrazolato de bromo]. Ambos os extratos evidenciaram atividade antiviral frente ao BVDV e CAV-2 quando acrescidos ao cultivo celular anteriormente à inoculação viral. Os extratos foram menos efetivos contra o FCV em comparação aos resultados obtidos com os outros vírus, e a atividade antiviral neste caso foi observada apenas quando a própolis estava presente após a inoculação viral. O extrato obtido no laboratório (EP1 apresentou valores mais altos de índice de seletividade (IS=CC50/ CE50, quando comparado à outra amostra (EP2. Em resumo, a própolis apresentou atividade antiviral frente a três diferentes vírus, o que a torna alvo para o desenvolvimento de novos compostos naturais com atividade antiviral.Propolis is a resinous substance produced by bees for which several biological activities have been attributed. In this article, the antiviral activity of two propolis extracts was tested against bovine viral diarrhea virus (BVDV, canine adenovirus type 2 (CAV-2, and feline calicivirus (FCV. One of the extracts was obtained by ethanolic extraction of propolis from the Santa

  6. Non-isothermal crystallization kinetics and phase transformation of Bi2O3-SiO2 glass-ceramics

    Directory of Open Access Journals (Sweden)

    Guo H.W.

    2011-01-01

    Full Text Available The Bi2O3-SiO2 (BS glass-ceramics were prepared by melt-quench technique, and the crystallization kinetics and phase transformation behavior were investigated in accordance with Kissinger and Johson-Mehl-Avrami equation, DSC, XRD and SEM. The results show that in the heat treatment process (or termed as re-crystallizing process Bi2SiO5 and Bi4Si3O12 crystals were found consequently. Respectively, the crystallization activation energies of the two crystals are Ep1=14.8kJ/mol and Ep2=34.1kJ/mol. And the average crystallization index of n1=1.73 and n2=1.38 suggested volume nucleation, one-dimensional growth and surface nucleation, one-dimensional growth from surface to the inside respectively. The meta-stable needle-like Bi2SiO5 crystals are easily to be transformed into stable prismatic Bi4Si3O12 crystals. By quenching the melt and hold in 850°C for 1h, the homogenous single Bi4Si3O12 crystals were found in the polycrystalline phase of the BS glassceramics system.

  7. Interhospital transfer of children in respiratory failure: a clinician interview qualitative study.

    Science.gov (United States)

    Odetola, Folafoluwa O; Anspach, Renee R; Han, Yong Y; Clark, Sarah J

    2017-02-01

    To investigate the decision making underlying transfer of children with respiratory failure from level II to level I pediatric intensive care unit care. Interviews with 19 eligible level II pediatric intensive care unit physicians about a hypothetical scenario of a 2-year-old girl in respiratory failure: RESULTS: At baseline, indices critical to management were as follows: OI (53%), partial pressure of oxygen in arterial blood (Pao 2 )/Fio 2 (32%), and inflation pressure (16%). Poor clinical response was signified by high OI, inflation pressure, and Fio 2 , and low Pao 2 /Fio 2 . At EP 1, 18 of 19 respondents would initiate high-frequency oscillatory ventilation, and 1 would transfer. At EP 2, 15 of 18 respondents would maintain high-frequency oscillatory ventilation, 9 of them calling to discuss transfer. All respondents would transfer if escalated therapies failed to reverse the patient's clinical deterioration. Interhospital transfer of children in respiratory failure is triggered by poor response to escalation of locally available care modalities. This finding provides new insight into decision making underlying interhospital transfer of children with respiratory failure. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Effects of a low-energy proton irradiation on n+/p-AlInGaP solar cells

    International Nuclear Information System (INIS)

    Lee, H.S.; Yamaguchi, M.; Ekins-Daukes, N.J.; Khan, A.; Takamoto, T.; Imaizumi, M.; Ohshima, T.; Itoh, H.

    2006-01-01

    For the first time, by deep-level transient spectroscopy, 30keV proton irradiation-induced defects in n + /p-AlInGaP solar cells have been observed. After the 30keV proton irradiation, new deep-level defects such as two majority-carrier (hole) traps HP1 (E V +0.98eV, N T =3.8x10 14 cm -3 ) and HP2, and two minority-carrier (electron) traps EP1 (E C -0.71eV, N T =2.0x10 15 cm -3 ) and EP2 have been observed in p-AlInGaP. The introduction rate of majority-carrier trap center (HP1) is 380cm -1 , which is lower than that (1500cm -1 ) in 100keV proton-irradiated p-InGaP. From the minority-carrier injection annealing for HP1 defect and carrier concentration in 30keV proton-irradiated p-AlInGaP, HP1 defect is likely to act as a recombination center as well as a compensator center

  9. Steady-state evoked potentials to study the processing of tactile and nociceptive somatosensory input in the human brain.

    Science.gov (United States)

    Colon, E; Legrain, V; Mouraux, A

    2012-10-01

    The periodic presentation of a sensory stimulus induces, at certain frequencies of stimulation, a sustained electroencephalographic response of corresponding frequency, known as steady-state evoked potentials (SS-EP). In visual, auditory and vibrotactile modalities, studies have shown that SS-EP reflect mainly activity originating from early, modality-specific sensory cortices. Furthermore, it has been shown that SS-EP have several advantages over the recording of transient event-related brain potentials (ERP), such as a high signal-to-noise ratio, a shorter time to obtain reliable signals, and the capacity to frequency-tag the cortical activity elicited by concurrently presented sensory stimuli. Recently, we showed that SS-EP can be elicited by the selective activation of skin nociceptors and that nociceptive SS-EP reflect the activity of a population of neurons that is spatially distinct from the somatotopically-organized population of neurons underlying vibrotactile SS-EP. Hence, the recording of SS-EP offers a unique opportunity to study the cortical representation of nociception and touch in humans, and to explore their potential crossmodal interactions. Here, (1) we review available methods to achieve the rapid periodic stimulation of somatosensory afferents required to elicit SS-EP, (2) review previous studies that have characterized vibrotactile and nociceptive SS-EP, (3) discuss the nature of the recorded signals and their relationship with transient event-related potentials and (4) outline future perspectives and potential clinical applications of this technique. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  10. A qualitative study exploring perceptions and attitudes of community pharmacists about extended pharmacy services in Lahore, Pakistan.

    Science.gov (United States)

    Hashmi, Furqan K; Hassali, Mohamed Azmi; Khalid, Adnan; Saleem, Fahad; Aljadhey, Hisham; Babar, Zaheer Ud Din; Bashaar, Mohammad

    2017-07-19

    In recent decades, community pharmacies reported a change of business model, whereby a shift from traditional services to the provision of extended roles was observed. However, such delivery of extended pharmacy services (EPS) is reported from the developed world, and there is scarcity of information from the developing nations. Within this context, the present study was aimed to explore knowledge, perception and attitude of community pharmacists (CPs) about EPS and their readiness and acceptance for practice change in the city of Lahore, Pakistan. A qualitative approach was used to gain an in-depth knowledge of the issues. By using a semi-structured interview guide, 12 CPs practicing in the city of Lahore, Pakistan were conveniently selected. All interviews were audio-taped, transcribed verbatim, and were then analyzed for thematic contents by the standard content analysis framework. Thematic content analysis yielded five major themes. (1) Familiarity with EPS, (2) current practice of EPS, (3) training needed to provide EPS, (4) acceptance of EPS and (5) barriers toward EPS. Majority of the CPs were unaware of EPS and only a handful had the concept of extended services. Although majority of our study respondents were unaware of pharmaceutical care, they were ready to accept practice change if provided with the required skills and training. Lack of personal knowledge, poor public awareness, inadequate physician-pharmacist collaboration and deprived salary structures were reported as barriers towards the provision of EPS at the practice settings. Although the study reported poor awareness towards EPS, the findings indicated a number of key themes that can be used in establishing the concept of EPS in Pakistan. Over all, CPs reported a positive attitude toward practice change provided to the support and facilitation of health and community based agencies in Pakistan.

  11. Exopolysaccharide (EPS synthesis by Oenococcus oeni: from genes to phenotypes.

    Directory of Open Access Journals (Sweden)

    Maria Dimopoulou

    Full Text Available Oenococcus oeni is the bacterial species which drives malolactic fermentation in wine. The analysis of 50 genomic sequences of O. oeni (14 already available and 36 newly sequenced ones provided an inventory of the genes potentially involved in exopolysaccharide (EPS biosynthesis. The loci identified are: two gene clusters named eps1 and eps2, three isolated glycoside-hydrolase genes named dsrO, dsrV and levO, and three isolated glycosyltransferase genes named gtf, it3, it4. The isolated genes were present or absent depending on the strain and the eps gene clusters composition diverged from one strain to another. The soluble and capsular EPS production capacity of several strains was examined after growth in different culture media and the EPS structure was determined. Genotype to phenotype correlations showed that several EPS biosynthetic pathways were active and complementary in O. oeni. Can be distinguished: (i a Wzy-dependent synthetic pathway, allowing the production of heteropolysaccharides made of glucose, galactose and rhamnose, mainly in a capsular form, (ii a glucan synthase pathway (Gtf, involved in β-glucan synthesis in a free and a cell-associated form, giving a ropy phenotype to growth media and (iii homopolysaccharide synthesis from sucrose (α-glucan or β-fructan by glycoside-hydrolases of the GH70 and GH68 families. The eps gene distribution on the phylogenetic tree was examined. Fifty out of 50 studied genomes possessed several genes dedicated to EPS metabolism. This suggests that these polymers are important for the adaptation of O. oeni to its specific ecological niche, wine and possibly contribute to the technological performance of malolactic starters.

  12. EI/DSD : ejercicio práctico 1, febrero 2013

    OpenAIRE

    Universitat Oberta de Catalunya

    2013-01-01

    Exercici pràctic 1 (EP1)d'estructura de la informació, disseny d'estructures de dades. Ejercicio práctico 1 (EP1) de estructura de la información, diseño de estructuras de datos. Exercise 1 (EP1) about information structure, data structure design.

  13. EI/DSD : exercici pràctic 1, febrer 2013

    OpenAIRE

    Blasco Planesas, Jordi

    2013-01-01

    Exercici pràctic 1 (EP1)d'estructura de la informació, disseny d'estructures de dades. Ejercicio práctico 1 (EP1) de estructura de la información, diseño de estructuras de datos. Exercise 1 (EP1) about information structure, data structure design.

  14. Plasma Detachment Mechanisms in Propulsive Magnetic Nozzles

    Science.gov (United States)

    2013-03-07

    tested HPHall2 code used in our group,12 originally conceived for ∗PhD student, Equipo de Propulsión Espacial y Plasmas (EP2), web.fmetsia.upm.es...the main characteristics of the updated DIMAGNO model. Sections ∗PhD student, Equipo de Propulsión Espacial y Plasmas (EP2, web.fmetsia.upm.es/ep2

  15. Single dose (400 mg) versus 7 day (200 mg) daily dose itraconazole in the treatment of tinea versicolor: a randomized clinical trial.

    Science.gov (United States)

    Wahab, M A; Ali, M E; Rahman, M H; Chowdhury, S A; Monamie, N S; Sultana, N; Khondoker, L

    2010-01-01

    Tinea (pityriasis) versicolor is a superficial fungal infection and one of the most commonly found pigmentary disorders of skin caused by the yeast Malassezia. Multiple topical as well as systemic therapies are available for treatment. Systemic therapies are used for extensive disease, frequent relapse or where topical agents have failed. The aim that translates the rationale of the study was to compare the efficacy, safety, tolerability and cost effectiveness of single dose 400mg versus 7 day 200 mg daily dose of itraconazole in the treatment of tinea versicolor. A clinical study was done to compare the efficacy of single dose (400 mg) of itraconazole and 7 day 200 mg daily dose of itraconazole in the treatment of extensive tinea versicolor. Total 60 patients (aged 18-50 years) were selected for the study during the period of June 2007 to May 2008 in the department of Dermatology of three different hospitals in Bangladesh. Cases having with extensive involvement, diagnosed clinically and confirmed by wood's lamp and KOH microscopy were taken. Patients were randomly allocated into equal groups. Group A was given single dose 400 mg itraconazole and Group B was given 7 day 200 mg daily itraconazole. Fifty three (88%) male and 7(12%) female were included in the study. The mean age of group A was 32.37+/-9 years and in group B 33.23+/-8 years. The mean duration of the disease in group A was 2.63+/-2 months and 2.76+/-2 months in group B. In group A clinical responders was found cure 22(73.33%) and improvement 5(16.33%) and in group B it was found cure 24(79.99%) and improvement 4(13.33%). The measure at the End point (EP1) equals to 90% response and in-group B it was found cure 24 (79.99%) and improvement 4(13.33%). (Here the End point EP2) equals to 93.33%. The EP clinical analysis however shows 91.66% response. Both single dose and 7 day daily dose of itraconazole can be effective in the treatment of tinea versicolor with extensive involvement but single dose appears

  16. A unique polysaccharide purified from Hericium erinaceus mycelium prevents oxidative stress induced by H2O2 in human gastric mucosa epithelium cell.

    Science.gov (United States)

    Wang, Mingxing; Kanako, Nakajima; Zhang, Yanqiu; Xiao, Xulang; Gao, Qipin; Tetsuya, Konishi

    2017-01-01

    Hericium erinaceus (HE) has been used both as a traditional Chinese medicine and home remedy for treatment of gastric and duodenal ulcers and gastritis. EP-1, a purified polysaccharide isolated from HE mycelium, has recently been identified as the active component responsible for HE anti-gastritis activity. Because oxidative stress has been implicated as a pathogenic cause of gastritis and gastric ulcers, EP-1 antioxidant properties were systematically examined in vitro using the human gastric mucosal epithelial cell line, GES-1. Results showed that EP-1 possessed higher oxygen radical absorbance capacity (ORAC) and 2-3 times higher ability to scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH), superoxide and hydroxyl radicals than a hot water extract of commercially available HE fruiting body. A crude mycelial polysaccharide (CMPS) extract of HE, from which EP-1 was purified, showed slightly stronger radical scavenging activity and ORAC than EP-1, with the exception of DPPH-scavenging activity. Antioxidant activities of these extracts were further studied using hydrogen peroxide (H2O2)-abused GES-1 cells; EP-1 dose-dependently preserved cell viability of abused cells as assessed via MTT assay. Moreover, FACS analysis revealed that EP-1 prevented H2O2-induced apoptotic cell death by inhibiting activation of apoptotic cellular signals within mitochondria-dependent apoptotic pathways. CMPS also prevented H2O2-induced oxidative stress, but to a lesser degree than did EP-1, even though CMPS exhibited comparable or stronger in vitro antioxidant activity than did EP-1.

  17. Revealing the characteristics of a novel bioflocculant and its flocculation performance in Microcystis aeruginosa removal

    Science.gov (United States)

    Sun, Pengfei; Hui, Cai; Bai, Naling; Yang, Shengmao; Wan, Li; Zhang, Qichun; Zhao, Yuhua

    2015-12-01

    In the present work, a novel bioflocculant, EPS-1, was prepared and used to flocculate the kaolin suspension and Microcystis aeruginosa. We focused on the characteristics and flocculation performance of EPS-1, especially with regard to its protein components. An important attribute of EPS-1 was its protein content, with 18 protein types identified that occupied a total content of 31.70% in the EPS-1. Moreover, the flocculating activity of these protein components was estimated to be no less than 33.93%. Additionally, polysaccharides that occupied 57.12% of the total EPS-1 content consisted of four monosaccharides: maltose, D-xylose, mannose, and D-fructose. In addition, carbonyl, amino, and hydroxyl groups were identified as the main functional groups. Three main elements, namely C1s, N1s, and O1s, were present in EPS-1 with relative atomic percentages of 62.63%, 24.91%, and 10.5%, respectively. Zeta potential analysis indicated that charge neutralization contributed to kaolin flocculation, but was not involved in M. aeruginosa flocculation. The flocculation conditions of EPS-1 were optimized, and the maximum flocculating efficiencies were 93.34% within 2 min for kaolin suspension and 87.98% within 10 min for M. aeruginosa. These results suggest that EPS-1 could be an alternative to chemical flocculants for treating wastewaters and cyanobacterium-polluted freshwater.

  18. Chromosomal Location by Use of Trisomics and New Alleles of an Endopeptidase in Zea Mays

    DEFF Research Database (Denmark)

    Nielsen, Gunnar Gissel; Scandalios, John G.

    1974-01-01

    An association was found earlier between the Ep1 gene locus coding for an endopeptidase and the endosperm color gene Y1 on chromosome 6 of Zea mays. By employing primary trisomics we have unequivocally placed the Ep1 gene on chromosome 6, closely linked to the Y1 locus. Additionally we describe new...

  19. Operação de Blalock-Taussig modificada para o tratamento paliativo de cardiopatias congênitas com hipofluxo pulmonar Blalock-Taussig operation for palliative treatment of congenital heart disease with low pulmonary flow

    Directory of Open Access Journals (Sweden)

    Miguel A Maluf

    1995-09-01

    Full Text Available De janeiro de 1990 a novembro de 1994, 72 pacientes portadores de cardiopatias congênitas com hipofluxo pulmonar foram submetidos à operação de Blalock-Taussig. A idade variou entre 2 dias e 11 anos (M:9,0 meses; 44 (61,1% eram do sexo masculino e 28 (38,8% do feminino; 38 (52,8% casos portadores de tétrade de Fallot; 7 (9,7% atresia pulmonar com septo interventricular íntegro (AP c/ SIVI; 6 (8,4% transposição das grandes artérias (TGA + estenose pulmonar (EP; 6 (8,4% atresia tricúspide (AT + EP; 6 (8,4% dupla via de entrada (DVE do ventrículo direito (VD ou ventrículo esquerdo (VE + (EP; 3 (4,2% transposição corrigida das grandes artérias (TCGA + comunicação interventricular (CIV + EP; 2 (2,7% dupla via de saída (DVS de VD ou VE + EP; 2 (2,7% defeito septal atrioventricular (DSAV + EP; 2 (2,7% isomerismo direito (D ou (E + EP. Os critérios de indicação foram: a neonatos com cardiopatias "dueto dependente"; b lactentes com piora de cianose ou crise de hipoxia; c crianças durante a infância com cardiopatias sem chance de uma correção biventricular. A técnica empregada foi a operação de Blalock-Taussig modificada, interpondo prótese entre artéria subclávia e artéria pulmonar. A prótese de Polytetrafluoroethylene (PTFE foi usada em 69 (94,5% casos, veia umbilical em 3 (4,1% casos e artéria mamária bovina em 1 (1,4% caso. Durante o ato operatório foi administrada dose única de heparina (1mg x kg peso, não sendo neutralizada no pós-operatório (PO e no seguimento tardio, dispensado o uso de anticoagulantes ou antiagregantes plaquetários. Houve 8 (11,1% óbitos no PO imediato: 5 (6,9% casos por obstrução da prótese (3 foram reoperados, 2 (2,7% casos por morte súbita (AP c/ SIVI e 1 (1,3% devido a processo infeccioso pulmonar. A obstrução da prótese como principal causa de óbito esteve diretamente relacionada à anatomia dos vasos (calibre da artéria subclávia e pulmonar e ou problemas de técnica cir

  20. Efferent projections of the ectostriatum in the pigeon (Columba livia)

    Science.gov (United States)

    Husband, S. A.; Shimizu, T.

    1999-01-01

    The ectostriatum is a major visual component of the avian telencephalon. The core region of the ectostriatum (Ec) receives visual input from the optic tectum through thalamic nuclei. In the present study, the efferent projections of the ectostriatum were investigated by using the anterograde tracers Phaseolus vulgaris leucoagglutinin and biotinylated dextran amine. Projection patterns resulting from these tracers were confirmed by the retrograde tracer cholera toxin subunit B. When anterograde tracers were injected in Ec, primary projections were seen traveling dorsolaterally to the belt region of the ectostriatum (Ep) and the neostriatal area immediately surrounding Ep (Ep2). Neurons in Ep sent projections primarily to the overlying Ep2. The efferents of Ep2 traveled dorsolaterally to terminate in three telencephalic regions, from anterior to posterior: (1) neostriatum frontale, pars lateralis (NFL), (2) area temporo-parieto-occipitalis (TPO), and (3) neostriatum intermedium, pars lateralis (NIL). A part of the archistriatum intermedium and the lateral part of the neostriatum caudale also received somewhat minor projections. In addition, some neurons in Ec were also the source of direct, but minor, projections to the NFL, TPO, NIL, and archistriatum intermedium. The topographical relationship among the primary (Ec), secondary (Ep and Ep2), and tertiary (NFL, TPO, NIL) areas indicate that the neural populations for visual processing are organized along the rostral-caudal axis. Thus, the anterior Ec sent efferents to the anterior Ep, which in turn sent projections to anterior Ep2. Neurons in the anterior Ep2 sent projections to NFL and the anterior TPO. Similarly, the intermediate and posterior Ec sent projections to corresponding parts of Ep, whose efferents projected to intermediate and posterior Ep2, respectively. The intermediate Ep2 gave rise to major projections to TPO, whereas posterior Ep2 neurons sent efferents primarily to NIL. The organization of this

  1. A unique polysaccharide purified from Hericium erinaceus mycelium prevents oxidative stress induced by H2O2 in human gastric mucosa epithelium cell.

    Directory of Open Access Journals (Sweden)

    Mingxing Wang

    Full Text Available Hericium erinaceus (HE has been used both as a traditional Chinese medicine and home remedy for treatment of gastric and duodenal ulcers and gastritis. EP-1, a purified polysaccharide isolated from HE mycelium, has recently been identified as the active component responsible for HE anti-gastritis activity. Because oxidative stress has been implicated as a pathogenic cause of gastritis and gastric ulcers, EP-1 antioxidant properties were systematically examined in vitro using the human gastric mucosal epithelial cell line, GES-1. Results showed that EP-1 possessed higher oxygen radical absorbance capacity (ORAC and 2-3 times higher ability to scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH, superoxide and hydroxyl radicals than a hot water extract of commercially available HE fruiting body. A crude mycelial polysaccharide (CMPS extract of HE, from which EP-1 was purified, showed slightly stronger radical scavenging activity and ORAC than EP-1, with the exception of DPPH-scavenging activity. Antioxidant activities of these extracts were further studied using hydrogen peroxide (H2O2-abused GES-1 cells; EP-1 dose-dependently preserved cell viability of abused cells as assessed via MTT assay. Moreover, FACS analysis revealed that EP-1 prevented H2O2-induced apoptotic cell death by inhibiting activation of apoptotic cellular signals within mitochondria-dependent apoptotic pathways. CMPS also prevented H2O2-induced oxidative stress, but to a lesser degree than did EP-1, even though CMPS exhibited comparable or stronger in vitro antioxidant activity than did EP-1.

  2. The European positional paper on rhinosinusitis and nasal polyps: has the introduction of guidance on the management of sinus disease affected uptake of surgery and acute admissions for sinusitis?

    Science.gov (United States)

    Cosway, Ben; Tomkinson, Alun; Owens, David

    2013-03-01

    Rhinosinusitis is a common condition with adults experiencing 2-5 episodes per year. The European Positional Paper on Rhinosinusitis and Nasal Polyps (EP3OS) published in 2005 and updated in 2007 provided evidence-based guidelines on the management of sinus disease promoting a conservative approach to treatment. This study examines the effect of EP3OS on sinus surgery uptake and acute admissions for sinusitis in England and Wales. A retrospective study using the national electronic health databases of England (Hospital Episodes Statistics, HES online) and Wales (Patient Episodes Database of Wales, PEDW) was undertaken from 2000 to 2010 using the OPCS-4 codes E12-E17 (sinus surgery) and ICD10 code J01 (acute admission for sinusitis). Data were analysed for effect following the introduction of the EP3OS in 2005 using linear regression and Chi squared analysis. 116,370 sinus procedures and 10,916 acute admissions for sinusitis were made during the study period. No significant decrease in sinus surgery procedures occurred following the introduction of the EP3OS as may have been expected (p > 0.05), although subgroup analysis suggested a significant increase in Wales (p introduction of EP3OS (p 0.05). The EP3OS appears to have had little impact on the rates of sinus surgery but more conservative approaches to managing of sinus disease may have led to an increase in acute admissions. Further research is required to investigate whether changes in practice were adopted.

  3. Influência do extrato pirolenhoso na calda de pulverização sobre o teor foliar de nutrientes em limoeiro 'Cravo' Effect of pyroligneous acid in the spraymg solutions on foliar nutrients content of 'Rangpur' lime

    Directory of Open Access Journals (Sweden)

    Marcelo Zanetti

    2004-12-01

    Full Text Available Com o objetivo de avaliar o efeito da presença do extrato pirolenhoso (EP na calda de pulverização sobre o teor foliar de nutrientes de limoeiro 'Cravo' (Citrus limonia Osbeck, foi desenvolvido um experimento com seis tratamentos e quatro repetições, em blocos ao acaso, em ambiente protegido. Os tratamentos constituíram da pulverização das soluções: T0 = água; T1 = solução de micronutrientes sem EP; T2 = solução de micronutrientes + EP (1cm³ dm-3; T3 = solução de micronutrientes + EP (2 cm³ dm-3; T4 = solução de micronutrientes + EP (5cm³ dm-3; T5 = solução de micronutrientes + EP (10 cm³ dm-3. A solução de micronutrientes foi preparada com sulfatos de Cu, Fe, Mn, Zn (250 mg dm-3 do elemento e ácido bórico (42,5 mg dm-3 de B. As plantas foram cultivadas em tubetes cônicos de 0,280 dm³, com substrato sem a adição de micronutrientes na formulação. As soluções foram pulverizadas uma única vez, aos 140 dias após o plantio (DAP, momento em que as plantas apresentavam aproximadamente 20 cm de altura. Ao final do experimento (160 DAP, quantificaram-se a massa seca e os teores de macro e micronutrientes da parte aérea e sistema radicular. A presença do extrato pirolenhoso na solução de micronutrientes não interferiu na concentração foliar de B, Fe e Zn em mudas de limoeiro 'Cravo'. Entretanto, na concentração de 10 cm³ dm-3, aumentou a concentração foliar de Cu e Mn. Observou-se também que as plantas pulverizadas com soluções contendo EP (1 a 10 cm³ dm-3 + micronutrientes apresentaram menor teor de Fe e maior teor de Ca no sistema radicular.This research studied the effect of pyroligneous acid (PA presence in the micronutrient solution sprayed on leaves on the foliar nutrient content of 'Rangpur lime' (Citrus limonia Osbeck0 seedlings, under screen house. An experiment in a randomized complete block design with six treatments and four replicates was set up. Treatments consisted of leaf spraying with

  4. A Peptide Derived from the HIV-1 gp120 Coreceptor-Binding Region Promotes Formation of PAP248-286 Amyloid Fibrils to Enhance HIV-1 Infection.

    Directory of Open Access Journals (Sweden)

    Jinquan Chen

    Full Text Available Semen is a major vehicle for HIV transmission. Prostatic acid phosphatase (PAP fragments, such as PAP248-286, in human semen can form amyloid fibrils to enhance HIV infection. Other endogenous or exogenous factors present during sexual intercourse have also been reported to promote the formation of seminal amyloid fibrils.Here, we demonstrated that a synthetic 15-residue peptide derived from the HIV-1 gp120 coreceptor-binding region, designated enhancing peptide 2 (EP2, can rapidly self-assemble into nanofibers. These EP2-derivated nanofibers promptly accelerated the formation of semen amyloid fibrils by PAP248-286, as shown by Thioflavin T (ThT and Congo red assays. The amyloid fibrils presented similar morphology, assessed via transmission electron microscopy (TEM, in the presence or absence of EP2. Circular dichroism (CD spectroscopy revealed that EP2 accelerates PAP248-286 amyloid fibril formation by promoting the structural transition of PAP248-286 from a random coil into a cross-β-sheet. Newly formed semen amyloid fibrils effectively enhanced HIV-1 infection in TZM-bl cells and U87 cells by promoting the binding of HIV-1 virions to target cells.Nanofibers composed of EP2 promote the formation of PAP248-286 amyloid fibrils and enhance HIV-1 infection.

  5. Antibiotic prescribing in patients with acute rhinosinusitis is not in agreement with European recommendations

    DEFF Research Database (Denmark)

    Jørgensen, Lars Christian; Friis Christensen, Sarah; Cordoba Currea, Gloria

    2013-01-01

    Abstract Objective. To assess the potential overprescribing in patients with acute rhinosinusitis across six countries with different antibiotic prescribing rates and different prevalence of antibiotic resistance. Design, setting and subjects. A cross-sectional study including GPs from two Nordic...... tract infections" (HAPPY AUDIT). Main outcome measures. Use of antibiotics for acute rhinosinusitis based on the recommendations in the European Position Paper on Rhinosinusitis and Nasal Polyps 2007 (EP3OS). Results. In total, 618 participating GPs registered 33 273 patients with RTI of whom 1150 (3...... overprescribing) and 23% had symptoms recommendations (EP3OS guidelines). To prevent overprescribing, efforts should be made to implement...

  6. Lactobacillus plantarum inhibits growth of Listeria monocytogenes in an in vitro continuous flow gut model, but promotes invasion of L. monocytogenes in the gut of gnotobiotic rats

    DEFF Research Database (Denmark)

    Bernbom, Nete; Licht, Tine Rask; Saadbye, Peter

    2006-01-01

    The ability of the pediocin AcH producing Lactobacillus plantarum DDEN 11007 and its non-producing plasmid-cured isogenic variant, DDEN 12305 to prevent the persistence and growth of Listeria monocytogenes EP2 in two gastrointestinal (GI) tract models was examined. In vitro studies conducted...... in a two-stage continuous flow system showed that L. plantarum DDEN 11007 inhibited L. monocytogenes EP2 under these conditions, while less effect was seen of the non-bacteriocin producing variant. The inhibitory effect was more pronounced at pH 5 than at pH 7. No effect on persistence of L. monocytogenes...... in the GI tract was seen in gnotobiotic rats colonized with either the pediocin AcH producing or the non-bacteriocin producing variant of L. plantarum when compared to rats inoculated with L. monocytogenes EP2 alone. Surprisingly, inoculation of the gnotobiotic animals with either of the L. plantarum...

  7. A relationship between seed development, Arabinogalactan-proteins (AGPs) and the AGP mediated promotion of somatic embryogenesis

    NARCIS (Netherlands)

    Hengel, van A.J.; Kammen, van A.; Vries, de S.C.

    2002-01-01

    Arabinogalactan-protein (AGP) epitopes are known to display developmentally regulated patterns of expression in several plant tissues. Therefore, AGPs have been suggested to play a role in plant development. Somatic embryogenesis is regulated by AGPs as well as by EP3 endochitinases. Using four

  8. Diagnosing chronic rhinosinusitis

    DEFF Research Database (Denmark)

    Lange, B; Thilsing, T; Baelum, J

    2013-01-01

    The European Position Paper on Rhinosinusitis and Nasal Polyps (EP3OS) incorporates symptomatic and endo- scopic criteria in the clinical diagnosis of chronic rhinosinusitis (CRS), while in epidemiological studies the definition is based on symptoms only. The aim of this study was to evaluate...

  9. Rethinking the Educator Portfolio: An Innovative Criteria-Based Model.

    Science.gov (United States)

    Shinkai, Kanade; Chen, Chen Amy; Schwartz, Brian S; Loeser, Helen; Ashe, Cynthia; Irby, David M

    2017-11-07

    Academic medical centers struggle to achieve parity in advancement and promotions between educators and discovery-oriented researchers in part because of narrow definitions of scholarship, lack of clear criteria for measuring excellence, and barriers to making educational contributions available for peer review. Despite recent progress in expanding scholarship definitions and identifying excellence criteria, these advances are not integrated into educator portfolio (EP) templates or curriculum vitae platforms. From 2013 to 2015, a working group from the Academy of Medical Educators (AME) at the University of California, San Francisco (UCSF) designed a streamlined, criteria-based EP (EP 2.0) template highlighting faculty members' recent activities in education and setting rigorous evaluation methods to enable educational scholarship to be objectively evaluated for academic advancement, AME membership, and professional development. The EP 2.0 template was integrated into the AME application, resulting in high overall satisfaction among candidates and the selection committee and positive feedback on the template's transparency, ease of use, and streamlined format. In 2016, the EP 2.0 template was integrated into the campus-wide curriculum vitae platform and academic advancement system. The authors plan to increase awareness of the EP 2.0 template by educating promotions committees and faculty at UCSF and partnering with other institutions to disseminate it for use. They also plan to study the impact of the template on supporting educators by making their important scholarly contributions available for peer review, providing guidance for professional development, and decreasing disparities in promotions.

  10. 40 CFR 158.400 - Product performance data requirements table.

    Science.gov (United States)

    2010-07-01

    ... associated with human and animal wastes NR NR NR NR NR NR NR NR CR NR EP 1 91-8 Products for treating water... vertebrates (such as rodents, birds, bats, canids, and skunks) that may directly or indirectly transmit diseases to humans. However each registrant must ensure through testing that his product is efficacious...

  11. 78 FR 18327 - Decision and Order Granting a Waiver to LG Electronics, Inc. From the Department of Energy...

    Science.gov (United States)

    2013-03-26

    ... products use shared compressor systems that are controlled by a 3-way valve. This type of system, LG argued... the following: 5.2.1.4 Dual Compressor Systems with Dual Automatic Defrost. The two-part test method... defrost systems; EP1 is the dual compressor energy expended during the first part of the test (it is...

  12. The 52Cr(p, γ)53Mn reaction

    NARCIS (Netherlands)

    Vuister, P.H.

    The 52Cr(p, γ)53Mn reaction was investigated in the energy region Ep = 1.36–2.26 MeV. The resonance energies, the corresponding 53Mn excitation energies and the resonance strengths of 199 resonances, assigned to this reaction, are reported. The excitation energies and gamma-ray branchings of 13

  13. 40 CFR 158.2171 - Experimental use permit microbial pesticides product analysis data requirements table.

    Science.gov (United States)

    2010-07-01

    ... conducted at the point in the production process after which there would be no potential for microbial... Identity R MP EP -- 885.1200 Manufacturing process R TGAI and MP TGAI and EP 1, 2 Deposition of a sample in... -- 830.6313 Stability to normal and elevated temperatures, metals and metal ions R TGAI TGAI -- 830.6317...

  14. Functional differences in yeast protein disulfide isomerases

    DEFF Research Database (Denmark)

    Nørgaard, P; Westphal, V; Tachibana, C

    2001-01-01

    PDI1 is the essential gene encoding protein disulfide isomerase in yeast. The Saccharomyces cerevisiae genome, however, contains four other nonessential genes with homology to PDI1: MPD1, MPD2, EUG1, and EPS1. We have investigated the effects of simultaneous deletions of these genes. In several...

  15. Depauperate genetic variability detected in the American and European bison using genomic techniques

    DEFF Research Database (Denmark)

    Pertoldi, Cino; Tokarska, Magorzata; Wójcik, Jan M

    2009-01-01

    , likely reflecting drift overwhelming selection. We suggest that utilization of genome-wide screening technologies, followed by utilization of less expensive techniques (e.g. VeraCode and Fluidigm EP1), holds large potential for genetic monitoring of populations. Additionally, these techniques will allow...

  16. High resolution investigation of the 30Si(þ, þ)30Si reaction

    NARCIS (Netherlands)

    Walinga, J.; Rinsvelt, H.A. van; Endt, P.M.

    The differential cross section for elastic scattering of protons on 30Si was measured with surface barrier counters at four angles. Thirty-six 30Si(þ, γ)31P resonances are known in the Ep=1–2MeV region. Fifteen of these were also observed in the 30Si(þ, þ)30Si reaction, with natural widths varying

  17. seeds

    African Journals Online (AJOL)

    Owner

    peptidohydrolase (8.0%) from mung bean seedlings. (Baumgartner and Chrispeels, 1977), EP-HG (4.5%) from horse gram seedlings ( Rajeswari, 1997), acidic protease (15%) from germinating winged-bean seeds. (Usha and Singh, 1996) and EP-1 (1.6%) from barley seedlings and GA3-induced cysteine protease (3.38%).

  18. The socio-technical organisation of community pharmacies as a factor in the Electronic Prescription Service Release Two implementation: a qualitative study

    Science.gov (United States)

    2012-01-01

    Background The introduction of a new method of transmitting prescriptions from general practices to community pharmacies in England (Electronic Prescription Service Release 2 (EPS2)) has generated debate on how it will change work practice. As EPS2 will be a key technical element in dispensing, we reviewed the literature to find that there were no studies on how social and technical elements come together to form work practice in community pharmacies. This means the debate has little point of reference. Our aim therefore was to study the ways social and technical elements of a community pharmacy are used to achieve dispensing through the development of a conceptual model on pharmacy work practice, and to consider how a core technical element such the EPS2 could change work practice. Method We used ethnographic methods inclusive of case-study observations and interviews to collect qualitative data from 15 community pharmacies that were in the process of adopting or were soon to adopt EPS2. We analysed the case studies thematically and used rigorous multi-dimensional and multi-disciplinary interpretive validation techniques to cross analyse findings. Results In practice, dispensing procedures were not designed to take into account variations in human and technical integration, and assumed that repetitive and collective use of socio-technical elements were at a constant. Variables such as availability of social and technical resources, and technical know-how of staff were not taken into account in formalised procedures. Yet community pharmacies were found to adapt their dispensing in relation to the balance of social and technical elements available, and how much of the social and technical elements they were willing to integrate into dispensing. While some integrated as few technical elements as possible, some depended entirely on technical artefacts. This pattern also applied to the social elements of dispensing. Through the conceptual model development process, we

  19. The socio-technical organisation of community pharmacies as a factor in the Electronic Prescription Service Release Two implementation: a qualitative study.

    Science.gov (United States)

    Harvey, Jasmine; Avery, Anthony J; Waring, Justin; Barber, Nick

    2012-12-20

    The introduction of a new method of transmitting prescriptions from general practices to community pharmacies in England (Electronic Prescription Service Release 2 (EPS2)) has generated debate on how it will change work practice. As EPS2 will be a key technical element in dispensing, we reviewed the literature to find that there were no studies on how social and technical elements come together to form work practice in community pharmacies. This means the debate has little point of reference. Our aim therefore was to study the ways social and technical elements of a community pharmacy are used to achieve dispensing through the development of a conceptual model on pharmacy work practice, and to consider how a core technical element such the EPS2 could change work practice. We used ethnographic methods inclusive of case-study observations and interviews to collect qualitative data from 15 community pharmacies that were in the process of adopting or were soon to adopt EPS2. We analysed the case studies thematically and used rigorous multi-dimensional and multi-disciplinary interpretive validation techniques to cross analyse findings. In practice, dispensing procedures were not designed to take into account variations in human and technical integration, and assumed that repetitive and collective use of socio-technical elements were at a constant. Variables such as availability of social and technical resources, and technical know-how of staff were not taken into account in formalised procedures. Yet community pharmacies were found to adapt their dispensing in relation to the balance of social and technical elements available, and how much of the social and technical elements they were willing to integrate into dispensing. While some integrated as few technical elements as possible, some depended entirely on technical artefacts. This pattern also applied to the social elements of dispensing. Through the conceptual model development process, we identified three

  20. Characteristic dynamics near two coalescing eigenvalues incorporating continuum threshold effects

    Science.gov (United States)

    Garmon, Savannah; Ordonez, Gonzalo

    2017-06-01

    It has been reported in the literature that the survival probability P(t) near an exceptional point where two eigenstates coalesce should generally exhibit an evolution P (t ) ˜t2e-Γ t, in which Γ is the decay rate of the coalesced eigenstate; this has been verified in a microwave billiard experiment [B. Dietz et al., Phys. Rev. E 75, 027201 (2007)]. However, the heuristic effective Hamiltonian that is usually employed to obtain this result ignores the possible influence of the continuum threshold on the dynamics. By contrast, in this work we employ an analytical approach starting from the microscopic Hamiltonian representing two simple models in order to show that the continuum threshold has a strong influence on the dynamics near exceptional points in a variety of circumstances. To report our results, we divide the exceptional points in Hermitian open quantum systems into two cases: at an EP2A two virtual bound states coalesce before forming a resonance, anti-resonance pair with complex conjugate eigenvalues, while at an EP2B two resonances coalesce before forming two different resonances. For the EP2B, which is the case studied in the microwave billiard experiment, we verify that the survival probability exhibits the previously reported modified exponential decay on intermediate time scales, but this is replaced with an inverse power law on very long time scales. Meanwhile, for the EP2A the influence from the continuum threshold is so strong that the evolution is non-exponential on all time scales and the heuristic approach fails completely. When the EP2A appears very near the threshold, we obtain the novel evolution P (t ) ˜1 -C1√{t } on intermediate time scales, while further away the parabolic decay (Zeno dynamics) on short time scales is enhanced.

  1. Role of prostaglandins in spinal transmission of the exercise pressor reflex in decerebrated rats.

    Science.gov (United States)

    Stone, A J; Copp, S W; Kaufman, M P

    2014-09-26

    Previous studies found that prostaglandins in skeletal muscle play a role in evoking the exercise pressor reflex; however the role played by prostaglandins in the spinal transmission of the reflex is not known. We determined, therefore, whether or not spinal blockade of cyclooxygenase (COX) activity and/or spinal blockade of endoperoxide (EP) 2 or 4 receptors attenuated the exercise pressor reflex in decerebrated rats. We first established that intrathecal doses of a non-specific COX inhibitor Ketorolac (100 μg in 10 μl), a COX-2-specific inhibitor Celecoxib (100 μg in 10 μl), an EP2 antagonist PF-04418948 (10 μg in 10 μl), and an EP4 antagonist L-161,982 (4 μg in 10 μl) effectively attenuated the pressor responses to intrathecal injections of arachidonic acid (100 μg in 10 μl), EP2 agonist Butaprost (4 ng in 10 μl), and EP4 agonist TCS 2510 (6.25 μg in 2.5 μl), respectively. Once effective doses were established, we statically contracted the hind limb before and after intrathecal injections of Ketorolac, Celecoxib, the EP2 antagonist and the EP4 antagonist. We found that Ketorolac significantly attenuated the pressor response to static contraction (before Ketorolac: 23 ± 5 mmHg, after Ketorolac 14 ± 5 mmHg; preflex, and that the spinal prostaglandins produced by this enzyme are most likely activating spinal EP4 receptors, but not EP2 receptors. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  2. The role of prostaglandins in spinal transmission of the exercise pressor reflex in decerebrate rats

    Science.gov (United States)

    Stone, Audrey J.; Copp, Steven W.; Kaufman, Marc P.

    2014-01-01

    Previous studies found that prostaglandins in skeletal muscle play a role in evoking the exercise pressor reflex; however the role played by prostaglandins in the spinal transmission of the reflex is not known. We determined, therefore, whether or not spinal blockade of cyclooxygenase (COX) activity and/or spinal blockade of endoperoxide receptor (EP) 2 or EP4 receptors attenuated the exercise pressor reflex in decerebrate rats. We first established that intrathecal doses of a non-specific COX inhibitor Ketorolac (100ug in 10ul), a COX-2 specific inhibitor Celecoxib (100μg in 10μl), an EP2 antagonist PF-04418948 (10μg in 10μl), and an EP4 antagonist L-161,982 (4μg in 10μl) effectively attenuated the pressor responses to intrathecal injections of Arachidonic Acid (100μg in 10μl), EP2 agonist Butaprost (4ng in 10 μl), and EP4 agonist TCS 2510 (6.25μg in 2.5 μl), respectively. Once effective doses were established, we statically contracted the hindlimb before and after intrathecal injections of Ketorolac, Celecoxib, the EP2 antagonist and the EP4 antagonist. We found that Ketorolac significantly attenuated the pressor response to static contraction (before Ketorolac: 23±5 mmHg, after Ketorolac 14±5 mmHg; preflex, and that the spinal prostaglandins produced by this enzyme are most likely activating spinal EP4 receptors, but not EP2 receptors. PMID:25003710

  3. The infrared problem for the dressed non-relativistic electron in a magnetic field

    International Nuclear Information System (INIS)

    Amour, L.; Faupin, J.; Grebert, B.; Guillot, J.C.

    2008-01-01

    We consider a non-relativistic electron interacting with a classical magnetic field pointing along the x 3 -axis and with a quantized electromagnetic field. The system is translation invariant in the x 3 -direction and the corresponding Hamiltonian has a decomposition H ≅∫ R + H(P 3 )dP 3 . For a fixed momentum P 3 sufficiently small, we prove that H(P 3 ) has a ground state in the Fock representation if and only if E'(P 3 )=0, where P 3 →E'(P 3 ) is the derivative of the map P 3 →E(P 3 )=infσ(H(P 3 )). If E'(P 3 )≠0, we obtain the existence of a ground state in a non-Fock representation. This result holds for sufficiently small values of the coupling constant. (authors)

  4. SIMPLE MODELS OF THREE COUPLED PT -SYMMETRIC WAVE GUIDES ALLOWING FOR THIRD-ORDER EXCEPTIONAL POINTS

    Directory of Open Access Journals (Sweden)

    Jan Schnabel

    2017-12-01

    Full Text Available We study theoretical models of three coupled wave guides with a PT-symmetric distribution of gain and loss. A realistic matrix model is developed in terms of a three-mode expansion. By comparing with a previously postulated matrix model it is shown how parameter ranges with good prospects of finding a third-order exceptional point (EP3 in an experimentally feasible arrangement of semiconductors can be determined. In addition it is demonstrated that continuous distributions of exceptional points, which render the discovery of the EP3 difficult, are not only a feature of extended wave guides but appear also in an idealised model of infinitely thin guides shaped by delta functions.

  5. Countering Air and Missile Threats

    Science.gov (United States)

    2012-03-23

    and surveillance, targeting, AR, and EW (e.g., AWACS, Rivet Joint, JSTARS, Compass Call, Cobra Ball, U-2, E-2C, and EP-3). Depending on the defensive...This list is a critical tool in the management of the use of the electromagnetic spectrum, and it specifies protected frequencies that should not be...means may be either active or passive. (a) Active means include EA, directed energy, electromagnetic jamming, electromagnetic deception, expendables

  6. Prime Contract Awards Over $25,000 by Major System, Contractor and State, FY83.

    Science.gov (United States)

    1983-01-01

    EQUIPMENT 100 EP3CO INC ILLIN 6130 CONVERTERS ELECTRICAL NON ROTATING 201 EQUUS TOOL CORP OHIO 2540 VEHICULAR FURNITURE AND ACCESSORIES 74 Ea 4710 PIPE...LOUISVILLE UNIVERSITY OF KENTU 1095 MISCELLANEOUS WEAPONS MARCONI INSTRUMENTS NEW J 6115 GENERATORS AND GENERATOR SETS ELECTRICAL OLIN CORP ILLIN 1305...AMOUNT FSF ARMY CARTRI DOE--------------------- 50 CAL 4 BALL I TRACER OLIN CORP FLORI 1376 BULK EXPLOSIVES S 17,633 FUK ARMY CARTRIDE

  7. Analysis list: HIVEP3 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available HIVEP3 Digestive tract + hg19 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/HIV...EP3.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/HIVEP3.5.tsv http://dbarchive.bioscien...cedbc.jp/kyushu-u/hg19/target/HIVEP3.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/HIVEP3.Dige

  8. Genetic deletion of the P2Y2 receptor offers significant resistance to development of lithium-induced polyuria accompanied by alterations in PGE2 signaling.

    Science.gov (United States)

    Zhang, Yue; Pop, Ioana L; Carlson, Noel G; Kishore, Bellamkonda K

    2012-01-01

    Lithium (Li)-induced polyuria is due to resistance of the medullary collecting duct (mCD) to the action of arginine vasopressin (AVP), apparently mediated by increased production of PGE(2). We previously reported that the P2Y(2) receptor (P2Y(2)-R) antagonizes the action of AVP on the mCD and may play a role in Li-induced polyuria by enhancing the production of PGE(2) in mCD. Hence, we hypothesized that genetic deletion of P2Y(2)-R should ameliorate Li-induced polyuria. Wild-type (WT) or P2Y(2)-R knockout (KO) mice were fed normal or Li-added diets for 14 days and euthanized. Li-induced polyuria, and decreases in urine osmolality and AQP2 protein abundance in the renal medulla, were significantly less compared with WT mice despite the lack of differences in Li intake or terminal serum or inner medullary tissue Li levels. Li-induced increased urinary excretion of PGE(2) was not affected in KO mice. However, prostanoid EP(3) receptor (EP3-R) protein abundance in the renal medulla of KO mice was markedly lower vs. WT mice, irrespective of the dietary regimen. The protein abundances of other EP-Rs were not altered across the groups irrespective of the dietary regimen. Ex vivo stimulation of mCD with PGE(2) generated significantly more cAMP in Li-fed KO mice (130%) vs. Li-fed WT mice (100%). Taken together, these data suggest 1) genetic deletion of P2Y(2)-R offers significant resistance to the development of Li-induced polyuria; and 2) this resistance is apparently due to altered PGE(2) signaling mediated by a marked decrease in EP3-R protein abundance in the medulla, thus attenuating the EP3-mediated decrease in cAMP levels in mCD.

  9. The U.S. Navy in the World (1970-1980): Context for U.S. Navy Capstone Strategies and Concepts

    Science.gov (United States)

    2011-12-01

    PHIBLEX PHIBLEX SUBSALVEX Bicentennial INR Global DEFCON 3 alert: Oct 1973 SS, SSN, P-3, EP-3 ISR ops SSBN deterrent patrols Undersea surveillance system...a few USN communities (submarines, NAVFACs, intelligence, etc.) Deployment of Soviet Delta-class SSBNs w/ long-range SLBMs to bastions , however...1970s: US-flag Merchant Marine (V)  Seatrain introduced container “land bridge ” across US, competing with seaborne commerce (1971) U.S. private

  10. Tight Bounds for Distributed Functional Monitoring

    DEFF Research Database (Denmark)

    Woodruff, David P.; Zhang, Qin

    2011-01-01

    $, our bound resolves their main open question. Our lower bounds are based on new direct sum theorems for approximate majority, and yield significant improvements to problems in the data stream model, improving the bound for estimating $F_p, p > 2,$ in $t$ passes from $\\tilde{\\Omega}(n^{1-2/p}/(\\eps^{2/p......} t))$ to $\\tilde{\\Omega}(n^{1-2/p}/(\\eps^{4/p} t))$, giving the first bound for estimating $F_0$ in $t$ passes of $\\Omega(1/(\\eps^2 t))$ bits of space that does not use the gap-hamming problem, and showing a distribution for the gap-hamming problem with high external information cost or super...

  11. Moessbauer spectrometric data acquisition based on FPGA

    International Nuclear Information System (INIS)

    Zhang Yuan; Li Shimin; Chen Nan; Zhu Jingbo; Xia Yuanfu

    2008-01-01

    FPGA(Field Programmable Gate Array) is a programmable device with strong logical function and timing control ability. It is extremely potent in acquiring and processing timing signals. By replacing the traditional used SCM (Single-Chip Microcomputer) with FPGA, counting speed of Moessbauer spectrometric data acquisition can be improved markedly with significantly decreased size of the spectrometer. The counter, RAM and RS-232 communication of the module are developed on Altera Cyclone series chip EP1C6T144C8 with Quartus II. EP1C6T144C8 has 5980 logical units accompanied by 92160 bits of memory space. It is so powerful that all needs in data acquisition of the Moessbauer spectrometer can be perfectly satisfied while allowing modifications in functions and parameters. (authors)

  12. Optical constants and self-assembly of phenylene ethynylene oligomer monolayers

    DEFF Research Database (Denmark)

    Marx, E.; Walzer, Karsten; Less, R.J.

    2004-01-01

    This paper studies the self-assembly on gold surfaces of 1,4-ethynylphenyl-4'-ethynylphenyl-2'-nitro-1-benzenedithiolate (EP2NO(2)), a substituted phenylene ethynylene trimer with applications in molecular electronics. We develop an ellipsometric technique to measure the optical constants...... of these self-assembled monolayers, and we also use attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy and scanning tunneling microscopy (STM) to confirm the structure of the films....

  13. Comparison of single nucleotide polymorphisms and microsatellites in non-invasive genetic monitoring of a wolf population

    DEFF Research Database (Denmark)

    Fabbri, Elena; Caniglia, R.; Mucci, Nadia

    2012-01-01

    Single nucleotide polymorphisms (SNPs) which represent the most widespread source of sequence variation in genomes, are becoming a routine application in several fields such as forensics, ecology and conservation genetics. Their use, requiring short amplifications, may allow a more efficient geno....... We evaluated the cost, laboratory effort and reliability of these different markers and discuss the possible future use of VeraCode, SNPlex and Fluidigm EP1 system in wild population monitoring....

  14. Prophylactic Injection of Recombinant Alpha-Enolase Reduces Arthritis Severity in the Collagen-Induced Arthritis Mice Model.

    Directory of Open Access Journals (Sweden)

    Clément Guillou

    Full Text Available To evaluate the ability of the glycolytic enzyme alpha-enolase (ENO1 or its immunodominant peptide (pEP1 to reduce the severity of CIA in DBA/1 mice when injected in a prophylactic way.Mice were treated with mouse ENO1 or pEP1 one day prior to collagen II immunization. Clinical assessment was evaluated using 4 parameters (global and articular scores, ankle thickness and weight. Titers of serum anti-ENO1, anti-cyclic citrullinated peptides (anti-CCP and anti-CII (total IgG and IgG1/IgG2a isotypes antibodies were measured by ELISA at different time-points. Disease activity was assessed by histological analysis of both anterior and hind paws at the end of experimentation.Prophylactic injection of 100 μg of ENO1 reduced severity of CIA. Serum levels of anti-CII antibodies were reduced in ENO1-treated mice. Concordantly, ENO1-treated mice joints presented less severe histological signs of arthritis. ENO1 did not induce a shift toward a Th2 response since IgG1/IgG2a ratio of anti-CII antibodies remained unchanged and IL-4 serum levels were similar to those measured in the control group.Pre-immunization with ENO1 or its immunodominant peptide pEP1 reduces CIA severity at the clinical, immunological and histological levels. Effects of pEP1 were less pronounced. This immunomodulatory effect is associated with a reduction in anti-CII antibodies production but is not due to a Th1/Th2 shift.

  15. Prophylactic Injection of Recombinant Alpha-Enolase Reduces Arthritis Severity in the Collagen-Induced Arthritis Mice Model

    Science.gov (United States)

    Guillou, Clément; Derambure, Céline; Fréret, Manuel; Verdet, Mathieu; Avenel, Gilles; Golinski, Marie-Laure; Sabourin, Jean-Christophe; Loarer, François Le; Adriouch, Sahil; Boyer, Olivier; Lequerré, Thierry; Vittecoq, Olivier

    2015-01-01

    Objective To evaluate the ability of the glycolytic enzyme alpha-enolase (ENO1) or its immunodominant peptide (pEP1) to reduce the severity of CIA in DBA/1 mice when injected in a prophylactic way. Methods Mice were treated with mouse ENO1 or pEP1 one day prior to collagen II immunization. Clinical assessment was evaluated using 4 parameters (global and articular scores, ankle thickness and weight). Titers of serum anti-ENO1, anti-cyclic citrullinated peptides (anti-CCP) and anti-CII (total IgG and IgG1/IgG2a isotypes) antibodies were measured by ELISA at different time-points. Disease activity was assessed by histological analysis of both anterior and hind paws at the end of experimentation. Results Prophylactic injection of 100 μg of ENO1 reduced severity of CIA. Serum levels of anti-CII antibodies were reduced in ENO1-treated mice. Concordantly, ENO1-treated mice joints presented less severe histological signs of arthritis. ENO1 did not induce a shift toward a Th2 response since IgG1/IgG2a ratio of anti-CII antibodies remained unchanged and IL-4 serum levels were similar to those measured in the control group. Conclusions Pre-immunization with ENO1 or its immunodominant peptide pEP1 reduces CIA severity at the clinical, immunological and histological levels. Effects of pEP1 were less pronounced. This immunomodulatory effect is associated with a reduction in anti-CII antibodies production but is not due to a Th1/Th2 shift. PMID:26302382

  16. Emmprin, released as a microvesicle in epithelioid sarcoma, interacts with fibroblasts.

    Science.gov (United States)

    Aoki, Mikiko; Koga, Kaori; Hamasaki, Makoto; Egawa, Nagayasu; Nabeshima, Kazuki

    2017-06-01

    Emmprin (extracellular matrix metalloproteinase inducer, CD147) is a glycosylated transmembrane protein, consisting of two immunoglobulin domains, that stimulates the production of matrix metalloproteinases (MMPs) by tumor-associated fibroblasts. These effects play important roles in tumor invasion and metastasis. However, the precise mechanisms by which emmprin acts on fibroblasts have not been fully elucidated, especially in sarcoma cells. Previously, we demonstrated that emmprin, expressed in conditioned medium collected from the epithelioid sarcoma cell line (FU-EPS-1), stimulates MMP-2 production via interactions with fibroblasts. In this study, we used microvesicles derived from sarcoma cells, and determined whether emmprin exists in the microvesicles, which enhance the production of MMP-2 via fibroblasts. Microvesicles released from FU-EPS-1 cells were shown to contain full-length emmprin, identified as a 45-kDa protein characterized by polylactosamine glycosylation. Microvesicles collected from FU-EPS-1 cells transfected with emmprin-specific siRNA or transduced with shRNA displayed significantly reduced MMP-2 production by fibroblasts compared with those from control-transfected cells. Our findings show that emmprin is released through microvesicle shedding in sarcoma cells, and emmprin in microvesicles regulates MMP-2 production by influencing the activity of fibroblasts located at sites distant from the tumor cells.

  17. A Fungal Effector With Host Nuclear Localization and DNA-Binding Properties Is Required for Maize Anthracnose Development.

    Science.gov (United States)

    Vargas, Walter A; Sanz-Martín, José M; Rech, Gabriel E; Armijos-Jaramillo, Vinicio D; Rivera, Lina P; Echeverria, María Mercedes; Díaz-Mínguez, José M; Thon, Michael R; Sukno, Serenella A

    2016-02-01

    Plant pathogens have the capacity to manipulate the host immune system through the secretion of effectors. We identified 27 putative effector proteins encoded in the genome of the maize anthracnose pathogen Colletotrichum graminicola that are likely to target the host's nucleus, as they simultaneously contain sequence signatures for secretion and nuclear localization. We functionally characterized one protein, identified as CgEP1. This protein is synthesized during the early stages of disease development and is necessary for anthracnose development in maize leaves, stems, and roots. Genetic, molecular, and biochemical studies confirmed that this effector targets the host's nucleus and defines a novel class of double-stranded DNA-binding protein. We show that CgEP1 arose from a gene duplication in an ancestor of a lineage of monocot-infecting Colletotrichum spp. and has undergone an intense evolution process, with evidence for episodes of positive selection. We detected CgEP1 homologs in several species of a grass-infecting lineage of Colletotrichum spp., suggesting that its function may be conserved across a large number of anthracnose pathogens. Our results demonstrate that effectors targeted to the host nucleus may be key elements for disease development and aid in the understanding of the genetic basis of anthracnose development in maize plants.

  18. A polysaccharide from cultured mycelium of Hericium erinaceus and its anti-chronic atrophic gastritis activity.

    Science.gov (United States)

    Wang, Mingxing; Gao, Yang; Xu, Duoduo; Gao, Qipin

    2015-11-01

    A polysaccharide named EP-1 was found by screening cultured mycelium of Hericium erinaceus, which was extracted and subjected to precipitation with ethanol, hollow-fiber ultrafiltration and ion-exchange chromatography. The polysaccharide has a molecular weight of approximately 3100Da and is composed of glucose, mannose and galactose, thus being a heteroglycan. EP-1 has a backbone of α-d-Glc(1→3) and β-d-Glc(1→3). The β-d-Glc(1→3) and α-d-Gal-(1→3) were regarded as branches attached to the C-4 position. The α-d-Man was regarded as a terminal residue. The anti-CAG activity was evaluated in experimental systems using a cell model for identification. The polysaccharide significantly inhibited the growth of MC cells obtained from human gastric mucosa epithelium (GES-1) cells transformed by MNNG, which were used as a chronic atrophic gastritis cell model. It also interfered with the MC cells by inducing cell cycle arrest. Thus, EP-1 shows potential for the development of new functional foods and drugs. Copyright © 2015. Published by Elsevier B.V.

  19. Prostaglandins in Cancer Cell Adhesion, Migration, and Invasion

    Directory of Open Access Journals (Sweden)

    David G. Menter

    2012-01-01

    Full Text Available Prostaglandins exert a profound influence over the adhesive, migratory, and invasive behavior of cells during the development and progression of cancer. Cyclooxygenase-2 (COX-2 and microsomal prostaglandin E2 synthase-1 (mPGES-1 are upregulated in inflammation and cancer. This results in the production of prostaglandin E2 (PGE2, which binds to and activates G-protein-coupled prostaglandin E1-4 receptors (EP1-4. Selectively targeting the COX-2/mPGES-1/PGE2/EP1-4 axis of the prostaglandin pathway can reduce the adhesion, migration, invasion, and angiogenesis. Once stimulated by prostaglandins, cadherin adhesive connections between epithelial or endothelial cells are lost. This enables cells to invade through the underlying basement membrane and extracellular matrix (ECM. Interactions with the ECM are mediated by cell surface integrins by “outside-in signaling” through Src and focal adhesion kinase (FAK and/or “inside-out signaling” through talins and kindlins. Combining the use of COX-2/mPGES-1/PGE2/EP1-4 axis-targeted molecules with those targeting cell surface adhesion receptors or their downstream signaling molecules may enhance cancer therapy.

  20. Screening and identification of dietary oils and unsaturated fatty acids in inhibiting inflammatory prostaglandin E2 signaling in fat stromal cells

    Directory of Open Access Journals (Sweden)

    Ruan Diana

    2012-08-01

    Full Text Available Abstract Background The molecular mechanisms of dietary oils (such as fish oil and unsaturated fatty acids, which are widely used by the public for anti-inflammation and vascular protection, have not been settled yet. In this study, prostaglandin E2 (PGE2-mediated calcium signaling was used to screen dietary oils and eight unsaturated fatty acids for identification of their anti-inflammatory mechanisms. Isolated fat/stromal cells expressing endogenous PGE2 receptors and an HEK293 cell line specifically expressing the recombinant human PGE2 receptor subtype-1 (EP1 were cultured and used in live cell calcium signaling assays. The different dietary oils and unsaturated fatty acids were used to affect cell signaling under the specific stimulation of a pathological amount of inflammatory PGE2. Results It was identified that fish oil best inhibited the PGE2 signaling in the primary cultured stromal cells. Second, docosahexaenoic acid (DHA, found in abundance in fish oil, was identified as a key factor of inhibition of PGE2 signaling. Eicosapentaenoic acid (EPA, another major fatty acid found in fish oil and tested in this study was found to have small effect on EP1 signaling. The study suggested one of the four PGE2 subtype receptors, EP1 as the key target for the fish oil and DHA target. These findings were further confirmed by using the recombinant EP1 expressed in HEK293 cells as a target. Conclusion This study demonstrated the new mechanism behind the positive effects of dietary fish oils in inhibiting inflammation originates from the rich concentration of DHA, which can directly inhibit the inflammatory EP1-mediated PGE2 receptor signaling, and that the inflammatory response stimulated by PGE2 in the fat stromal cells, which directly related to metabolic diseases, could be down regulated by fish oil and DHA. These findings also provided direct evidence to support the use of dietary oils and unsaturated fatty acids for protection against heart

  1. The socio-technical organisation of community pharmacies as a factor in the Electronic Prescription Service Release Two implementation: a qualitative study

    Directory of Open Access Journals (Sweden)

    Harvey Jasmine

    2012-12-01

    Full Text Available Abstract Background The introduction of a new method of transmitting prescriptions from general practices to community pharmacies in England (Electronic Prescription Service Release 2 (EPS2 has generated debate on how it will change work practice. As EPS2 will be a key technical element in dispensing, we reviewed the literature to find that there were no studies on how social and technical elements come together to form work practice in community pharmacies. This means the debate has little point of reference. Our aim therefore was to study the ways social and technical elements of a community pharmacy are used to achieve dispensing through the development of a conceptual model on pharmacy work practice, and to consider how a core technical element such the EPS2 could change work practice. Method We used ethnographic methods inclusive of case-study observations and interviews to collect qualitative data from 15 community pharmacies that were in the process of adopting or were soon to adopt EPS2. We analysed the case studies thematically and used rigorous multi-dimensional and multi-disciplinary interpretive validation techniques to cross analyse findings. Results In practice, dispensing procedures were not designed to take into account variations in human and technical integration, and assumed that repetitive and collective use of socio-technical elements were at a constant. Variables such as availability of social and technical resources, and technical know-how of staff were not taken into account in formalised procedures. Yet community pharmacies were found to adapt their dispensing in relation to the balance of social and technical elements available, and how much of the social and technical elements they were willing to integrate into dispensing. While some integrated as few technical elements as possible, some depended entirely on technical artefacts. This pattern also applied to the social elements of dispensing. Through the conceptual

  2. The Relationship Between Engagement and Neurophysiological Measures of Attention in Motion-Controlled Video Games: A Randomized Controlled Trial.

    Science.gov (United States)

    Leiker, Amber M; Miller, Matthew; Brewer, Lauren; Nelson, Monica; Siow, Maria; Lohse, Keith

    2016-04-21

    Video games and virtual environments continue to be the subject of research in health sciences for their capacity to augment practice through user engagement. Creating game mechanics that increase user engagement may have indirect benefits on learning (ie, engaged learners are likely to practice more) and may also have direct benefits on learning (ie, for a fixed amount of practice, engaged learners show superior retention of information or skills). To manipulate engagement through the aesthetic features of a motion-controlled video game and measure engagement's influence on learning. A group of 40 right-handed participants played the game under two different conditions (game condition or sterile condition). The mechanics of the game and the amount of practice were constant. During practice, event-related potentials (ERPs) to task-irrelevant probe tones were recorded during practice as an index of participants' attentional reserve. Participants returned for retention and transfer testing one week later. Although both groups improved in the task, there was no difference in the amount of learning between the game and sterile groups, countering previous research. A new finding was a statistically significant relationship between self-reported engagement and the amplitude of the early-P3a (eP3a) component of the ERP waveform, such that participants who reported higher levels of engagement showed a smaller eP3a (beta=-.08, P=.02). This finding provides physiological data showing that engagement elicits increased information processing (reducing attentional reserve), which yields new insight into engagement and its underlying neurophysiological properties. Future studies may objectively index engagement by quantifying ERPs (specifically the eP3a) to task-irrelevant probes.

  3. Investigation of the sources and evolution processes of severe haze pollution in Beijing in January 2013

    Science.gov (United States)

    Sun, Yele; Jiang, Qi; Wang, Zifa; Fu, Pingqing; Li, Jie; Yang, Ting; Yin, Yan

    2014-04-01

    China experienced severe haze pollution in January 2013. Here we have a detailed characterization of the sources and evolution mechanisms of this haze pollution with a focus on four haze episodes that occurred during 10-14 January in Beijing. The main source of data analyzed is from submicron aerosol measurements by an Aerodyne Aerosol Chemical Speciation Monitor. The average PM1 mass concentration during the four haze episodes ranged from 144 to 300 µg m-3, which was more than 10 times higher than that observed during clean periods. All submicron aerosol species showed substantial increases during haze episodes with sulfate being the largest. Secondary inorganic species played enhanced roles in the haze formation as suggested by their elevated contributions during haze episodes. Positive matrix factorization analysis resolved six organic aerosol (OA) factors including three primary OA (POA) factors from traffic, cooking, and coal combustion emissions, respectively, and three secondary OA (SOA) factors. Overall, SOA contributed 41-59% of OA with the rest being POA. Coal combustion OA (CCOA) was the largest primary source, on average accounting for 20-32% of OA, and showed the most significant enhancement during haze episodes. A regional SOA (RSOA) was resolved for the first time which showed a pronounced peak only during the record-breaking haze episode (Ep3) on 12-13 January. The regional contributions estimated based on the steep evolution of air pollutants were found to play dominant roles for the formation of Ep3, on average accounting for 66% of PM1 during the peak of Ep3 with sulfate, CCOA, and RSOA being the largest fractions (> ~ 75%). Our results suggest that stagnant meteorological conditions, coal combustion, secondary production, and regional transport are four main factors driving the formation and evolution of haze pollution in Beijing during wintertime.

  4. Variants of Phosphotriesterase for the Enhanced Detoxification of the Chemical Warfare Agent VR.

    Science.gov (United States)

    Bigley, Andrew N; Mabanglo, Mark F; Harvey, Steven P; Raushel, Frank M

    2015-09-08

    The V-type organophosphorus nerve agents are among the most hazardous compounds known. Previous efforts to evolve the bacterial enzyme phosphotriesterase (PTE) for the hydrolytic decontamination of VX resulted in the identification of the variant L7ep-3a, which has a kcat value more than 2 orders of magnitude higher than that of wild-type PTE for the hydrolysis of VX. Because of the relatively small size of the O-ethyl, methylphosphonate center in VX, stereoselectivity is not a major concern. However, the Russian V-agent, VR, contains a larger O-isobutyl, methylphosphonate center, making stereoselectivity a significant issue since the SP-enantiomer is expected to be significantly more toxic than the RP-enantiomer. The three-dimensional structure of the L7ep-3a variant was determined to a resolution of 2.01 Å (PDB id: 4ZST ). The active site of the L7ep-3a mutant has revealed a network of hydrogen bonding interactions between Asp-301, Tyr-257, Gln-254, and the hydroxide that bridges the two metal ions. A series of new analogues that mimic VX and VR has helped to identify critical structural features for the development of new enzyme variants that are further enhanced for the catalytic detoxification of VR and VX. The best of these mutants has been shown to have a reversed stereochemical preference for the hydrolysis of VR-chiral center analogues. This mutant hydrolyzes the two enantiomers of VR 160- and 600-fold faster than wild-type PTE hydrolyzes the SP-enantiomer of VR.

  5. Carry-chain propagation delay impacts on resolution of FPGA-based TDC

    International Nuclear Information System (INIS)

    Dong Lei; Yang Junfeng; Song Kezhu

    2014-01-01

    The architecture of carry chains in Field-Programmable Gate Array (FPGA) is introduced in this paper. The propagation delay time of the rising and falling edges in the carry chains are calculated according to the architecture and they are predicted not equal in most cases. Tests show that the measuring results of the propagation delay time in EP3C120F484C8N series FPGA of Altera are in line with the inference. The difference of propagation delay time results in different accuracies of Time-to-Digital Converter (TDC). This phenomenon shall be considered in the design of TDC implemented in FPGA. It can ensure better accuracy. (authors)

  6. Apache, Santa Fe energy units awarded two Myanmar blocks

    International Nuclear Information System (INIS)

    Anon.

    1992-01-01

    This paper reports that Myanmar's state oil company has awarded production sharing contracts (PSCs) on two blocks to units of Apache Corp. and Santa Fe Energy Resources Inc., both of Houston. That comes on the heels of a report by County NatWest Woodmac that notes Myanmar's oil production, currently meeting less than half the country's demand, is set to fall further this year. 150 line km of new seismic data could be acquired and one well drilled. During the initial 2 year exploration period on Block EP-3, Apache will conduct geological studies and conduct at least 200 line km of seismic data

  7. Online Learning Activities: Beginning An International Collaboration

    Directory of Open Access Journals (Sweden)

    Tom Nickel

    2002-04-01

    Full Text Available Early Sunday morning, April 1, 2001, a U.S. Navy EP-3E Aries II surveillance plane collided with a Chinese fighter jet, causing the death of the Chinese pilot and forcing an emergency landing by the U.S. aircraft on Hainan Island, in the People’s Republic of China. Political relations between the United States and China had been deteriorating for months during the Spring of 2001 –- it was the stated intention of newly-elected President George W. Bush to move American policy toward China from “strategic partnership” to “strategic competition.”

  8. Delay model and performance testing for FPGA carry chain TDC

    International Nuclear Information System (INIS)

    Kang Xiaowen; Liu Yaqiang; Cui Junjian Yang Zhangcan; Jin Yongjie

    2011-01-01

    Time-of-flight (TOF) information would improve the performance of PET (position emission tomography). TDC design is a key technique. It proposed Carry Chain TDC Delay model. Through changing the significant delay parameter of model, paper compared the difference of TDC performance, and finally realized Time-to-Digital Convertor (TDC) based on Carry Chain Method using FPGA EP2C20Q240C8N with 69 ps LSB, max error below 2 LSB. Such result could meet the TOF demand. It also proposed a Coaxial Cable Measuring method for TDC testing, without High-precision test equipment. (authors)

  9. Corn silk induced cyclooxygenase-2 in murine macrophages.

    Science.gov (United States)

    Kim, Kyung A; Shin, Hyun-Hee; Choi, Sang Kyu; Choi, Hye-Seon

    2005-10-01

    Stimulation of murine macrophages with corn silk induced cyclooxygenase (COX)-2 with secretion of PGE2. Expression of COX-2 was inhibited by pyrolidine dithiocarbamate (PDTC), and increased DNA binding by nuclear factor kappa B (NF-kappaB), indicating that COX-2 induction proceeds also via the NF-kappaB signaling pathway. A specific inhibitor of COX-2 decreased the expression level of inducible nitric oxide synthase (iNOS) stimulated by corn silk. PGE2 elevated the expression level of iNOS, probably via EP2 and EP4 receptors on the surface of the macrophages.

  10. Design and FPGA Implementation of a new hyperchaotic system

    International Nuclear Information System (INIS)

    Wang Guangyi; Bao Xulei; Wang Zhonglin

    2008-01-01

    In this paper, a new four-dimensional autonomous hyperchaotic system is designed for generating complex chaotic signals. In the design, its parameters are selected according to the requirements for chaos and hyperchaos. The hyperchaotic Nature is verified theoretically by using the bifurcation analysis and demonstrated experimentally by the implementation of an analogue electronic circuit. Moreover, the Field Programmable Gate Array (FPGA) technology is applied to implementing a continuous system in a digital form by using a chip of Altera Cyclone II EP2C35F484C8. The digital sequence generated from the FPGA device is observed in our experimental setup. (general)

  11. Work plan for the fabrication of the radioisotope thermoelectric generator transportation system package mounting

    International Nuclear Information System (INIS)

    Satoh, J.A.

    1994-01-01

    The Radioisotope Thermoelectric Generator (RTG) has available a dedicated system for the transportation of RTG payloads. The RTG Transportation System (System 100) is comprised of four systems; the Package (System 120), the Semi-trailer (System 140), the Gas Management (System 160), and the Facility Transport (System 180). This document provides guidelines on the fabrication, technical requirements, and quality assurance of the Package Mounting (Subsystem 145), part of System 140. The description follows the Development Control Requirements of WHC-CM-6-1, EP 2.4, Rev. 3

  12. Hardware Prototyping of Neural Network based Fetal Electrocardiogram Extraction

    Science.gov (United States)

    Hasan, M. A.; Reaz, M. B. I.

    2012-01-01

    The aim of this paper is to model the algorithm for Fetal ECG (FECG) extraction from composite abdominal ECG (AECG) using VHDL (Very High Speed Integrated Circuit Hardware Description Language) for FPGA (Field Programmable Gate Array) implementation. Artificial Neural Network that provides efficient and effective ways of separating FECG signal from composite AECG signal has been designed. The proposed method gives an accuracy of 93.7% for R-peak detection in FHR monitoring. The designed VHDL model is synthesized and fitted into Altera's Stratix II EP2S15F484C3 using the Quartus II version 8.0 Web Edition for FPGA implementation.

  13. Experimental Research Into High Barometric Oxygen Prevention of Guinea Pig Hearing Loss,

    Science.gov (United States)

    1992-08-28

    PREVENTION OF GUINEA PIG HEARING LOSS by Yin Jiacai, Sun Fang ren, et al. DTIC MLECTE •<• EP 2 9 1992 Approved for public release, Distribution unlimited...PREVENTION OF GUINEA PIG HEARING LOSS By: Yin Jiacai, Sun Fang ren, et al. English pages: 9 Source: Chung-Hua I Shueh Tsa Chih, Vol. 65, Nr. 11, Nov.eember...Distributionf._DL~~~t .•b • / or __ Dlist szeccat .lef ’ ~1 EXPERIMENTAL RESEARCH INTO HIGH BAROMETRIC OXYGEN PREVENTION OF GUINEA PIG HEARING LOSS BY: Yin

  14. Configuration Management Program Application at KNPP Units 5 and 6 Modernization Program

    International Nuclear Information System (INIS)

    Manchev, B.; Yordanova, V.; Nenkova, B.

    2006-01-01

    The need for Configuration Management Program development, became very clear after the initiation of the Modernization Program for Units 5and6, because KNPP personnel needed a good and safe way to control the huge amount of data which were transferred into two directions - input data (design and operational documents from KNPP to Contractors) and the design, vendor, procurement, etc. documents (from Contractors to KNPP). Moreover, most of the measures are in fact design changes and it appeared to be extremely important to track these design changes and their reflection into design and operational documents. It is even more important to obtain a successful transfer of all this information to the operating organization (EP-2) after the completion. The proposal for development of Configuration Management (CM) Program for KNPP Units 5and6 Modernization program was divided into three phases: 1. Information Control (Document Control and Records Management) 2.Technical Decision System (Change Control) 3. Master Equipment List (MEL), (as part of the Design requirements element) Information Control Element was chosen to be developed first. Implementation of Information Control element comprised of: Review and assessment of existing situation (procedures for document control and records Management), Development of new/revision of existing procedure for Document Control and Records Management, Development of SmartDoc software application in support of document control and records management and for measure documentation tracking (with its specifics), Data entry for MP5and6 measures, Implementation at EP-2 (with successful data migration from the existing databases). The SmartDoc development was completed at the end of 2002 and after a testing period it was implemented at Modernization and Investment Department first. Then the data for documents were transferred from the existing databases at EP-2 and the system was implemented at EP-2 and other KNPP facilities. Development

  15. Interplacental uterine expression of genes involved in prostaglandin synthesis during canine pregnancy and at induced prepartum luteolysis/abortion

    Science.gov (United States)

    2014-01-01

    Background In the non-pregnant dog, ovarian cyclicity is independent of a uterine luteolysin. This is in contrast to pregnant animals where a prepartum increase of luteolytic PGF2α occurs, apparently originating in the pregnant uterus. Recently, the placenta as a source of prepartum prostaglandins (PGs) was investigated, indicating fetal trophoblast cells as the likely main source. However, the possible contribution of uterine interplacental tissues to the production of these hormones has not yet been thoroughly examined in the dog. Methods Several key factors involved in the production and/or actions of PGs were studied: cyclooxygenase 2 (COX2, PTGS2), PGF2α-synthase (PGFS/AKR1C3), PGE2-synthase (PGES), and the respective receptors FP (PTGFR), EP2 (PTGER2) and EP4 (PGTER4), 15-hydroxyprostaglandin dehydrogenase (HPGD), PG-transporter (PGT, SLCO2A1) and progesterone receptor. Their expression and localization patterns were assessed by Real Time PCR and immunohistology in the interplacental uterine sites from pregnant dogs during the pre-implantation period (days 8–12), post-implantation (days 18–25), mid-gestation (days 35–40) and during antigestagen-induced luteolysis/abortion. Results Whereas only low COX2 expression was observed in uterine samples at all the selected time points, expression of PGFS/AKR1C3 strongly increased post-implantation. A gradual increase in PGES-mRNA expression was noted towards mid-gestation. FP-mRNA expression decreased significantly with the progression of pregnancy until mid-gestation. This was associated with clearly detectable expression of HPGD, which did not change significantly over time. The expression of FP and EP2-mRNA decreased significantly over time while EP4-mRNA expression remained unaffected. The antigestagen-treatment led to a significant increase in expression of COX2, PGES, EP2 and PGT (SLCO2A1) mRNA. COX2 was localized predominantly in the myometrium. The expression of PGFS/AKR1C3, which was unchanged, was

  16. Implementation of the KASKAD computer code system for WWER-440 at Kozloduy NPP

    International Nuclear Information System (INIS)

    Antonov, A.; Georgieva, N.; Spasova, V.

    2003-01-01

    Since 2002 at Kozloduy NPP - EP1 the code package KASKAD is used for WWER-440 reactor core calculations. The main codes entering this package are: BIPR-7A: 3-D diffusion and core analysis code; PERMAK-A: 2-D fine mesh diffusion code. The burnup calculations were performed for all cycles of the Kozloduy NPP Unit 1, Unit 2, Unit 3 and Unit 4. For the last 4-5 cycles of the Units were calculated control rods worth, critical boron concentration at zero power, reactivity coefficients and linear power. These results were analysed and were compared with experimental data. Some results were given in this paper

  17. Bayesian inference in dynamic domains using logical OR gates

    CSIR Research Space (South Africa)

    Claessens, R

    2016-04-01

    Full Text Available Figure 5 (Equation 9), is given by Equation 10 (in which η is the normalization factor). P(PEk,t = true|ZP1:t ,ZR1:t ,EP1:t ,ER1:t ,EVu1:t ,XRa1:t )k = η∑ TP ∑ RP ∑ Vu ∑ Ra [ P(PEk,t = true|Vuk,t ,TPk,t ,RPk,t ,RaPk,t) · P(PRk,t |PEk,t = true) · ∑ We [ P...

  18. Exploration of joint systems and major horizontal stress direction in HDR drillholes of the Soultz site (Alsace, France)

    Energy Technology Data Exchange (ETDEWEB)

    Genter, A [BRGM/GIG, Orleans (France); Tenzer, H [Stadtwerke Bad Urach (Germany)

    1997-12-01

    Borehole imaging logs enable continuous recording of natural and artificial planar discontinuities on the drillhole wall and data of the drillhole geometry to be made. Efforts were made to resolve the orientation and characterization of the natural joint system, the active fault pattern, the alteration zones, the orientation of microcracks and the direction of maximum horizontal stress. Intense logging operations and measurements were carried out in the HDR drillholes GPK1 and EPS1 between 1000 and 3600 m depth in the Muschelkalk, Bunter and Granite at Soultz sous Forets. With the help of investigations on subvertical fractures the orientation of the maximum horizontal stress direction was determined as N175 E{+-}17 . These results are consistent with previous investigations performed in the horeholes GPK-1 and EPS-1. (orig./AKF) [Deutsch] Bohrlochmessungen mit dem akustschen Borehole Televiewer und elektrischen Formation MicroScanner (Imager) sowie dem Azimuthal Resistivity Imager und verschiedenen Sonic-Sonden ermoeglichen eine kontinuierliche Aufnahme sowohl von natuerlichen und kuenstlich erzeugten planaren Diskontinuitaeten an der Bohrlochwand als auch der Bohrlochgeometrie. Es wurden die Orientierung und Charakterisierung des natuerlichen Kluftsystems, das aktive Stoerungsmuster, die Alterationszonen, die Orientierung von Mikrorissen und die Orientierung der maximalen horizontalen Hauptspannungsrichtung ermittelt. Die Verfuegbarkeit von Strukturdaten aus Bohrloechern durch Bohrlochmessungen und hydraulischen Testen ermoeglicht die Bestimmung von hydraulisch aktiven Klueften und deren Beziehung zum regionalen Spannungsfeld. Mit Hilfe spezieller Bohrloch-Logs wurden die Orientierung und Haeufigkeit planarer Diskontinuitaeten und ihre scheinbare Oeffnungsweite sowie die Vorzugsrichtung der verschiedenen scheinbaren Weiten bestimmt. Innerhalb des gemeinsamen europaeischen Hot-Dry-Rock-Geothermal-Forschungsprogramms wurden vielfaeltige Bohrlochmessungen in den

  19. Palladium(0) NHC complexes : a new avenue to highly efficient phosphorescence

    OpenAIRE

    Henwood, Adam Francis; Lesieur, Mathieu; Bansal, Ashu Kumar; Lemaur, Vincent; Beljonne, David; Thompson, David G.; Graham, Duncan; Slawin, Alexandra Martha Zoya; Samuel, Ifor David William; Cazin, Catherine S.J.; Zysman-Colman, Eli

    2015-01-01

    The authors are grateful to the Royal Society (University Research Fellowship to CSJC and Wolfson Research Merit Award for IDWS) and to EPSRC (grant: EP1J01771X) for financial support. EZ-C thanks the University of St Andrews for funding. We report the first examples of highly luminescent di-coordinated Pd(0) complexes. Five complexes of the form [Pd(L)(L’)] were synthesized, where L = IPr, SIPr or IPr* NHC ligands and L’ = PCy3, or IPr and SIPr NHC ligands. The photophysical properties of...

  20. A One-Component, Fast-Cure, and Economical Epoxy Resin System Suitable for Liquid Molding of Automotive Composite Parts

    Directory of Open Access Journals (Sweden)

    Yiru Wang

    2018-04-01

    Full Text Available Imidazole cured epoxy resin systems were evaluated for one-component, fast-curing resins for liquid molding of automotive composite parts according to industry requirements. It was demonstrated that an epoxy resin-1-(cyanoethyl-2-ethyl-4-methylimidazol(EP-1C2E4MIM system would cure in a few minutes at 120 °C, while exhibiting acceptable pot life, viscosity profiles, and low water absorption. Moreover, this system yielded high Tg parts with mechanical properties similar to the amine-epoxy systems, which are the mainstream two-component epoxy resin systems for automobiles.

  1. Delaware River Dredging Disposal Study, Stage 1 Reconnaissance Report.

    Science.gov (United States)

    1979-06-01

    Ep1iAiu rupILcoa (Kurtz 1860) C x FamilIy Ca Iyp tra oi dae C rmep-idu. Ia fon- nic -tal (Linne 1758) S Crepiduloa convexad Say 1822 SF x x Crepidula...Penn’s home. This reconstruction, based on Penn’s correspondence, was constructed in 1939. Nat. Reg. PB 01 Andalusia (Nicholas Biddle Estate) Pa32...earlier structure. Nicholas Biddle politician and financier of the Revolution designed the classical motif and lived here. NHL. PB 28 St. Elizabeth’s

  2. Standard-B auto grab sampler hydrogen monitoring system, Acceptance Test Report

    International Nuclear Information System (INIS)

    Lott, D.T.

    1995-01-01

    Project W-369, Watch List Tank Hydrogen Monitors, installed a Standard-C Hydrogen Monitoring System (SHMS) on the Flammable gas waste tank AN-104. General Support Projects (8K510) was support by Test Engineering (7CH30) in the performance of the Acceptance Test Procedures (ATP) to qualify the SHMS cabinets on the waste tank. The ATP's performance was controlled by Tank Farm work package. This completed ATP is transmitted by EDT-601748 as an Acceptance Test Report (ATR) in accordance with WHC-6-1, EP 4.2 and EP 1.12

  3. Immunomodulatory Effects of CP-25 on Splenic T Cells of Rats with Adjuvant Arthritis.

    Science.gov (United States)

    Wang, Yang; Han, Chen-Chen; Cui, Dongqian; Luo, Ting-Ting; Li, Yifan; Zhang, Yuwen; Ma, Yang; Wei, Wei

    2018-06-01

    Rheumatoid arthritis (RA) is an autoimmune disease in which T cells play an important role. Paeoniflorin-6-oxy-benzenesulfonate (CP-25) shows a strong anti-inflammatory and immunomodulatory effect in the joint of adjuvant arthritis (AA) rats, but the role of the spleen function is still unclear. The aim of this study was to research how CP-25 regulated spleen function of AA rats. Male Sprague-Dawley rats were administered with CP-25 (50 mg/kg) orally from day 17 to 29 after immunization. The spleen histopathological changes were analyzed by hematoxylin-eosin staining. G protein-coupled receptor kinases (GRKs) and prostaglandin receptor subtypes (EPs) were screened by Western blot and immunohistochemistry. The co-expression of GRK2 and EP2 as well as GRK2 and EP4 was measured by immunofluorescence and co-immunoprecipitation. The expression of GRK2 and EP4 in splenic T cells was further detected by immunofluorescence. CP-25 was found to relieve the secondary paw swelling, attenuate histopathologic changes, and downregulate GRK2, EP2 and EP4 expression in AA rats. Additionally, CP-25 not only downregulated the co-expression of GRK2 and EP4 but also downregulated GRK2, EP4 expression in splenic T cells of AA rats. From these results, we can infer that CP-25 play an anti-inflammatory and immune function by affecting the function of the splenic T cells.

  4. Optical design of beam lines at the KEK-PS new experimental hall

    International Nuclear Information System (INIS)

    Tanaka, K.H.; Ieiri, M.; Noumi, H.; Minakawa, M.; Yamanoi, Y.; Kato, Y.; Ishii, H.; Suzuki, Y.; Takasaki, M.

    1995-01-01

    A new counter experimental hall [K.H. Tanaka et al., IEEE Trans. Magn. 28 (1992) 697] was designed and constructed at the KEK 12-GeV Proton Synchrotron (KEK-PS). The extracted proton beam from the KEK-PS is introduced to the new hall through the newly-prepared primary beam line, EP1, and hits two production targets in cascade. The upstream target provides secondary particles to the low momentum (0.4-0.6 GeV/c) separated beam line, K5, and the downstream target is connected to the medium momentum (0.6-2.0 GeV/c) separated beam line, K6. Several new ideas were employed in the beam optical designs of EP1, K5 and K6 in order to increase the number and the purity of the short-lived secondary particles, such as kaons and pions, under the limited energy and intensity of the primary protons provided by the KEK-PS. These new ideas are described in this paper as well as the first commissioning results. (orig.)

  5. Prostaglandin E(2) mediates acid-induced heartburn in healthy volunteers.

    Science.gov (United States)

    Kondo, Takashi; Oshima, Tadayuki; Tomita, Toshihiko; Fukui, Hirokazu; Watari, Jiro; Okada, Hiroki; Kikuchi, Shojiro; Sasako, Mitsuru; Matsumoto, Takayuki; Knowles, Charles H; Miwa, Hiroto

    2013-03-15

    Prostaglandin E(2) (PGE(2)) plays a major role in pain processing and hypersensitivity. This study investigated whether PGE(2) levels are increased in the esophageal mucosa after acid infusion and whether increases in PGE(2) are associated with heartburn. Furthermore, expression of the PGE(2) receptor EP1 was investigated in human esophageal mucosa. Fourteen healthy male volunteers were randomized to 30-min lower esophageal acid (1% HCl) or saline perfusion. Before and after acid perfusion, endoscopic biopsies were taken from the distal esophagus. PGE(2) concentration (pg/mg protein) and EP1 mRNA and protein in biopsy samples were measured by ELISA, RT-PCR, and Western blotting. Symptom status of heartburn was evaluated with a validated categorical rating scale with a higher values corresponding to increasing intensity. PGE(2) levels in the esophageal mucosa significantly increased after acid infusion (before vs. after acid infusion: 23.2 ± 8.6 vs. 68.6 ± 18.3, P heartburn in the acid-infusion group was also significantly greater compared with saline (saline vs. acid infusion: 54.3 ± 13.1 vs. 178.5 ± 22.8, P heartburn.

  6. Optical properties of the main electron-irradiation-induced defects in p-type InP: Comparison with calculations for the isolated and acceptor-paired phosphorus vacancy

    International Nuclear Information System (INIS)

    Bretagnon, T.; Bastide, G.; Rouzeyre, M.; Delerue, C.; Lannoo, M.

    1990-01-01

    Optical capacitance spectroscopy and thermal annealing of defects have been used to study both the electron traps EP 1 ,E 11 and the dominant hole traps (H 3 -H 4 -H 4 ' ) produced by low-energy electron irradiation in Zn-doped p-type InP. This shows that the 1.1-eV onset in the photoionization cross sections (PCS's) previously attributed to (H 3 -H 4 ) is actually due to the unrelated electron trap EP 1 . The true PCS's σ p 0 of (H 3 ,H 4 ) are compared with PCS tight-binding Green's function calculations to test the earlier proposal that the (H 2 -H 3 -H 4 -H 4 ' ,E 11 ) series might arise from different states of (V P -Zn) complexes. The model yields an effective agreement as concerns both the energy location of the hole-levels series in the forbidden gap and the vanishingly small contribution to the PCS's of the four equivalent L valence-band minima. The proposal that E 11 might correspond to the ionization of an e state of the V P -Zn complex also agrees with the experimental observation of both optical transitions to the valence band and to the conduction band but cannot account for the midgap position of E 11

  7. Prevotella intermedia induces prostaglandin E2 via multiple signaling pathways.

    Science.gov (United States)

    Guan, S-M; Fu, S-M; He, J-J; Zhang, M

    2011-01-01

    Prostaglandin E(2) (PGE(2)) plays important roles in the bone resorption of inflammatory diseases such as rheumatoid arthritis and periodontitis via specific prostaglandin receptors (i.e., EP1-EP4). In this study, the authors examined whether Prevotella intermedia regulates PGE(2) production and EP expression in human periodontal ligament fibroblasts (hPDLs); they also explored the potential signaling pathways involved in PGE(2) production. P. intermedia induced PGE(2) production and cyclooxygenase-2 (COX-2) expression in a dose- and time-dependent manner. Indomethacin and NS-398 completely abrogated the P. intermedia-induced PGE(2) production without modulating COX-2 expression. Specific inhibitors of extracellular signal-regulated kinase, c-Jun N-terminal kinase, p38, phosphatidylinositol 3-kinase, and protein kinase C--but not c-AMP and protein kinase A--significantly attenuated the P. intermedia-induced COX-2 and PGE(2) expression. P. intermedia reduced EP1 expression in a concentration- and time-dependent manner. The results indicate that the COX-2-dependent induction of PGE(2) by P. intermedia in hPDLs is mediated by multiple signaling pathways.

  8. Television systems for radioactive waste management

    International Nuclear Information System (INIS)

    Quartly, J.R.

    1989-01-01

    Radiation-tolerant television cameras, widely used for the inspection of nuclear plants, are now used for monitoring radioactive waste management processes. Two systems are described in this paper that differ in the methods of maintaining the camera equipment. At the British Nuclear Fuels plc (BNFL) Sellafield plant, a major capital investment program is under way that includes plants for spent-fuel reprocessing and radioactive waste management. The Windscale vitrification plant (WVP) will convert highly active liquid waste to a solid glass-like form. The WVP television system was based on in-cell cameras designed to be removable by remote-handling equipment. The plant to encapsulate medium active solid waste, encapsulation plant 1 (EP1) used through-wall and through-roof viewing systems with a glass viewing dome as the biological shield, allowing the camera and optics to be withdrawn to a safe area for maintenance. Both systems used novel techniques to obtain a record of the waste-processing operations. The WVP system used a microcomputer to overlay reference information onto the television picture and a motion detector to automatically trigger the video recording. The television system for EP1 included automatic character recognition to generate a computer data record of drum serial numbers

  9. Increased Amplitude of the P3a ERP Component as a Neurocognitive Marker for Differentiating Amnestic Subtypes of Mild Cognitive Impairment

    Directory of Open Access Journals (Sweden)

    Kenia S. Correa-Jaraba

    2018-02-01

    Full Text Available The event-related potential (ERP technique has been shown to be useful for evaluating changes in brain electrical activity associated with different cognitive processes, particularly in Alzheimer’s disease (AD. Longitudinal studies have shown that a high proportion of people with amnestic mild cognitive impairment (aMCI go on to develop AD. aMCI is divided into two subtypes according to the presence of memory impairment only (single-domain aMCI: sdaMCI or impairment of memory and other cognitive domains (multi-domain aMCI: mdaMCI. The main aim of this study was to examine the effects of sdaMCI and mdaMCI on the P3a ERP component associated with the involuntary orientation of attention toward unattended infrequent novel auditory stimuli. Participants performed an auditory-visual distraction-attention task, in which they were asked to ignore the auditory stimuli (standard, deviant, and novel and to attend to the visual stimuli (responding to some of them: Go stimuli. P3a was identified in the Novel minus Standard difference waveforms, and reaction times (RTs and hits (in response to Go stimuli were also analyzed. Participants were classified into three groups: Control, 20 adults (mean age (M: 65.8 years; sdaMCI, 19 adults (M: 67 years; and mdaMCI, 11 adults (M: 71 years. In all groups, the RTs were significantly longer when Go stimuli were preceded by novel (relative to standard auditory stimuli, suggesting a distraction effect triggered by novel stimuli; mdaMCI participants made significantly fewer hits than control and sdaMCI participants. P3a comprised two consecutive phases in all groups: early-P3a (e-P3a, which may reflect the orienting response toward the irrelevant stimuli, and late-P3a (l-P3a, which may be a correlate of subsequent evaluation of these stimuli. The e-P3a amplitude was significantly larger in mdaMCI than in sdaMCI participants, and the l-P3a amplitude was significantly larger in mdaMCI than in sdaMCI and Control participants, indicating greater involuntary capture of attention to unattended novel auditory stimuli and allocation of more attentional resources for the subsequent evaluation of these stimuli in mdaMCI participants. The e-P3a and l-P3a components showed moderate to high sensitivity and specificity for distinguishing between groups, suggesting that both may represent optimal neurocognitive markers for differentiating aMCI subtypes.

  10. Modifying of Cotton Fabric Surface with Nano-ZnO Multilayer Films by Layer-by-Layer Deposition Method

    Directory of Open Access Journals (Sweden)

    Sarıışık Merih

    2010-01-01

    Full Text Available Abstract ZnO nanoparticle–based multilayer nanocomposite films were fabricated on cationized woven cotton fabrics via layer-by-layer molecular self-assembly technique. For cationic surface charge, cotton fabrics were pretreated with 2,3-epoxypropyltrimethylammonium chloride (EP3MAC by pad-batch method. XPS and SEM were used to examine the deposited nano-ZnO multilayer films on the cotton fabrics. The nano-ZnO films deposited on cotton fabrics exhibited excellent antimicrobial activity against Staphylococcus aureus bacteria. The results also showed that the coated fabrics with nano-ZnO multilayer films enhanced the protection of cotton fabrics from UV radiation. Physical tests (tensile strength of weft and warp yarns, air permeability and whiteness values were performed on the fabrics before and after the treatment with ZnO nanoparticles to evaluate the effect of layer-by-layer (LbL process on cotton fabrics properties.

  11. Simple Hybrid Scaling-Free CORDIC Solution for FPGAs

    Directory of Open Access Journals (Sweden)

    Leonid Moroz

    2014-01-01

    Full Text Available COordinate Rotation DIgital Computer (CORDIC is an effective method that is used in digital signal processing applications for computing various trigonometric, hyperbolic, linear, and transcendental functions. This paper presents the theoretical basis and practical implementation of circular (sine-cosine CORDIC-based generator. Synthesis results of this generator based on Altera Stratix III FPGA (EP3SL340F1517C2 using Quartus II version 9.0 show that the proposed hybrid FPGA architecture significantly reduces latency (42% reduction with a small area overhead, compared to the conventional version. The proposed algorithm has been simulated for sine and cosine function evaluation, and it has been verified that the accuracy is comparable with conventional algorithm.

  12. Determination of phthalate monoesters in human milk, consumer milk, and infant formula by tandem mass spectrometry (LC-MS-MS)

    DEFF Research Database (Denmark)

    Mortensen, Gerda Krog; Main, Katharina M; Andersson, Anna-Maria

    2005-01-01

    these phthalates were present, albeit at different concentrations. Median values (microg L(-1)) obtained were 0.11 (mMP), 0.95 (mEP), 3.5 (mBP), 0.8 (mBzP), 9.5 (mEHP), and 101 (mNP). We also analysed seven samples of consumer milk and ten samples of infant formula. Only mBP and mEHP were detected in these samples......Daily exposure of humans to phthalates may be a health risk because animal experiments have shown these compounds can affect the differentiation and function of the reproductive system. Because milk is the main source of nutrition for infants, knowledge of phthalate levels is important for exposure...

  13. Sensitivity of global ocean biogeochemical dynamics to ecosystem structure in a future climate

    Science.gov (United States)

    Manizza, Manfredi; Buitenhuis, Erik T.; Le Quéré, Corinne

    2010-07-01

    Terrestrial and oceanic ecosystem components of the Earth System models (ESMs) are key to predict the future behavior of the global carbon cycle. Ocean ecosystem models represent low complexity compared to terrestrial ecosystem models. In this study we use two ocean biogeochemical models based on the explicit representation of multiple planktonic functional types. We impose to the models the same future physical perturbation and compare the response of ecosystem dynamics, export production (EP) and ocean carbon uptake (OCU) to the same physical changes. Models comparison shows that: (1) EP changes directly translate into changes of OCU on decadal time scale, (2) the representation of ecosystem structure plays a pivotal role at linking OCU and EP, (3) OCU is highly sensitive to representation of ecosystem in the Equatorial Pacific and Southern Oceans.

  14. Occupational and environmental risk factors for chronic rhinosinusitis in China: a multicentre cross-sectional study.

    Science.gov (United States)

    Gao, Wen-Xiang; Ou, Chun-Quan; Fang, Shu-Bin; Sun, Yue-Qi; Zhang, Hua; Cheng, Lei; Wang, Yan-Jun; Zhu, Dong-Dong; Lv, Wei; Liu, Shi-Xi; Li, P Z; Xu, Geng; Shi, Jianbo; Fu, Qing-Ling

    2016-05-17

    Chronic rhinosinusitis (CRS) is defined as a condition of inflammation in the paranasal sinus mucosa persisting for more than 12 weeks. We previously reported that the prevalence of CRS was about 8 % in China. Here, we aim to investigate the occupational and environmental risk factors associated with CRS. Data were collected from seven Chinese cities: Urumqi, Changchun, Beijing, Wuhan, Chengdu, Huaian and Guangzhou. CRS was diagnosed according to the European Position Paper on Rhinosinusitis and Nasal Polyps (EP(3)OS) document. Participants were asked to complete a standardized questionnaire, which was developed by the Global Allergy and Asthma European Network (GA(2)LEN) project and covered sociodemographic characteristics, CRS-related symptoms and occupational and environmental exposures. We evaluated the association between CRS and various occupational and environmental factors using odds ratios (ORs) and 95 % confidence intervals (95 % CIs). The total study population consisted of 10,633 subjects, 850 (7.99 %) of whom were defined as having CRS according to the EP(3)OS criteria. We found that there were significant associations between occupational and environmental factors and CRS. Specifically, having a clearance-related job, occupational exposure to dust, occupational exposure to poisonous gas, a pet at home or carpet at home or at the workplace were risk factors for CRS. Additionally, the method used to keep warm in winter, the duration of time spent using air conditioning in summer and the frequency of exposure to mouldy or damp environments were significantly different in subjects with and without CRS. Our data showed that some occupational and environmental exposures are strongly associated with CRS, which aids in understanding the epidemiology of CRS.

  15. Prostaglandin E2 potentiation of P2X3 receptor mediated currents in dorsal root ganglion neurons

    Directory of Open Access Journals (Sweden)

    Huang Li-Yen

    2007-08-01

    Full Text Available Abstract Prostaglandin E2 (PGE2 is a well-known inflammatory mediator that enhances the excitability of DRG neurons. Homomeric P2X3 and heteromeric P2X2/3 receptors are abundantly expressed in dorsal root ganglia (DRG neurons and participate in the transmission of nociceptive signals. The interaction between PGE2 and P2X3 receptors has not been well delineated. We studied the actions of PGE2 on ATP-activated currents in dissociated DRG neurons under voltage-clamp conditions. PGE2 had no effects on P2X2/3 receptor-mediated responses, but significantly potentiated fast-inactivating ATP currents mediated by homomeric P2X3 receptors. PGE2 exerted its action by activating EP3 receptors. To study the mechanism underlying the action of PGE2, we found that the adenylyl cyclase activator, forskolin and the membrane-permeable cAMP analogue, 8-Br-cAMP increased ATP currents, mimicking the effect of PGE2. In addition, forskolin occluded the enhancement produced by PGE2. The protein kinase A (PKA inhibitors, H89 and PKA-I blocked the PGE2 effect. In contrast, the PKC inhibitor, bisindolymaleimide (Bis did not change the potentiating action of PGE2. We further showed that PGE2 enhanced α,β-meATP-induced allodynia and hyperalgesia and the enhancement was blocked by H89. These observations suggest that PGE2 binds to EP3 receptors, resulting in the activation of cAMP/PKA signaling pathway and leading to an enhancement of P2X3 homomeric receptor-mediated ATP responses in DRG neurons.

  16. JET neutral beam duct Optical Interlock

    Energy Technology Data Exchange (ETDEWEB)

    Ash, A.D.; Jones, T.T.C.; Surrey, E.; Ćirić, D.; Hall, S.I.; Young, D.; Afzal, M.; Hackett, L.; Day, I.E.; King, R.

    2015-10-15

    Highlights: • Optical Interlocks were installed on the JET NBI system as part of the EP2 upgrade. • The system protects the JET tokamak and NBI systems from thermal load damage. • Balmer-α beam emission is used to monitor the neutral beam-line pressure. • We demonstrate an improved trip delay of 2 ms compared to 50 ms before EP2. - Abstract: The JET Neutral Beam Injection (NBI) system is the most powerful neutral beam plasma heating system currently operating. Optical Interlocks were installed on the beam lines in 2011 for the JET Enhancement Project 2 (EP2), when the heating power was increased from 23 MW to 34 MW. JET NBI has two beam lines. Each has eight positive ion injectors operating in deuterium at 80 kV–125 kV (accelerator voltage) and up to 65 A (beam current). Heating power is delivered through two ducts where the central power density can be more than 100 MW/m{sup 2}. In order to deliver this safely, the beam line pressure should be below 2 × 10{sup −5} mbar otherwise the power load on the duct from the re-ionised fraction of the beam is excessive. The new Optical Interlock monitors the duct pressure by measuring the Balmer-α beam emission (656 nm). This is proportional to the instantaneous beam flux and the duct pressure. Light is collected from a diagnostic window and focused into 1-mm diameter fibres. The Doppler shifted signal is selected using an angle-tuned interference filter. The light is measured by a photo-multiplier module with a logarithmic amplifier. The interlock activation time of 2 ms is sufficient to protect the system from a fully re-ionised beam—a significant improvement on the previous interlock. The dynamic range is sufficient to see bremsstrahlung emission from JET plasma and not saturate during plasma disruptions. For high neutron flux operations the optical fibres within the biological shield can be annealed to 350 °C. A self-test is possible by illuminating the diagnostic window with a test lamp and measuring

  17. Spacecraft-plasma-debris interaction in an ion beam shepherd mission

    Science.gov (United States)

    Cichocki, Filippo; Merino, Mario; Ahedo, Eduardo

    2018-05-01

    This paper presents a study of the interaction between a spacecraft, a plasma thruster plume and a free floating object, in the context of an active space debris removal mission based on the ion beam shepherd concept. The analysis is performed with the EP2PLUS hybrid code and includes the evaluation of the transferred force and torque to the target debris, its surface sputtering due to the impinging hypersonic ions, and the equivalent electric circuit of the spacecraft-plasma-debris interaction. The electric potential difference that builds up between the spacecraft and the debris, the ion backscattering and the backsputtering contamination of the shepherd satellite are evaluated for a nominal scenario. A sensitivity analysis is carried out to evaluate quantitatively the effects of electron thermodynamics, ambient plasma, heavy species collisions, and debris position.

  18. Performance evaluation of heart sound cancellation in FPGA hardware implementation for electronic stethoscope.

    Science.gov (United States)

    Chao, Chun-Tang; Maneetien, Nopadon; Wang, Chi-Jo; Chiou, Juing-Shian

    2014-01-01

    This paper presents the design and evaluation of the hardware circuit for electronic stethoscopes with heart sound cancellation capabilities using field programmable gate arrays (FPGAs). The adaptive line enhancer (ALE) was adopted as the filtering methodology to reduce heart sound attributes from the breath sounds obtained via the electronic stethoscope pickup. FPGAs were utilized to implement the ALE functions in hardware to achieve near real-time breath sound processing. We believe that such an implementation is unprecedented and crucial toward a truly useful, standalone medical device in outpatient clinic settings. The implementation evaluation with one Altera cyclone II-EP2C70F89 shows that the proposed ALE used 45% resources of the chip. Experiments with the proposed prototype were made using DE2-70 emulation board with recorded body signals obtained from online medical archives. Clear suppressions were observed in our experiments from both the frequency domain and time domain perspectives.

  19. Performance Evaluation of Heart Sound Cancellation in FPGA Hardware Implementation for Electronic Stethoscope

    Directory of Open Access Journals (Sweden)

    Chun-Tang Chao

    2014-01-01

    Full Text Available This paper presents the design and evaluation of the hardware circuit for electronic stethoscopes with heart sound cancellation capabilities using field programmable gate arrays (FPGAs. The adaptive line enhancer (ALE was adopted as the filtering methodology to reduce heart sound attributes from the breath sounds obtained via the electronic stethoscope pickup. FPGAs were utilized to implement the ALE functions in hardware to achieve near real-time breath sound processing. We believe that such an implementation is unprecedented and crucial toward a truly useful, standalone medical device in outpatient clinic settings. The implementation evaluation with one Altera cyclone II–EP2C70F89 shows that the proposed ALE used 45% resources of the chip. Experiments with the proposed prototype were made using DE2-70 emulation board with recorded body signals obtained from online medical archives. Clear suppressions were observed in our experiments from both the frequency domain and time domain perspectives.

  20. Emerging migraine treatments and drug targets

    DEFF Research Database (Denmark)

    Olesen, Jes; Ashina, Messoud

    2011-01-01

    Migraine has a 1-year prevalence of 10% and high socioeconomic costs. Despite recent drug developments, there is a huge unmet need for better pharmacotherapy. In this review we discuss promising anti-migraine strategies such as calcitonin gene-related peptide (CGRP) receptor antagonists and 5....... Tonabersat, a cortical spreading depression inhibitor, has shown efficacy in the prophylaxis of migraine with aura. Several new drug targets such as nitric oxide synthase, the 5-HT(1D) receptor, the prostanoid receptors EP(2) and EP(4), and the pituitary adenylate cyclase receptor PAC1 await development....... The greatest need is for new prophylactic drugs, and it seems likely that such compounds will be developed in the coming decade....

  1. Field programmable gate array (FPGA implementation of novel complex PN-code-generator- based data scrambler and descrambler

    Directory of Open Access Journals (Sweden)

    Shabir A. Parah

    2010-04-01

    Full Text Available A novel technique for the generation of complex and lengthy code sequences using low- length linear feedback shift registers (LFSRs for data scrambling and descrambling is proposed. The scheme has been implemented using VHSIC hardware description language (VHDL approach which allows the reconfigurability of the proposed system such that the length of the generated sequences can be changed as per the security requirements. In the present design consideration the power consumption and chip area requirements are small and the operating speed is high compared to conventional discrete I.C. design, which is a pre-requisite for any system designer. The design has been synthesised on device EP2S15F484C3 of Straitx II FPGA family, using Quarts Altera version 8.1. The simulation results have been found satisfactory and are in conformity with the theoretical observations.

  2. Emerging migraine treatments and drug targets

    DEFF Research Database (Denmark)

    Olesen, Jes; Ashina, Messoud

    2011-01-01

    Migraine has a 1-year prevalence of 10% and high socioeconomic costs. Despite recent drug developments, there is a huge unmet need for better pharmacotherapy. In this review we discuss promising anti-migraine strategies such as calcitonin gene-related peptide (CGRP) receptor antagonists and 5......-hydroxytrypamine (5-HT)(1F) receptor agonists, which are in late-stage development. Nitric oxide antagonists are also in development. New forms of administration of sumatriptan might improve efficacy and reduce side effects. Botulinum toxin A has recently been approved for the prophylaxis of chronic migraine....... Tonabersat, a cortical spreading depression inhibitor, has shown efficacy in the prophylaxis of migraine with aura. Several new drug targets such as nitric oxide synthase, the 5-HT(1D) receptor, the prostanoid receptors EP(2) and EP(4), and the pituitary adenylate cyclase receptor PAC1 await development...

  3. Development of residual gas ionization profile monitor for high intensity proton beams

    CERN Document Server

    Sato, Y; Hirose, E; Ieiri, M; Igarashi, Y; Inaba, S; Katoh, Y; Minakawa, M; Noumi, H; Saitó, M; Suzuki, Y; Takahashi, H; Takasaki, M; Tanaka, K; Toyoda, A; Yamada, Y; Yamanoi, Y; Watanabe, H

    2006-01-01

    Nondestructive beam profile monitor utilizing ionizations of residual gas has been developed for continuous monitoring of 3?0(J-PARC). Knock-on electrons produced in the ionizations of residual gas vacuumed to 1 Pa are collected with a uniform electric field applied between electrodes. Applying a uniform electric field parallel to the electric field is essential to reduce diffusion of electrons crossing over magnetic flux. A prototype monitor has been constructed and installed in EP2-C beam line at KEK 12 GeV proton synchrotron (12 Ge V-PS). The profiles measured with the present monitor agree with the ones measured with the existing destructive profile monitor. The present monitor shows sufficient performances as a candidate of the profile monitor at J-PARC. In the present article, the working principle of the present monitor, the results of test experiments, and further developments are described in detail.

  4. Enhancement productivity of lactic acid bacteria (LAB) to produced ex polysaccharide

    International Nuclear Information System (INIS)

    EL-Fouly, M.; Meleigy, S.A; Hendawy, W.S.; Magdoub, M.I.N.; Aita, O.A.

    2010-01-01

    Isolation and characterization of exo cellular polysaccharide was studied in order to evaluate some parameters in the synthesis of exo polysaccharide (EPS) and improve their production through submerged fermentation processes. Isolation strains Lactobacillus delbrueckii ssp bulgaricus (IS1), Lactococcus lactis ssp cremoris (IS2) and Lactobacillus delbrueckii ssp bulgaricus (IS3) were studied in shake flasks using yeast extract, surfactants and different exposure doses of gamma irradiation. The optimum concentration of (EPS) formation (0.762 g/l) by Lactococcus lactis ssp cremoris (IS2) at and 3.0(g/l) yeast extract, 1.72 (g/l) at 0.5 (%) surfactant Triton X-100. Also, EPS (1.842 g/l) was produced when Lactococcus lactis ssp cremoris (IS2) exposed to 0.2 kGy dose level

  5. Energye and environment

    International Nuclear Information System (INIS)

    Stamenov, I. N.

    2013-01-01

    Energy production and environmental consequences are the border topics in frame of the satisfaction of the energy needs of the society and their use. The present paper discusses only the energy sources and the correspondent processes to obtain energy and mainly electricity. The human health and all elements of the environment are studied in connection with some waste production or their influences. Nevertheless the main energy source for our Earth is the Sun and the exotic processes connected with energy production as well their spatial influence to the Earth are not taken into account. The terrestrial energy is only partly analyzed and hazards excluded. The basic information used are based on publications of IAE, NRA, and the position paper of NPB of EPS[1

  6. Current Reactor Physics Benchmark Activities at the Idaho National Laboratory

    International Nuclear Information System (INIS)

    Bess, John D.; Marshall, Margaret A.; Gorham, Mackenzie L.; Christensen, Joseph; Turnbull, James C.; Clark, Kim

    2011-01-01

    The International Reactor Physics Experiment Evaluation Project (IRPhEP) (1) and the International Criticality Safety Benchmark Evaluation Project (ICSBEP) (2) were established to preserve integral reactor physics and criticality experiment data for present and future research. These valuable assets provide the basis for recording, developing, and validating our integral nuclear data, and experimental and computational methods. These projects are managed through the Idaho National Laboratory (INL) and the Organisation for Economic Co-operation and Development Nuclear Energy Agency (OECD-NEA). Staff and students at the Department of Energy - Idaho (DOE-ID) and INL are engaged in the development of benchmarks to support ongoing research activities. These benchmarks include reactors or assemblies that support Next Generation Nuclear Plant (NGNP) research, space nuclear Fission Surface Power System (FSPS) design validation, and currently operational facilities in Southeastern Idaho.

  7. Structural features of subtype-selective EP receptor modulators.

    Science.gov (United States)

    Markovič, Tijana; Jakopin, Žiga; Dolenc, Marija Sollner; Mlinarič-Raščan, Irena

    2017-01-01

    Prostaglandin E2 is a potent endogenous molecule that binds to four different G-protein-coupled receptors: EP1-4. Each of these receptors is a valuable drug target, with distinct tissue localisation and signalling pathways. We review the structural features of EP modulators required for subtype-selective activity, as well as the structural requirements for improved pharmacokinetic parameters. Novel EP receptor subtype selective agonists and antagonists appear to be valuable drug candidates in the therapy of many pathophysiological states, including ulcerative colitis, glaucoma, bone healing, B cell lymphoma, neurological diseases, among others, which have been studied in vitro, in vivo and in early phase clinical trials. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  8. Electron energy distribution function in the positive column of a neon glow discharge using the black wall approximation

    International Nuclear Information System (INIS)

    Al-Hawat, Sh; Naddaf, M

    2005-01-01

    The electron energy distribution function (EEDF) was determined from the second derivative of the I-V Langmuir probe characteristics and, thereafter, theoretically calculated by solving the plasma kinetic equation, using the black wall (BW) approximation, in the positive column of a neon glow discharge. The pressure has been varied from 0.5 to 4 Torr and the current from 10 to 30 mA. The measured electron temperature, density and electric field strength were used as input data for solving the kinetic equation. Comparisons were made between the EEDFs obtained from experiment, the BW approach, the Maxwellian distribution and the Rutcher solution of the kinetic equation in the elastic energy range. The best conditions for the BW approach are found to be under the discharge conditions: current density j d = 4.45 mA cm -2 and normalized electric field strength E/p = 1.88 V cm -1 Torr -1

  9. Electron energy distribution function in the positive column of a neon glow discharge using the black wall approximation

    Science.gov (United States)

    Al-Hawat, Sh; Naddaf, M.

    2005-04-01

    The electron energy distribution function (EEDF) was determined from the second derivative of the I-V Langmuir probe characteristics and, thereafter, theoretically calculated by solving the plasma kinetic equation, using the black wall (BW) approximation, in the positive column of a neon glow discharge. The pressure has been varied from 0.5 to 4 Torr and the current from 10 to 30 mA. The measured electron temperature, density and electric field strength were used as input data for solving the kinetic equation. Comparisons were made between the EEDFs obtained from experiment, the BW approach, the Maxwellian distribution and the Rutcher solution of the kinetic equation in the elastic energy range. The best conditions for the BW approach are found to be under the discharge conditions: current density jd = 4.45 mA cm-2 and normalized electric field strength E/p = 1.88 V cm-1 Torr-1.

  10. Isolation and Characterization of Lactic Acid Bacteria (LAB) Produced Exo cellular Polysaccharide

    International Nuclear Information System (INIS)

    Meleigy, S.A.; Hendawy, W.S.

    2009-01-01

    Isolation and characterization of exo cellular polysaccharide was studied in order to evaluate some parameters in the synthesis of exo polysaccharide (EPS) and improve their production through submerged fermentation processes. Isolation strains Lactobacillus delbrueckii ssp bulgaricus (IS 1 ), Lactococcus lactis ssp cremoris (IS 2 ) and Lactobacillus delbrueckii ssp bulgaricus (IS 3 ) were studied in shake flasks using yeast extract, surfactants and different exposure doses of gamma irradiation.The optimum concentration of (EPS) formation (0.762 g/l) by Lactococcus lactis ssp cremoris (IS 2 ), 3.0 (g/l) yeast extract, 1.72 (g/l) at 0.5 (%) surfactant Triton X-100. Also, EPS (1.842 g/l) was produced when Lactococcus lactis ssp cremoris (IS 2 ) exposed to 0.2 kGy dose level.

  11. Majority- and minority-carrier deep level traps in proton-irradiated n+/p-InGaP space solar cells

    International Nuclear Information System (INIS)

    Dharmarasu, Nethaji; Yamaguchi, Masafumi; Bourgoin, Jacques C.; Takamoto, Tatsuya; Ohshima, Takeshi; Itoh, Hisayoshi; Imaizumi, Mitsuru; Matsuda, Sumio

    2002-01-01

    We report the properties of observed defects in n + /p-InGaP solar cells created by irradiation of protons of different energies. Three majority (hole) and a minority-carrier traps, labeled respectively as HP1 (E v +0.90±0.05 eV), HP2 (E v +0.73±0.05 eV), H2 (E v +0.55 eV), and EP1 (E c -0.54 eV), were identified using deep level transient spectroscopy. All majority-carrier traps were found to act as recombination centers. While the H2 trap present in the proton-irradiated p-InGaP was found to anneal out by minority-carrier injection, the other traps were not

  12. The Multiple Faces of Prostaglandin E2 G-Protein Coupled Receptor Signaling during the Dendritic Cell Life Cycle

    Directory of Open Access Journals (Sweden)

    Alessandra Cambi

    2013-03-01

    Full Text Available Many processes regulating immune responses are initiated by G-protein coupled receptors (GPCRs and report biochemical changes in the microenvironment. Dendritic cells (DCs are the most potent antigen-presenting cells and crucial for the regulation of innate and adaptive immune responses. The lipid mediator Prostaglandin E2 (PGE2 via four GPCR subtypes (EP1-4 critically regulates DC generation, maturation and migration. The role of PGE2 signaling in DC biology was unraveled by the characterization of EP receptor subtype expression in DC progenitor cells and DCs, the identification of the signaling pathways initiated by these GPCR subtypes and the classification of DC responses to PGE2 at different stages of differentiation. Here, we review the advances in PGE2 signaling in DCs and describe the efforts still to be made to understand the spatio-temporal fine-tuning of PGE2 responses by DCs.

  13. Fiber-optic laser sensor for mine detection and verification

    International Nuclear Information System (INIS)

    Bohling, Christian; Scheel, Dirk; Hohmann, Konrad; Schade, Wolfgang; Reuter, Matthias; Holl, Gerhard

    2006-01-01

    What we believe to be a new optical approach for the identification of mines and explosives by analyzing the surface materials and not only bulk is developed. A conventional manually operated mine prodder is upgraded by laser-induced breakdown spectroscopy (LIBS). In situ and real-time information of materials that are in front of the prodder are obtained during the demining process in order to optimize the security aspects and the speed of demining. A Cr4+:Nd3+:YAG microchip laser is used as a seed laser for an ytterbium-fiber amplifier to generate high-power laser pulses at 1064 nm with pulse powers up to Ep=1 mJ, a repetition rate of frep.=2-20 kHz and a pulse duration of tp=620 ps. The recorded LIBS signals are analyzed by applying neural networks for the data analysis

  14. Tissue distribution of 3H-corticosterone in response to stress

    International Nuclear Information System (INIS)

    Kolta, M.G.; Soliman, K.F.A.

    1981-01-01

    The level and distribution of 3 H-corticosterone ( 3 H-B) was investigated in adult male Sprague-Dawley rats in response to diethyl ether stress, epinephrine (EP) and/or dexamethasone administration. Diethyl ether stress caused a significant increase in the 3 H-B counts by some of the body tissues and brain regions studied. Plasma 3 H-B counts in the stressed rats were found to be twice as much as in the control animals. When EP (1.0 mg/kg) was injected, the tissue-plasma ratios of 3 H-B were significantly lower (P 3 H-B count in the plasma in response to diethyl ether stress or EP may indicate a decline in rate of corticosterone metabolism. (author)

  15. Prostaglandin E2 blocks menadione-induced apoptosis through the Ras/Raf/Erk signaling pathway in promonocytic leukemia cell lines.

    Science.gov (United States)

    Yeo, Hyun-Seok; Shehzad, Adeeb; Lee, Young Sup

    2012-04-01

    Altered oxidative stress has long been observed in cancer cells, and this biochemical property of cancer cells represents a specific vulnerability that can be exploited for therapeutic benefit. The major role of an elevated oxidative stress for the efficacy of molecular targeted drugs is under investigation. Menadione is considered an attractive model for the study of oxidative stress, which can induce apoptosis in human leukemia HL-60 cell lines. Prostaglandin E(2) (PGE(2)) via its receptors not only promotes cell survival but also reverses apoptosis and promotes cancer progression. Here, we present evidence for the biological role of PGE(2) as a protective agent of oxidative stress-induced apoptosis in monocytic cells. Pretreatment of HL-60 cells with PGE(2) markedly ameliorated the menadione-induced apoptosis and inhibited the degradation of PARP and lamin B. The EP(2) receptor antagonist AH6809 abrogated the inhibitory effect of PGE(2), suggesting the role of the EP(2)/cAMP system. The PKA inhibitor H89 also reversed apoptosis and decreased the PKA activity that was elevated 10-fold by PGE(2). The treatment of HL-60 cells with NAC or zinc chloride showed a similar protective effect as with PGE(2) on menadione-treated cells. Furthermore, PGE(2) activated the Ras/Raf/MEK pathway, which in turn initiated ERK activation, and ultimately protected menadione-induced apoptosis. These results imply that PGE(2) via cell survival pathways may protect oxidative stress-induced apoptosis in monocytic cells. This study warrants further pre-clinical investigation as well as application towards leukemia clinics.

  16. MDMA Increases Excitability in the Dentate Gyrus: Role of 5HT2A Receptor Induced PGE2 Signaling

    Science.gov (United States)

    Collins, Stuart A.; Huff, Courtney; Chiaia, Nicolas; Gudelsky, Gary A.; Yamamoto, Bryan K.

    2015-01-01

    MDMA is a widely abused psychostimulant which causes release of serotonin in various forebrain regions. Recently, we reported that MDMA increases extracellular glutamate concentrations in the dentate gyrus, via activation of 5HT2A receptors. We examined the role of prostaglandin signaling in mediating the effects of 5HT2A receptor activation on the increases in extracellular glutamate and the subsequent long-term loss of parvalbumin interneurons in the dentate gyrus caused by MDMA. Administration of MDMA into the dentate gyrus of rats increased PGE2 concentrations which was prevented by coadministration of MDL100907, a 5HT2A receptor antagonist. MDMA-induced increases in extracellular glutamate were inhibited by local administration of SC-51089, an inhibitor of the EP1 prostaglandin receptor. Systemic administration of SC-51089 during injections of MDMA prevented the decreases in parvalbumin interneurons observed 10 days later. The loss of parvalbumin immunoreactivity after MDMA exposure coincided with a decrease in paired-pulse inhibition and afterdischarge threshold in the dentate gyrus. These changes were prevented by inhibition of EP1 and 5HT2A receptors during MDMA. Additional experiments revealed an increased susceptibility to kainic acid-induced seizures in MDMA treated rats which could be prevented with SC51089 treatments during MDMA exposure. Overall, these findings suggest that 5HT2A receptors mediate MDMA-induced PGE2 signaling and subsequent increases in glutamate. This signaling mediates parvalbumin cell losses as well as physiologic changes in the dentate gyrus, suggesting that the lack of the inhibition provided by these neurons increases the excitability within the dentate gyrus of MDMA treated rats. PMID:26670377

  17. Kidins220/ARMS depletion is associated with the neural-to Schwann-like transition in a human neuroblastoma cell line model.

    Science.gov (United States)

    Rogers, Danny A; Schor, Nina F

    2013-03-10

    Peripheral neuroblastic tumors exist as a heterogeneous mixture of neuroblastic (N-type) cells and Schwannian stromal (S-type) cells. These stromal cells not only represent a differentiated and less aggressive fraction of the tumor, but also have properties that can influence the further differentiation of nearby malignant cells. In vitro neuroblastoma cultures exhibit similar heterogeneity with N-type and S-type cells representing the neuroblastic and stromal portions of the tumor, respectively, in behavior, morphology, and molecular expression patterns. In this study, we deplete kinase D-interacting substrate of 220kD (Kidins220) with an shRNA construct and thereby cause morphologic transition of the human SH-SY5Y neuroblastoma cell line from N-type to S-type. The resulting cells have similar morphology and expression profile to SH-EP1 cells, a native S-type cell line from the same parent cell line, and to SH-SY5Y cells treated with BrdU, a treatment that induces S-type morphology. Specifically, both Kidins220-deficient SH-SY5Y cells and native SH-EP1 cells demonstrate down-regulation of the genes DCX and STMN2, markers for the neuronal lineage. We further show that Kidins220, DCX and STMN2 are co-down-regulated in cells of S-type morphology generated by methods other than Kidins220 depletion. Finally, we report that the association of low Kidins220 expression with S-type morphology and low DCX and STMN2 expression is demonstrated in spontaneously occurring human peripheral neuroblastic tumors. We propose that Kidins220 is critical in N- to S-type transition of neural crest tumor cells. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Dual interaction of agmatine with the rat α2D-adrenoceptor: competitive antagonism and allosteric activation

    Science.gov (United States)

    Molderings, G J; Menzel, S; Kathmann, M; Schlicker, E; Göthert, M

    2000-01-01

    In segments of rat vena cava preincubated with [3H]-noradrenaline and superfused with physiological salt solution, the influence of agmatine on the electrically evoked [3H]-noradrenaline release, the EP3 prostaglandin receptor-mediated and the α2D-adrenoceptor-mediated inhibition of evoked [3H]-noradrenaline release was investigated. Agmatine (0.1–10 μM) by itself was without effect on evoked [3H]-noradrenaline release. In the presence of 10 μM agmatine, the prostaglandin E2(PGE2)-induced EP3-receptor-mediated inhibition of [3H]-noradrenaline release was not modified, whereas the α2D-adrenoceptor-mediated inhibition of [3H]-noradrenaline release induced by noradrenaline, moxonidine or clonidine was more pronounced than in the absence of agmatine. However, 1 mM agmatine antagonized the moxonidine-induced inhibition of [3H]-noradrenaline release. Agmatine concentration-dependently inhibited the binding of [3H]-clonidine and [3H]-rauwolscine to rat brain cortex membranes (Ki values 6 μM and 12 μM, respectively). In addition, 30 and 100 μM agmatine increased the rate of association and decreased the rate of dissociation of [3H]-clonidine resulting in an increased affinity of the radioligand for the α2D-adrenoceptors. [14C]-agmatine labelled specific binding sites on rat brain cortex membranes. In competition experiments. [14C]-agmatine was inhibited from binding to its specific recognition sites by unlabelled agmatine, but not by rauwolscine and moxonidine. In conclusion, the present data indicate that agmatine both acts as an antagonist at the ligand recognition site of the α2D-adrenoceptor and enhances the effects of α2-adrenoceptor agonists probably by binding to an allosteric binding site of the α2D-adrenoceptor which seems to be labelled by [14C]-agmatine. PMID:10928978

  19. Empirical parametrization of the two-photon-exchange effect contributions to the electron-proton elastic scattering cross section

    International Nuclear Information System (INIS)

    Qattan, I. A.; Alsaad, A.

    2011-01-01

    The most recent electron-proton elastic scattering data were re-analyzed using an empirical parametrization of the two-photon-exchange (TPE) effect contributions to σ R . The TPE effect contribution F(Q 2 ,ε) was double Taylor series expanded as a polynomial of order n keeping only terms linear in ε to account for the experimentally observed and verified linearity of the Rosenbluth plots. We fix the ratio R=G Ep /G Mp to be that obtained from a fit to the recoil-polarization data and parametrize σ R first by a three-parameter formula (fit I) and then by a two-parameter formula (fit III). In contrast to previous analyses, the fit parameter G Mp 2 as obtained from these fits is either smaller or equal to the values obtained from our conventional Rosenbluth fit (fit II) but never larger. The ratio g(Q 2 )/G Mp 2 which represents the ratio of the TPE and one-photon-exchange (OPE) effect contributions to the intercept of σ R is large and it ranges 3%-88%. The ratio R 1γx2γ =τf(Q 2 )/G Ep 2 which represents the ratio of the TPE and OPE effect contributions to the slope of σ R is also large, reaching a value of 12.0-14.4 at Q 2 = 5.25 (GeV/c) 2 . The ratio R 1γx2γ as obtained from fits I and III is consistent, within error, with those obtained from previous analyses. Our formulas seem to explain the linearity of σ R . Moreover, our analysis shows that the extracted G Ep 2 and G Mp 2 using the conventional Rosenbluth separation method can in fact be broken into the usual OPE and TPE contributions. Therefore, σ R can in fact be derived under weaker conditions than those imposed by the Born approximation. Our results show that the TPE amplitudes, g(Q 2 )/G Mp 2 and f(Q 2 )/G Mp 2 , are sizable and grow with Q 2 value up to Q 2 ∼6 (GeV/c) 2 in agreement with previous studies. A revision of and comparison to previous analyses are also presented.

  20. Nicotine impairs cyclooxygenase-2-dependent kinin-receptor-mediated murine airway relaxations

    International Nuclear Information System (INIS)

    Xu, Yuan; Cardell, Lars-Olaf

    2014-01-01

    Introduction: Cigarette smoke induces local inflammation and airway hyperreactivity. In asthmatics, it worsens the symptoms and increases the risk for exacerbation. The present study investigates the effects of nicotine on airway relaxations in isolated murine tracheal segments. Methods: Segments were cultured for 24 h in the presence of vehicle, nicotine (10 μM) and/or dexamethasone (1 μM). Airway relaxations were assessed in myographs after pre-contraction with carbachol (1 μM). Kinin receptors, cyclooxygenase (COX) and inflammatory mediator expressions were assessed by real-time PCR and confocal-microscopy-based immunohistochemistry. Results: The organ culture procedure markedly increased bradykinin- (selective B 2 receptor agonist) and des-Arg 9 -bradykinin- (selective B 1 receptor agonist) induced relaxations, and slightly increased relaxation induced by isoprenaline, but not that induced by PGE 2 . The kinin receptor mediated relaxations were epithelium-, COX-2- and EP2-receptor-dependent and accompanied by drastically enhanced mRNA levels of kinin receptors, as well as inflammatory mediators MCP-1 and iNOS. Increase in COX-2 and mPGES-1 was verified both at mRNA and protein levels. Nicotine selectively suppressed the organ-culture-enhanced relaxations induced by des-Arg 9 -bradykinin and bradykinin, at the same time reducing mPGES-1 mRNA and protein expressions. α7-nicotinic acetylcholine receptor inhibitors α-bungarotoxin and MG624 both blocked the nicotine effects on kinin B 2 receptors, but not those on B 1 . Dexamethasone completely abolished kinin-induced relaxations. Conclusion: It is tempting to conclude that a local inflammatory process per se could have a bronchoprotective component by increasing COX-2 mediated airway relaxations and that nicotine could impede this safety mechanism. Dexamethasone further reduced airway inflammation together with relaxations. This might contribute to the steroid resistance seen in some patients with asthma

  1. Minoxidil activates β-catenin pathway in human dermal papilla cells: a possible explanation for its anagen prolongation effect.

    Science.gov (United States)

    Kwack, Mi Hee; Kang, Bo Mi; Kim, Moon Kyu; Kim, Jung Chul; Sung, Young Kwan

    2011-06-01

    It is believed that the length of the actively growing phase of the anagen hair cycle mainly contributes to hair length. Recent studies showed that maintenance of β-catenin activity in the dermal papilla cells (DPCs) enables hair follicles to keep actively growing. Topical minoxidil treatment promotes hair growth in men with androgenetic alopecia, suggesting that minoxidil may prolong the actively growing phase of the anagen hair cycle. To investigate whether minoxidil prolongs the anagen hair cycle in mice and, if so, to investigate whether minoxidil activates β-catenin pathway in human DPCs. Dorsal skins of C57BL/6 mice were depilated to synchronize the hair cycle. After 10 days, 3% minoxidil were topically applied daily for 10 days. Sections of back skins were stained with hematoxylin and eosin. Hair follicles were graded and hair cycle score (HCS) was calculated. Cultured human DPCs were transiently transfected with the β-catenin responsive TCF reporter plasmid (pTopflash) and corresponding negative control reporter (pFopflash) to assess the activity of β-catenin signaling by minoxidil. Immunofluorescence staining and immunoblot were performed to examine the expression and localization of β-catenin in the presence or absence of minoxidil. Phosphorylation of GSK3β, PKA and PKB were also examined by immunoblot after minoxidil treatment. RT-PCR analysis and immunoblot were employed to investigate the expression of β-catenin pathway targets in DPCs, such as Axin2, Lef-1, and EP2. Modest extension of anagen phase thereby delay of catagen progression was observed by application of minoxidil in mice. Minoxidil stimulated the transcriptional activity of pTopflash but not pFopflash. Nuclear accumulation of β-catenin was also observed after minoxidil treatment. Immunoblot further showed that minoxidil treatment increases the phosphorylation of GSK3β, PKA and PKB. Moreover, minoxidil induced Axin2, Lef-1, and EP2 expression. Our results strongly suggest that

  2. Nicotine impairs cyclooxygenase-2-dependent kinin-receptor-mediated murine airway relaxations

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Yuan, E-mail: yuan.xu@ki.se; Cardell, Lars-Olaf

    2014-02-15

    Introduction: Cigarette smoke induces local inflammation and airway hyperreactivity. In asthmatics, it worsens the symptoms and increases the risk for exacerbation. The present study investigates the effects of nicotine on airway relaxations in isolated murine tracheal segments. Methods: Segments were cultured for 24 h in the presence of vehicle, nicotine (10 μM) and/or dexamethasone (1 μM). Airway relaxations were assessed in myographs after pre-contraction with carbachol (1 μM). Kinin receptors, cyclooxygenase (COX) and inflammatory mediator expressions were assessed by real-time PCR and confocal-microscopy-based immunohistochemistry. Results: The organ culture procedure markedly increased bradykinin- (selective B{sub 2} receptor agonist) and des-Arg{sup 9}-bradykinin- (selective B{sub 1} receptor agonist) induced relaxations, and slightly increased relaxation induced by isoprenaline, but not that induced by PGE{sub 2}. The kinin receptor mediated relaxations were epithelium-, COX-2- and EP2-receptor-dependent and accompanied by drastically enhanced mRNA levels of kinin receptors, as well as inflammatory mediators MCP-1 and iNOS. Increase in COX-2 and mPGES-1 was verified both at mRNA and protein levels. Nicotine selectively suppressed the organ-culture-enhanced relaxations induced by des-Arg{sup 9}-bradykinin and bradykinin, at the same time reducing mPGES-1 mRNA and protein expressions. α7-nicotinic acetylcholine receptor inhibitors α-bungarotoxin and MG624 both blocked the nicotine effects on kinin B{sub 2} receptors, but not those on B{sub 1}. Dexamethasone completely abolished kinin-induced relaxations. Conclusion: It is tempting to conclude that a local inflammatory process per se could have a bronchoprotective component by increasing COX-2 mediated airway relaxations and that nicotine could impede this safety mechanism. Dexamethasone further reduced airway inflammation together with relaxations. This might contribute to the steroid resistance seen in

  3. The description of a method for accurately estimating creatinine clearance in acute kidney injury.

    Science.gov (United States)

    Mellas, John

    2016-05-01

    Acute kidney injury (AKI) is a common and serious condition encountered in hospitalized patients. The severity of kidney injury is defined by the RIFLE, AKIN, and KDIGO criteria which attempt to establish the degree of renal impairment. The KDIGO guidelines state that the creatinine clearance should be measured whenever possible in AKI and that the serum creatinine concentration and creatinine clearance remain the best clinical indicators of renal function. Neither the RIFLE, AKIN, nor KDIGO criteria estimate actual creatinine clearance. Furthermore there are no accepted methods for accurately estimating creatinine clearance (K) in AKI. The present study describes a unique method for estimating K in AKI using urine creatinine excretion over an established time interval (E), an estimate of creatinine production over the same time interval (P), and the estimated static glomerular filtration rate (sGFR), at time zero, utilizing the CKD-EPI formula. Using these variables estimated creatinine clearance (Ke)=E/P * sGFR. The method was tested for validity using simulated patients where actual creatinine clearance (Ka) was compared to Ke in several patients, both male and female, and of various ages, body weights, and degrees of renal impairment. These measurements were made at several serum creatinine concentrations in an attempt to determine the accuracy of this method in the non-steady state. In addition E/P and Ke was calculated in hospitalized patients, with AKI, and seen in nephrology consultation by the author. In these patients the accuracy of the method was determined by looking at the following metrics; E/P>1, E/P1 and 0.907 (0.841, 0.973) for 0.95 ml/min accurately predicted the ability to terminate renal replacement therapy in AKI. Include the need to measure urine volume accurately. Furthermore the precision of the method requires accurate estimates of sGFR, while a reasonable measure of P is crucial to estimating Ke. The present study provides the practitioner with a new tool to estimate real time K in AKI with enough precision to predict the severity of the renal injury, including progression, stabilization, or improvement in azotemia. It is the author's belief that this simple method improves on RIFLE, AKIN, and KDIGO for estimating the degree of renal impairment in AKI and allows a more accurate estimate of K in AKI. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Resistance to Inhibitors of Cholinesterase 3 (Ric-3 Expression Promotes Selective Protein Associations with the Human α7-Nicotinic Acetylcholine Receptor Interactome.

    Directory of Open Access Journals (Sweden)

    Matthew J Mulcahy

    Full Text Available The α7-nicotinic acetylcholine receptor (α7-nAChR is a ligand-gated ion channel widely expressed in vertebrates and is associated with numerous physiological functions. As transmembrane ion channels, α7-nAChRs need to be expressed on the surface of the plasma membrane to function. The receptor has been reported to associate with proteins involved with receptor biogenesis, modulation of receptor properties, as well as intracellular signaling cascades and some of these associated proteins may affect surface expression of α7-nAChRs. The putative chaperone resistance to inhibitors of cholinesterase 3 (Ric-3 has been reported to interact with, and enhance the surface expression of, α7-nAChRs. In this study, we identified proteins that associate with α7-nAChRs when Ric-3 is expressed. Using α-bungarotoxin (α-bgtx, we isolated and compared α7-nAChR-associated proteins from two stably transfected, human tumor-derived cell lines: SH-EP1-hα7 expressing human α7-nAChRs and the same cell line further transfected to express Ric-3, SH-EP1-hα7-Ric-3. Mass spectrometric analysis of peptides identified thirty-nine proteins that are associated with α7-nAChRs only when Ric-3 was expressed. Significantly, and consistent with reports of Ric-3 function in the literature, several of the identified proteins are involved in biological processes that may affect nAChR surface expression such as post-translational processing of proteins, protein trafficking, and protein transport. Additionally, proteins affecting the cell cycle, the cytoskeleton, stress responses, as well as cyclic AMP- and inositol triphosphate-dependent signaling cascades were identified. These results illuminate how α-bgtx may be used to isolate and identify α7-nAChRs as well as how the expression of chaperones such as Ric-3 can influence proteins associating with α7-nAChRs. These associating proteins may alter activities of α7-nAChRs to expand their functionally-relevant repertoire as

  5. Role of contractile prostaglandins and Rho-kinase in growth factor-induced airway smooth muscle contraction

    Directory of Open Access Journals (Sweden)

    Zaagsma Johan

    2005-07-01

    Full Text Available Abstract Background In addition to their proliferative and differentiating effects, several growth factors are capable of inducing a sustained airway smooth muscle (ASM contraction. These contractile effects were previously found to be dependent on Rho-kinase and have also been associated with the production of eicosanoids. However, the precise mechanisms underlying growth factor-induced contraction are still unknown. In this study we investigated the role of contractile prostaglandins and Rho-kinase in growth factor-induced ASM contraction. Methods Growth factor-induced contractions of guinea pig open-ring tracheal preparations were studied by isometric tension measurements. The contribution of Rho-kinase, mitogen-activated protein kinase (MAPK and cyclooxygenase (COX to these reponses was established, using the inhibitors Y-27632 (1 μM, U-0126 (3 μM and indomethacin (3 μM, respectively. The Rho-kinase dependency of contractions induced by exogenously applied prostaglandin F2α (PGF2α and prostaglandin E2 (PGE2 was also studied. In addition, the effects of the selective FP-receptor antagonist AL-8810 (10 μM and the selective EP1-antagonist AH-6809 (10 μM on growth factor-induced contractions were investigated, both in intact and epithelium-denuded preparations. Growth factor-induced PGF2α-and PGE2-release in the absence and presence of Y-27632, U-0126 and indomethacin, was assessed by an ELISA-assay. Results Epidermal growth factor (EGF-and platelet-derived growth factor (PDGF-induced contractions of guinea pig tracheal smooth muscle preparations were dependent on Rho-kinase, MAPK and COX. Interestingly, growth factor-induced PGF2α-and PGE2-release from tracheal rings was significantly reduced by U-0126 and indomethacin, but not by Y-27632. Also, PGF2α-and PGE2-induced ASM contractions were largely dependent on Rho-kinase, in contrast to other contractile agonists like histamine. The FP-receptor antagonist AL-8810 (10 μM significantly

  6. Evaluation of infectious bronchitis virus Arkansas-type vaccine failure in commercial broilers.

    Science.gov (United States)

    Roh, Ha-Jung; Hilt, Deborah A; Williams, Susan M; Jackwooda, Mark W

    2013-06-01

    Infectious bronchitis virus (IBV) causes an upper respiratory tract disease in chickens and is highly contagious. Many different types of the virus exist, but only a few types are used as attenuated live vaccines in the commercial poultry industry. Of the vaccine types used, the Arkansas (Ark)-type virus is most frequently reisolated from vaccinated broilers. Previous research has suggested that incomplete clearance of Ark-type vaccine virus plays a role in the inadequate protection observed when vaccinated broilers are challenged with pathogenic Ark virus. In this study, we examine routes of vaccine administration using multiple IBV types including Ark in an effort to understand why Ark vaccines do not provide good protection and persist in commercial broilers. We found that interference between different types of IBV vaccines was not occurring when combined and administered using a commercial hatchery spray cabinet. Also, Ark vaccine virus was not efficacious in 1-day-old broilers when sprayed using a hatchery spray cabinet, but it gave good protection when administrated by eyedrop inoculation. We also found that the amount of Ark vaccine virus was low or undetectable in choanal swabs out to 35 days postvaccination when vaccine was administered by eyedrop or drinking water. Alternatively, a subpopulation of the Ark vaccine isolated from a vaccinated bird, Ark-RI-EP1, showed a peak titer at 7-10 days of age when given by the same routes, suggesting that the Ark-RI-EP1 was more fit with regard to infection, replication in the birds, or both. Moreover, we found that detection of IBV vaccine virus early after administration, regardless of strain or route, correlated with protection against homologous challenge and may thus be a good indicator of vaccine efficacy in the field because humoral antibody titers are typically low or undetectable after vaccination. These experiments provided key findings that can be used to direct efforts for improving the efficacy of IBV

  7. Determination of Ionization Coefficient of Atmospheric Helium in Dielectric Barrier Discharge

    International Nuclear Information System (INIS)

    Zhuo, Liang; Hai-Yun, Luo; Xin-Xin, Wang; Bo, Lv; Zhi-Cheng, Guan; Li-Ming, Wang

    2008-01-01

    A weakly luminous layer close to the anode is observed at time far ahead of the current pulse in dielectric barrier discharge of helium at atmospheric pressure and it is considered as the result of a very weak Townsend discharge. Based on the assumption that the space charge produced by this Townsend discharge is too small to distort the uniform electric field in the gas gap, the electrons have more or less the same energy over the entire gap and the spatial distribution of the discharge light is proportional to the distribution of electron density. This light distribution is obtained by processing side-view photograph of discharge gap using an intensified charge coupled device camera with an exposure time of 20 ns. By fitting a theoretically derived formula with the measured curve of light distribution, the Townsend electron ionization coefficient a is determined to be 31 cm −1 at E/p = 3.6 V·cm −1 ·Torr −1 , which is much higher than that obtained by solving the Boltzmann equation of pure helium. It is believed that penning ionization of helium metastables with impurity of nitrogen molecules makes great contribution to the experimentally determined α value. The contribution of this penning ionization to α is roughly estimated. (physics of gases, plasmas, and electric discharges)

  8. Laser photoelectron spectrometry of Sc- and Y-

    International Nuclear Information System (INIS)

    Feigerle, C.S.; Herman, Z.; Lineberger, W.C.

    1981-01-01

    The photoelectron spectra of Sc - and Y - have been obtained in a crossed ion- and laser-beam experiment. Analysis of the Sc - spectrum yields two bound terms of 3d4s 2 4p configuration ( 1 D 0 and 3 D 0 ), with EA(Sc) = 0.189 +- 0.020 eV and an excited-state binding energy of 0.042 +- 0.020 eV. Similarly, the (4d5s 2 5p) 1 D 0 ground state of Y - is bound by 0.308 +- 0.012 eV and a (4d5s 2 5p) 3 D 0 excited term is bound by 0.165 +- 0.025 eV. With the determination of the bound electronic configuration of Sc - as 3d4s 2 4p, the order of filling of electron shells of the first transition series negative ions is found to be 4s 2 ep, 3d4s 2 4p, the order of filling of electron shells of the first transition series negative ions is found to be 4s 2 4p, 3d4s 2 4p, followed by 3dsup(k) 4s 2 (k = 3, 4, ..., 10). (orig.)

  9. Mechanism-based inactivation of cytochrome P-450 dependent benzo[a]pyrene hydroxylase activity by acetylenic and olefinic polycyclic arylhydrocarbons

    International Nuclear Information System (INIS)

    Gan, L.S.

    1986-01-01

    A series of aryl acetylenes and aryl olefins have been examined as substrates and inhibitors of cytochrome P-450 dependent monooxygenases in liver microsomes from 5,6-benzoflavone or phenobarbital pretreated rats. 1-Ethynylpyrene (EP), 3-ethynylperylene (EPL), cis- and trans-1-(2-bromo-vinyl)pyrene (c-BVP and t-BVP), and 1-allylpyrene (AP) serve as mechanism-based irreversible inactivators (suicide inhibitors) of benzo(a)pyrene (BP) hydroxylase, while 1-vinyl-pyrene (VP) and phenyl 1-pyrenyl acetylene (PPA) do not cause a detectable suicide inhibition of the BP hydroxylase. The mechanism-based loss of BP hydroxylase activity caused by the aryl acetylenes is not accompanied by a corresponding loss of the P-450 content of the microsomes. In the presence of NADPH, 3 H-labeled EP covalently attached to P-450 isozymes with a measured stoichiometry of one mole of EP per mole of the P-450 heme. The results of the effects of these aryl derivatives in the mammalian cell-mediated mutagenesis assay and toxicity assay show that none of the compounds examined nor any of the their metabolites produced in the incubation system are cytotoxic to V79 cells

  10. Bosonic Spectral Function and the Electron-Phonon Interaction in HTSC Cuprates

    International Nuclear Information System (INIS)

    Maksimov, E. G.; Tamm, I. E.; Kulic, M.L.; Kulic, M.L.; Dolgov, O. V.

    2010-01-01

    In this paper we discuss experimental evidence related to the structure and origin of the bosonic spectral function a2F(ο) in high-temperature superconducting (HTSC) cuprates at and near optimal doping. Global properties of a2F(ο), such as number and positions of peaks, are extracted by combining optics, neutron scattering, ARPES and tunnelling measurements. These methods give evidence for strong electron-phonon interaction (EPI) with 1<λep <3.5 in cuprates near optimal doping. We clarify how these results are in favor of the modified Migdal-Eliashberg (ME) theory for HTSC cuprates near optimal doping. In Section 2 we discuss theoretical ingredients such as strong EPI, strong correlations which are necessary to explain the mechanism of d-wave pairing in optimally doped cuprates. These comprise the ME theory for EPI in strongly correlated systems which give rise to the forward scattering peak. The latter is supported by the long-range part of EPI due to the weakly screened Madelung interaction in the ionic-metallic structure of layered HTSC cuprates. In this approach EPI is responsible for the strength of pairing while the residual Coulomb interaction and spin fluctuations trigger the d-wave pairing.

  11. Analysis and Implementation of Cryptographic Hash Functions in Programmable Logic Devices

    Directory of Open Access Journals (Sweden)

    Tautvydas Brukštus

    2016-06-01

    Full Text Available In this day’s world, more and more focused on data pro-tection. For data protection using cryptographic science. It is also important for the safe storage of passwords for this uses a cryp-tographic hash function. In this article has been selected the SHA-256 cryptographic hash function to implement and explore, based on fact that it is now a popular and safe. SHA-256 cryp-tographic function did not find any theoretical gaps or conflict situations. Also SHA-256 cryptographic hash function used cryptographic currencies. Currently cryptographic currency is popular and their value is high. For the measurements have been chosen programmable logic integrated circuits as they less effi-ciency then ASIC. We chose Altera Corporation produced prog-rammable logic integrated circuits. Counting speed will be inves-tigated by three programmable logic integrated circuit. We will use programmable logic integrated circuits belong to the same family, but different generations. Each programmable logic integ-rated circuit made using different dimension technology. Choo-sing these programmable logic integrated circuits: EP3C16, EP4CE115 and 5CSEMA5F31. To compare calculations perfor-mances parameters are provided in the tables and graphs. Re-search show the calculation speed and stability of different prog-rammable logic circuits.

  12. Emulación en hardware de circuitos cuánticos basados en compuertas Toffoli

    Directory of Open Access Journals (Sweden)

    Jorge E. Duarte-Sánchez

    2014-01-01

    Full Text Available Este trabajo presenta el diseño de una arquitectura hardware para emular circuitos cuánticos basados en compuertas tipo Toffoli con la cual se pueden emular circuitos de más de 50 qubits. El estado del sistema se obtiene procesando independientemente cada estado base mediante las funciones determinadas por las compuertas cuánticas para cada qubit; el tiempo requerido para la emulación crece exponencialmente en función del número de qubits que se usan solamente para generar una superposición de estados, y no en función de la cantidad total de qubits del sistema como ocurre cuando se usa la representación matricial convencional. Adicionalmente, se diseñó un arreglo de unidades de procesamiento para disminuir el tiempo de ejecución. Los resultados de síntesis permiten concluir que se requieren 9,35 segundos para emular la exponenciación modular de 8 bits, la cual utiliza 48 qubits, 155.312 compuertas cuánticas y requiere procesar 131.072 estados base. Estos resultados también permiten estimar que se pueden implementar 256 unidades de procesamiento de 52 qubits en el FPGA EP3C120F780I7.

  13. Analysis of the wind influence on the aerodynamic drag in the case of a certain emplacement of the pantograph on the electric rail vehicles

    Directory of Open Access Journals (Sweden)

    Sorin ARSENE

    2015-03-01

    Full Text Available The wind gusts with high speed can negative affect the operation of the railway electric vehicles. These vehicles can achieve high performances, as long as the power supply is ensured, without discontinuities or interruptions in the process. This work aims at conducting an analysis regarding the wind influence with regard to the energy collector placed on the vehicle bodywork taking in account a certain positioning of the active pantograph. To this end, in a first step, the EP3 pantograph which was raised to its maximum working height was 3-D modeled. As regards the simulation, we consider the case in which the equipment is placed on the vehicle so that the angle formed by the articulation of the arms is pointing in the direction of the air flow. The simulation is carried out for different points of the angles ranging between [0o, 180o] at the relative velocity of the fluid of 0m / s, 10m / s, 20m / s and 30m / s.

  14. Toward development of a comprehensive external quality assurance program for polyfunctional intracellular cytokine staining assays.

    Science.gov (United States)

    Staats, Janet S; Enzor, Jennifer H; Sanchez, Ana M; Rountree, Wes; Chan, Cliburn; Jaimes, Maria; Chan, Ray Chun-Fai; Gaur, Amitabh; Denny, Thomas N; Weinhold, Kent J

    2014-07-01

    The External Quality Assurance Program Oversight Laboratory (EQAPOL) Flow Cytometry Program assesses the proficiency of NIH/NIAID/DAIDS-supported and potentially other interested research laboratories in performing Intracellular Cytokine Staining (ICS) assays. The goal of the EQAPOL Flow Cytometry External Quality Assurance Program (EQAP) is to provide proficiency testing and remediation for participating sites. The program is not punitive; rather, EQAPOL aims to help sites identify areas for improvement. EQAPOL utilizes a highly standardized ICS assay to minimize variability and readily identify those sites experiencing technical difficulties with their assays. Here, we report the results of External Proficiency 3 (EP3) where participating sites performed a 7-color ICS assay. On average, sites perform well in the Flow Cytometry EQAP (median score is "Good"). The most common technical issues identified by the program involve protocol adherence and data analysis; these areas have been the focus of site remediation. The EQAPOL Flow Cytometry team is now in the process of expanding the program to 8-color ICS assays. Evaluating polyfunctional ICS responses would align the program with assays currently being performed in support of HIV immune monitoring assays. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Morphology and thickness of the diffusion of resin through demineralized or unconditioned dentinal matrix

    Directory of Open Access Journals (Sweden)

    Arrais César Augusto Galvão

    2002-01-01

    Full Text Available The formation of a hybrid layer is the main bonding mechanism of current dentin-bonding systems. This study evaluated the morphology and thickness of the resin-infiltrated dentinal layer after the application of adhesive systems. The dentin-bonding agents were evaluated on flat dentinal preparations confected on the occlusal surfaces of human teeth. The test specimens were prepared and inspected under scanning electron microscopy at a magnification of X 2,000. The adhesive systems were responsible for different hybrid layer thicknesses (p < 0.05, and the mean values were: for Scotchbond MP Plus (SM, 7.41 ± 1.24mum; for Single Bond (SB, 5.55 ± 0.82mum; for Etch & Prime 3.0 (EP, 3.86 ± 1.17mum; and for Clearfil SE Bond (CB, 1.22 ± 0.45mum. The results suggest that the conventional three-step adhesive system (SM was responsible for the thickest hybrid layer, followed by the one-bottle adhesive (SB. The self-etching adhesives, EP and CB, produced the formation of the thinnest hybrid layers.

  16. Impact of a novel phosphorus-nitrogen flame retardant curing agent on the properties of epoxy resin

    Science.gov (United States)

    Liu, Xiaoli; Liang, Bing

    2017-12-01

    A phosphorus-nitrogen flame retardant curing agent diethyl phosphonic p-Phenylenediamine diamide (DEPPPD) was synthesized. The chemical structure of the obtained compound was identified by Fourier transform infrared (FTIR), 1H nuclear magnetic resonance (1HNMR), and mass spectroscopies. A series of t hermosetting systems were prepared by conventional epoxy resins (E-44) and DEPPPD. The effects of DEPPPD on flame retardancy, thermal degradation behavior, mechanical properties and the morphologies of char residues of EP/DEPPPD thermosets were investigated. The results demonstrated that when the phosphorus content of 2.88 wt%, EP-3 successfully passed UL-94 V-0 flammability rating, the LOI value was as high as 31.1%, the impact strength and tensile strength of it was 6.50 KJ m-2 and 48.21 MPa, the adhesive strength could reach 14.61 MPa, respectively. The TGA results indicated that the introduction of DEPPPD promoted EP matrix decomposed at a lower temperature, the rate of the thermal decomposition also decreased compared with EP-0. The residual char ratio of 800 °C was increased whether in nitrogen or in the air. The morphological structures of char residue were more compact and homogeneous which could prevent the heat transmission and diffusion, limit the production of combustible gases and reduced the heat release rate.

  17. Mesenchymal stem cells increase antioxidant capacity in intestinal ischemia/reperfusion damage.

    Science.gov (United States)

    Inan, M; Bakar, E; Cerkezkayabekir, A; Sanal, F; Ulucam, E; Subaşı, C; Karaöz, E

    2017-07-01

    Mesenchymal stem cells (MSCs) may have beneficial effects in reversing intestinal damage resulting from circulatory disorders. The hypothesis of this study is that MSCs increase antioxidant capacity of small bowel tissue following intestinal ischemia reperfusion (I/R) damage. A total of 100 rats were used for the control group and three experimental groups, as follows: the sham control, local MSC, and systemic MSC groups. Each group consisted of 10 animals on days 1, 4, and 7 of the experiment. Ischemia was established by clamping the superior mesenteric artery (SMA) for 45min; following this, reperfusion was carried out for 1, 4, and 7days in all groups. In the local and systemic groups, MSCs were administered intravenously and locally just after the ischemia, and they were investigated after 1, 4, and 7days. The superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (Gpx) activities, as well as malondialdehyde (MDA) and total protein levels, were measured. Histopathological analysis was performed using light and electron microscopy. The indicators of proliferation from the effects of anti- and pro-inflammatory cytokines were evaluated using immunohistochemistry. MDA was increased (Pcytokines interleukin-1β (IL1β), transforming growth factor-β1 (TGFβ1), tumor necrosis factor-α (TNFα), IL6, MIP2, and MPO decreased (Pcytokines EP3 and IL1ra increased (poxygen radicals, suppression of pro-inflammatory cytokines, and increasing the expression of anti-inflammatory cytokines. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. A high-resolution programmable Vernier delay generator based on carry chains in FPGA.

    Science.gov (United States)

    Cui, Ke; Li, Xiangyu; Zhu, Rihong

    2017-06-01

    This paper presents an architecture of a high-resolution delay generator implemented in a single field programmable gate array chip by exploiting the method of utilizing dedicated carry chains. It serves as the core component in various physical instruments. The proposed delay generator contains the coarse delay step and the fine delay step to guarantee both large dynamic range and high resolution. The carry chains are organized in the Vernier delay loop style to fulfill the fine delay step with high precision and high linearity. The delay generator was implemented in the EP3SE110F1152I3 Stratix III device from Altera on a self-designed test board. Test results show that the obtained resolution is 38.6 ps, and the differential nonlinearity/integral nonlinearity is in the range of [-0.18 least significant bit (LSB), 0.24 LSB]/(-0.02 LSB, 0.01 LSB) under the nominal supply voltage of 1100 mV and environmental temperature of 20  ° C. The delay generator is rather efficient concerning resource cost, which uses only 668 look-up tables and 146 registers in total.

  19. Effect of ultrasonic pretreatment on anaerobic digestion and its sludge dewaterability.

    Science.gov (United States)

    Xu, Huacheng; He, Pinjing; Yu, Guanghui; Shao, Liming

    2011-01-01

    To investigate the effect of ultrasonic pretreatment on anaerobic digestion and sludge dewaterability and further to probe into the influencing factors on sludge dewaterability, sludge flocs were stratified into four fractions: (1) slime; (2) loosely bound extracellular polymeric substances (LB-EPS); (3) tightly bound EPS (TB-EPS); and (4) EPS-free pellets. The results showed that ultrasonic pretreatment increased the anaerobic digestion efficiency by 7%-8%. Anaerobic digestion without ultrasonic pretreatment deteriorated the sludge dewaterability, with the capillary suction time (CST) increased from 1.42 to 47.3 (sec x L)/g-TSS. The application of ultrasonic pretreatment firstly deteriorated the sludge dewaterability (normalized CST increased to 44.4 (sec x L)/g-TSS), while subsequent anaerobic digestion offset this effect and ultimately decreased the normalized CST to 23.2 (sec x L)/g-TSS. The dewaterability of unsonicated sludge correlated with protein (p = 0.003) and polysaccharide (p = 0.004) concentrations in the slime fraction, while that of sonicated sludge correlated with protein concentrations in the slime and LB-EPS fractions (p anarobic digestion.

  20. A high-resolution programmable Vernier delay generator based on carry chains in FPGA

    Science.gov (United States)

    Cui, Ke; Li, Xiangyu; Zhu, Rihong

    2017-06-01

    This paper presents an architecture of a high-resolution delay generator implemented in a single field programmable gate array chip by exploiting the method of utilizing dedicated carry chains. It serves as the core component in various physical instruments. The proposed delay generator contains the coarse delay step and the fine delay step to guarantee both large dynamic range and high resolution. The carry chains are organized in the Vernier delay loop style to fulfill the fine delay step with high precision and high linearity. The delay generator was implemented in the EP3SE110F1152I3 Stratix III device from Altera on a self-designed test board. Test results show that the obtained resolution is 38.6 ps, and the differential nonlinearity/integral nonlinearity is in the range of [-0.18 least significant bit (LSB), 0.24 LSB]/(-0.02 LSB, 0.01 LSB) under the nominal supply voltage of 1100 mV and environmental temperature of 2 0°C. The delay generator is rather efficient concerning resource cost, which uses only 668 look-up tables and 146 registers in total.

  1. Residual strength of repaired graphite/epoxy laminates after 5 years of outdoor exposure

    Science.gov (United States)

    Deaton, Jerry W.

    1990-01-01

    The NASA Langley Research Center has sponsored research to develop generic repair techniques and processes for advanced graphite/epoxy (Gr/Ep) composites applicable to secondary structures for commercial transport aircraft. The long-term durability of such repairs is being addressed in a 10-year outdoor exposure program at the Langley Research Center. Details of the program and results of residual strength tests after 5 years of outdoor exposure are presented. Four repair methods are being evaluated. These include: (1) externally bolted aluminum-plus adhesive; (2) precured, bonded external Gr/Ep; (3) cure-in-place external Gr/Ep; and (4) cure-in-place flush Gr/Ep. Repaired specimens as well as undamaged and damaged unrepaired controls are being exposed outdoors for 1, 3, 5, 7, and 10 years. The residual tensile strength of stressed, unstressed, and fatigue specimens from each group is reported and compared with the tensile strength of baseline specimens which received no outdoor exposure. Identification of the commercial products and companies is used to describe adequately the test materials. The identification of these commercial products does not constitute endorsement, expressed or implied, of such products by the National Aeronautics and Space Administration.

  2. Rheological Characterization as an Alternative Method to Indentation for Determining the Setting Time of Restorative and Endodontic Cements

    Directory of Open Access Journals (Sweden)

    William N. Ha

    2017-12-01

    Full Text Available This study explored an alternative approach using rheology to assess setting time. The following cements were tested: ProRoot® MTA (Dentsply, Tulsa, OK, USA, Biodentine® (Septodont, Saint Maur des Fosses, France, Fuji VII®, FujiVII® EP, and Fuji IX® (from GC Corporation, Tokyo, Japan, RealSeal SE™ Sealer (SybronEndo, Amersfoort, The Netherlands, AH 26® and AH Plus (both from Dentsply DeTrey, Konstanz, Germany. Freshly mixed cements were placed into a strain-controlled rheometer (1 rad·s−1 with an applied strain of 0.01%. From measurements of elastic modulus over time, the time taken to reach 90% of the plateau elastic modulus (designated as the setting time was determined for each cement. In increasing order, the setting times were as follows: Fuji VII EP 3.3 min, Fuji VII 3.6 min, Fuji IX 3.7 min, ProRoot MTA 5.1 min, Biodentine 15.9 min, RealSeal 22.2 min, AH Plus 5933 min, and AH 26 5067 min. However, ProRoot MTA did not yield reliable results. The time to reach the 90% plateau elastic modulus correlates well with the setting time of glass ionomer cements and Biodentine. Using this approach gives much longer setting times for endodontic sealers than previously recognized.

  3. FPGA BASED ASYNCHRONOUS PIPELINED MB-OFDM UWB TRANSMITTER BACKEND MODULES

    Directory of Open Access Journals (Sweden)

    M. Santhi

    2010-03-01

    Full Text Available In this paper, a novel scheme is proposed which comprises the advantages of asynchronous pipelining techniques and the advantages of FPGAs for implementing a 200Mbps MB-OFDM UWB transmitter digital backend modules. In asynchronous pipelined system, registers are used as in synchronous system. But they are controlled by handshaking signals. Since FPGAs are rich in registers, design and implementation of asynchronous pipelined MBOFDM UWB transmitter on FPGA using four-phase bundled-data protocol is considered in this paper. Novel ideas have also been proposed for designing asynchronous OFDM using Modified Radix-24 SDF and asynchronous interleaver using two RAM banks. Implementation has been performed on ALTERA STRATIX II EP2S60F1020C4 FPGA and it is operating at a speed of 350MHz. It is assured that the proposed MB-OFDM UWB system can be made to work on STRATIX III device with the operating frequency of 528MHz in compliance to the ECMA-368 standard. The proposed scheme is also applicable for FPGA from other vendors and ASIC.

  4. 2003 - 2004 ACADEMIC TRAINING PROGRAMME: 2nd Term - 12 January to 31 March 2004

    CERN Multimedia

    2003-01-01

    ACADEMIC TRAINING Françoise Benz tel. 73127 academic.training@cern.ch REGULAR LECTURE PROGRAMME 12, 13, 14 January Microelectronics and Nanoelectronics: Trends, and Applications to HEP Instrumentation by P. Jarron / CERN-EP 2, 3, 4 February Quantum Teleportation : Principles and Applications by N. Gisin / Univ. of Geneva, CH 16, 17, 18, 19, 20 February Physics of Extra Dimensions by V. Rubakov / Russian Academy of Sciences, Moscow, RU 1, 2, 3, 4, March Physics of Shower Simulation at LHC at the Example of GEANT4 by J.P. Wellisch / CERN-EP 8, 9, 11, 12 March Introduction to Cryogenic Engineering by H. Quack / Technische Universität Dresden, D 22, 23, 24, 25, 26 March Neutrinos By Y. Nir / Weizmann Institute of Science, Rehovot, IL LECTURE SERIES FOR POSTGRADUATE STUDENTS 29, 30, 31 March, 1, 2 April Physics beyond the Standard Model by L. Ibanez / CERN-TH The lectures are open to all those interested, without application. The abstract of the lectures, as well as any chang...

  5. 2003 - 2004 ACADEMIC TRAINING PROGRAMME: 2nd Term - 12 January to 31 March 2004

    CERN Multimedia

    2004-01-01

    ACADEMIC TRAINING Françoise Benz tel. 73127 academic.training@cern.ch REGULAR LECTURE PROGRAMME 12, 13, 14 January Microelectronics and Nanoelectronics: Trends, and Applications to HEP Instrumentation by P. Jarron / CERN-EP 2, 3, 4 February Quantum Teleportation : Principles and Applications by N. Gisin / Univ. of Geneva, CH 16, 17, 18, 19, 20 February Physics of Extra Dimensions by V. Rubakov / Russian Academy of Sciences, Moscow, RU 1, 2, 3, 4, March Physics of Shower Simulation at LHC at the Example of GEANT4 by J.P. Wellisch / CERN-EP 8, 9, 11, 12 March Introduction to Cryogenic Engineering by H. Quack / Technische Universität Dresden, D 22, 23, 24, 25, 26 March Neutrinos By Y. Nir / Weizmann Institute of Science, Rehovot, IL LECTURE SERIES FOR POSTGRADUATE STUDENTS 29, 30, 31 March, 1, 2 April Physics beyond the Standard Model by L. Ibanez / CERN-TH The lectures are open to all those interested, without application. The abstract of the lectures, as well as any change to...

  6. Influence of Macro-Topography on Damage Tolerance and Fracture Toughness of 0.1 wt % Multi-Layer Graphene/Clay-Epoxy Nanocomposites

    Directory of Open Access Journals (Sweden)

    Rasheed Atif

    2016-07-01

    Full Text Available Influence of topographical features on mechanical properties of 0.1 wt % Multi-Layer Graphene (MLG/clay-epoxy nanocomposites has been studied. Three different compositions were made: (1 0.1 wt % MLG-EP; (2 0.1 wt % clay-EP and (3 0.05 wt % MLG-0.05 wt % clay-EP. The objective of making hybrid nanocomposites was to determine whether synergistic effects are prominent at low weight fraction of 0.1 wt % causing an improvement in mechanical properties. The topographical features studied include waviness (Wa, roughness average (Ra, root mean square value (Rq and maximum roughness height (Rmax or Rz. The Rz of as-cast 0.1 wt % MLG-EP, clay-EP and 0.05 wt % MLG-0.05 wt % clay-EP nanocomposites were 43.52, 48.43 and 41.8 µm respectively. A decrease in Rz values was observed by treating the samples with velvet cloth and abrasive paper 1200P while increased by treating with abrasive papers 320P and 60P. A weight loss of up to 16% was observed in samples after the treatment with the abrasive papers. It was observed that MLG is more effective in improving the mechanical properties of epoxy than nanoclay. In addition, no significant improvement in mechanical properties was observed in hybrid nanocomposites indicating that 0.1 wt % is not sufficient to generate conspicuous synergistic effects.

  7. Celecoxib and octreotide synergistically ameliorate portal hypertension via inhibition of angiogenesis in cirrhotic rats.

    Science.gov (United States)

    Gao, Jin-Hang; Wen, Shi-Lei; Feng, Shi; Yang, Wen-Juan; Lu, Yao-Yao; Tong, Huan; Liu, Rui; Tang, Shi-Hang; Huang, Zhi-Yin; Tang, Ying-Mei; Yang, Jin-Hui; Xie, Hui-Qi; Tang, Cheng-Wei

    2016-10-01

    Abnormal angiogenesis is critical for portal hypertension in cirrhosis. Except for etiological treatment, no efficient medication or regime has been explored to treat the early stage of cirrhosis when angiogenesis is initiated or overwhelming. In this study, we explored an anti-angiogenesis effort through non-cytotoxic drugs octreotide and celecoxib to treat early stage of cirrhotic portal hypertension in an animal model. Peritoneal injection of thioacetamide (TAA) was employed to induce liver cirrhosis in rats. A combination treatment of celecoxib and octreotide was found to relieve liver fibrosis, portal venous pressure, micro-hepatic arterioportal fistulas, intrahepatic and splanchnic angiogenesis. Celecoxib and octreotide exerted their anti-angiogenesis effect via an axis of cyclooxygenase-2/prostaglandin E2/EP-2/somatostatin receptor-2, which consequently down-regulated phosphorylation of extracellular signal-regulated kinase (p-ERK)-hypoxia-inducible factor-1α (HIF-1α)-vascular endothelial growth factor (VEGF) integrated signaling pathways. In conclusions, combination of celecoxib and octreotide synergistically ameliorated liver fibrosis and portal hypertension of the cirrhotic rats induced by TAA via the inhibition of intrahepatic and extrahepatic angiogenesis. The potential mechanisms behind the regimen may due to the inactivation of p-ERK-HIF-1α-VEGF signaling pathway.

  8. Feedback amplification of fibrosis through matrix stiffening and COX-2 suppression

    Science.gov (United States)

    Liu, Fei; Mih, Justin D.; Shea, Barry S.; Kho, Alvin T.; Sharif, Asma S.; Tager, Andrew M.

    2010-01-01

    Tissue stiffening is a hallmark of fibrotic disorders but has traditionally been regarded as an outcome of fibrosis, not a contributing factor to pathogenesis. In this study, we show that fibrosis induced by bleomycin injury in the murine lung locally increases median tissue stiffness sixfold relative to normal lung parenchyma. Across this pathophysiological stiffness range, cultured lung fibroblasts transition from a surprisingly quiescent state to progressive increases in proliferation and matrix synthesis, accompanied by coordinated decreases in matrix proteolytic gene expression. Increasing matrix stiffness strongly suppresses fibroblast expression of COX-2 (cyclooxygenase-2) and synthesis of prostaglandin E2 (PGE2), an autocrine inhibitor of fibrogenesis. Exogenous PGE2 or an agonist of the prostanoid EP2 receptor completely counteracts the proliferative and matrix synthetic effects caused by increased stiffness. Together, these results demonstrate a dominant role for normal tissue compliance, acting in part through autocrine PGE2, in maintaining fibroblast quiescence and reveal a feedback relationship between matrix stiffening, COX-2 suppression, and fibroblast activation that promotes and amplifies progressive fibrosis. PMID:20733059

  9. Biocatalysis conversion of methanol to methane in an upflow anaerobic sludge blanket (UASB) reactor: Long-term performance and inherent deficiencies.

    Science.gov (United States)

    Lu, Xueqin; Zhen, Guangyin; Chen, Mo; Kubota, Kengo; Li, Yu-You

    2015-12-01

    Long-term performance of methanol biocatalysis conversion in a lab-scale UASB reactor was evaluated. Properties of granules were traced to examine the impact of methanol on granulation. Methanolic wastewater could be stably treated during initial 240d with the highest biogas production rate of 18.6 ± 5.7 L/Ld at OLR 48 g-COD/Ld. However, the reactor subsequently showed severe granule disintegration, inducing granule washout and process upsets. Some steps (e.g. increasing influent Ca(2+) concentration, etc.) were taken to prevent rising dispersion, but no clear improvement was observed. Further characterizations in granules revealed that several biotic/abiotic factors all caused the dispersion: (1) depletion of extracellular polymeric substances (EPS) and imbalance of protein/polysaccharide ratio in EPS; (2) restricted formation of hard core and weak Ca-EPS bridge effect due to insufficient calcium supply; and (3) simplification of species with the methanol acclimation. More efforts are required to solve the technical deficiencies observed in methanolic wastewater treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. SU(6)-strong breaking: structure functions and small momentum transfer properties of the nucleon

    International Nuclear Information System (INIS)

    Le Yaouanc, A.; Oliver, L.; Pene, O.; Raynal, J.C.

    1975-01-01

    A new approach in the study of the SU(6) symmetry breaking (in particular in deep inelastic electron-nucleon scattering) is presented. It is shown that there is a connection between deep inelastic and low momentum transfer or static properties of the nucleon, which extends much beyond the common SU(6) 56-assignments of the nucleon in both cases. This connection is provided by the realistic quark model (in which quarks are considered as real entities moving inside the hadron). Using this connection it is shown that the breaking of the prediction Fsub(2)sup(en)/Fsub(2)sup(ep)=2/3 is not truly related to chiral configuration mixings. An alternative solution, based on a true modification of the 56-assignment of the nucleon to a (56,L=0)+(70,L=0) mixing (called SU(6) strong mixing) is proposed. It is shown that the 'good' predictions of SU(6) are not much changed by this mixing. A complete description of the deep inelastic scattering including gluons and pairs is presented

  11. Protective function of complement against alcohol-induced rat liver damage.

    Science.gov (United States)

    Bykov, Igor L; Väkevä, Antti; Järveläinen, Harri A; Meri, Seppo; Lindros, Kai O

    2004-11-01

    The complement system can promote tissue damage or play a homeostatic role in the clearance and disposal of damaged tissue. We assessed the role of the terminal complement pathway in alcohol-induced liver damage in complement C6 (C6-/-) genetically deficient rats. C6-/- and corresponding C6+/+ rats were continuously exposed to ethanol by feeding ethanol-supplemented liquid diet for six weeks. Liver samples were analyzed for histopathology and complement component deposition by immunofluorescence microscopy. Prostaglandin E receptors and cytokine mRNA levels were analyzed by RT-PCR and plasma cytokines by ELISA. Deposition of complement components C1, C3, C8 and C9 was observed in C6+/+ rats, but not in C6-/- animals. The histopathological changes, the liver weight increase and the elevation of the plasma pro-/anti-inflammatory TNF-alpha/IL-10 ratio were, on the other hand, more marked in C6-/- rats. Furthermore, ethanol enhanced the hepatic mRNA expression of the prostaglandin E receptors EP2R and EP4R exclusively in the C6-/- rats. Our results indicate that a deficient terminal complement pathway predisposes to tissue injury and promotes a pro-inflammatory cytokine response. This suggests that an intact complement system has a protective function in the development of alcoholic liver damage.

  12. Engineering work plan for PFP criticality alarm panel first unit re-build

    International Nuclear Information System (INIS)

    Clem, W.E.

    1994-01-01

    This document describes the first step in increasing the quality, reliability, and ease of maintenance of the nine Criticality Alarm Panels (CAP) at PFP. Development control practices and guidelines of WHC-CM-6-1, EP-2.4 and WHC-IP-1026, EPG-2.4 are applied to develop a prototype of a replacement Criticality Alarm Panel (CAP) with facility-use potential. During the development of the prototype CAP, the design requirements of all of PFP's nine CAPs are considered to develop standardized hardware and detailed design drawings that are tailored to PFP maintenance needs. Increased quality and reliability is achieved through quality hardware, proven technology and design techniques, and the use of the Class 1E workmanship standards of WHC-CM-8-1. The end result of the work described by this work plan is a verified/read-to-install replacement for CAP Z4 and verified/released H-2 drawings that are formatted such that they can easily be replicated when producing design drawings for the other eight CAPs

  13. A selective role for α3 subunit glycine receptors in inflammatory pain

    Directory of Open Access Journals (Sweden)

    Victoria L Harvey

    2009-11-01

    Full Text Available GlyR α3 has previously been found to play a critical role in pain hypersensitivity following spinal PGE2 injection, complete Freund’s adjuvant (CFA and zymosan induced peripheral inflammation. In this study, although all models displayed typical phenotypic behaviours, no significant differences were observed when comparing the pain behaviours of Glra3-/- and wild-type littermates following the injection of capsaicin, carrageenan, kaolin/ carrageenan or monosodium iodoacetate, models of rheumatoid and osteoarthritis, respectively. However, clear differences were observed following CFA injection (p < 0.01. No significant differences were observed in the pain behaviours of Glra3-/- and wild-type littermates following experimentally induced neuropathic pain (partial sciatic nerve ligation. Similarly, Glra3-/- and wild-type littermates displayed indistinguishable visceromotor responses to colorectal distension (a model of visceral pain and in vivo spinal cord dorsal horn electrophysiology revealed no differences in responses to multimodal suprathreshold stimuli, intensities which equate to higher pain scores such as those reported in the clinic. These data suggest that apart from its clear role in CFA- and zymosan-induced pain sensitisation, hypersensitivity associated with other models of inflammation, neuropathy and visceral disturbances involves mechanisms other than the EP2 receptor - GlyR α3 pathway.

  14. Design and implementation of a multiband digital filter using FPGA to extract the ECG signal in the presence of different interference signals.

    Science.gov (United States)

    Aboutabikh, Kamal; Aboukerdah, Nader

    2015-07-01

    In this paper, we propose a practical way to synthesize and filter an ECG signal in the presence of four types of interference signals: (1) those arising from power networks with a fundamental frequency of 50Hz, (2) those arising from respiration, having a frequency range from 0.05 to 0.5Hz, (3) muscle signals with a frequency of 25Hz, and (4) white noise present within the ECG signal band. This was done by implementing a multiband digital filter (seven bands) of type FIR Multiband Least Squares using a digital programmable device (Cyclone II EP2C70F896C6 FPGA, Altera), which was placed on an education and development board (DE2-70, Terasic). This filter was designed using the VHDL language in the Quartus II 9.1 design environment. The proposed method depends on Direct Digital Frequency Synthesizers (DDFS) designed to synthesize the ECG signal and various interference signals. So that the synthetic ECG specifications would be closer to actual ECG signals after filtering, we designed in a single multiband digital filter instead of using three separate digital filters LPF, HPF, BSF. Thus all interference signals were removed with a single digital filter. The multiband digital filter results were studied using a digital oscilloscope to characterize input and output signals in the presence of differing sinusoidal interference signals and white noise. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Interplanetary Parameters Leading to Relativistic Electron Enhancement and Persistent Depletion Events at Geosynchronous Orbit and Potential for Prediction

    Science.gov (United States)

    Pinto, Victor A.; Kim, Hee-Jeong; Lyons, Larry R.; Bortnik, Jacob

    2018-02-01

    We have identified 61 relativistic electron enhancement events and 21 relativistic electron persistent depletion events during 1996 to 2006 from the Geostationary Operational Environmental Satellite (GOES) 8 and 10 using data from the Energetic Particle Sensor (EPS) >2 MeV fluxes. We then performed a superposed epoch time analysis of the events to find the characteristic solar wind parameters that determine the occurrence of such events, using the OMNI database. We found that there are clear differences between the enhancement events and the persistent depletion events, and we used these to establish a set of threshold values in solar wind speed, proton density and interplanetary magnetic field (IMF) Bz that can potentially be useful to predict sudden increases in flux. Persistent depletion events are characterized by a low solar wind speed, a sudden increase in proton density that remains elevated for a few days, and a northward turning of IMF Bz shortly after the depletion starts. We have also found that all relativistic electron enhancement or persistent depletion events occur when some geomagnetic disturbance is present, either a coronal mass ejection or a corotational interaction region; however, the storm index, SYM-H, does not show a strong connection with relativistic electron enhancement events or persistent depletion events. We have tested a simple threshold method for predictability of relativistic electron enhancement events using data from GOES 11 for the years 2007-2010 and found that around 90% of large increases in electron fluxes can be identified with this method.

  16. LDUA software custodian's notebook

    International Nuclear Information System (INIS)

    Aftanas, B.L.

    1998-01-01

    This plan describes the activities to be performed and controls to be applied to the process of specifying, obtaining, and qualifying the control and data acquisition software for the Light Duty Utility Arm (LDUA) System. It serves the purpose of a software quality assurance plan, a verification and validation plan, and a configuration management plan. This plan applies to all software that is an integral part of the LDUA control and data acquisition system, that is, software that is installed in the computers that are part of the LDUA system as it is deployed in the field. This plan applies to the entire development process, including: requirements; design; implementation; and operations and maintenance. This plan does not apply to any software that is not integral with the LDUA system. This plan has-been prepared in accordance with WHC-CM-6-1 Engineering Practices, EP-2.1; WHC-CM-3-10 Software Practices; and WHC-CM-4-2, QR 19.0, Software Quality Assurance Requirements

  17. Supercritical Fluid Chromatography with Photodiode Array Detection in the Determination of Fat-Soluble Vitamins in Hemp Seed Oil and Waste Fish Oil

    Directory of Open Access Journals (Sweden)

    Katarzyna Tyśkiewicz

    2018-05-01

    Full Text Available In the presented study for the first time a new, optimized, fast SFC (supercritical fluid chromatography method was applied to separate in one run fat-soluble vitamins from waste fish oil, including cis-and trans-retinyl palmitate, cis- and trans-retinyl acetate, retinol, α-tocopherol, β-tocopherol, γ‑tocopherol, δ-tocopherol, ergocalciferol (D2, cholecalciferol (D3, cis- and trans-phylloquinone (K1 and menaquinone-4 (K2-MK4. Vitamins were baseline separated on an Acquity UPC2 (ultra performance convergence chromatography HSS C18 SB (highly strength chemically modified silica column within 13 min. The influence of the stationary phase, such as Torus 1-AA (1-aminoanthracene, Torus Diol (high density diol, Torus DEA (diethylamine, BEH (silica with no bonding, BEH-2EP (2-ethylpirydine, CSH Fluoro-Phenyl (silica with fluoro-phenyl groups, column temperature, flow rate and back pressure on the separation of the compounds was described. The application of the modified saponification procedure allowed us to increase concentration in the sample prepared for the analysis of γ‑tocopherol from less than 1% (wt % to 14% for the first time. In addition, α‑tocopherol, γ‑tocopherol, δ‑tocopherol and retinol were identified in waste fish oil. Vitamin purification and analysis in waste fish oil are reported for the first time here. Due to the short time and effectiveness of the proposed method, it can be easily applied in industrial processes.

  18. Prostaglandin E2 Regulates Liver versus Pancreas Cell Fate Decisions and Endodermal Outgrowth

    Science.gov (United States)

    Nissim, Sahar; Sherwood, Richard I.; Wucherpfennig, Julia; Saunders, Diane; Harris, James M.; Esain, Virginie; Carroll, Kelli J.; Frechette, Gregory M.; Kim, Andrew J.; Hwang, Katie L.; Cutting, Claire C.; Elledge, Susanna; North, Trista E.; Goessling, Wolfram

    2014-01-01

    SUMMARY The liver and pancreas arise from common endodermal progenitors. How these distinct cell fates are specified is poorly understood. Here, we describe prostaglandin E2 (PGE2) as a regulator of endodermal fate specification during development. Modulating PGE2 activity has opposing effects on liver-versus-pancreas specification in zebrafish embryos as well as mouse endodermal progenitors. The PGE2 synthetic enzyme cox2a and receptor ep2a are patterned such that cells closest to PGE2 synthesis acquire a liver fate whereas more distant cells acquire a pancreas fate. PGE2 interacts with the bmp2b pathway to regulate fate specification. At later stages of development, PGE2 acting via the ep4a receptor promotes outgrowth of both the liver and pancreas. PGE2 remains important for adult organ growth, as it modulates liver regeneration. This work provides in vivo evidence that PGE2 may act as a morphogen to regulate cell fate decisions and outgrowth of the embryonic endodermal anlagen. PMID:24530296

  19. Occurrence of high-beta superthermal plasma events in the close environment of Jupiter's bow shock as observed by Ulysses

    International Nuclear Information System (INIS)

    Marhavilas, P. K.; Sarris, E. T.; Anagnostopoulos, G. C.

    2011-01-01

    The ratio of the plasma pressure to the magnetic field pressure (or of their energy densities) which is known as the plasma parameter 'beta'(β) has important implications to the propagation of energetic particles and the interaction of the solar wind with planetary magnetospheres. Although in the scientific literature the contribution of the superthermal particles to the plasma pressure is generally assumed negligible, we deduced, by analyzing energetic particles and magnetic field measurements recorded by the Ulysses spacecraft, that in a series of events, the energy density contained in the superthermal tail of the particle distribution is comparable to or even higher than the energy density of the magnetic field, creating conditions of high-beta plasma. More explicitly, in this paper we analyze Ulysses/HI-SCALE measurements of the energy density ratio (parameter β ep ) of the energetic ions'(20 keV to ∼5 MeV) to the magnetic field's in order to find occurrences of high-beta (β ep >1) superthermal plasma conditions in the environment of the Jovian magnetosphere, which is an interesting plasma laboratory and an important source of emissions in our solar system. In particular, we examine high-beta ion events close to Jupiter's bow shock, which are produced by two processes: (a) bow shock ion acceleration and (b) ion leakage from the magnetosphere.

  20. Representaciones sociales de la Educación para la Salud: docentes Facultad de Medicina, Universidad de Antioquia

    Directory of Open Access Journals (Sweden)

    Margarita M. Gómez G.

    2015-02-01

    Full Text Available Objetivo: reconocer las representaciones sociales (rs sobre Educación para la Salud (EpS presentes en los docentes de la Facultad de Medicina de la Universidad de Antioquia de la ciudad de Medellín. Metodología: estudio cualitativo desde el enfoque de las (rs, donde se analizaron 93 respuestas de docentes a la pregunta: ¿Qué es para usted la EpS? Resultados: del análisis de los datos emergieron como rs de la EpS: 1 Educación médica, asociada a su quehacer docente; 2 Educación a individuos y comunidades, asociada al ejercicio profesional como agentes de salud; y 3 Apropiación del conocimiento que hace el sujeto para su autocuidado. Discusión: las RS de los docentes sobre EpS permitieron comprender que no hay en la enseñanza una intencionalidad política para la trasformación social; que el modelo de comunicación que subyace en la educación es el informacional, aunque hay presencia del modelo relacional; que existe una concepción instrumental de la EpS. Es necesario concientizar al personal de salud de la importancia que para la educación tiene el modelo de comunicación relacional.

  1. Co-design for an SoC embedded network controller

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    With the development of Ethernet systems and the growing capacity of modern silicon technology, embedded communication networks are playing an increasingly important role in embedded and safety critical systems. Hardware/software co-design is a methodology for solving design problems in processor based embedded systems. In this work, we implemented a new 1-cycle pipeline microprocessor and a fast Ethernet transceiver and established a low cost, high performance embedded network controller, and designed a TCP/IP stack to access the Internet. We discussed the hardware/software architecture in the forepart, and then the whole system-on-a-chip on Altera Stratix EP1S25F780C6 device. Using the FPGA environment and SmartBit tester, we tested the system's throughput. Our simulation results showed that the maximum throughput of Ethernet packets is up to 7 Mbps, that of UDP packets is up to 5.8 Mbps, and that of TCP packets is up to 3.4 Mbps, which showed that this embedded system can easily transmit basic voice and video signals through Ethernet, and that using only one chip can realize that many electronic devices access to the Internet directly and get high performance.

  2. COMPOSITION OF THE JOINT ADVISORY APPEALS BOARD & DISCIPLINARY BOARD 1999-2000 EXERCISE

    CERN Multimedia

    Division des ressources humaines

    2000-01-01

     Appointed by the Director-GeneralAppointed by the Staff AssociationMembersBertrand Frammery / PSDaniel Boimond/ PS1st deputiesSue Foffano / ASJean-Claude Carlier / TIS2nd deputiesWolfgangvon Rüden / ITPoul Frandsen / LHCMessrs. Frammery and Boimond have drawn up the following list of staff members from among whom the Chairman of the Board may be chosen when required:Jean-Luc Baldy / STGuy Maurin / EPJean-Paul Fabre / EPMichel Rabany / LHCSverre Jarp / ITJean-Pierre Riunaud / PSLennart Jirden / SPLRoberto Saban / ACRobin Lauckner / SLMarilena Streit-Bianchi /TISMediators [see Administrative Circular N¡ 6 (Rev. 1) entitled 'Review procedure'] will also be selected from this list of ten staff members.COMPOSITION OF THE JOINT ADVISORY DISCIPLINARY BOARD1999-2000 Exercise Appointed by the Director-GeneralAppointed by the Staff AssociationMembersAchille Petrilli / ASMichel Bonnet / EP1st deputiesWisla Carena / EPIrene Seis / IT2nd deputiesRoland Garoby / PSJuan Diaz-Montoya / AC...

  3. TGF-β1 downregulates COX-2 expression leading to decrease of PGE2 production in human lung cancer A549 cells, which is involved in fibrotic response to TGF-β1.

    Directory of Open Access Journals (Sweden)

    Erina Takai

    Full Text Available Transforming growth factor-ß1 (TGF-β1 is a multifunctional cytokine that is involved in various pathophysiological processes, including cancer progression and fibrotic disorders. Here, we show that treatment with TGF-β1 (5 ng/mL induced downregulation of cyclooxygenase-2 (COX-2, leading to reduced synthesis of prostaglandin E2 (PGE2, in human lung cancer A549 cells. Treatment of cells with specific inhibitors of COX-2 or PGE2 receptor resulted in growth inhibition, indicating that the COX-2/PGE2 pathway contributes to proliferation in an autocrine manner. TGF-β1 treatment induced growth inhibition, which was attenuated by exogenous PGE2. TGF-β1 is also a potent inducer of epithelial mesenchymal transition (EMT, a phenotype change in which epithelial cells differentiate into fibroblastoid cells. Supplementation with PGE2 or PGE2 receptor EP4 agonist PGE1-alcohol, as compared with EP1/3 agonist sulprostone, inhibited TGF-β1-induced expression of fibronectin and collagen I (extracellular matrix components. Exogenous PGE2 or PGE2 receptor agonists also suppressed actin remodeling induced by TGF-β1. These results suggest that PGE2 has an anti-fibrotic effect. We conclude that TGF-β1-induced downregulation of COX-2/PGE2 signaling is involved in facilitation of fibrotic EMT response in A549 cells.

  4. U-Pb dating of two granite types from Soultz (Rhine Graben, France); Datation U-Pb des deux facies du granite de Soultz (fosse rhenan, France)

    Energy Technology Data Exchange (ETDEWEB)

    Cocherie, A.; Guerrot, C.; Genter, A. [Bureau de Recherches Geologiques et Minieres (BRGM), 45 - Orleans (France); Fanning, C.M. [Research School of Earth Sciences, ANU, Canberra, (Australia)

    2004-07-01

    Deep boreholes drilled in the basement of the Rhine Graben at Soultz-sous-Forets have shown the presence of an ubiquitous monzogranite. Borehole GPK-2, with a total depth of 5090 m, also intersected a more leucocratic fine-grained two-mica granite, locally present below 4860 m depth and continuously found between 5047 and 5090 m. Thanks to trace elements and in particular to REE (rare-earth elements), it could be shown that the leucocratic rock is a differentiated expression of the potassic magma that was at the origin of the monzogranite pluton. This model agrees with Sr-Nd isotope data, even though a slight contribution from the pre-existing basement should be considered as well. Use of the U-Pb method on monzogranite from EPS-1 - after zircon dissolution - has yielded an emplacement age of 334.0 + 3.8/-3.5 Ma (2 {sigma}). Point dates obtained by SHRIMP II on the rare zircons from the fine-grained granite showed that it was emplaced in a basement with very heterogeneous ages, ranging from Early Proterozoic to Silurian. (author)

  5. Study of K, L vacancies production mechanisms by X spectrometry in the interaction induced by a few MeV/A charged particles

    International Nuclear Information System (INIS)

    Andriamonje, S.

    1982-01-01

    The analysis of different mechanisms producing electronic inner shell vacancies in ion atom collisions at a few MeV/A charged is presented. The mutual influence of nuclear and atomic excitation in the ionization probability has been discussed. The 106 Cd(p,p') 106 Cd reaction (Ep=10 MeV) has been particularly investigated from this point. The investigation is followed up by the description of the theoretical and experimental methods which permit the determination of the total and/or differential X rays production cross section for different interaction. The gold sub-shell L 1 , L 2 , L 3 ionization probability has been studied in the Au(H + ,H + )Au reaction at Ep=1 MeV. In the second part of the manuscript we investigate in detail the influence of the charge exchange process on inner shell vacancy production. The N 2 , Ar, Kr targets have been produced by a system jet gas and bombarded by 0.8 28 Si 14+ ions at E=125 MeV. The cross section for the capture of an electron in K shell, L shell and total charge exchange have been measured and compared to the CDW theory (Continuum Distorted Wave). In the CDW validity domain the experimental and theoretical results are a good agreement. In the collisions induced by H + , ionization is found to be the main excitation process. On the contrary, in collisions induced by 28 Si 14+ charge exchange is dominant compared to ionization [fr

  6. Electron energy distribution function in the positive column of a neon glow discharge using the black wall approximation

    Energy Technology Data Exchange (ETDEWEB)

    Al-Hawat, Sh; Naddaf, M [Physics Department, Atomic Energy Commission, PO Box 6091, Damascus (Syrian Arab Republic)

    2005-04-21

    The electron energy distribution function (EEDF) was determined from the second derivative of the I-V Langmuir probe characteristics and, thereafter, theoretically calculated by solving the plasma kinetic equation, using the black wall (BW) approximation, in the positive column of a neon glow discharge. The pressure has been varied from 0.5 to 4 Torr and the current from 10 to 30 mA. The measured electron temperature, density and electric field strength were used as input data for solving the kinetic equation. Comparisons were made between the EEDFs obtained from experiment, the BW approach, the Maxwellian distribution and the Rutcher solution of the kinetic equation in the elastic energy range. The best conditions for the BW approach are found to be under the discharge conditions: current density j{sub d} = 4.45 mA cm{sup -2} and normalized electric field strength E/p = 1.88 V cm{sup -1} Torr{sup -1}.

  7. Thujone inhibits the function of α7-nicotinic acetylcholine receptors and impairs nicotine-induced memory enhancement in one-trial passive avoidance paradigm.

    Science.gov (United States)

    Sultan, Ahmed; Yang, Keun-Hang Susan; Isaev, Dmitro; Nebrisi, Eslam El; Syed, Nurulain; Khan, Nadia; Howarth, Christopher F; Sadek, Bassem; Oz, Murat

    2017-06-01

    Effects of thujone, a major ingredient of absinthe, wormwood oil and some herbal medicines, were tested on the function of α 7 subunit of the human nicotinic acetylcholine (α 7 nACh) receptor expressed in Xenopus oocytes using the two-electrode voltage-clamp technique. Thujone reversibly inhibited ACh (100μM)-induced currents with an IC 50 value of 24.7μM. The effect of thujone was not dependent on the membrane potential and did not involve Ca 2+ -dependent Cl - channels expressed endogenously in oocytes. Inhibition by thujone was not reversed by increasing ACh concentrations. Moreover, specific binding of [ 125 I] α-bungarotoxin was not altered by thujone. Further experiments in SH-EP1 cells expressing human α 7 nACh receptor indicated that thujone suppressed choline induced Ca 2+ transients in a concentration-dependent manner. In rat hippocampal CA3-dentate gyrus synapses, nicotine-induced enhancement of long-term potentiation was also inhibited by thujone. Furthermore, the results observed in in-vivo one-trial passive avoidance paradigm show that thujone (1.25mg/kg, i.p.) significantly impaired nicotine-induced enhancement of learning and memory in Wistar rats. Collectively, our results indicate that thujone inhibits the function of the α7-nACh receptor and impairs cellular and behavioral correlates of cholinergic modulation of learning and memory. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Thujone inhibits the function of α7-nicotinic acetylcholine receptors and impairs nicotine-induced memory enhancement in one-trial passive avoidance paradigm

    International Nuclear Information System (INIS)

    Sultan, Ahmed; Yang, Keun-Hang Susan; Isaev, Dmitro; Nebrisi, Eslam El; Syed, Nurulain; Khan, Nadia; Howarth, Christopher F.; Sadek, Bassem; Oz, Murat

    2017-01-01

    Effects of thujone, a major ingredient of absinthe, wormwood oil and some herbal medicines, were tested on the function of α 7 subunit of the human nicotinic acetylcholine (α 7 nACh) receptor expressed in Xenopus oocytes using the two-electrode voltage-clamp technique. Thujone reversibly inhibited ACh (100 μM)-induced currents with an IC 50 value of 24.7 μM. The effect of thujone was not dependent on the membrane potential and did not involve Ca 2+ -dependent Cl − channels expressed endogenously in oocytes. Inhibition by thujone was not reversed by increasing ACh concentrations. Moreover, specific binding of [ 125 I] α-bungarotoxin was not altered by thujone. Further experiments in SH-EP1 cells expressing human α 7 nACh receptor indicated that thujone suppressed choline induced Ca 2+ transients in a concentration-dependent manner. In rat hippocampal CA3-dentate gyrus synapses, nicotine-induced enhancement of long-term potentiation was also inhibited by thujone. Furthermore, the results observed in in-vivo one-trial passive avoidance paradigm show that thujone (1.25 mg/kg, i.p.) significantly impaired nicotine-induced enhancement of learning and memory in Wistar rats. Collectively, our results indicate that thujone inhibits the function of the α7-nACh receptor and impairs cellular and behavioral correlates of cholinergic modulation of learning and memory.

  9. Fisetin inhibits UVB-induced cutaneous inflammation and activation of PI3K/AKT/NFκB signaling pathways in SKH-1 hairless mice†

    Science.gov (United States)

    Pal, Harish Chandra; Athar, Mohammad; Elmets, Craig A.; Afaq, Farrukh

    2014-01-01

    Solar ultraviolet B (UVB) radiation has been shown to induce inflammation, DNA damage, p53 mutations, and alterations in signaling pathways eventually leading to skin cancer. In the present study, we investigated whether fisetin reduces inflammatory responses and modulates PI3K/AKT/NFκB cell survival signaling pathways in UVB exposed SKH-1 hairless mouse skin. Mice were exposed to 180 mJ/cm2 of UVB radiation on alternate days for a total of seven exposures, and fisetin (250 and 500 nmol) was applied topically after 15 min of each UVB exposure. Fisetin treatment to UVB exposed mice resulted in decreased hyperplasia and reduced infiltration of inflammatory cells. Fisetin treatment also reduced inflammatory mediators such as COX-2, PGE2 as well as its receptors (EP1- EP4), and MPO activity. Furthermore, fisetin reduced the level of inflammatory cytokines TNFα, IL-1β and IL-6 in UVB exposed skin. Fisetin treatment also reduced cell proliferation markers as well as DNA damage as evidenced by increased expression of p53 and p21 proteins. Further studies revealed that fisetin inhibited UVB-induced expression of PI3K, phosphorylation of AKT, and activation of the NFκB signaling pathway in mouse skin. Overall, these data suggest that fisetin may be useful against UVB-induced cutaneous inflammation and DNA damage. PMID:25169110

  10. Fisetin inhibits UVB-induced cutaneous inflammation and activation of PI3K/AKT/NFκB signaling pathways in SKH-1 hairless mice.

    Science.gov (United States)

    Pal, Harish Chandra; Athar, Mohammad; Elmets, Craig A; Afaq, Farrukh

    2015-01-01

    Solar ultraviolet B (UVB) radiation has been shown to induce inflammation, DNA damage, p53 mutations and alterations in signaling pathways eventually leading to skin cancer. In this study, we investigated whether fisetin reduces inflammatory responses and modulates PI3K/AKT/NFκB cell survival signaling pathways in UVB-exposed SKH-1 hairless mouse skin. Mice were exposed to 180 mJ cm(-2) of UVB radiation on alternate days for a total of seven exposures, and fisetin (250 and 500 nmol) was applied topically after 15 min of each UVB exposure. Fisetin treatment to UVB-exposed mice resulted in decreased hyperplasia and reduced infiltration of inflammatory cells. Fisetin treatment also reduced inflammatory mediators such as COX-2, PGE2 as well as its receptors (EP1-EP4) and MPO activity. Furthermore, fisetin reduced the level of inflammatory cytokines TNFα, IL-1β and IL-6 in UVB-exposed skin. Fisetin treatment also reduced cell proliferation markers as well as DNA damage as evidenced by increased expression of p53 and p21 proteins. Further studies revealed that fisetin inhibited UVB-induced expression of PI3K, phosphorylation of AKT and activation of the NFκB signaling pathway in mouse skin. Overall, these data suggest that fisetin may be useful against UVB-induced cutaneous inflammation and DNA damage. © 2014 The American Society of Photobiology.

  11. Autonomous miniaturised device with USB interface for pulse height analysis and multi-channel scaling (TUKAN-8K-USB)

    International Nuclear Information System (INIS)

    Guzik, Z.; Borsuk, S.; Plominski, M.; Traczyk, K.

    2005-01-01

    We present autonomous a 8K-channel miniature device designed for spectroscopy or intensity vs. time measurements. The device (TUKAN-8K-USB) is based on the USB interface, and is contained in a screened separate box - it can be proved either directly from the USB port or from an external DC source (wall adapter of battery). The device may work in two independent operational modes: Multi-Channel Analysis (MCA) and Multi-Channel Scaling (MCS). The crucial MCA component - Peak detect and Hold circuitry - is featuring a novel architecture based on a diamond transistor. Its analog stage can accept analog pulses with front edges down to 100 ns and has a differential linearity below 0.5% (full scale sliding scale averaging). Automatic stops on count in Region-Of-Interest (ROI) and on preset live or real time are implemented. The MCS works at medium speed counting rates (up to 8 MHz), with preset dwell time, number of channels and multi-sweep mode. Each these parameters can also be controlled externally. Digital interfacing is based on four used configurable logical I/O lines. A single CYCLONE EP1C3 Altera FPGA provides all control functions. The USB communication is based on FYDI FIFO controller. The analyzer is equipped with advanced, user-friendly software, which is subjected of another publication. )author)

  12. Correlational study between sorption and goo apparent organoclays; Estudo correlacional entre sorcao e viscosidade aparente em argilas organofilicas

    Energy Technology Data Exchange (ETDEWEB)

    Silva, D.L.; Silva, M.R.O.; Ferreira, H.S.; Brasileiro, C.T., E-mail: darciely_lin@hotmail.com, E-mail: marcusraffael@outlook.com, E-mail: hebersivini@gmail.com, E-mail: camilabrasileiro@globo.com [Universidade Federal da Paraiba (UFPB), PB (Brazil)

    2016-07-01

    The sorption of surfactants in bentonite clay can occur through the mechanism of adsorption and absorption, this being a very supple phenomenon according clay and surfactant utilized. Thus the more surfactant sorbed at the organoclay it becomes, and can be used in various applications, including in oil drilling fluid. This study aimed to correlate the sorption of surfactants with the rheological properties of non-aqueous fluids (oil base). In organophilization process was used Bentongel clay which had its concentration varied from 3.16 to 7.16% by weight of clay. It was used to organophilization an ionic surfactant Praepagem WB with 75% of active matter, where its concentration ranged from 127-181 mEq. After organophilizated the clays were filtered, dried in an oven for 48 hours and passed in ABNT sieve No. 200, to be so characterized. Sorption was calculated from mathematical equations. Non-aqueous fluids were prepared according to standard Petrobras (EP-1EP-00023A) for rheological testing. Correlating the sorption of surfactant, and the rheological properties of non-aqueous fluid, obtained satisfactory results where observed through the scatter plots there is a strong correlation between the variables sorption and apparent viscosity, it should also be noted that the viscosity is a variable which increases with an increase in sorption, confirming that the surfactant concentration influences the viscosity. (author)

  13. Cost-Effective Video Filtering Solution for Real-Time Vision Systems

    Directory of Open Access Journals (Sweden)

    Karl Martin

    2005-08-01

    Full Text Available This paper presents an efficient video filtering scheme and its implementation in a field-programmable logic device (FPLD. Since the proposed nonlinear, spatiotemporal filtering scheme is based on order statistics, its efficient implementation benefits from a bit-serial realization. The utilization of both the spatial and temporal correlation characteristics of the processed video significantly increases the computational demands on this solution, and thus, implementation becomes a significant challenge. Simulation studies reported in this paper indicate that the proposed pipelined bit-serial FPLD filtering solution can achieve speeds of up to 97.6 Mpixels/s and consumes 1700 to 2700 logic cells for the speed-optimized and area-optimized versions, respectively. Thus, the filter area represents only 6.6 to 10.5% of the Altera STRATIX EP1S25 device available on the Altera Stratix DSP evaluation board, which has been used to implement a prototype of the entire real-time vision system. As such, the proposed adaptive video filtering scheme is both practical and attractive for real-time machine vision and surveillance systems as well as conventional video and multimedia applications.

  14. Shall we trust WDDL?

    Science.gov (United States)

    Guilley, Sylvain; Chaudhuri, Sumanta; Sauvage, Laurent; Graba, Tarik; Danger, Jean-Luc; Hoogvorst, Philippe; Vong, Vinh-Nga; Nassar, Maxime; Flament, Florent

    Security is not only a matter of cryptographic algorithms robustness but becomes also a question of securing their implementation. P. Kocher’s differential power analysis (DPA) is one of the many side-channel attacks that are more and more studied by the security community. Indeed, side-channel attacks (SCA) have proved to be very powerful on cryptographic algorithms such as DES and AES, customarily implemented in a wide variety of devices, ranging from smart-cards or ASICs to FPGAs. Among the proposed countermeasures, the “dual-rail with precharge logic” (DPL) aims at hiding information leaked by the circuit by making the power consumption independent of the calculation. However DPL logic could be subject to second order attacks exploiting timing difference between dual nets. In this article, we characterize by simulation, the vulnerability due to timing unbalance in the eight DES substitution boxes implemented in DPL WDDL style. The characterization results in a classification of the nodes according to their timing unbalance. Our results show that the timing unbalance is a major weakness of the WDDL logic, and that it could be used to retrieve the key using a DPA attack. This vulnerability has been experimentally observed on a full DES implementation using WDDL style for Altera Stratix EP1S25 FPGA.

  15. Animal model of acid-reflux esophagitis: pathogenic roles of acid/pepsin, prostaglandins, and amino acids.

    Science.gov (United States)

    Takeuchi, Koji; Nagahama, Kenji

    2014-01-01

    Esophagitis was induced in rats within 3 h by ligating both the pylorus and transitional region between the forestomach and glandular portion under ether anesthesia. This esophageal injury was prevented by the administration of acid suppressants and antipepsin drug and aggravated by exogenous pepsin. Damage was also aggravated by pretreatment with indomethacin and the selective COX-1 but not COX-2 inhibitor, whereas PGE2 showed a biphasic effect depending on the dose; a protection at low doses, and an aggravation at high doses, with both being mediated by EP1 receptors. Various amino acids also affected this esophagitis in different ways; L-alanine and L-glutamine had a deleterious effect, while L-arginine and glycine were highly protective, both due to yet unidentified mechanisms. It is assumed that acid/pepsin plays a major pathogenic role in this model of esophagitis; PGs derived from COX-1 are involved in mucosal defense of the esophagus; and some amino acids are protective against esophagitis. These findings also suggest a novel therapeutic approach in the treatment of esophagitis, in addition to acid suppressant therapy. The model introduced may be useful to test the protective effects of drugs on esophagitis and investigate the mucosal defense mechanism in the esophagus.

  16. Correlational study between sorption and goo apparent organoclays

    International Nuclear Information System (INIS)

    Silva, D.L.; Silva, M.R.O.; Ferreira, H.S.; Brasileiro, C.T.

    2016-01-01

    The sorption of surfactants in bentonite clay can occur through the mechanism of adsorption and absorption, this being a very supple phenomenon according clay and surfactant utilized. Thus the more surfactant sorbed at the organoclay it becomes, and can be used in various applications, including in oil drilling fluid. This study aimed to correlate the sorption of surfactants with the rheological properties of non-aqueous fluids (oil base). In organophilization process was used Bentongel clay which had its concentration varied from 3.16 to 7.16% by weight of clay. It was used to organophilization an ionic surfactant Praepagem WB with 75% of active matter, where its concentration ranged from 127-181 mEq. After organophilizated the clays were filtered, dried in an oven for 48 hours and passed in ABNT sieve No. 200, to be so characterized. Sorption was calculated from mathematical equations. Non-aqueous fluids were prepared according to standard Petrobras (EP-1EP-00023A) for rheological testing. Correlating the sorption of surfactant, and the rheological properties of non-aqueous fluid, obtained satisfactory results where observed through the scatter plots there is a strong correlation between the variables sorption and apparent viscosity, it should also be noted that the viscosity is a variable which increases with an increase in sorption, confirming that the surfactant concentration influences the viscosity. (author)

  17. A Polysaccharide Isolated from Mycelia of the Lion's Mane Medicinal Mushroom Hericium erinaceus (Agaricomycetes) Induced Apoptosis in Precancerous Human Gastric Cells.

    Science.gov (United States)

    Wang, Mingxing; Zhang, Yanqiu; Xiao, Xulang; Xu, Duoduo; Gao, Yang; Gao, Qipin

    2017-01-01

    Hericium erinaceus is typically used in traditional Chinese medicine for mucosal protection, healing of gastric ulcers, and treatment of gastritis. We purified from the cultured mycelia of H. erinaceus a polysaccharide with anti-gastric ulcer and antigastritis activity, but its effects on gastric malignancy have not been elucidated. We examined the differential effects of this purified polysaccharide, named EP-1, on the human gastric (GES-1) cell line and a precancerous cell line (MC) that was transformed from GES-1 using N-methyl-N'-nitro-N-nitrosoguanidine. We observed that the polysaccharide potently induced cell apoptosis and cell cycle arrest at the G0/G1 phase in the MC cell line but did not have any effect on the GES-1 cell line at the same doses. Further mechanistic studies revealed that the polysaccharide exerted its activity through an apoptosis-associated pathway by modulating the expression of Bax, Bcl-2, and caspase-3. Differential effects of the polysaccharide on the GES-1 and MC cell lines indicate that the polysaccharide was effective in preventing gastric cancer progression.

  18. cAMP/PKA-CREB-BDNF signaling pathway in hippocampus mediates cyclooxygenase 2-induced learning/memory deficits of rats subjected to chronic unpredictable mild stress.

    Science.gov (United States)

    Luo, Ying; Kuang, Shengnan; Li, Huan; Ran, Dongzhi; Yang, Junqing

    2017-05-30

    To investigate the mechanism of cyclooxygenase 2 (COX2) in learning and memory impairments in rats subjected to chronic unpredictable mild stress (CUMS), meloxicam was used intragastrically to inhibit the activity of cyclooxygenase 2. Moreover, cyclooxygenase 2 over-expressing or RNA interfere lentivirus was injected intraventricularly to increase or decrease the enzyme's expression, respectively. The body weights and sucrose consumption were used to analyze depressive behaviors, while the Morris water maze and step-down-type passive avoidance tests were carried out to evaluate the learning-memory functions. The levels of inflammatory cytokines were measured to estimate inflammation and the contents of cyclic adenosine monophosphate (cAMP) were used to measure the levels of the second messenger. Changes in cyclooxygenase 2 mRNA levels were analyzed using reverse transcription polymerase chain reaction. Moreover, the expression of cyclooxygenase 2, brain-derived neurotrophic factor (BDNF), prostaglandins receptor 3 (EP3), protein kinase A (PKA), cAMP response element binding protein (CREB), and phosphorylated CREB were estimated using immunohistochemical staining or western blotting. The results showed that CUMS led to significant depressive-like behaviors and learning and memory dysfunctions. Also, the cAMP levels decreased significantly, while levels of inflammatory cytokines and prostaglandins E2 increased significantly. The expressions of PKA, BDNF, phosphorylated CREB/CREB declined and cyclooxygenase 2 was increased. Meloxicam and cyclooxygenase 2 RNA interfere lentivirus reversed the changes caused by CUMS while cyclooxygenase 2-overexpressing lentivirus worsened these abnormalities. The findings also showed that CUMS increased cyclooxygenase 2 expression, which can cause learning and memory impairments, mainly through activating the hippocampal neuronal cAMP/PKA-CREB-BDNF signaling pathways.

  19. Transport of Escherichia coli phage through saturated porous media considering managed aquifer recharge.

    Science.gov (United States)

    Zhang, Wenjing; Li, Shuo; Wang, Shuang; Lei, Liancheng; Yu, Xipeng; Ma, Tianyi

    2018-03-01

    Virus is one of the most potentially harmful microorganisms in groundwater. In this paper, the effects of hydrodynamic and hydrogeochemical conditions on the transportation of the colloidal virus considering managed aquifer recharge were systematically investigated. Escherichia coli phage, vB_EcoM-ep3, has a broad host range and was able to lyse pathogenic Escherichia coli. Bacteriophage with low risk to infect human has been found extensively in the groundwater environment, so it is considered as a representative model of groundwater viruses. Laboratory studies were carried out to analyze the transport of the Escherichia coli phage under varying conditions of pH, ionic strength, cation valence, flow rate, porous media, and phosphate buffer concentration. The results indicated that decreasing the pH will increase the adsorption of Escherichia coli phage. Increasing the ionic strength, either Na + or Ca 2+ , will form negative condition for the migration of Escherichia coli phage. A comparison of different cation valence tests indicated that changes in transport and deposition were more pronounced with divalent Ca 2+ than monovalent Na + . As the flow rate increases, the release of Escherichia coli phage increases and the retention of Escherichia coli phage in the aquifer medium reduces. Changes in porous media had a significant effect on Escherichia coli phage migration. With increase of phosphate buffer concentration, the suspension stability and migration ability of Escherichia coli phage are both increased. Based on laboratory-scale column experiments, a one-dimensional transport model was established to quantitatively describe the virus transport in saturated porous medium.

  20. Pro-inflammatory cytokines upregulate sympathoexcitatory mechanisms in the subfornical organ of the rat

    Science.gov (United States)

    Wei, Shun-Guang; Yu, Yang; Zhang, Zhi-Hua; Felder, Robert B.

    2015-01-01

    Our previous work indicated that the subfornical organ (SFO) is an important brain sensor of blood-borne pro-inflammatory cytokines, mediating their central effects on autonomic and cardiovascular function. However, the mechanisms by which SFO mediates the central effects of circulating pro-inflammatory cytokines remain unclear. We hypothesized that pro-inflammatory cytokines act within the SFO to upregulate the expression of excitatory and inflammatory mediators that drive sympathetic nerve activity. In urethane-anesthetized Sprague-Dawley rats, direct microinjection of TNF-α (25 ng) or IL-1β (25 ng) into SFO increased mean blood pressure, heart rate and renal sympathetic nerve activity within 15–20 minutes, mimicking the response to systemically administered pro-inflammatory cytokines. Pretreatment of SFO with microinjections of the angiotensin II type 1 receptor (AT1R) blocker losartan (1 µg), angiotensin-converting enzyme (ACE) inhibitor captopril (1 µg) or cyclooxygenase (COX)-2 inhibitor NS-398 (2 µg) attenuated those responses. Four hours after the SFO microinjection of TNF-α (25 ng) or IL-1β (25 ng), mRNA for ACE, AT1R, TNF-α and the p55 TNF-α receptor TNFR1, IL-1β and the IL-1R receptor, and COX-2 had increased in SFO, and mRNA for ACE, AT1R and COX-2 had increased downstream in the hypothalamic paraventricular nucleus. Confocal immunofluorescent images revealed that immunoreactivity for TNFR1 and the IL-1 receptor accessory protein, a subunit of the IL-1 receptor, co-localized with ACE, AT1R-like, COX-2 and prostaglandin E2 EP3 receptor immunoreactivity in SFO neurons. These data suggest that pro-inflammatory cytokines act within the SFO to upregulate the expression of inflammatory and excitatory mediators that drive sympathetic excitation. PMID:25776070

  1. KOMUNITAS ARTHROPODA TANAH DI KAWASAN SUMUR MINYAK BUMI DI DESA MANGUNJAYA, KECAMATAN BABAT TOMAN, KABUPATEN MUSI BANYUASIN, PROVINSI SUMATERA SELATAN

    Directory of Open Access Journals (Sweden)

    Risda Muli

    2016-03-01

    levels were measured and analyzed to determine its effect on the diversity index, dominance, and evenness of arthropods. The research has been done in the petroleum wells in Mangunjaya village of Babat Toman Toman districts on February 19 to 24, 2015. Arthropods samples were taken using pit fall traps and funnel barlese-tullgren, total sampling points are 96 points. Identification of the arthropod family has been done in Entomology Laboratory of the Agriculture Plant Disease Faculty Sriwijaya University. Analysis of soil TPH levels are using Gravimetry methods carried out in the Chemistry Laboratory of Science Faculty, Sriwijaya University. The results showed an average TPH and pH of soil in petroleum exploration conducted by Pertamina EP 1 Field Asset Ramba lower than in locations that made exploration by the public. Moisture and soil temperature at the location of the exploration by Pertamina EP 1 Field Asset Ramba are higher than in public exploration location. TPH levels, pH, moisture, and soil temperature do not affect the diversity, dominance, and evenness arhtropod index. However, the average index of arthropod diversity is low with an index value of less than 1.

  2. Prostaglandin E2 produced by Entamoeba histolytica binds to EP4 receptors and stimulates interleukin-8 production in human colonic cells.

    Science.gov (United States)

    Dey, Indranil; Chadee, Kris

    2008-11-01

    Entamoeba histolytica pathogenesis in the colon occurs in a stepwise fashion. It begins with colonization of the mucin layer, which is followed by stimulation of a proinflammatory response that causes nonspecific tissue damage that may facilitate parasite invasion of the underlying colonic mucosa. Unfortunately, the parasite and/or host factors that stimulate a proinflammatory response in the gut are poorly understood. In this study, we found that live E. histolytica or secretory or proteins (SP) and soluble ameba components (SAP) can markedly increase interleukin-8 (IL-8) mRNA expression and protein production in colonic epithelial cells. The IL-8-stimulating molecule produced by live amebae was identified as prostaglandin E(2) (PGE(2)) as trophozoites treated with cyclooxygenase inhibitors inhibited the biosynthesis of PGE(2) and eliminated IL-8 production induced by live parasites or ameba components. Moreover, using specific prostaglandin EP2 and EP4 receptor agonists and antagonists, we found that PGE(2) binds exclusively through EP4 receptors in colonic epithelial cells to stimulate IL-8 production. Silencing of EP4 receptors with EP4 small interfering RNA completely eliminated SP- and SAP-induced IL-8 production. These studies identified bioactive PGE(2) as a one of the major virulence factors produced by E. histolytica that can stimulate the potent neutrophil chemokine and activator IL-8, which can trigger an acute host inflammatory response. Thus, the induction of IL-8 production in response to E. histolytica-derived PGE(2) may be a mechanism that explains the initiation and amplification of acute inflammation associated with intestinal amebiasis.

  3. A Comparison Study of Communication Skills between General Surgery and General Practice Residents on First-time Patient Visits

    Directory of Open Access Journals (Sweden)

    Ahmed Al Ansari

    2012-04-01

    Full Text Available Background: There is little published research about differences in doctor-patient communication of different specialties. Accordingly, we compared doctor-patient communication skills in two different specialties, general surgery (GS and general practice (GP. Methods: Twenty residents training at the Bahrain Defence Force Hospital (10 men and 10 women; mean age 28 years; 10 GS and 10 GP participated in 200 patient first visit consultations. The consultations were video-recorded and analysed by four trained observers using the MAAS Global scale. Results: 1 Internal consistency reliability of the MAAS Global (> 0.91 and Ep2 = 0.84 for raters was high, 2 GP residents spent more time (12 minutes than GS residents (7 minutes, in the visits, 3 There were several differences on the MAAS Global items between GP and GS residents (GS > GP, p GS, p < 0.05 on information giving, and 4 The present participants performed well compared to normative samples as well as to criterion-referenced cut-off scores. The general level of communication skills in both specialties, however, was ‘unsatisfactory’ and ‘doubtful’, as it is for normative samples. Conclusion: Excellent doctor-patient communication is essential but does not appear to receive the amount of attention that it deserves in practice settings. There are some differences between specialties as well as unsatisfactory communication skills for both specialties, since residents from both programs spent less time than recommended on each consultation. Our findings emphasize the need to improve the communication skills of physicians in general and for surgeons in particular.

  4. Induction of porcine host defense peptide gene expression by short-chain fatty acids and their analogs.

    Directory of Open Access Journals (Sweden)

    Xiangfang Zeng

    Full Text Available Dietary modulation of the synthesis of endogenous host defense peptides (HDPs represents a novel antimicrobial approach for disease control and prevention, particularly against antibiotic-resistant infections. However, HDP regulation by dietary compounds such as butyrate is species-dependent. To examine whether butyrate could induce HDP expression in pigs, we evaluated the expressions of a panel of porcine HDPs in IPEC-J2 intestinal epithelial cells, 3D4/31 macrophages, and primary monocytes in response to sodium butyrate treatment by real-time PCR. We revealed that butyrate is a potent inducer of multiple, but not all, HDP genes. Porcine β-defensin 2 (pBD2, pBD3, epididymis protein 2 splicing variant C (pEP2C, and protegrins were induced markedly in response to butyrate, whereas pBD1 expression remained largely unaltered in any cell type. Additionally, a comparison of the HDP-inducing efficacy among saturated free fatty acids of different aliphatic chain lengths revealed that fatty acids containing 3-8 carbons showed an obvious induction of HDP expression in IPEC-J2 cells, with butyrate being the most potent and long-chain fatty acids having only a marginal effect. We further investigated a panel of butyrate analogs for their efficacy in HDP induction, and found glyceryl tributyrate, benzyl butyrate, and 4-phenylbutyrate to be comparable with butyrate. Identification of butyrate and several analogs with a strong capacity to induce HDP gene expression in pigs provides attractive candidates for further evaluation of their potential as novel alternatives to antibiotics in augmenting innate immunity and disease resistance of pigs.

  5. Compensatory Cellular Reactions to Nonsteroidal Anti-Inflammatory Drugs on Osteogenic Differentiation in Canine Bone Marrow-Derived Mesenchymal Stem Cells

    Science.gov (United States)

    OH, Namgil; KIM, Sangho; HOSOYA, Kenji; OKUMURA, Masahiro

    2014-01-01

    ABSTRACT The suppressive effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on the bone healing process have remained controversial, since no clinical data have clearly shown the relationship between NSAIDs and bone healing. The aim of this study was to assess the compensatory response of canine bone marrow-derived mesenchymal stem cells (BMSCs) to several classes of NSAIDs, including carprofen, meloxicam, indomethacin and robenacoxib, on osteogenic differentiation. Each of the NSAIDs (10 µM) was administered during 20 days of the osteogenic process with human recombinant IL-1β (1 ng/ml) as an inflammatory stimulator. Gene expression of osteoblast differentiation markers (alkaline phosphatase and osteocalcin), receptors of PGE2 (EP2 and EP4) and enzymes for prostaglandin (PG) E2 synthesis (COX-1, COX-2, cPGES and mPGES-1) was measured by using quantitative reverse transcription-polymerase chain reaction. Protein production levels of alkaline phosphatase, osteocalcin and PGE2 were quantified using an alkaline phosphatase activity assay, osteocalcin immunoassay and PGE2 immunoassay, respectively. Histologic analysis was performed using alkaline phosphatase staining, von Kossa staining and alizarin red staining. Alkaline phosphatase and calcium deposition were suppressed by all NSAIDs. However, osteocalcin production showed no significant suppression by NSAIDs. Gene expression levels of PGE2-related receptors and enzymes were upregulated during continuous treatment with NSAIDs, while certain channels for PGE2 synthesis were utilized differently depending on the kind of NSAIDs. These data suggest that canine BMSCs have a compensatory mechanism to restore PGE2 synthesis, which would be an intrinsic regulator to maintain differentiation of osteoblasts under NSAID treatment. PMID:24419976

  6. Particle size of radioactive aerosols generated during machine operation in high-energy proton accelerators

    International Nuclear Information System (INIS)

    Oki, Yuichi; Kanda, Yukio; Kondo, Kenjiro; Endo, Akira

    2000-01-01

    In high-energy accelerators, non-radioactive aerosols are abundantly generated due to high radiation doses during machine operation. Under such a condition, radioactive atoms, which are produced through various nuclear reactions in the air of accelerator tunnels, form radioactive aerosols. These aerosols might be inhaled by workers who enter the tunnel just after the beam stop. Their particle size is very important information for estimation of internal exposure doses. In this work, focusing on typical radionuclides such as 7 Be and 24 Na, their particle size distributions are studied. An aluminum chamber was placed in the EP2 beam line of the 12-GeV proton synchrotron at High Energy Accelerator Research Organization (KEK). Aerosol-free air was introduced to the chamber, and aerosols formed in the chamber were sampled during machine operation. A screen-type diffusion battery was employed in the aerosol-size analysis. Assuming that the aerosols have log-normal size distributions, their size distributions were obtained from the radioactivity concentrations at the entrance and exit of the diffusion battery. Radioactivity of the aerosols was measured with Ge detector system, and concentrations of non-radioactive aerosols were obtained using condensation particle counter (CPC). The aerosol size (radius) for 7 Be and 24 Na was found to be 0.01-0.04 μm, and was always larger than that for non-radioactive aerosols. The concentration of non-radioactive aerosols was found to be 10 6 - 10 7 particles/cm 3 . The size for radioactive aerosols was much smaller than ordinary atmospheric aerosols. Internal doses due to inhalation of the radioactive aerosols were estimated, based on the respiratory tract model of ICRP Pub. 66. (author)

  7. Factors affecting remote handling productivity during installation of the ITER-like wall at JET

    International Nuclear Information System (INIS)

    Collins, S.; Matthews, G.; Thomas, J.; Hermon, G.

    2013-01-01

    Highlights: ► The paper describes the challenges to achieve the installation of the ILW beryllium sliced wall. ► Examines the factual difference between estimated remote handling in-vessel durations and those achieved, with a view to quantifying the typical disparity between the two. ► The paper will elaborate and highlight the contributing factors. This offers an opportunity to provide provenance for availability estimates of devices such as ITER and DEMO. ► The paper will identify and describe the factors influencing the ratio between estimated versus the actual durations for remote handling operations. -- Abstract: Remote handling operations at JET have encountered many challenges to achieve the installation of the ILW beryllium sliced wall during the Enhanced Performance stage 2 (EP2) shutdown of JET. This was a demanding and challenging activity which was based on the experience gained from a period of over 15 years (20,000 h operations) of JET In-Vessel remote handling operations. This paper describes the difference between estimated remote handling in-vessel durations and those actually achieved with a view to quantifying the typical disparity between them. There are many factors that affect productivity of the remote handling operations and it is important to accommodate these either in the design of the component or within the production of the operational procedures with a view to minimise all impact on the final task duration. Some factors that affect the efficiency are outside the control of the design and operational procedures. These are unforeseen anomalies that were encountered during the removal, naked wall survey and installation of the components. Recoveries from these anomalies are extremely challenging and need to be addressed efficiently in order to minimise the impact on the shutdown duration and prevent optimised panned activities from becoming inefficient by fragmentation

  8. Changes in basal cell mitosis and transepidermal water loss in skin cultures treated with vitamins C and E.

    Science.gov (United States)

    Parish, W E; Read, J; Paterson, S E

    2005-09-01

    Three variants of the living skin equivalent cultures were compared in order to determine the most suitable to grow human differentiated epidermis to test beneficial properties of nutrients. Criteria of culture quality were mitotic index and transepidermal water loss (TEWL) assayed by means of a ServoMed Evaporimeter EP-2TM (ServoMed, Kinna, Sweden). Standards were donor skin mean mitotic index 11.1% and TEWL of living subjects mean 6.4 g/m(2)/h. Cultures (i) in 5% serum, 10 ng/ml of epidermal growth factor (EGF) at 37 degrees C and 95% relative humidity (RH); mitotic index on day 14, 19.2%, but on day 21, 1.8% and TEWL 9.5 g/m(2)/h on day 18. (ii) In 1% serum, no EGF, 33 degrees C and 95% RH, mitotic index on day 21, 9.1% and TEWL, 9.5% on day 18. (iii) Culture in same medium, 33 degrees C and 60% RH, mitotic index on day 28, 9.5% and TEWL 6.1 g/m(2)/h on day 18 as in vivo. Incubation in 60% RH was achieved using a novel chamber and dishes exposing only the corneum, sealing the medium. Vitamins C and E were used as model test nutrients. Culture conditions were 1% serum, no EGF at 33 degrees C and 95% RH. Vitamin C at 142 and 284 microM increased the mitotic index after 10- and 15-day treatment, but at 586 microM it was weakly toxic. Vitamin E at 20 and 40 microM did not. Both vitamins reduced TEWL providing functional data in support of previous reports on barrier properties. These are functional biomarkers of skin benefit relevant to skin in vivo.

  9. Compilation and evaluation of a Paso del Norte emission inventory

    Energy Technology Data Exchange (ETDEWEB)

    Funk, T.H.; Chinkin, L.R.; Roberts, P.T. [Sonoma Technology, Inc., 1360 Redwood Way, Suite C, 94954-1169 Petaluma, CA (United States); Saeger, M.; Mulligan, S. [Pacific Environmental Services, 5001 S. Miami Blvd., Suite 300, 27709 Research Triangle Park, NC (United States); Paramo Figueroa, V.H. [Instituto Nacional de Ecologia, Avenue Revolucion 1425, Nivel 10, Col. Tlacopac San Angel, Delegacion Alvaro Obregon, C.P., 01040, D.F. Mexico (Mexico); Yarbrough, J. [US Environmental Protection Agency - Region 6, 1445 Ross Avenue, Suite 1200, 75202-2733 Dallas, TX (United States)

    2001-08-10

    Emission inventories of ozone precursors are routinely used as input to comprehensive photochemical air quality models. Photochemical model performance and the development of effective control strategies rely on the accuracy and representativeness of an underlying emission inventory. This paper describes the tasks undertaken to compile and evaluate an ozone precursor emission inventory for the El Paso/Ciudad Juarez/Southern Dona Ana region. Point, area and mobile source emission data were obtained from local government agencies and were spatially and temporally allocated to a gridded domain using region-specific demographic and land-cover information. The inventory was then processed using the US Environmental Protection Agency (EPA) recommended Emissions Preprocessor System 2.0 (UAM-EPS 2.0) which generates emissions files compatible with the Urban Airshed Model (UAM). A top-down evaluation of the emission inventory was performed to examine how well the inventory represented ambient pollutant compositions. The top-down evaluation methodology employed in this study compares emission inventory ratios of non-methane hydrocarbon (NMHC)/nitrogen oxide (NO{sub x}) and carbon monoxide (CO)/NO{sub x} ratios to corresponding ambient ratios. Detailed NMHC species comparisons were made in order to investigate the relative composition of individual hydrocarbon species in the emission inventory and in the ambient data. The emission inventory compiled during this effort has since been used to model ozone in the Paso del Norte airshed (Emery et al., CAMx modeling of ozone and carbon monoxide in the Paso del Norte airshed. In: Proc of Ninety-Third Annual Meeting of Air and Waste Management Association, 18-22 June 2000, Air and Waste Management Association, Pittsburgh, PA, 2000)

  10. Canolol inhibits gastric tumors initiation and progression through COX-2/PGE2 pathway in K19-C2mE transgenic mice.

    Directory of Open Access Journals (Sweden)

    Donghui Cao

    Full Text Available 4-Vinyl-2, 6-dimethoxyphenol (canolol is an antioxidant phenolic compound extracted from crude canola oil. In current research, K19-C2mE transgenic mice, developing hyperplastic tumors spontaneously in the glandular stomach, were used to study the mechanisms involved in the anti-inflammation and anti-tumor effects of canolol. Tg mice receiving canolol diet had a reduced tumor incidence, to 41.2%, compared with Non-treatment Tg mice, 77.8% of which had gastric tumor (P=0.002. Besides that, the mean tumor diameter was decreased from 6.5 mm to 4.5 mm (P<0.001 after canolol administration. COX-2/PGE2 pathway is known to play pivotal role in inflammation-induced gastric tumorigenesis. The neutrophils and lymphocytes infiltration was suppressed significantly, and the mRNA levels of the proinflammatory cytokines COX-2, IL-1β and IL-12b were also downregulated in gastric mucosa. Additionally, immunohistochemical analysis showed that COX-2, EP2, Gαs and β-catenin, key factors involving in PGE2 signal transduction, were positive staining with higher H scores in Non-treatment Tg mice, while the expressions were suppressed significantly by 0.1% canolol (P<0.001. In addition, tumor-suppressor miR-7 was reactivated after canolol administration, and COX-2 was showed to be a functional target of miR-7 to suppress the tumor progression. In conclusion, canolol could inhibit the gastritis-related tumor initiation and progression, and the suppression effect was correlated with the blocking up of canonical COX-2/PGE2 signaling pathway and might be regulated by miR-7.

  11. Increased risk for invasive breast cancer associated with hormonal therapy: a nation-wide random sample of 65,723 women followed from 1997 to 2008.

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    Jung-Nien Lai

    Full Text Available BACKGROUND: Hormonal therapy (HT either estrogen alone (E-alone or estrogen plus progesterone (E+P appears to increase the risk for breast cancer in Western countries. However, limited information is available on the association between HT and breast cancer in Asian women characterized mainly by dietary phytoestrogens intake and low prevalence of contraceptive pills prescription. METHODOLOGY: A total of 65,723 women (20-79 years of age without cancer or the use of Chinese herbal products were recruited from a nation-wide one-million representative sample of the National Health Insurance of Taiwan and followed from 1997 to 2008. Seven hundred and eighty incidents of invasive breast cancer were diagnosed. Using a reference group that comprised 40,052 women who had never received a hormone prescription, Cox proportional hazard models were constructed to determine the hazard ratios for receiving different types of HT and the occurrence of breast cancer. CONCLUSIONS: 5,156 (20% women ever used E+P, 2,798 (10.8% ever used E-alone, and 17,717 (69% ever used other preparation types. The Cox model revealed adjusted hazard ratios (HRs of 2.05 (95% CI 1.37-3.07 for current users of E-alone and 8.65 (95% CI 5.45-13.70 for current users of E+P. Using women who had ceased to take hormonal medication for 6 years or more as the reference group, the adjusted HRs were significantly elevated and greater than current users and women who had discontinued hormonal medication for less than 6 years. Current users of either E-alone or E+P have an increased risk for invasive breast cancer in Taiwan, and precautions should be taken when such agents are prescribed.

  12. Enterococci Isolated from Japanese Quails Exposed to Microgravity Conditions and Stability of their Properties

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    Andrea Lauková

    2009-01-01

    Full Text Available Enterococci isolated from the crop and caecum of Japanese quails exposed to 7 day conditions of microgravity were re-vitalized after their dry-freezing long storage. Originally, the strains were isolated from Japanese quails after their landing from flight onboard the orbital station Mir during the experiment in August 1990. Because taxonomy as well as the studies concerning the bacteriocins, especially those produced by enterococci, have been continually developed for years, the aim of this study was to confirm species identification, stability of the properties of enterococci as well as to test new properties after their long storage. Genotyping allotted the strains to the species E. faecium. Lactic acid production was detected in similar amounts in the strains before and after their long-storage in dry-frozen form. The strains were vancomycinsensitive and kanamycin-resistant before as well as after their long-time storage. Variability in sensitivity to different antibiotics was found among the strains tested even before and after longtime storage. Each of the strains possessed at least one structural enterocin gene. The structural genes for enterocin A, P, B, L50B were detected in E. faecium EP7. E. faecium EP2, EEP4 have the genes for ent A, B, L50B. The gene for ent P was detected only in the strain EP7. The most often detected was ent A gene followed by ent genes B, L50B. All strains inhibited growth of at least 4 out of 15 indicators. The stability of the enterococcal properties determined before as well as after their dry-freezing was not influenced during their long-term storage; moreover, new properties were determined.

  13. Cyclooxygenase-2 up-regulates CCR7 expression via AKT-mediated phosphorylation and activation of Sp1 in breast cancer cells.

    Science.gov (United States)

    Chuang, Chun-Wei; Pan, Mei-Ren; Hou, Ming-Feng; Hung, Wen-Chun

    2013-02-01

    Up-regulation of cyclooxygenase-2 (COX-2) is frequently found in human cancers and is significantly associated with tumor metastasis. Our previous results demonstrate that COX-2 and its metabolite prostaglandin E2 (PGE2) stimulate the expression of CCR7 chemokine receptor via EP2/EP4 receptors to promote lymphatic invasion in breast cancer cells. In this study, we address the underlying mechanism of COX-2/PGE2-induced CCR7 expression. We find that COX-2/PGE2 increase CCR7 expression via the AKT signaling pathway in breast cancer cells. Promoter deletion and mutation assays identify the Sp1 site located at the -60/-57 region of CCR7 gene promoter is critical for stimulation. Chromatin immunoprecipitation (ChIP) assay confirms that in vivo binding of Sp1 to human CCR7 promoter is increased by COX-2 and PGE2. Knockdown of Sp1 by shRNA reduces the induction of CCR7 by PGE2. We demonstrate for the first time that AKT may directly phosphorylate Sp1 at S42, T679, and S698. Phosphorylation-mimic Sp1 protein harboring S42D, T679D, and S698D mutation strongly activates CCR7 expression. In contrast, change of these three residues to alanine completely blocks the induction of CCR7 by PGE2. Pathological investigation demonstrates that CCR7 expression is strongly associated with phospho-AKT and Sp1 in 120 breast cancer tissues. Collectively, our results demonstrate that COX-2 up-regulates CCR7 expression via AKT-mediated phosphorylation and activation of Sp1 and this pathway is highly activated in metastatic breast cancer. Copyright © 2012 Wiley Periodicals, Inc.

  14. Sistema traductor de la lengua de señas colombiana a texto basado en FPGA

    Directory of Open Access Journals (Sweden)

    Juan David Guerrero-Balaguera

    2015-01-01

    Full Text Available Este trabajo presenta el desarrollo de un sistema diseñado para facilitar la comunicación e interacción de personas con discap acidad auditiva severa con las demás personas. El sistema emplea técni cas de visión artificial para el reconocimiento de las señas es táticas de la Lengua de Señas Colombiana (LSC. El sistema tiene cuatro etapa s: Captura de la imagen, preprocesamiento, extracción de características y reconocimiento. La imagen es capturada median te una cámara digital TRDBD5M diseñada para tarjetas de desarr ollo de DE1 y DE2 Altera. En la etapa de preprocesamiento, la seña es extraída del fondo de la imagen mediante el método de segmen tación por umbral; posteriormente, la ima gen segmentada es filtrada us ando una operación morfológica para eliminar el ruido. La etapa de extracción de características está basada en la creación de dos vectores que caracterizan la forma de la mano mediante la que se realiza la seña. La etapa de reconocimiento está constituida por una red n euronal artificial perceptrón multicapa (MLP, la cual actúa co mo clasificador. El sistema fue imp lementado en el dispositivo FPG A Cyclone II EP2C70F896C6 y no requiere el uso de guantes o marcadores visuales para su correcto funcionamiento. Los result ados muestran que el sistema tiene la capacidad para reconocer todas las 23 señas estáticas de la LSC con una taza de reconocimiento del 98.15 %.

  15. Supply and demand of board-certified emergency physicians by U.S. state, 2005.

    Science.gov (United States)

    Sullivan, Ashley F; Ginde, Adit A; Espinola, Janice A; Camargo, Carlos A

    2009-10-01

    The objective was to estimate the emergency medicine (EM) board-certified emergency physician (EP) workforce supply and demand by U.S. state. The 2005 National Emergency Department Inventories-USA provided annual visit volumes for U.S. emergency departments (EDs). We estimated full-time equivalent (FTE) EP demand at each ED by dividing the actual number of visits by the estimated average EP visit volume (3,548 visits/year) and then summing FTEs by state. Our model assumed that at least one EP should be present 24/7 in each ED. The number of EM board-certified EPs per state was provided by the American Board of Medical Specialties (American Board of Emergency Medicine, American Board of Pediatrics) and the American Osteopathic Board of Emergency Medicine. We used U.S. Census Bureau civilian population estimates to calculate EP population density by state. The supply of EM board-certified EPs was 58% of required FTEs to staff all EDs nationally and ranged from 10% in South Dakota to 104% in Hawai'i (i.e., there were more EPs than the estimated need). Texas and Florida had the largest absolute shortages of EM board-certified EPs (2,069 and 1,146, respectively). The number of EM board-certified EPs per 100,000 U.S. civilian population ranged from 3.6 in South Dakota to 13.8 in Washington, DC. States with a higher population density of EM board-certified EPs had higher percent high school graduates and a lower percent rural population and whites. The supply and demand of EM board-certified EPs varies by state. Only one state had an adequate supply of EM board-certified EPs to fully staff its EDs.

  16. Production of extracellular polymeric substances (EPS) by Serratia sp.1 using wastewater sludge as raw material and flocculation activity of the EPS produced.

    Science.gov (United States)

    Bezawada, J; Hoang, N V; More, T T; Yan, S; Tyagi, N; Tyagi, R D; Surampalli, R Y

    2013-10-15

    Growth profile and extracellular polymeric substances (EPS) production of Serratia sp.1 was studied in shake flask fermentation for 72 h using wastewater sludge as raw material. Maximum cell concentration of 6.7 × 10(9) cfu/mL was obtained at 48 h fermentation time. EPS dry weight, flocculation activity and dewaterability of different EPS (tightly bound or TB-EPS, loosely bound or LB-EPS and broth-EPS or B-EPS) were also measured. The highest concentration of LB-EPS (2.45 g/L) and TB-EPS (0.99 g/L) were attained at 48 h of fermentation. Maximum flocculation activity and dewaterability (ΔCST) of TB-EPS (76.4%, 14.5s and 76.5%, 15.5s), LB-EPS (67.8%, 8.1s and 64.7%, 7.6s) and broth EPS (61%, 6.1s and 70.4%, 6.8s) were obtained at 36 and 48 h of growth. Higher flocculation activity and dewaterability were achieved with TB-EPS than with the two other EPS. Characterization of TB-EPS and LB-EPS was done in terms of their protein and carbohydrate content. Protein content was much higher in TB-EPS where as carbohydrate content was only slightly higher in TB-EPS than LB-EPS. Morphology of the Serratia strain after fermentation in sludge and TSB was observed under a scanning electron microscope and the cell size was found to be bigger in the sludge medium than the TSB medium. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Parallel processing method for high-speed real time digital pulse processing for gamma-ray spectroscopy

    International Nuclear Information System (INIS)

    Fernandes, A.M.; Pereira, R.C.; Sousa, J.; Neto, A.; Carvalho, P.; Batista, A.J.N.; Carvalho, B.B.; Varandas, C.A.F.; Tardocchi, M.; Gorini, G.

    2010-01-01

    A new data acquisition (DAQ) system was developed to fulfil the requirements of the gamma-ray spectrometer (GRS) JET-EP2 (joint European Torus enhancement project 2), providing high-resolution spectroscopy at very high-count rate (up to few MHz). The system is based on the Advanced Telecommunications Computing Architecture TM (ATCA TM ) and includes a transient record (TR) module with 8 channels of 14 bits resolution at 400 MSamples/s (MSPS) sampling rate, 4 GB of local memory, and 2 field programmable gate array (FPGA) able to perform real time algorithms for data reduction and digital pulse processing. Although at 400 MSPS only fast programmable devices such as FPGAs can be used either for data processing and data transfer, FPGA resources also present speed limitation at some specific tasks, leading to an unavoidable data lost when demanding algorithms are applied. To overcome this problem and foreseeing an increase of the algorithm complexity, a new digital parallel filter was developed, aiming to perform real time pulse processing in the FPGAs of the TR module at the presented sampling rate. The filter is based on the conventional digital time-invariant trapezoidal shaper operating with parallelized data while performing pulse height analysis (PHA) and pile up rejection (PUR). The incoming sampled data is successively parallelized and fed into the processing algorithm block at one fourth of the sampling rate. The following data processing and data transfer is also performed at one fourth of the sampling rate. The algorithm based on data parallelization technique was implemented and tested at JET facilities, where a spectrum was obtained. Attending to the observed results, the PHA algorithm will be improved by implementing the pulse pile up discrimination.

  18. Regulation of Expression of Renal Organic Anion Transporters OAT1 and OAT3 in a Model of Ischemia/Reperfusion Injury

    Directory of Open Access Journals (Sweden)

    Christina Preising

    2015-08-01

    Full Text Available Background: Recently, we gained evidence that impairment of rOat1 and rOat3 expression induced by ischemic acute kidney injury (AKI is mediated by COX metabolites and this suppression might be critically involved in renal damage. Methods: (i Basolateral organic anion uptake into proximal tubular cells after model ischemia and reperfusion (I/R was investigated by fluorescein uptake. The putative promoter sequences from hOAT1 (SLC22A6 and hOAT3 (SCL22A8 were cloned into a reporter plasmid, transfected into HEK cells and (ii transcriptional activity was determined after model ischemia and reperfusion as a SEAP reporter gen assay. Inhibitors or antagonists were applied with the beginning of reperfusion. Results: By using inhibitors of PKA (H89 and PLC (U73122, antagonists of E prostanoid receptor type 2 (AH6809 and type 4 (L161,982, we gained evidence that I/R induced down regulation of organic anion transport is mediated by COX1 metabolites via E prostanoid receptor type 4. The latter signaling was confirmed by application of butaprost (EP2 agonist or TCS2510 (EP4 agonist to control cells. In brief, the latter signaling was verified for the transcriptional activity in the reporter gen assay established. Therein, selective inhibitors for COX1 (SC58125 and COX2 (SC560 were also applied. Conclusion: Our data show (a that COX1 metabolites are involved in the regulation of renal organic anion transport(ers after I/R via the EP4 receptor and (b that this is due to transcriptional regulation of the respective transporters. As the promoter sequences cloned were of human origin and expressed in a human renal epithelial cell line we (c hypothesize that the regulatory mechanisms described after I/R is meaningful for humans as well.

  19. The ion-acoustic soliton: A gas-dynamic viewpoint

    International Nuclear Information System (INIS)

    McKenzie, J.F.

    2002-01-01

    The properties of fully nonlinear ion-acoustic solitons are investigated by interpreting conservation of total momentum as the structure equation for the proton flow in the wave. In most studies momentum conservation is regarded as the first integral of the Poisson equation for the electric potential and is interpreted as being analogous to a particle moving in a pseudo-potential well. By adopting an essentially gas-dynamic viewpoint, which emphasizes momentum conservation and the properties of the Bernoulli-type energy equations, the crucial role played by the proton sonic point becomes apparent. The relationship (implied by energy conservation) between the electron and proton speeds in the transition yields a locus--the hodograph of the system-which shows that, in the first half of the soliton, the electrons initially lag behind the protons until the charge neutral point is reached, after which they run ahead of the protons. The system reaches an equilibrium point (the center of the soliton) before the proton flow goes sonic. It follows that the critical ion-acoustic Mach number, M c , above which smooth, continuous solitons cannot be constructed, stems from the requirement that the two equilibrium points of the structure equation coalesce at the proton sonic point of the flow. In general the range of the ion-acoustic Mach numbers, M ep , in which solitons exist, is extended beyond the classical range 1 ep 2 shaped pulses characteristic of weakly nonlinear waves and shows that solitons exist only if 1 ep e and 10kT e depending upon the values of the adiabatic indices of the electrons and protons and the proton Mach number

  20. Natural bond orbital analysis of molecular interactions: Theoretical study of W(CO)5 complexes with E(PH3)2 and NHEMe ligands (E=C, Si, Ge, Sn, Pb)

    International Nuclear Information System (INIS)

    Nguyen Thi Ai Nhung; Huynh Thi Phuong Loan; Duong Tuan Quang; Pham Van Tat

    2014-01-01

    The complexes with ligands carbodiphosphorane-analogues (called tetrylones) [(CO) 5 W-{E(PH 3 ) 2 }] (W5-EP 2 ) and N-heterocyclic carbene-analogues (called tetrylenes) [(CO) 5 W-{NHE Me }] (W5-NHE Me ) when E=C-Pb have been studied using natural bond orbital (NBO) method. The NBO analysis provides a consistent picture of the chemical bonding is two entire families of transition metal complexes of tetrylone and tetrylene ligands in term of donor-acceptor interactions, showing the correlation of these interactions with Wiberg bond indies (WBI), natural partial charges, and the energetically highest lying occupied molecular orbitals for σ and π orbitals of free ligands E(PH 3 ) 2 and NHE Me . Analysis of the bonding situation reveals that in E(PH 3 ) 2 and NHE Me ligands, the energy level of the π orbital rises, whereas that of the σ orbital decreases as atom E becomes heavier. The complexes with head-on-bonded ligands have (CO) 5 W←E donation which comes from the σ-lone-pair orbital of E(PH 3 ) 2 and NHE Me where E=C for tetrylones and E=C, Si, Ge for tetrylenes, whereas the (CO) 5 W←E donation in the side-on bonded complexes when E becomes heavier arises from the π-lone-pair orbital of E(PH 3 ) 2 and NHE Me ligands which is the HOMO of the free ligands. This makes the heavier adducts of tetrylones and tetrylenes become stronger donors than the lighter systems. The NBO analysis suggests that the E(PH 3 ) 2 ligands are strong σ-donors and strong π-acceptors while the NHE Me ligands are strong σ-donors and weak π-acceptors. This is possible for tetrylones that have two lone-pair orbitals available for donation, whereas the tetrylenes have only one lone-pair orbital available for donation. (author)

  1. A role for inflammatory mediators in heterologous desensitization of CysLT1 receptor in human monocytes

    Science.gov (United States)

    Capra, Valérie; Accomazzo, Maria Rosa; Gardoni, Fabrizio; Barbieri, Silvia; Rovati, G. Enrico

    2010-01-01

    Cysteinyl-leukotrienes (cysteinyl-LT) are rapidly generated at sites of inflammation and, in addition to their role in asthma, rhinitis, and other immune disorders, are increasingly regarded as significant inflammatory factors in cancer, gastrointestinal, cardiovascular diseases. We recently demonstrated that in monocyte/macrophage–like U937 cells, extracellular nucleotides heterologously desensitize CysLT1 receptor (CysLT1R)-induced Ca2+ transients. Given that monocytes express a number of other inflammatory and chemoattractant receptors, this study was aimed at characterizing transregulation between these different stimuli. We demonstrate that in U937 cells and in primary human monocytes, a series of inflammatory mediators activating Gi-coupled receptor (FPR1, BLT1) desensitize CysLT1R-induced Ca2+ response unidirectionally through activation of PKC. Conversely, PAF-R, exclusively coupled to Gq, cross-desensitizes CysLT1R without the apparent involvement of any kinase. Interestingly, Gs-coupled receptors (β2AR, H1/2R, EP2/4R) are also able to desensitize CysLT1R response through activation of PKA. Heterologous desensitization seems to affect mostly the Gi-mediated signaling of the CysLT1R. The hierarchy of desensitization among agonists may be important for leukocyte signal processing at the site of inflammation. Considering that monocytes/macrophages are likely to be the major source of cysteinyl-LT in many immunological and inflammatory processes, shedding light on how their receptors are regulated will certainly help to better understand the role of these cells in orchestrating this complex network of integrated signals. PMID:19965602

  2. Exclusive experiment on nuclei with backward emitted particles by electron-nucleus collision in ∼ 10 GeV energy range

    International Nuclear Information System (INIS)

    Saito, T.; Takagi, F.

    1994-01-01

    Since the evidence of strong cross section in proton-nucleus backward scattering was presented in the early of 1970 years, this phenomena have been interested from the point of view to be related to information on the short range correlation between nucleons or on high momentum components of the wave function of the nucleus. In the analysis of the first experiment on protons from the carbon target under bombardment by 1.5-5.7 GeV protons, indications are found of an effect analogous to scaling in high-energy interactions of elementary particles with protons. Moreover it is found that the function f(p 2 )/σ tot , which describes the spectra of the protons and deuterons emitted backward from nuclei in the laboratory system, does not depend on the energy and the type of the incident particle or on the atomic number of the target nucleus. In the following experiments the spectra of the protons emitted from the nuclei C, Al, Ti, Cu, Cd and Pb were measured in the inclusive reactions with incident particles of negative pions (1.55-6.2 GeV/c) and protons (6.2-9.0 GeV/C). The cross section f is described by f = E/p 2 d 2 σ/dpdΩ = C exp (-Bp 2 ), where p is the momentum of hadron. The function f depends linearly on the atomic weight A of the target nuclei. The slope parameter B is independent of the target nucleus and of the sort and energy of the bombarding particles. The invariant cross section ρ = f/σ tot is also described by exponential A 0 exp (-A 1p 2 ), where p becomes independent of energy at initial particle energies ≥ 1.5 GeV for C nucleus and ≥ 5 GeV for the heaviest of the investigated Pb nuclei

  3. Changes in performance: a 5-year longitudinal study of participants in a multi-source feedback programme.

    Science.gov (United States)

    Violato, Claudio; Lockyer, Jocelyn M; Fidler, Herta

    2008-10-01

    Multi-source feedback (MSF) enables performance data to be provided to doctors from patients, co-workers and medical colleagues. This study examined the evidence for the validity of MSF instruments for general practice, investigated changes in performance for doctors who participated twice, 5 years apart, and determined the association between change in performance and initial assessment and socio-demographic characteristics. Data for 250 doctors included three datasets per doctor from, respectively, 25 patients, eight co-workers and eight medical colleagues, collected on two occasions. There was high internal consistency (alpha > 0.90) and adequate generalisability (Ep(2) > 0.70). D study results indicate adequate generalisability coefficients for groups of eight assessors (medical colleagues, co-workers) and 25 patient surveys. Confirmatory factor analyses provided evidence for the validity of factors that were theoretically expected, meaningful and cohesive. Comparative fit indices were 0.91 for medical colleague data, 0.87 for co-worker data and 0.81 for patient data. Paired t-test analysis showed significant change between the two assessments from medical colleagues and co-workers, but not between the two patient surveys. Multiple linear regressions explained 2.1% of the variance at time 2 for medical colleagues, 21.4% of the variance for co-workers and 16.35% of the variance for patient assessments, with professionalism a key variable in all regressions. There is evidence for the construct validity of the instruments and for their stability over time. Upward changes in performance will occur, although their effect size is likely to be small to moderate.

  4. Incremental value of diffusion weighted and dynamic contrast enhanced MRI in the detection of locally recurrent prostate cancer after radiation treatment: preliminary results

    International Nuclear Information System (INIS)

    Akin, Oguz; Vargas, Hebert Alberto; Hricak, Hedvig; Gultekin, David H.; Zheng, Junting; Moskowitz, Chaya; Pei, Xin; Sperling, Dahlia; Zelefsky, Michael J.; Schwartz, Lawrence H.

    2011-01-01

    To assess the incremental value of diffusion-weighted (DW-MRI) and dynamic contrast-enhanced MRI (DCE-MRI) to T2-weighted MRI (T2WI) in detecting locally recurrent prostate cancer after radiotherapy. Twenty-four patients (median age, 70 years) with a history of radiotherapy-treated prostate cancer underwent multi-parametric MRI (MP-MRI) and transrectal prostate biopsy. Two readers independently scored the likelihood of cancer on a 1-5 scale, using T2WI alone and then adding DW-MRI and DCE-MRI. Areas under receiver operating characteristic curves (AUCs) were estimated at the patient and prostate-side levels. The apparent diffusion coefficient (ADC) from DW-MRI and the K trans , k ep , v e , AUGC90 and AUGC180 from DCE-MRI were recorded. Biopsy was positive in 16/24 (67%) and negative in 8/24 (33%) patients. AUCs for readers 1 and 2 increased from 0.64 and 0.53 to 0.95 and 0.86 with MP-MRI, at the patient level, and from 0.73 and 0.66 to 0.90 and 0.79 with MP-MRI, at the prostate-side level (p values -3 mm 2 /s)], median K trans [1.07 vs. 0.34 (1/min)], and k ep [2.06 vs 1.0 (1/min)] (p values < 0.05). MP-MRI was significantly more accurate than T2WI alone in detecting locally recurrent prostate cancer after radiotherapy. (orig.)

  5. Incremental value of diffusion weighted and dynamic contrast enhanced MRI in the detection of locally recurrent prostate cancer after radiation treatment: preliminary results

    Energy Technology Data Exchange (ETDEWEB)

    Akin, Oguz; Vargas, Hebert Alberto; Hricak, Hedvig [Memorial Sloan-Kettering Cancer Center, Department of Radiology, New York, NY (United States); Gultekin, David H. [Memorial Sloan-Kettering Cancer Center, Medical Physics, New York, NY (United States); Zheng, Junting; Moskowitz, Chaya [Memorial Sloan-Kettering Cancer Center, Epidemiology and Biostatistics, New York, NY (United States); Pei, Xin; Sperling, Dahlia; Zelefsky, Michael J. [Memorial Sloan-Kettering Cancer Center, Radiation Oncology, New York, NY (United States); Schwartz, Lawrence H. [Columbia University College of Physicians and Surgeons, Radiology, New York, NY (United States)

    2011-09-15

    To assess the incremental value of diffusion-weighted (DW-MRI) and dynamic contrast-enhanced MRI (DCE-MRI) to T2-weighted MRI (T2WI) in detecting locally recurrent prostate cancer after radiotherapy. Twenty-four patients (median age, 70 years) with a history of radiotherapy-treated prostate cancer underwent multi-parametric MRI (MP-MRI) and transrectal prostate biopsy. Two readers independently scored the likelihood of cancer on a 1-5 scale, using T2WI alone and then adding DW-MRI and DCE-MRI. Areas under receiver operating characteristic curves (AUCs) were estimated at the patient and prostate-side levels. The apparent diffusion coefficient (ADC) from DW-MRI and the K{sup trans}, k{sub ep}, v{sub e}, AUGC90 and AUGC180 from DCE-MRI were recorded. Biopsy was positive in 16/24 (67%) and negative in 8/24 (33%) patients. AUCs for readers 1 and 2 increased from 0.64 and 0.53 to 0.95 and 0.86 with MP-MRI, at the patient level, and from 0.73 and 0.66 to 0.90 and 0.79 with MP-MRI, at the prostate-side level (p values < 0.05). Biopsy-positive and biopsy-negative prostate sides differed significantly in median ADC [1.44 vs. 1.68 (x 10{sup -3} mm{sup 2}/s)], median K{sup trans} [1.07 vs. 0.34 (1/min)], and k{sub ep} [2.06 vs 1.0 (1/min)] (p values < 0.05). MP-MRI was significantly more accurate than T2WI alone in detecting locally recurrent prostate cancer after radiotherapy. (orig.)

  6. Canine placental prostaglandin E2 synthase: expression, localization, and biological functions in providing substrates for prepartum PGF2alpha synthesis.

    Science.gov (United States)

    Gram, Aykut; Fox, Barbara; Büchler, Urs; Boos, Alois; Hoffmann, Bernd; Kowalewski, Mariusz P

    2014-12-01

    The prepartum output of PGF2alpha in the bitch is associated with increased placental PGE2-synthase (PTGES) mRNA levels. Contrasting with this is a decreased expression of PGF2alpha-synthase (PGFS/AKR1C3) in uteroplacental compartments during prepartum luteolysis, suggesting an involvement of alternative synthetic pathways in PGF2alpha synthesis, for example, conversion of PGE2 to PGF2alpha. However, because the expression and possible functions of the respective PTGES proteins remained unknown, no further conclusion could be drawn. Therefore, a canine-specific PTGES antibody was generated and used to investigate the expression, cellular localization, and biochemical activities of canine uteroplacental PTGES throughout pregnancy and at prepartum luteolysis. Additionally, the biochemical activities of these tissues involved in the conversion of PGE2 to PGF2alpha were investigated. The endometrial PTGES was localized in the uterine surface epithelium at preimplantation and in superficial and deep uterine glands, endothelial cells, and myometrium throughout pregnancy and at parturition. Placental signals were mostly in the trophoblast. The biochemical properties of recombinant PTGES protein were confirmed. Additionally, expression of two PGE2-receptors, PTGER2/EP2 and PTGER4/EP4, revealed their decreasing expression during luteolysis. In contrast, the uteroplacental expression of prostaglandin transporter (PGT) was strongly elevated prior to parturition. These localization patterns resembled that of PTGES. The increased expression of PTGES and PGT at parturition, together with the accompanying decreased levels of PGE2-receptors and the capability of canine uterine and placental homogenates to take part in the conversion of PGE2 to PGF2alpha, as found in this study, suggest that PGE2 could be used locally as a substrate for prepartum PGF2alpha synthesis in the dog. © 2014 by the Society for the Study of Reproduction, Inc.

  7. Determination of Interference During In Vitro Pyrogen Detection: Development and Characterization of a Cell-Based Assay.

    Science.gov (United States)

    Palma, Linda; Rossetti, Francesca; Dominici, Sabrina; Buondelmonte, Costantina; Rocchi, Marco B L; Rizzardi, Gian P; Vallanti, Giuliana; Magnani, Mauro

    Contamination of pharmaceutical products and medical devices with pyrogens such as endotoxins is the most common cause of systemic inflammation and, in worst cases, of septic shock. Thus, quantification of pyrogens is crucial. The limulus amebocyte lysate (LAL)-based assays are the reference tests for in vitro endotoxin detection, in association with the in vivo rabbit pyrogen test (RPT), according to European Pharmacopoeia (EP 2.6.14), and U.S. Pharmacopoeia (USP ). However, several substances interfere with LAL assay, while RPT is not accurate, not quantitative, and raises ethical limits. Biological assays, as monocyte activation tests, have been developed and included in European Pharmacopoeia (EP 7.0; 04/2010:20630) guidelines as an alternative to RPT and proved relevant to the febrile reaction in vivo. Because this reaction is carried out by endogenous mediators under the transcriptional control of nuclear factor-kappaB (NF-kappaB), we sought to determine whether a NF-kappaB reporter-gene assay, based on MonoMac-6 (MM6) cells, could reconcile the basic mechanism of innate immune response with the relevance of monocytoid cell lines to the organism reaction to endotoxins. This article describes both optimization and characterization of the reporter cells-based assay, which overall proved the linearity, accuracy, and precision of the test, and demonstrated the sensitivity of the assay to 0.24 EU/mL endotoxin, close to the pyrogenic threshold in humans. Moreover, the assay was experimentally compared to the LAL test in the evaluation of selected interfering samples. The good performance of the MM6 reporter test demonstrates the suitability of this assay to evaluate interfering or false-positive samples.

  8. H2S-induced HCO3- secretion in the rat stomach--involvement of nitric oxide, prostaglandins, and capsaicin-sensitive sensory neurons.

    Science.gov (United States)

    Takeuchi, Koji; Ise, Fumitaka; Takahashi, Kento; Aihara, Eitaro; Hayashi, Shusaku

    2015-04-30

    Hydrogen sulfide (H2S) is known to be an important gaseous mediator that affects various functions under physiological and pathological conditions. We examined the effects of NaHS, a H2S donor, on HCO3(-) secretion in rat stomachs and investigated the mechanism involved in this response. Under urethane anesthesia, rat stomachs were mounted on an ex vivo chamber and perfused with saline. Acid secretion had been inhibited by omeprazole. The secretion of HCO3(-) was measured at pH 7.0 using a pH-stat method and by the addition of 10 mM HCl. NaHS (0.5-10 mM) was perfused in the stomach for 5 min. Indomethacin or L-NAME was administered s.c. before NaHS treatment, while glibenclamide (a KATP channel blocker), ONO-8711 (an EP1 antagonist), or propargylglycine (a cystathionine γ-lyase inhibitor) was given i.p. before. The mucosal perfusion of NaHS dose-dependently increased the secretion of HCO3(-), and this effect was significantly attenuated by indomethacin, L-NAME, and sensory deafferentation, but not by glibenclamide or ONO-8711. The luminal output of nitric oxide, but not the mucosal production of prostaglandin E2, was increased by the perfusion of NaHS. Mucosal acidification stimulated HCO3(-) secretion, and this response was inhibited by sensory deafferentation, indomethacin, L-NAME, and ONO-8711, but not by propargylglycine. These results suggested that H2S increased HCO3(-) secretion in the stomach, and this effect was mediated by capsaicin-sensitive afferent neurons and dependent on nitric oxide and prostaglandins, but not ATP-sensitive K(+) channels. Further study is needed to define the role of endogenous H2S in the mechanism underlying acid-induced gastric HCO3(-) secretion. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Genome-Wide Identification, Characterization, and Expression Profiling of Glutathione S-Transferase (GST) Family in Pumpkin Reveals Likely Role in Cold-Stress Tolerance

    Science.gov (United States)

    Abdul Kayum, Md.; Nath, Ujjal Kumar; Park, Jong-In; Choi, Eung Kyoo; Song, Jae-Young; Kim, Hoy-Taek; Nou, Ill-Sup

    2018-01-01

    Plant growth and development can be adversely affected by cold stress, limiting productivity. The glutathione S-transferase (GST) family comprises important detoxifying enzymes, which play major roles in biotic and abiotic stress responses by reducing the oxidative damage caused by reactive oxygen species. Pumpkins (Cucurbita maxima) are widely grown, economically important, and nutritious; however, their yield can be severely affected by cold stress. The identification of putative candidate genes responsible for cold-stress tolerance, including the GST family genes, is therefore vital. For the first time, we identified 32 C. maxima GST (CmaGST) genes using a combination of bioinformatics approaches and characterized them by expression profiling. These CmaGST genes represent seven of the 14 known classes of plant GSTs, with 18 CmaGSTs categorized into the tau class. The CmaGSTs were distributed across 13 of pumpkin’s 20 chromosomes, with the highest numbers found on chromosomes 4 and 6. The large number of CmaGST genes resulted from gene duplication; 11 and 5 pairs of CmaGST genes were segmental- and tandem-duplicated, respectively. In addition, all CmaGST genes showed organ-specific expression. The expression of the putative GST genes in pumpkin was examined under cold stress in two lines with contrasting cold tolerance: cold-tolerant CP-1 (C. maxima) and cold-susceptible EP-1 (Cucurbita moschata). Seven genes (CmaGSTU3, CmaGSTU7, CmaGSTU8, CmaGSTU9, CmaGSTU11, CmaGSTU12, and CmaGSTU14) were highly expressed in the cold-tolerant line and are putative candidates for use in breeding cold-tolerant crop varieties. These results increase our understanding of the cold-stress-related functions of the GST family, as well as potentially enhancing pumpkin breeding programs. PMID:29439434

  10. Sequence analysis and identification of new isoform of EP4 receptors in different atlantic salmon tissues (Salmo salar L. and its role in PGE2 induced immunomodulation in vitro.

    Directory of Open Access Journals (Sweden)

    Tz Chun Guo

    Full Text Available PGE2 plays an important role in a broad spectrum of physiological and pathological processes mediated through a membrane-bound G protein-coupled receptor (GPCR called EP receptor. In mammals, four subtypes of EP receptor (EP 1-4 are identified and each of them functions through different signal transduction pathways. Orthologous EP receptors have also been identified in other non-mammalian species, such as chicken and zebrafish. EP4 is the only identified PGE2 receptor to date in Atlantic salmon but its tissue distribution and function have not been studied in any detail. In this study, we first sequenced EP4 receptor in different tissues and found that the presence of the 3nt deletion in the 5' untranslated region was accompanied by silent mutation at nt 668. While attempting to amplify the same sequence in TO cells (an Atlantic salmon macrophage-like cell line, we failed to obtain the full-length product. Further investigation revealed different isoform of EP4 receptor in TO cells and we subsequently documented its presence in different Atlantic salmon tissues. These two isoforms of EP4 receptor share high homology in their first half of sequence but differ in the second half part with several deletion segments though the final length of coding sequence is the same for two isoforms. We further studied the immunomodulation effect of PGE2 in TO cells and found that PGE2 inhibited the induction of CXCL-10, CCL-4, IL-8 and IL-1β genes expression in a time dependent manner and without cAMP upregulation.

  11. Genetic analysis of partial egg production records in Japanese quail using random regression models.

    Science.gov (United States)

    Abou Khadiga, G; Mahmoud, B Y F; Farahat, G S; Emam, A M; El-Full, E A

    2017-08-01

    The main objectives of this study were to detect the most appropriate random regression model (RRM) to fit the data of monthly egg production in 2 lines (selected and control) of Japanese quail and to test the consistency of different criteria of model choice. Data from 1,200 female Japanese quails for the first 5 months of egg production from 4 consecutive generations of an egg line selected for egg production in the first month (EP1) was analyzed. Eight RRMs with different orders of Legendre polynomials were compared to determine the proper model for analysis. All criteria of model choice suggested that the adequate model included the second-order Legendre polynomials for fixed effects, and the third-order for additive genetic effects and permanent environmental effects. Predictive ability of the best model was the highest among all models (ρ = 0.987). According to the best model fitted to the data, estimates of heritability were relatively low to moderate (0.10 to 0.17) showed a descending pattern from the first to the fifth month of production. A similar pattern was observed for permanent environmental effects with greater estimates in the first (0.36) and second (0.23) months of production than heritability estimates. Genetic correlations between separate production periods were higher (0.18 to 0.93) than their phenotypic counterparts (0.15 to 0.87). The superiority of the selected line over the control was observed through significant (P egg production in earlier ages (first and second months) than later ones. A methodology based on random regression animal models can be recommended for genetic evaluation of egg production in Japanese quail. © 2017 Poultry Science Association Inc.

  12. Iptakalim inhibits nicotinic acetylcholine receptor-mediated currents in dopamine neurons acutely dissociated from rat substantia nigra pars compacta.

    Science.gov (United States)

    Hu, J; DeChon, J; Yan, K C; Liu, Q; Hu, G; Wu, J

    2006-07-31

    Iptakalim hydrochloride, a novel cardiovascular ATP-sensitive K(+) (K(ATP)) channel opener, has shown remarkable antihypertensive and neuroprotective effects in a variety of studies using in vivo and in vitro preparations. We recently found that iptakalim blocked human alpha4-containing nicotinic acetylcholine receptors (nAChRs) heterologously expressed in the human SH-EP1 cell line. In the present study, we examined the effects of iptakalim on several neurotransmitter-induced current responses in single DA neurons freshly dissociated from rat substantia nigra pars compacta (SNc), using perforated patch-clamp recordings combined with a U-tube rapid drug application. In identified DA neurons under voltage-clamp configuration, glutamate-, NMDA-, and GABA-induced currents were insensitive to co-application with iptakalim (100 microM), while whole-cell currents induced by ACh (1 mM+1 microM atropine) or an alpha4beta2 nicotinic acetylcholine receptors relatively selective agonist, RJR-2403 (300 microM), were eliminated by iptakalim. Iptakalim inhibited RJR-2403-induced current in a concentration-dependent manner, and reduced maximal RJR-2403-induced currents at the highest agonist concentration, suggesting a non-competitive block. In current-clamp mode, iptakalim failed to affect resting membrane potential and spontaneous action potential firing, but abolished RJR-2403-induced neuronal firing acceleration. Together, these results indicate that in dissociated SNc DA neurons, alpha4-containing nAChRs, rather than ionotropic glutamate receptors, GABA(A) receptors or perhaps K-ATP channels are the sensitive targets to mediate iptakalim's pharmacological roles.

  13. Genome comparison of the epiphytic bacteria Erwinia billingiae and E. tasmaniensis with the pear pathogen E. pyrifoliae

    Directory of Open Access Journals (Sweden)

    Kuhl Heiner

    2010-06-01

    Full Text Available Abstract Background The genus Erwinia includes plant-associated pathogenic and non-pathogenic Enterobacteria. Important pathogens such as Erwinia amylovora, the causative agent of fire blight and E. pyrifoliae causing bacterial shoot blight of pear in Asia belong to this genus. The species E. tasmaniensis and E. billingiae are epiphytic bacteria and may represent antagonists for biocontrol of fire blight. The presence of genes that are putatively involved in virulence in E. amylovora and E. pyrifoliae is of special interest for these species in consequence. Results Here we provide the complete genome sequences of the pathogenic E. pyrifoliae strain Ep1/96 with a size of 4.1 Mb and of the non-pathogenic species E. billingiae strain Eb661 with a size of 5.4 Mb, de novo determined by conventional Sanger sequencing and next generation sequencing techniques. Genome comparison reveals large inversions resulting from homologous recombination events. Furthermore, comparison of deduced proteins highlights a relation of E. billingiae strain Eb661 to E. tasmaniensis strain Et1/99 and a distance to E. pyrifoliae for the overall gene content as well as for the presence of encoded proteins representing virulence factors for the pathogenic species. Pathogenicity of E. pyrifoliae is supposed to have evolved by accumulation of potential virulence factors. E. pyrifoliae carries factors for type III secretion and cell invasion. Other genes described as virulence factors for E. amylovora are involved in the production of exopolysaccharides, the utilization of plant metabolites such as sorbitol and sucrose. Some virulence-associated genes of the pathogenic species are present in E. tasmaniensis but mostly absent in E. billingiae. Conclusion The data of the genome analyses correspond to the pathogenic lifestyle of E. pyrifoliae and underlines the epiphytic localization of E. tasmaniensis and E. billingiae as a saprophyte.

  14. Stochastic Frontier Analysis of Maize Farmers in Azad Jammu and Kashmir, Pakistan

    International Nuclear Information System (INIS)

    Zhang, F.; Wang, Y.; Yu, H.; Zhu, K.; Zhang, Z.; Zou, F. L. J.

    2015-01-01

    The research study was carried out to analyze the technical efficiency of maize growers through Cobb-Douglas type Stochastic Frontier Analysis in four villages of Muzaffarabad district, Azad Jammu and Kashmir (AJK), Pakistan. The proportional sampling allocation sampling technique was adopted to collect primary data from 80 sampled respondents in 2013-14. The maximum likelihood estimates of major inputs showed that seed, tractor hours, FYM and labor days have contributed significantly to increase the maize yield. However, the DAP and urea have shown no effect on maize yield. The mean technical efficiency was estimated at 83%, implying that the farmers can still enhance their technical efficiency by 11% within the given inputs and technology. The results have demonstrated that maize crop is lucrative crop in the study area as maize growers have received increasing return to scale i.e., 1.90 (Ep>1), hence economies of scale exists. The variance parameter lambda and gamma both were significant indicating the good fitness of model and inefficiency impact, respectively. The estimated value for gamma was 0.77 underscores that 77% variation in the production frontier was explained by technical inefficiency effect. The inefficiency indices showed that farmers with more schooling years and more number of contacts with extension agents were more efficient. Contrarily, age of the farmer and large farm size have inverse relation to technical efficiency of the farmers. This research study concludes that the use of more labor and application of farm yard manure is contributing significantly. It is recommended that the high input prices may be leveled off by the regulatory authorities so that farmers can apply the required crop inputs such as DAP and urea in study area. (author)

  15. Microsomal Prostaglandin E Synthase-1 Facilitates an Intercellular Interaction between CD4⁺ T Cells through IL-1β Autocrine Function in Experimental Autoimmune Encephalomyelitis.

    Science.gov (United States)

    Takemiya, Takako; Takeuchi, Chisen; Kawakami, Marumi

    2017-12-19

    Microsomal prostaglandin synthetase-1 (mPGES-1) is an inducible terminal enzyme that produces prostaglandin E₂ (PGE₂). In our previous study, we investigated the role of mPGES-1 in the inflammation and demyelination observed in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, using mPGES - 1 -deficient ( mPGES-1 -/- ) and wild-type (wt) mice. We found that mPGES-1 facilitated inflammation, demyelination, and paralysis and was induced in vascular endothelial cells and macrophages and microglia around inflammatory foci. Here, we investigated the role of interleukin-1β (IL-1β) in the intercellular mechanism stimulated by mPGES-1 in EAE spinal cords in the presence of inflammation. We found that the area invaded by CD4-positive (CD4⁺) T cells was extensive, and that PGE₂ receptors EP1-4 were more induced in activated CD4⁺ T cells of wt mice than in those of mPGES - 1 -/- mice. Moreover, IL-1β and IL-1 receptor 1 (IL-1r1) were produced by 65% and 48% of CD4⁺ T cells in wt mice and by 44% and 27% of CD4⁺ T cells in mPGES-1 -/- mice. Furthermore, interleukin-17 (IL-17) was released from the activated CD4⁺ T cells. Therefore, mPGES-1 stimulates an intercellular interaction between CD4⁺ T cells by upregulating the autocrine function of IL-1β in activated CD4⁺ T cells, which release IL-17 to facilitate axonal and myelin damage in EAE mice.

  16. Neurophysiological mechanisms of bradykinin-evoked mucosal chloride secretion in guinea pig small intestine.

    Science.gov (United States)

    Qu, Mei-Hua; Ji, Wan-Sheng; Zhao, Ting-Kun; Fang, Chun-Yan; Mao, Shu-Mei; Gao, Zhi-Qin

    2016-02-15

    To investigate the mechanism for bradykinin (BK) to stimulate intestinal secretomotor neurons and intestinal chloride secretion. Muscle-stripped guinea pig ileal preparations were mounted in Ussing flux chambers for the recording of short-circuit current (Isc). Basal Isc and Isc stimulated by BK when preincubated with the BK receptors antagonist and other chemicals were recorded using the Ussing chamber system. Prostaglandin E2 (PGE2) production in the intestine was determined by enzyme immunologic assay (EIA). Application of BK or B2 receptor (B2R) agonist significantly increased the baseline Isc compared to the control. B2R antagonist, tetrodotoxin and scopolamine (blockade of muscarinic receptors) significantly suppressed the increase in Isc evoked by BK. The BK-evoked Isc was suppressed by cyclooxygenase (COX)-1 or COX-2 specific inhibitor as well as nonselective COX inhibitors. Preincubation of submucosa/mucosa preparations with BK for 10 min significantly increased PGE2 production and this was abolished by the COX-1 and COX-2 inhibitors. The BK-evoked Isc was suppressed by nonselective EP receptors and EP4 receptor antagonists, but selective EP1 receptor antagonist did not have a significant effect on the BK-evoked Isc. Inhibitors of PLC, PKC, calmodulin or CaMKII failed to suppress BK-induced PGE2 production. The results suggest that BK stimulates neurogenic chloride secretion in the guinea pig ileum by activating B2R, through COX increasing PGE2 production. The post-receptor transduction cascade includes activation of PLC, PKC, CaMK, IP3 and MAPK.

  17. Patients' Preferences Related to Benefits, Risks, and Formulations of Schizophrenia Treatment.

    Science.gov (United States)

    Levitan, Bennett; Markowitz, Michael; Mohamed, Ateesha F; Johnson, F Reed; Alphs, Larry; Citrome, Leslie; Bridges, John F P

    2015-07-01

    The objective of this study was to quantify patients' preferences related to benefits and risks of antipsychotic treatments for schizophrenia and to assess the relative importance of treatment attributes and adherence. Treatment-related preferences among U.S. residents with a self-reported physician diagnosis of schizophrenia were assessed via a discrete-choice experiment. Patients chose between competing hypothetical scenarios characterized by improvements in positive symptoms, negative symptoms, and social functioning; incidence of weight gain, extrapyramidal symptoms (EPS), hyperprolactinemia, and hyperglycemia; and medication formulation. Preferences were estimated by using a random-parameters logit model, and the impact of adherence was estimated with conditional logit models. The final sample consisted of 271 patients. Complete improvement in positive symptoms was the most preferred outcome (relative importance score of 10.0), followed by elimination of hyperglycemia (3.6, 95% confidence interval [CI]=2.6-4.6), improvement in negative symptoms (3.0, CI=1.6-4.3), reduced weight gain (2.6, CI=1.2-4.0), avoidance of hyperprolactinemia (1.7, CI=.9-2.6), improved social functioning (1.5, CI=.4-2.5), and avoidance of EPS (1.0, CI=.3-1.8). Patients judged a daily pill superior to monthly injections (p<.01) and monthly injections superior to injections every three months (p<.01) for adherent patients and monthly injections superior to a daily pill for nonadherent patients (p=.01). Persons who self-identified as having schizophrenia judged improvement in positive symptoms as the most important treatment benefit. Hyperglycemia was identified as the most important adverse event. Patients judged oral formulations to be better than monthly injections for adherent patients and monthly injections to be a better choice for nonadherent patients.

  18. Effect of carboxymethylcellulose on the rheological and filtration properties of bentonite clay samples determined by experimental planning and statistical analysis

    Directory of Open Access Journals (Sweden)

    B. M. A. Brito

    Full Text Available Abstract Over the past few years, considerable research has been conducted using the techniques of mixture delineation and statistical modeling. Through this methodology, applications in various technological fields have been found/optimized, especially in clay technology, leading to greater efficiency and reliability. This work studied the influence of carboxymethylcellulose on the rheological and filtration properties of bentonite dispersions to be applied in water-based drilling fluids using experimental planning and statistical analysis for clay mixtures. The dispersions were prepared according to Petrobras standard EP-1EP-00011-A, which deals with the testing of water-based drilling fluid viscosifiers for oil prospecting. The clay mixtures were transformed into sodic compounds, and carboxymethylcellulose additives of high and low molar mass were added, in order to improve their rheology and filtrate volume. Experimental planning and statistical analysis were used to verify the effect. The regression models were calculated for the relation between the compositions and the following rheological properties: apparent viscosity, plastic viscosity, and filtrate volume. The significance and validity of the models were confirmed. The results showed that the 3D response surfaces of the compositions with high molecular weight carboxymethylcellulose added were the ones that most contributed to the rise in apparent viscosity and plastic viscosity, and that those with low molecular weight were the ones that most helped in the reduction of the filtrate volume. Another important observation is that the experimental planning and statistical analysis can be used as an important auxiliary tool to optimize the rheological properties and filtrate volume of bentonite clay dispersions for use in drilling fluids when carboxymethylcellulose is added.

  19. Parameters of anaerobic physiological profile of elite athletes

    Directory of Open Access Journals (Sweden)

    Karaba-Jakovljević Dea

    2015-01-01

    Full Text Available Introduction. Anaerobic capacity is much less evaluated in literature compared to aerobic component. Anaerobic performance of athletes can be measured using different motoric tests, lasting 20 to 30 seconds, one of them being the Wingate anaerobic test (WAnT. Objective. The aim of this study was to determine the work performed and power generated by athletes and non-athletes during a 30-second high intensity exercise, as well as to compare explosive characteristics of subjects using a new parameter of WAnT, named explosive power, or slope of power. Methods. All parameters of anaerobic power were investigated in 152 subjects classed into different groups depending on their physical fitness and sport specialties as follows: non-athletes (n=31, rowers (n=26, volleyball players (n=37, handball players (n=34 and judo players (n=24. The WAnT, as well as basic anthropometric measurements, was administrated to all participants. Results. Values of anaerobic parameters were higher in the group of athletes compared to physically inactive subjects. The highest values of the WAnT parameters were registered in the group of volleyball players (AP=1006 W; relative AP=11.4 W/ kg, AC=19.8 kJ, compared to athletes of other sport disciplines (volleyball, rowing and judo. The new parameter of the WAnT, explosive power, also showed highest values in volleyball players (EP=154 W/s; relative EP=1.74 W/s/kg. These differences were statistically significant (p<0.05. Conclusion. The results of laboratory tests can provide useful information on improvements in training processes. The new parameter of the WAnT could be implemented in further analyses of explosive characteristics of muscle contraction.

  20. The use of virtual reality and intelligent database systems for procedure planning, visualisation, and real-time component tracking in remote handling operations

    International Nuclear Information System (INIS)

    Robbins, Edward; Sanders, Stephen; Williams, Adrian; Allan, Peter

    2009-01-01

    The organisation of remote handling (RH) operations in fusion environments is increasingly critical as the number of tasks, components and tooling that RH operations teams must deal with inexorably rises. During the recent JET EP1 RH shutdown the existing virtual reality (VR) and procedural database systems proved essential for visualisation and tracking of operations, particularly due to the increasing complexity of remote tasks. A new task planning system for RH operations is in development, and is expected to be ready for use during the next major shutdown, planned for 2009. The system will make use of information available from the remote operations procedures, the RH equipment human-machine interfaces, the on-line RH equipment control systems and also the virtual reality (VR) system to establish a complete database for the location of plant items and RH equipment as RH operations progress. It is intended that the system be used during both preparation and implementation of shutdowns. In the preparations phase the system can be used to validate procedures and overall logistics by allowing an operator to increment through each operation step and to use the VR system to visualise the location and status of all components, manipulators and RH tools. During task development the RH operations engineers can plan and visualise movement of components and tooling to examine handling concepts and establish storage requirements. In the implementation of operations the daily work schedules information will be integrated with the RH operations procedures tracking records to enable the VR system to provide a visual representation of the status of remote operations in real time. Monitoring of the usage history of items will allow estimates of radiation dosage and contaminant exposure to be made. This paper describes the overall aims, structure and use of the system, discusses its application to JET and also considers potential future developments.

  1. Preliminary neutronic assessments for the development of the VIS/IR diagnostic systems located in the ITER EPP

    International Nuclear Information System (INIS)

    Palermo, Iole; Mota, Fernando; Rios, Luis; Catalán, Juan Pablo; Alonso, Javier; Ibarra, Angel

    2015-01-01

    Graphical abstract: - Highlights: • Neutronic and activation calculations for the VIS/IR ITER diagnostic. • Studied if silver could be used as a covering material for the Interspace components. • Determined the irradiation time in a gamma facility to test the vacuum window. • Neutron and gamma dose rate maps in the Port Area for proposed substrate and coatings. - Abstract: The paper focuses on the nuclear analyses of the ITER Equatorial Port Visible/Infrared Wide Angle Viewing System (VIS/IR WAVS). This instrument comprises of viewing systems in the 4 Equatorial Ports (EP) 3, 9, 12 and 17. The main mission of this diagnostic is to support the operation of the tokamak by providing visible and infrared viewing and temperature data of the first wall to protect it from damage. Its design is driven by both the tokamak severe environment and the high performances required for machine protection. New nuclear studies have been carried out for the development of the diagnostic and for test purposes under ITER-like irradiation conditions in order to choose the most appropriate materials for the optical components. Thus, three neutronic analyses have been carried out: the first in order to verify if silver could be used as a covering material for the optical components in different location of the Interspace area; the second in order to establish the irradiation time required in a Co-60 gamma facility (at CIEMAT) for testing purposes of the sapphire vacuum window; and the third to give more detailed specifications for the irradiation campaigns under gamma (in the Co-60 facility) and neutrons (at SCK·CEN BR2 reactor), about the time required to achieve the same dose than the one accumulated in ITER at the end-of-life (EOL) in the different components of the Port Area for the materials proposed as substrate and coatings. The neutronic and activation calculations have been performed using the Monte Carlo code MCNP5, the activation code ACAB and the cross section

  2. Preliminary neutronic assessments for the development of the VIS/IR diagnostic systems located in the ITER EPP

    Energy Technology Data Exchange (ETDEWEB)

    Palermo, Iole, E-mail: iole.palermo@ciemat.es [CIEMAT, Fusion National Laboratory, Av. Complutense 40, E-28040 Madrid (Spain); Mota, Fernando; Rios, Luis [CIEMAT, Fusion National Laboratory, Av. Complutense 40, E-28040 Madrid (Spain); Catalán, Juan Pablo [UNED, Department of Energy Engineering, c/ Juan del Rosal 12, E-28040 Madrid (Spain); Alonso, Javier; Ibarra, Angel [CIEMAT, Fusion National Laboratory, Av. Complutense 40, E-28040 Madrid (Spain)

    2015-11-15

    Graphical abstract: - Highlights: • Neutronic and activation calculations for the VIS/IR ITER diagnostic. • Studied if silver could be used as a covering material for the Interspace components. • Determined the irradiation time in a gamma facility to test the vacuum window. • Neutron and gamma dose rate maps in the Port Area for proposed substrate and coatings. - Abstract: The paper focuses on the nuclear analyses of the ITER Equatorial Port Visible/Infrared Wide Angle Viewing System (VIS/IR WAVS). This instrument comprises of viewing systems in the 4 Equatorial Ports (EP) 3, 9, 12 and 17. The main mission of this diagnostic is to support the operation of the tokamak by providing visible and infrared viewing and temperature data of the first wall to protect it from damage. Its design is driven by both the tokamak severe environment and the high performances required for machine protection. New nuclear studies have been carried out for the development of the diagnostic and for test purposes under ITER-like irradiation conditions in order to choose the most appropriate materials for the optical components. Thus, three neutronic analyses have been carried out: the first in order to verify if silver could be used as a covering material for the optical components in different location of the Interspace area; the second in order to establish the irradiation time required in a Co-60 gamma facility (at CIEMAT) for testing purposes of the sapphire vacuum window; and the third to give more detailed specifications for the irradiation campaigns under gamma (in the Co-60 facility) and neutrons (at SCK·CEN BR2 reactor), about the time required to achieve the same dose than the one accumulated in ITER at the end-of-life (EOL) in the different components of the Port Area for the materials proposed as substrate and coatings. The neutronic and activation calculations have been performed using the Monte Carlo code MCNP5, the activation code ACAB and the cross section

  3. Green tea polyphenol, (−)-epigallocatechin-3-gallate, induces toxicity in human skin cancer cells by targeting β-catenin signaling

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Tripti [Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); Katiyar, Santosh K., E-mail: skatiyar@uab.edu [Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); Birmingham Veterans Affairs Medical Center, Birmingham, AL 35233 (United States)

    2013-12-01

    The green tea polyphenol, (−)-epigallocatechin-3-gallate (EGCG), has been shown to have anti-carcinogenic effects in several skin tumor models, and efforts are continued to investigate the molecular targets responsible for its cytotoxic effects to cancer cells. Our recent observation that β-catenin is upregulated in skin tumors suggested the possibility that the anti-skin carcinogenic effects of EGCG are mediated, at least in part, through its effects on β-catenin signaling. We have found that treatment of the A431 and SCC13 human skin cancer cell lines with EGCG resulted in reduced cell viability and increased cell death and that these cytotoxic effects were associated with inactivation of β-catenin signaling. Evidence of EGCG-induced inactivation of β-catenin included: (i) reduced accumulation of nuclear β-catenin; (ii) enhanced levels of casein kinase1α, reduced phosphorylation of glycogen synthase kinase-3β, and increased phosphorylation of β-catenin on critical serine{sup 45,33/37} residues; and (iii) reduced levels of matrix metalloproteinase (MMP)-2 and MMP-9, which are down-stream targets of β-catenin. Treatment of cells with prostaglandin E2 (PGE{sub 2}) enhanced the accumulation of β-catenin and enhanced β-catenin signaling. Treatment with either EGCG or an EP2 antagonist (AH6809) reduced the PGE{sub 2}-enhanced levels of cAMP, an upstream regulator of β-catenin. Inactivation of β-catenin by EGCG resulted in suppression of cell survival signaling proteins. siRNA knockdown of β-catenin in A431 and SCC13 cells reduced cell viability. Collectively, these data suggest that induction of cytotoxicity in skin cancer cells by EGCG is mediated by targeting of β-catenin signaling and that the β-catenin signaling is upregulated by inflammatory mediators. - Highlights: • EGCG inhibits cancer cell viability through inactivation of β-catenin signaling. • Inactivation of β-catenin involves the downregulation of inflammatory mediators. • EGCG

  4. Prostaglandin E2 stimulates normal bronchial epithelial cell growth through induction of c-Jun and PDK1, a kinase implicated in oncogenesis.

    Science.gov (United States)

    Fan, Yu; Wang, Ye; Wang, Ke

    2015-12-18

    Cyclooxygenase-2-derived prostaglandin E2 (PGE2), a bioactive eicosanoid, has been implicated in many biological processes including reproduction, inflammation and tumor growth. We previously showed that PGE2 stimulated lung cancer cell growth and progression through PGE2 receptor EP2/EP4-mediated kinase signaling pathways. However, the role of PGE2 in controlling lung airway epithelial cell phenotype remains unknown. We evaluated the effects of c-Jun and 3-phosphoinositede dependent protein kinase-1 (PDK1) in mediating epithelial cell hyperplasia induced by PGE2. The bronchial epithelial cell lines BEAS-2B and HBEc14-KT were cultured and then treated with PGE2. PDK1 small interfering RNA (siRNA) and a PDK1 inhibitor, an antagonist of the PGE2 receptor subtype EP4 and EP4 siRNA, c-Jun siRNA, and overexpressions of c-Jun and PDK1 have been used to evaluate the effects on cell proliferation. We demonstrated that PGE2 increased normal bronchial epithelial cell proliferation through induction of PDK1, an ankyrin repeat-containing Ser/Thr kinase implicated in the induction of apoptosis and the suppression of tumor growth. PDK1 siRNA and a PDK1 inhibitor blocked the effects of PGE2 on normal cell growth. The PGE2-induced PDK1 expression was blocked by an antagonist of the PGE2 receptor subtype EP4 and by EP4 siRNA. In addition, we showed that induction of PDK1 by PGE2 was associated with induction of the transcription factor, c-Jun protein. Silencing of c-Jun using siRNA and point mutations of c-Jun sites in the PDK1 gene promoter resulted in blockade of PDK1 expression and promoter activity induced by PGE2. In contrast, overexpression of c-Jun induced PDK1 gene promoter activity and expression followed increased cell proliferation. PGE2 increases normal bronchial epithelial cell proliferation through increased PDK1 gene expression that is dependent on EP4 and induction of c-Jun. Therewith, our data suggest a new role of c-Jun and PDK1 in mediating epithelial cell

  5. Effects of intraluteal implants of prostaglandin E1 or E2 on angiogenic growth factors in luteal tissue of Angus and Brahman cows.

    Science.gov (United States)

    Weems, Yoshie S; Ma, Yan; Ford, Stephen P; Nett, Terry M; Vann, Rhonda C; Lewis, Andrew W; Neuendorff, Don A; Welsh, Thomas H; Randel, Ronald D; Weems, Charles W

    2014-12-01

    Previously, it was reported that intraluteal implants containing prostaglandin E1 or E2 (PGE1 and PGE2) in Angus or Brahman cows prevented luteolysis by preventing loss of mRNA expression for luteal LH receptors and luteal unoccupied and occupied LH receptors. In addition, intraluteal implants containing PGE1 or PGE2 upregulated mRNA expression for FP prostanoid receptors and downregulated mRNA expression for EP2 and EP4 prostanoid receptors. Luteal weight during the estrous cycle of Brahman cows was reported to be lesser than that of Angus cows but not during pregnancy. The objective of this experiment was to determine whether intraluteal implants containing PGE1 or PGE2 alter vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2), angiopoietin-1 (ANG-1), and angiopoietin-2 (ANG-2) protein in Brahman or Angus cows. On Day 13 of the estrous cycle, Angus cows received no intraluteal implant and corpora lutea were retrieved, or Angus and Brahman cows received intraluteal silastic implants containing vehicle, PGE1, or PGE2 on Day 13 and corpora lutea were retrieved on Day 19. Corpora lutea slices were analyzed for VEGF, FGF-2, ANG-1, and ANG-2 angiogenic proteins via Western blot. Day-13 Angus cow luteal tissue served as preluteolytic controls. Data for VEGF were not affected (P > 0.05) by day, breed, or treatment. PGE1 or PGE2 increased (P Angus cows compared with Day-13 and Day-19 Angus controls but decreased (P Angus controls. There was no effect (P > 0.05) of PGE1 or PGE2 on ANG-1 in Angus luteal tissue when compared with Day-13 or Day-19 controls, but ANG-1 was decreased (P Angus Vehicle controls when compared with Day-13 Angus controls, which was prevented (P Angus cows. There was no effect (P > 0.05) of PGE1 or PGE2 on ANG-2 in Brahman cows. PGE1 or PGE2 may alter cow luteal FGF-2, ANG-1, or ANG-2 but not VEGF to prevent luteolysis; however, species or breed differences may exist. Published by Elsevier Inc.

  6. Effects of different moving devices at loading on stress response and meat quality in pigs.

    Science.gov (United States)

    Correa, J A; Torrey, S; Devillers, N; Laforest, J P; Gonyou, H W; Faucitano, L

    2010-12-01

    Although there is increasing evidence regarding the negative welfare and meat quality implications of electric prod use for slaughter-weight pigs, this handling tool continues to be used. Therefore, the behavioral and physiological response and carcass and meat quality of 360 pigs being loaded onto a truck for transportation to slaughter according to 3 handling procedures were studied. The 3 handling procedures were 1) moving with an electric prod and board from the finishing pen to the truck (EP); 2) moving with a board and a paddle from the finishing pen to the truck (PAD); 3) moving with a board and a paddle from the finishing pen and using a compressed air prod in the ramp before going into the truck (CAP). A subpopulation of 144 pigs (48 pigs/treatment) was equipped with heart rate monitors. Blood samples were collected from the same animals at exsanguination for the analysis of creatine phosphokinase and lactate. Data were analyzed using an ANOVA for factorial design, with the animal as the experimental unit. Behavior was analyzed with MIXED model procedure with treatment as a fixed effect. During loading, EP pigs slipped and fell (P moved with PAD and CAP at loading (P < 0.001), wait at loading (P < 0.001), at unloading (P = 0.05), and in lairage (P = 0.02). Pigs loaded with EP had greater (P = 0.05) lactate concentrations in blood at exsanguination compared with pigs handled with CAP, with pigs loaded with PAD being intermediate. Furthermore, ultimate pH values in the semimembranosus and adductor muscles of EP pigs were greater (P = 0.002 and P = 0.004, respectively) compared with those from PAD and CAP pigs. Greater (P = 0.04) incidence of blood-splashed hams was found in EP pigs compared with PAD and CAP pigs. Therefore, considering animal welfare, carcass bruising, and blood splashes standpoints, EP should be replaced with PAD or CAP. However, additional research is necessary to identify methods that improve the loading efficiencies of PAD and CAP

  7. Raw and extruded pea (Pisum sativum and lupin (Lupinus albusvar. Multitalia seeds as protein sources in weaned piglets’ diets: effect on growth rate and blood parameters

    Directory of Open Access Journals (Sweden)

    Gianfranco Piva

    2010-01-01

    Full Text Available The 42 days trial was carried out using 140 piglets weaned at 28 days of age. The piglets were allocated according to  weight and sex to the 5 dietary treatments with 7 replicates for each treatments (4 pens x 4 castrated males and 3 pens  x 4 females. The piglets were fed according to the following experimental design: 1 control diet (CTR with soybean  meal (SBM 44% c.p. as protein source; 2 CRT diets with 200 g/kg of raw pea (Pisum sativum (RP; 3 CTR diet with  200 g/kg extruded pea (EP; 4 CRT diet with 170 g/kg raw lupin (Lupinus albusvar. Multitalia (RL; 5 CTR diet with  170 g/kg of extruded lupin (EL. During the trial, animals were weighed at 0 - 21 and 42 days from the start of the trial.  Feed intake was monitored and feed conversion ratio was calculated for the periods 0-21 d and 22-42 d. At the end of  the trial, blood samples were taken for 14 animals for each dietary treatment (2 animals per replicate and analysed for  total protein, urea and liver activity (ALT, AST and ALP parameters. Average daily weight gain and feed intake did not  differ according to dietary treatments whereas during the total experimental period (0-42 d, feed conversion ratio was  higher for EP vsCTR diet (2.35 vs2.09, respectively; P   compared with diets containing the raw ingredients did not differ. Feed conversion ratio for the RP was numerically high-  er than for the EP (2.35 vs2.16 and 2.76 vs2.32, respectively during 22-42 d and 0-42 d periods. Blood parameters  did not show significant difference among dietary treatments except for higher total protein for CTR diet vsRL diet, EL  and RP (67.3 vs62.2, 62.8 and 63.6 g/l, respectively; PvsRL  and RL (4.7 vs3.7 and 3.8 mmol/l respectively; P 

  8. MEASUREMENT OF LARGE-SCALE SOLAR POWER PLANT BY USING IMAGES ACQUIRED BY NON-METRIC DIGITAL CAMERA ON BOARD UAV

    Directory of Open Access Journals (Sweden)

    R. Matsuoka

    2012-07-01

    Full Text Available This paper reports an experiment conducted in order to investigate the feasibility of the deformation measurement of a large-scale solar power plant on reclaimed land by using images acquired by a non-metric digital camera on board a micro unmanned aerial vehicle (UAV. It is required that a root mean squares of errors (RMSE in height measurement should be less than 26 mm that is 1/3 of the critical limit of deformation of 78 mm off the plane of a solar panel. Images utilized in the experiment have been obtained by an Olympus PEN E-P2 digital camera on board a Microdrones md4-1000 quadrocopter. The planned forward and side overlap ratios of vertical image acquisition have been 60 % and 60 % respectively. The planned flying height of the UAV has been 20 m above the ground level and the ground resolution of an image is approximately 5.0 mm by 5.0 mm. 8 control points around the experiment area are utilized for orientation. Measurement results are evaluated by the space coordinates of 220 check points which are corner points of 55 solar panels selected from 1768 solar panels in the experiment area. Two teams engage in the experiment. One carries out orientation and measurement by using 171 images following the procedure of conventional aerial photogrammetry, and the other executes those by using 126 images in the manner of close range photogrammetry. The former fails to satisfy the required accuracy, while the RMSE in height measurement by the latter is 8.7 mm that satisfies the required accuracy. From the experiment results, we conclude that the deformation measurement of a large-scale solar power plant on reclaimed land by using images acquired by a nonmetric digital camera on board a micro UAV would be feasible if points utilized in orientation and measurement have a sufficient number of bundles in good geometry and self-calibration in orientation is carried out.

  9. Identification of Biomarkers of Impaired Sensory Profiles among Autistic Patients

    Science.gov (United States)

    El-Ansary, Afaf; Hassan, Wail M.; Qasem, Hanan; Das, Undurti N.

    2016-01-01

    Background Autism is a neurodevelopmental disorder that displays significant heterogeneity. Comparison of subgroups within autism, and analyses of selected biomarkers as measure of the variation of the severity of autistic features such as cognitive dysfunction, social interaction impairment, and sensory abnormalities might help in understanding the pathophysiology of autism. Methods and Participants In this study, two sets of biomarkers were selected. The first included 7, while the second included 6 biomarkers. For set 1, data were collected from 35 autistic and 38 healthy control participants, while for set 2, data were collected from 29 out of the same 35 autistic and 16 additional healthy subjects. These markers were subjected to a principal components analysis using either covariance or correlation matrices. Moreover, libraries composed of participants categorized into units were constructed. The biomarkers used include, PE (phosphatidyl ethanolamine), PS (phosphatidyl serine), PC (phosphatidyl choline), MAP2K1 (Dual specificity mitogen-activated protein kinase kinase 1), IL-10 (interleukin-10), IL-12, NFκB (nuclear factor-κappa B); PGE2 (prostaglandin E2), PGE2-EP2, mPGES-1 (microsomal prostaglandin synthase E-1), cPLA2 (cytosolic phospholipase A2), 8-isoprostane, and COX-2 (cyclo-oxygenase-2). Results While none of the studied markers correlated with CARS and SRS as measure of cognitive and social impairments, six markers significantly correlated with sensory profiles of autistic patients. Multiple regression analysis identifies a combination of PGES, mPGES-1, and PE as best predictors of the degree of sensory profile impairment. Library identification resulted in 100% correct assignments of both autistic and control participants based on either set 1 or 2 biomarkers together with a satisfactory rate of assignments in case of sensory profile impairment using different sets of biomarkers. Conclusion The two selected sets of biomarkers were effective to

  10. Suppression of annexin A2 by prostaglandin E₂ impairs phagocytic ability of peritoneal macrophages in women with endometriosis.

    Science.gov (United States)

    Wu, Meng-Hsing; Chuang, Pei-Chin; Lin, Yiu-Juian; Tsai, Shaw-Jenq

    2013-04-01

    Is annexin A2 involved in the reduced phagocytic ability of macrophages in endometriosis? Data from women with endometriosis and a murine model of the disease show that expression of annexin A2 in peritoneal macrophages is inhibited by prostaglandin E2 (PGE2) and this impairs the phagocytic ability of macrophages. Endometriosis is a chronic inflammatory disease that recruits many immune cells, especially macrophages, to the peritoneal cavity. The phagocytic ability of peritoneal macrophages isolated from women with endometriosis is reduced. A laboratory study. Thirty-five patients (20 with and 15 without endometriosis) of reproductive age with normal menstrual cycles were recruited. Peritoneal macrophages isolated from women with or without endometriosis were cultured and treated with vehicle, PGE2 and different EP receptor agonists, and the expression of annexin A2 was quantified by RT-PCR and western blotting. Annexin A2 was knocked down (by small interfering RNA) in normal macrophages or overexpressed (by treatment with recombinant protein) in endometriotic macrophages and their phagocytic ability was measured by flow cytometry. Peritoneal macrophages were isolated from a mouse model of endometriosis and treated with PGE2 or cyclo-oxygenase (COX) inhibitors, and annexin A2 mRNA was quantified. Levels of annexin A2 were markedly reduced in peritoneal macrophages from women with endometriosis versus controls (mRNA: P endometriosis versus control) via the EP2/EP4 receptor-dependent signaling pathway. Treatment with PGE2 or knockdown of annexin A2 inhibited the phagocytic ability of macrophages (P peritoneal macrophages were markedly reduced in mice treated with PGE2 (P peritoneal macrophages (P peritoneal cells from patients with endometriosis or that their endometriotic fluid contains increased amounts of PGE2 when compared with control subjects. Inhibiting PGE2 signaling, in order to restore or enhance the phagocytic capability of macrophages, may represent a new

  11. Modulation of insulin-like growth factor 1 levels in human osteoarthritic subchondral bone osteoblasts.

    Science.gov (United States)

    Massicotte, Frédéric; Fernandes, Julio Cesar; Martel-Pelletier, Johanne; Pelletier, Jean-Pierre; Lajeunesse, Daniel

    2006-03-01

    Human osteoarthritis (OA) is characterized by cartilage loss, bone sclerosis, osteophyte formation and inflammation of the synovial membrane. We previously reported that OA osteoblasts (Ob) show abnormal phenotypic characteristics possibly responsible for bone sclerosis and that two subgroups of OA patients can be identified by low or high endogenous production of prostaglandin E2 (PGE2) by OA Ob. Here, we determined that the elevated PGE2 levels in the high OA subgroup were linked with enhanced cyclooxygenase-2 (COX-2) protein levels compared to normal and low OA Ob. A linear relationship was observed between endogenous PGE2 levels and insulin-like growth factor 1 (IGF-1) levels in OA Ob. As parathyroid hormone (PTH) and PGE2 are known stimulators of IGF-1 production in Ob, we next evaluated their effect in OA Ob. Both subgroups increased their IGF-1 production similarly in response to PGE2, while the high OA subgroup showed a blunted response to PTH compared to the low OA group. Conversely, only the high OA group showed a significant inhibition of IGF-1 production when PGE2 synthesis was reduced with Naproxen, a non-steroidal antiinflammatory drug (NSAID) that inhibits cyclooxygenases (COX). The PGE2-dependent stimulation of IGF-1 synthesis was due in part to the cAMP/protein kinase A pathway since both the direct inhibition of this pathway with H-89 and the inhibition of EP2 or EP4 receptors, linked to cAMP production, reduced IGF-1 synthesis. The production of the most abundant IGF-1 binding proteins (IGFBPs) in bone tissue, IGFBP-3, -4, and -5, was lower in OA compared to normal Ob independently of the OA group. Under basal condition, OA Ob expressed similar IGF-1 mRNA to normal Ob; however, PGE2 stimulated IGF-1 mRNA expression more in OA than normal Ob. These data suggest that increased IGF-1 levels correlate with elevated endogenous PGE2 levels in OA Ob and that higher IGF-1 levels in OA Ob could be important for bone sclerosis in OA.

  12. "Since both of us are using antiretrovirals, we have been supportive to each other": facilitators and barriers of pre-exposure prophylaxis use in heterosexual HIV serodiscordant couples in Kisumu, Kenya.

    Science.gov (United States)

    Patel, Rena C; Stanford-Moore, Gaelen; Odoyo, Josephine; Pyra, Maria; Wakhungu, Imeldah; Anand, Keerthana; Bukusi, Elizabeth A; Baeten, Jared M; Brown, Joelle M

    2016-01-01

    Since 2015, the World Health Organization recommends pre-exposure prophylaxis (PrEP) for all persons at substantial risk for HIV, including HIV-uninfected partners in serodiscordant relationships in resource-limited settings. As PrEP moves from clinical trials to real-world use, understanding facilitators of and barriers to PrEP initiation and adherence is critical to successful PrEP implementation and rollout. We conducted 44 in-depth individual or couple interviews with 63 participants (30 without HIV and 33 with HIV) enrolled in the Partners Demonstration Project in Kisumu, Kenya, between August and September 2014. The semi-structured interviews discussed the following: 1) perceived advantages and disadvantages of antiretroviral therapy (ART)/PrEP; 2) reasons for accepting or declining ART/PrEP and 3) influence of prevention of transmission to partner or infant on ART/PrEP use. Transcripts from the interviews were iteratively analyzed using inductive content analysis. Our study identified three key factors that may facilitate initiation of PrEP in this population. First, participants using PrEP felt reduced stress and increased trust in their HIV serodiscordant relationships. Second, greater community-wide knowledge of PrEP was thought to likely increase PrEP acceptance. Third, greater education and counselling by providers on PrEP use was also considered to likely increase the adoption of PrEP. We also identified three key barriers to initiation of and adherence to PrEP. First, most participants who declined PrEP expressed doubts about the relative additional effectiveness of PrEP in combination with other prevention tools. Second, perceived stigma related to PrEP use was an important barrier to PrEP initiation. Third, many struggled with overcoming perceived side effects or logistical challenges of taking daily PrEP, particularly when they themselves were not ill. Leveraging the facilitators and overcoming barriers to PrEP uptake may enhance the successful

  13. A genitália externa na tribo Bolboderini (Hemiptera, Reduviidae, Triatominae

    Directory of Open Access Journals (Sweden)

    Herman Lent

    1984-03-01

    Full Text Available Sete espécies da tribo bolboderini, pertencentes aos gêneros Bolbodera, Belminus, Microtriatoma e Parabelminus, duas das quais já encontradas naturalmente infectadas com Trypanosoma cruzi, foram analisadas e comparadas tendo como enfoque oito estruturas da genitália externa dos machos: Processo mediano do pigóforo (PrP, Processo da conjuntiva (PrCj, Extensão mediana da placa basal (EPIb, Processo do endosoma (PrEn, Suporte do falosoma (SPh, Falosoma (Ph, Processo do gonoporo (PrG e a Vesica (V. Microtriatoma trinidadensis (lent, 1951 e M. borbai Lent & Wygodzinsky, 1979 mostraram um plano estrutural morfológico semelhante a Parabelminus yurupucu Lent & Wygodzinsky, 1979 e P. carioca Lent, 1943 e deferindo nitidamente de Belminus peruvianus Herrer, Lent & Wygodzinsky, 1954 e B. herreri Lent & Wygodzinsky, 1979 e de Bolbodera scabrosa, Valdés, 1910, não só pela ausência como pela forma de determinadas estruturas. Estas observações comparativas confirmam as afinidades entre Microtriatoma e Parabelminus e suas relações com belminus e Bolbodera.Seven species of the Bolboderini tribe belonging to the genera bolbodera, Belminus, Microtriatoma and Parabelminus, two of them found naturally infected with Trypanosoma cruzi, were analysed and compared emphasizing eight structures of the male external genitalia: median process of pygophore (PrP, conjunctiva process (PrCj, pedicel (EP1b, endosoma process (PrEn, struts (SPh, phallosoma (Ph, medium bridge (PrG and vesica (V. Microtriatoma trinidadensis (Lent, 1951 and M. borbai Lent & Wygodzinsky, 1979 have shown a structural morphological aspect similar to Parabelminus yurupucu Lent & Wygodzinsky, 1979 and P. carioca Lent, 1943 differing clearly from Belminus peruvianus Herrer, Lent & Wygodzinsky, 1954, B. herreri Lent & Wygodzinsky, 1979 and Bolbodera scabrosa valdés, 1910, not only by the absence but by the shape of some structures. These comparative observations confirm the affinity between

  14. Proneoplastic effects of PGE2 mediated by EP4 receptor in colorectal cancer.

    LENUS (Irish Health Repository)

    Doherty, Glen A

    2009-01-01

    BACKGROUND: Prostaglandin E2 (PGE2) is the major product of Cyclooxygenase-2 (COX-2) in colorectal cancer (CRC). We aimed to assess PGE2 cell surface receptors (EP 1-4) to examine the mechanisms by which PGE2 regulates tumour progression. METHODS: Gene expression studies were performed by quantitative RT-PCR. Cell cycle was analysed by flow cytometry with cell proliferation quantified by BrdU incorporation measured by enzyme immunoassay. Immunohistochemistry was employed for expression studies on formalin fixed paraffin embedded tumour tissue. RESULTS: EP4 was the most abundant subtype of PGE2 receptor in HT-29 and HCA7 cells (which show COX-2 dependent PGE2 generation) and was consistently the most abundant transcript in human colorectal tumours (n = 8) by qRT-PCR (ANOVA, p = 0.01). G0\\/G1 cell cycle arrest was observed in HT-29 cells treated with SC-236 5 microM (selective COX-2 inhibitor) for 24 hours (p = 0.02), an effect abrogated by co-incubation with PGE2 (1 microM). G0\\/G1 arrest was also seen with a specific EP4 receptor antagonist (EP4A, L-161982) (p = 0.01). Treatment of HT-29 cells with either SC-236 or EP4A caused reduction in intracellular cAMP (ANOVA, p = 0.01). Early induction in p21WAF1\\/CIP1 expression (by qRT-PCR) was seen with EP4A treatment (mean fold increase 4.4, p = 0.04) while other genes remained unchanged. Similar induction in p21WAF1\\/CIP1 was also seen with PD153025 (1 microM), an EGFR tyrosine kinase inhibitor, suggesting EGFR transactivation by EP4 as a potential mechanism. Additive inhibition of HCA7 proliferation was observed with the combination of SC-236 and neutralising antibody to amphiregulin (AR), a soluble EGFR ligand. Concordance in COX-2 and AR localisation in human colorectal tumours was noted. CONCLUSION: COX-2 regulates cell cycle transition via EP4 receptor and altered p21WAF1\\/CIP1 expression. EGFR pathways appear important. Specific targeting of the EP4 receptor or downstream targets may offer a safer alternative

  15. Quantitative multiparametric MRI in uveal melanoma: increased tumor permeability may predict monosomy 3

    Energy Technology Data Exchange (ETDEWEB)

    Kamrava, Mitchell; Wang, Pin-Chieh; Roberts, Kristofer; Demanes, D.J. [University of California Los Angeles, Department of Radiation Oncology, Los Angeles, CA (United States); Sepahdari, Ali R.; Leu, Kevin; Ellingson, Benjamin M. [University of California Los Angeles, Department of Radiological Sciences, Los Angeles, CA (United States); McCannel, Tara [University of California Los Angeles, Department of Ophthalmology, Los Angeles, CA (United States)

    2015-08-15

    Uveal melanoma is a rare intraocular tumor with heterogeneous biological behavior, and additional noninvasive markers that may predict outcome are needed. Diffusion- and perfusion-weighted imaging may prove useful but have previously been limited in their ability to evaluate ocular tumors. Our purpose was to show the feasibility and potential value of a multiparametric (mp-) MRI protocol employing state of the art diffusion- and perfusion-weighted imaging techniques. Sixteen patients with uveal melanoma were imaged with mp-MRI. Multishot readout-segmented echoplanar diffusion-weighted imaging, quantitative dynamic contrast-enhanced (DCE) MR perfusion imaging, and anatomic sequences were obtained. Regions of interest (ROIs) were drawn around tumors for calculation of apparent diffusion coefficient (ADC) and perfusion metrics (K{sup trans}, v{sub e}, k{sub ep}, and v{sub p}). A generalized linear fit model was used to compare various MRI values with the American Joint Commission on Cancer (AJCC) tumor group and monosomy 3 status with significance set at P < 0.05. mp-MRI was performed successfully in all cases. MRI tumor height (mean [standard deviation]) was 6.5 mm (3.0). ROI volume was 278 mm{sup 3} (222). ADC was 1.07 (0.27) x 10-3 mm{sup 2}/s. DCE metrics were K{sup trans} 0.085/min (0.063), v{sub e} 0.060 (0.052), k{sub ep} 1.20/min (0.32), and v{sub p} 1.48 % (0.82). Patients with >33 % monosomy 3 had higher K{sup trans} and higher v{sub e} values than those with disomy 3 or ≤33 % monosomy (P < 0.01). There were no significant differences between ADC (P = 0.07), k{sub ep} (P = 0.37), and v{sub p} with respect to monosomy 3. mp-MRI for ocular tumor imaging using multishot EPI DWI and quantitative DCE perfusion is technically feasible. mp-MRI may help predict monosomy 3 in uveal melanoma. (orig.)

  16. Coulomb excitation of radioactive Na21 and its stable mirror Ne21

    Science.gov (United States)

    Schumaker, M. A.; Cline, D.; Hackman, G.; Morton, A. C.; Pearson, C. J.; Svensson, C. E.; Wu, C. Y.; Andreyev, A.; Austin, R. A. E.; Ball, G. C.; Bandyopadhyay, D.; Becker, J. A.; Boston, A. J.; Boston, H. C.; Buchmann, L.; Churchman, R.; Cifarelli, F.; Cooper, R. J.; Cross, D. S.; Dashdorj, D.; Demand, G. A.; Dimmock, M. R.; Drake, T. E.; Finlay, P.; Gallant, A. T.; Garrett, P. E.; Green, K. L.; Grint, A. N.; Grinyer, G. F.; Harkness, L. J.; Hayes, A. B.; Kanungo, R.; Leach, K. G.; Lee, G.; Maharaj, R.; Martin, J.-P.; Moisan, F.; Mythili, S.; Nelson, L.; Newman, O.; Nolan, P. J.; Orce, J. N.; Padilla-Rodal, E.; Phillips, A. A.; Porter-Peden, M.; Ressler, J. J.; Roy, R.; Ruiz, C.; Sarazin, F.; Scraggs, D. P.; Waddington, J. C.; Wan, J. M.; Whitbeck, A.; Williams, S. J.; Wong, J.

    2008-10-01

    The low-energy structures of the mirror nuclei Ne21 and radioactive Na21 have been examined by using Coulomb excitation at the TRIUMF-ISAC radioactive ion beam facility. Beams of ~5×106 ions/s were accelerated to 1.7 MeV/A and Coulomb excited in a 0.5 mg/cm2 natTi target. Scattered beam and target particles were detected by the segmented Si detector BAMBINO, while γ rays were observed by using two TIGRESS HPGe clover detectors perpendicular to the beam axis. For each isobar, Coulomb excitation from the (3)/(2)+ ground state to the first excited (5)/(2)+ state was observed and B(E2) values were determined by using the 2+→0+ de-excitation in Ti48 as a reference. The ϕ segmentation of BAMBINO was used to deduce tentative assignments for the signs of the mixing ratios between the E2 and M1 components of the transitions. The resulting B(E2)↑ values are 131±9e2 fm4 (25.4±1.7 W.u.) for Ne21 and 205±14e2 fm4 (39.7±2.7 W.u.) for Na21. The fit to the present data and the known lifetimes determined E2/M1 mixing ratios and B(M1)↓ values of δ=(-)0.0767±0.0027 and 0.1274±0.0025μN2 and δ=(+)0.0832±0.0028 and 0.1513±0.0017μN2 for Ne21 and Na21, respectively (with Krane and Steffen sign convention). By using the effective charges ep=1.5e and en=0.5e, the B(E2) values produced by the p-sd shell model are 30.7 and 36.4 W.u. for Ne21 and Na21, respectively. This analysis resolves a significant discrepancy between a previous experimental result for Na21 and shell-model calculations.

  17. Characterisation of the exopolysaccharide (EPS)-producing Lactobacillus paraplantarum BGCG11 and its non-EPS producing derivative strains as potential probiotics.

    Science.gov (United States)

    Nikolic, Milica; López, Patricia; Strahinic, Ivana; Suárez, Ana; Kojic, Milan; Fernández-García, María; Topisirovic, Ljubisa; Golic, Natasa; Ruas-Madiedo, Patricia

    2012-08-17

    PBMC were stimulated with increasing concentrations of the purified ropy EPS (1, 10 and 100μg/ml) the cytokine profile was similar to that obtained with the EPS-producing lactobacilli, therefore pointing to a putative role of this biopolymer in its immune response. Copyright © 2012 Elsevier B.V. All rights reserved.

  18. Cytotoxic and pro-oxidative effects of Imperata cylindrica aerial part ethyl acetate extract in colorectal cancer in vitro.

    Science.gov (United States)

    Kwok, Amy Ho Yan; Wang, Yan; Ho, Wing Shing

    2016-05-15

    Colorectal cancer (CRC) is the third most common cancer. Its global incidence and mortality have been on the rise. Recent strategy of therapies has involved the use of non-steroid anti-inflammatory drugs and cyclooxygenase-selective inhibitors. Aerial parts of Imperata cylindrical L. Raeusch (IMP) have been used as an anti-inflammatory agent in traditional Chinese medicine. Asarachidonate acid cascadeis often involved in inflammation-related malignancy and IMP is an anti-inflammatory agent, hence it is hypothesized that IMP aerial part ethyl acetate extract exerts cytotoxic effects on colorectal cancer cells in vitro. The HT-29 adenocarcinoma cell line was used to elucidate its pro-apoptotic activities. Flow cytometry and fluorescent microscopy were performed to assess cell cycle arrest and the accumulation of reactive oxygen species (ROS). The mRNA and hormone levels of arachidonate acid pathways were studied via quantitative reverse transcription PCR (qRT-PCR) and ELISA. The 50% growth inhibitory effect (GI50) of the IMP extract on HT-29 was measured with a value of 14.5 µg/ml. Immuno-blot and caspase-3/7 activity assay showed the pro-apoptotic effect of IMP on the activation of caspase cascade. G2/M arrest was observed via flow cytometry. The ROS activity was modulated by the IMP extraction a concentration-dependent manner in HT-29 cells. The IMP extract increased PGE2 and PGF2α levels qRT-PCR revealed that transcripts of rate-limiting PGE2- and PGF2α-biosynthetic enzymes - COX-1, mPGES1 and AKR1C3 were notably up-regulated. Among the prostanoid receptors, EP1 and FP transcripts were up-regulated while EP4 transcripts decreased. The findings suggest that the proliferative effect of PGE2, which is generally believed to associate with heightened DNA synthesis and cross-talk with MAPK pathways, is likely triggered by the pro-apoptotic or -oxidative effects exerted by IMP extract in HT-29 cells. Concurring with this notion, indomethacin (COX-1/2-inhibitor) was

  19. Roles of iron species and pH optimization on sewage sludge conditioning with Fenton's reagent and lime.

    Science.gov (United States)

    Yu, Wenbo; Yang, Jiakuan; Shi, Yafei; Song, Jian; Shi, Yao; Xiao, Jun; Li, Chao; Xu, Xinyu; He, Shu; Liang, Sha; Wu, Xu; Hu, Jingping

    2016-05-15

    Conditioning sewage sludge with Fenton's reagent could effectively improve its dewaterability. However, drawbacks of conditioning with Fenton's reagent are requirement of acidic conditions to prevent iron precipitation and subsequent neutralization with alkaline additive to obtain the pH of the filtrate close to neutrality. In this study, roles of pH were thoroughly investigated in the acidification pretreatment, Fenton reaction, and the final filtrate after conditioning. Through the response surface methodology (RSM), the optimal dosages of H2SO4, Fe(2+), H2O2, and lime acted as a neutralizer were found to be 0 (no acidification), 47.9, 34.3 and 43.2 mg/g DS (dry solids). With those optimal doses, water content of the dewatered sludge cakes could be reduced to 55.8 ± 0.6 wt%, and pH of the final filtrate was 6.6 ± 0.2. Fenton conditioning without initial acidification can simplify the conditioning process and reduce the usage of lime. The Fe(3+) content in the sludge cakes showed a close correlation with the dewaterability of conditioned sludge, i.e., the water content of sludge cakes, SRF (specific resistance to filtration), CST (capillary suction time), bound water content, and specific surface area. It indicated that the coagulation by Fe(3+) species in Fenton reaction could play an important role, compared to traditional Fenton oxidation effect on sludge conditioning. Thus, a two-step mechanism of Fenton oxidation and Fe(III) coagulation was proposed in sewage sludge conditioning. The mechanisms include the following: (1) extracellular polymeric substances (EPS) were firstly degraded into dissolved organics by Fenton oxidation; (2) bound water was converted to free water due to degradation of EPS; (3) the sludge particles were disintegrated into small ones by oxidation; (4) Fe(3+) generated from Fenton reaction acted as a coagulant to agglomerate smaller sludge particles into larger dense particles with less bond water; (5) finally, the dewatered

  20. The development of antiretroviral therapy and its impact on the HIV-1/AIDS pandemic.

    Science.gov (United States)

    Broder, Samuel

    2010-01-01

    In the last 25 years, HIV-1, the retrovirus responsible for the acquired immunodeficiency syndrome (AIDS), has gone from being an "inherently untreatable" infectious agent to one eminently susceptible to a range of approved therapies. During a five-year period, starting in the mid-1980s, my group at the National Cancer Institute played a role in the discovery and development of the first generation of antiretroviral agents, starting in 1985 with Retrovir (zidovudine, AZT) in a collaboration with scientists at the Burroughs-Wellcome Company (now GlaxoSmithKline). We focused on AZT and related congeners in the dideoxynucleoside family of nucleoside reverse transcriptase inhibitors (NRTIs), taking them from the laboratory to the clinic in response to the pandemic of AIDS, then a terrifying and lethal disease. These drugs proved, above all else, that HIV-1 infection is treatable, and such proof provided momentum for new therapies from many sources, directed at a range of viral targets, at a pace that has rarely if ever been matched in modern drug development. Antiretroviral therapy has brought about a substantial decrease in the death rate due to HIV-1 infection, changing it from a rapidly lethal disease into a chronic manageable condition, compatible with very long survival. This has special implications within the classic boundaries of public health around the world, but at the same time in certain regions may also affect a cycle of economic and civil instability in which HIV-1/AIDS is both cause and consequence. Many challenges remain, including (1) the life-long duration of therapy; (2) the ultimate role of pre-exposure prophylaxis (PrEP); (3) the cardiometabolic side-effects or other toxicities of long-term therapy; (4) the emergence of drug-resistance and viral genetic diversity (non-B subtypes); (5) the specter of new cross-species transmissions from established retroviral reservoirs in apes and Old World monkeys; and (6) the continued pace of new HIV-1

  1. EP4 as a Therapeutic Target for Aggressive Human Breast Cancer

    Directory of Open Access Journals (Sweden)

    Mousumi Majumder

    2018-03-01

    selective EP4 antagonists (EP4A could mitigate all of these events tested with cells in vitro as well as in vivo in syngeneic COX-2 expressing mammary cancer bearing mice or immune-deficient mice bearing COX-2 over-expressing human breast cancer xenografts. We suggest that EP4A can avoid thrombo-embolic side effects of long term use of COX-2 inhibitors by sparing cardio-protective roles of PGI2 via IP receptor activation or PGE2 via EP3 receptor activation. Furthermore, we identified two COX-2/EP4 induced oncogenic and SLC-stimulating microRNAs—miR526b and miR655, one of which (miR655 appears to be a potential blood biomarker in breast cancer patients for monitoring SLC-ablative therapies, such as with EP4A. We suggest that EP4A will likely produce the highest benefit in aggressive breast cancers, such as COX-2 expressing triple-negative breast cancers, when combined with other newer agents, such as inhibitors of programmed cell death (PD-1 or PD-L1.

  2. Developing of Ytrium-90 Generator Based on Extraction Chromatography with Crown Ether

    International Nuclear Information System (INIS)

    Yassine, T.; Mukhallalati, Ch.H.

    2009-01-01

    Although the use of radionuclides for therapeutic purposed goes back to about 60 years ago, but interest in this therapy is rapidly increasing in the field of nuclear medicine. The introduction and acceleration of such techniques require the continuous availability and acceptable cost of therapeutic radionuclides and radiopharmaceuticals. Most of therapeutic radionuclides, are reactor (Ho-166, Lu-177 Sm-153, I-131...). Produced ones which makes the generator produced radionuclides such Y-90, is more convenient to start with for developing therapeutic radiopharmaceutical in countries where there are no reactor. Ytrium-90 is an important radionuclide for radioimmunotherapeutic and for radiosynviorethesis. It is pure single high energy beta emitter (Ep=2.3 Mev), decaying to stable Zirconium-90 with half-life of about 64 hrs. It is availability, as generator products resulting from the decay of the long lived strontium-90 (T1/2 = 28y) has increased its importance in nuclear medicine and accelerated its applications. The AECS has initiated wide Programme for development and production of radiopharmaceuticals for covering local and regional demands of nuclear medicine. Existed facility including Cyclotron (cyclon 30 IBA), technetium-99m generator and kits production lines and iodine-131 dispensing and labeling plant, needs to be enhanced by more therapeutic products. The absence of nuclear reactor for radionuclide production makes the generator technology to be a convenient choice. Therefore, Ytrium-90 radiopharmaceuticals were targeted and 90Sr/90Y generator was developed for these purposes. Several designs of Ytrium-90 generator were developed according to different separation techniques, such as solvent extraction, ion exchange, supported liquid membrane and electrodeposition, and each has deferent characterizations and Performances. We found that extraction Chromatography by 18C6 Crown ether loaded on Teflon resins (Sr-Spec) is very convenient for Production of ultra

  3. Effects of dietary fat and crude protein on feedlot performance, carcass characteristics, and meat quality in finishing steers fed differing levels of dried distillers grains with solubles.

    Science.gov (United States)

    Gunn, P J; Weaver, A D; Lemenager, R P; Gerrard, D E; Claeys, M C; Lake, S L

    2009-09-01

    The objective of this study was to evaluate the influence of dietary protein and fat from distillers dried grains with solubles (DDGS) on feedlot performance, carcass characteristics, and meat quality in finishing steers. Angus-cross steers (n = 105; 443 +/- 20 kg of BW) were blocked by BW and randomly assigned to 1 of 5 dietary treatments: 1) corn-based diet with DDGS included at 25% of DM (CON), 2) CON with DDGS included at twice the amount of CON (50% of DM; 50DDGS), 3) CON with added corn protein to equal the CP in the 50DDGS diet (CON+CP), 4) CON with added vegetable oil to equal the fat in the 50DDGS diet (CON+VO), and 5) CON with protein and fat added to equal the CP and fat in the 50DDGS diet (CON+CPVO). Steers were fed to a common 12th-rib fat depth endpoint (1.3 +/- 0.2 cm; 68 to 125 d on trial). Loins and rounds were collected from 44 carcasses for Warner-Bratzler shear force (WBSF), ether extract, and case-life analyses. Data were analyzed using the MIXED procedure of SAS. Contrasts between 1) CON vs. elevated CP diets (50DDGS, CON+CP, and CON+CPVO; EP), 2) CON vs. elevated fat diets (50DDGS, CON+VO, and CON+CPVO; EF) and 3) CON vs. diets with elevated CP and fat (50DDGS and CON+CPVO; EPF) were analyzed. There were no differences in days on feed or DMI among treatments. Steers fed CON had greater ADG (P EPF diets. Steers fed CON also had greater G:F (P EPF steers. Final BW was greater for CON than EP and EPF diets (P EPF steers (P = 0.04). Dressing percent, 12th-rib fat depth, LM area, KPH, and yield grade were not affected by treatment (P >or= 0.06). Steers fed the CON diet had greater marbling scores (P EPF diets. There were no differences in WBSF, ether extract, or lipid oxidation due to treatment (P >or= 0.44). However, CON steers had greater (P = 0.02) L* values than EF-fed steers and greater b* values than EP, EF, and EPF steers (P

  4. R and D relative to the serious accidents in the PWR type reactors: assessment and perspectives; R and D relative aux accidents graves dans les reacteurs a eau pressurisee: bilan et perspectives

    Energy Technology Data Exchange (ETDEWEB)

    Bentaib, A.; Bonneville, H.; Caroli, H.; Chaumont, B.; Clement, B.; Cranga, M.; Koundy, V.; Laurent, B.; Micaelli, J.C.; Meignen, R.; Pichereau, F.; Plassart, D.; Van-Dorsselaere, P. [Institut de Radioprotection et de Surete Nucleaire (IRSN), 92 - Clamart (France); Ducros, G.; Journeau, Ch.; Magallon, D. [CEA Cadarache, 13 - Saint Paul lez Durance (France); Durin, M.; Studer, E. [CEA Saclay 91 - Gif sur Yvette (France); Seiler, J.M. [CEA Grenoble, 38 (France); Ranval, W. [Electricite de France (EDF), 75 - Paris (France)

    2006-07-01

    This document presents the current state of the research relative to the grave accidents realized in France and abroad. It aims at giving the most exhaustive possible and objective vision of this original field of research. He allows to contribute to the identification and to the hierarchical organization of the needs of R and D, this hierarchical organization in front of, naturally, to be completed by a strong lighting on needs in terms of safety analyses associated with the different risks and the physical phenomena, in particular with the support of probability evaluations of safety level 2, whose the level of sharpness must be sufficient not to hide, by construction, physical phenomena of which the limited knowledge leads to important uncertainties. Let us note that neither the safety analyses, nor the E.P.S. 2 are presented in this document. This report presents the physical phenomena which can arise during a grave accident, in the reactor vessel and in the reactor containment, their chain and the means allowing to ease the effects. The corresponding scenarios are presented to the chapter 2. The chapter 3 is dedicated to the progress of the accident in the reactor vessel; the degradation of the core in reactor vessel (3.1), the behavior of the corium in bottom of reactor vessel (3.2) the break of the reactor vessel (3.3) and the fusion in pressure (3.4) are thus handled there. The chapter 4 concerns the phenomena which can lead to a premature failure of the containment, namely the direct heating of gases of the containment (4.1), the hydrogen risk (4.2) and the vapor explosion (4.3). The phenomenon which can lead to a delayed failure from the containment, namely the interaction corium-concrete, is approached on the chapter 5. The chapter 6 is dedicated to the problems connected to the keeping back and to the corium cooling in reactor vessel and out of reactor vessel, namely the keeping back in reactor vessel by re-flooding of the primary circuit or by re-flooding of the well of reactor vessel (6.1), the cooling of the corium under water in the course of interaction corium-concrete (6.2), the spreading of the corium (6.3) and the recuperator out of reactor vessel (6.4). The chapter 7 concerned the release and the transport of the fission products (P.F.); it thus approaches the subjects of the release of the P.F. in reactor vessel (7.1) and out of reactor vessel (7.3), of the transport of the P.F. in the primary and secondary circuits (7.2), the behavior of aerosols in the reactor containment (7.4) and the chemistry of the P.F. (7.5). Finally, the chapter 8 presents a state of the developments and the validation of the main codes 'grave accidents': A.S.T.E.C., M.A.A.P. and M.E.L.C.O.R.. In chapters 3 - 7, for each of the reserved subjects, the involved phenomena are reminded. The main experiments realized on the subject, recent, current and foreseen, as well as the main models and the specific codes are described then briefly (except complete codes) used to simulate the phenomena in question. A state of the acquired knowledge at the moment is established and the perspectives in terms notably of experimental programs and development of modelling tools are presented. (N.C.)

  5. Concentrations of 17beta-estradiol in Holstein whole milk.

    Science.gov (United States)

    Pape-Zambito, D A; Magliaro, A L; Kensinger, R S

    2007-07-01

    Some individuals have expressed concern about estrogens in food because of their potential to promote growth of estrogen-sensitive human cancer cells. Researchers have reported concentrations of estrogen in milk but few whole milk samples have been analyzed. Because estrogen associates with the fat phase of milk, the analysis of whole milk is an important consideration. The objectives of this study, therefore, were to quantify 17beta-estradiol (E2) in whole milk from dairy cows and to determine whether E2 concentrations in milk from cows in the second half of pregnancy were greater than that in milk from cows in the first half of pregnancy or in nonpregnant cows. Milk samples and weights were collected during a single morning milking from 206 Holstein cows. Triplicate samples were collected and 2 samples were analyzed for fat, protein, lactose, and somatic cell counts (SCC); 1 sample was homogenized and analyzed for E2. The homogenized whole milk (3 mL) was extracted twice with ethyl acetate and once with methanol. The extract was reconstituted in benzene:methanol (9:1, vol/vol) and run over a Sephadex LH-20 column to separate E2 from cholesterol and estrone before quantification using radioimmunoassay. Cows were classified as not pregnant (NP, n = 138), early pregnant (EP, 1 to 140 d pregnant, n = 47), or midpregnant (MP, 141 to 210 d pregnant, n = 21) at the time of milk sampling based on herd health records. Mean E2 concentration in whole milk was 1.4 +/- 0.2 pg/mL and ranged from nondetectable to 22.9 pg/mL. Milk E2 concentrations averaged 1.3, 0.9, and 3.0 pg/mL for NP, EP, and MP cows, respectively. Milk E2 concentrations for MP cows were greater and differed from those of NP and EP cows. Milk composition was normal for a Holstein herd in that log SCC values and percentages of fat, protein, and lactose averaged 4.9, 3.5, 3.1, and 4.8, respectively. Estradiol concentration was significantly correlated (r = 0.20) with percentage fat in milk. Mean milk yield was

  6. Crack Features and Shear-Wave Splitting Associated with Fracture Extension during Hydraulic Stimulation of the Geothermal Reservoir in Soultz-sous-Forêts

    Directory of Open Access Journals (Sweden)

    Adelinet M.

    2016-05-01

    Full Text Available The recent tomography results obtained within the scope of the Enhanced Geothermal System (EGS European Soultz project led us to revisit the meso-fracturing properties of Soultz test site. In this paper, we develop a novel approach coupling effective medium modeling and shear-wave splitting to characterize the evolution of crack properties throughout the hydraulic stimulation process. The stimulation experiment performed in 2000 consisted of 3 successive injection steps spanning over 6 days. An accurate 4-D tomographic image was first carried out based upon the travel-times measured for the induced seismicity [Calò M., Dorbath C., Cornet F.H., Cuenot N. (2011 Large-scale aseismic motion identified through 4-D P-wave tomography, Geophys. J. Int. 186, 1295-1314]. The current study shows how to take advantage of the resulting compressional wave (Calò et al., 2011 and shear-wave velocity models. These are given as input data to an anisotropic effective medium model and converted into crack properties. In short, the effective medium model aims to estimate the impact of cracks on velocities. It refers to a crack-free matrix and 2 families of penny-shaped cracks with orientations in agreement with the main observed geological features: North-South strike and dip of 65°East and 65°West [Genter A., Traineau H. (1996 Analysis of macroscopic fractures in granite in the HDR geothermal well EPS-1, Soultz-sous-Forêts, France, J. Vol. Geoth. Res. 72, 121-141], respectively. The resulting output data are the spatial distributions of crack features (lengths and apertures within the 3-D geological formation. We point out that a flow rate increase results in a crack shortening in the area imaged by both compressional and shear waves, especially in the upper part of the reservoir. Conversely, the crack length, estimated during continuous injection rate phases, is higher than during the increasing injection rate phases. A possible explanation for this is that

  7. O papel da biopsia pulmonar na indicação cirúrgica de cardiopatias congénitas The role of lung biopsy in the decision-making process for congenital heart disease

    Directory of Open Access Journals (Sweden)

    Solange Bordignon

    1992-12-01

    Full Text Available Objetivando relacionar o aspecto morfológico dos vasos pulmonares com os dados clínicos para auxiliar na decisão da cirurgia de cardiopatias congênitas com hipertensão pulmonar severa, em casos previamente avaliados por critérios clínicos, angiográficos e/ou hemodinâmicos, foram realizadas, de 1980 a 1991, no Instituto de Cardiologia do Rio Grande do Sul, 49 biópsias pulmonares. As idades dos pacientes variaram de 5m a 28a6m (média = 7a7m e os diagnósticos foram: CIV (16, PCA (3, CIVe ESubAo (1, PCA e CIV (2, PCA e Cl A (1 DSAV (7, DSAV incompl. e PCA (1, PCA e CoAo (1, Inter Arco Ao com PCA e CIV e/ou ESupraM e Anel SubAo (2, DVSVD com CIV e/ou PCA (6, DVSVE e EP (1, ATe ESubP. (1, TGV (1, TGV corrigida e CIV (1 e truncus arteriosus (5. Houve 3 (6,1 % óbitos no pós-operatório da biopsia. Baseado na classificação de Heath-Edwards, foram para correção cirúrgica 11 pacientes com cardiopatias simples (CIV, PCA, DSAV, cuja mortalidade foi 36,4%. Dez pacientes com cardiopatias complexas (DVSVD, DVSVE, TGV, truncus, inter arco Ao foram para cirurgia, com mortalidade de 30%. A evolução pós-operatória tardia foi favorável em 13 (62% pacientes. Conclui-se que a biopsia pulmonar pode ser útil na indicação cirúrgica das cardiopatias congênitas com hipertensão pulmonar severa e, por envolver riscos, sua utilização deve ser criteriosa. E valiosa para os pacientes que apresentam dúvidas quanto ao grau de doença vascular pulmonar ou quanto à natureza das lesões e o estudo clínico e hemodinâmico não são esclarecedores, ou mesmo quando apontarem para a contra-indicação cirúrgica.Open lung biopsy has been performed in patients with congenital heart disease and severe pulmonary hypertension in order to complement the decision-making process for surgical correction. All patients had clinical, hemodynamic and angiographic evaluation previously and would not be surgical candidates by conventional criteria. The 49 patients

  8. 聚磷酸铵-苯并噁嗪微胶囊的制备及其对环氧树脂燃烧性能影响%Preparation of Polybenzoxazine-ammonium Polyphosphate Microcapsules and Their Effects on the Flame Properties of Epoxy Resin

    Institute of Scientific and Technical Information of China (English)

    何达; 赵春霞; 王毅; 李云涛; 李姝靓; 岳杰

    2017-01-01

    以多聚甲醛、丙烯胺、苯酚为原料,通过Mannich反应合成烯丙基型苯并噁嗪单体(Bala),并通过核磁共振氢谱(1H-NMR)确定了其化学结构.将Bala在聚磷酸铵(APP)原位开环聚合后,制备APP微胶囊(BMAPP).傅里叶变换红外(FTIR)和静态接触角测试表明,Bala在APP表面成功聚合,并有效提高APP的疏水性,与纯APP相比,BMAPP的接触角从10.8°提高到了71.3°.将BMAPP添加到环氧树脂(EP)中,制备EP/BMAPP复合材料.通过热重分析仪(TGA)、垂直燃烧(UL-94)、极限氧指数(LOI)、锥型量热仪(CONE)和动态热机械分析仪(DMA)对EP和EP/BMAPP的热性能以及燃烧性能进行对比分析.结果显示,10%的BMAPP的成炭效果最佳,有良好的阻燃性能,可使EP的LOI值从22.6%提高到33.6%,并通过UL-94 V-0级,600℃下残炭率达26.3%.同时,BMAPP可大幅度降低EP燃烧过程中烟密度和热释放速率,提高EP的玻璃化转变温度(Tg).BMAPP/EP-1 0%中,PBala和APP协同后使EP热释放速率峰值(PHRR)由1247 kW·m-2降低到434 kW·m-2,生烟速率(SPR)降低67%左右,Tg从169℃提高到了173℃.%Allyl-containing benzoxazine (Bala) was synthesized via Mannich condensation reaction using paraformaldehyde,allylamine and phenol as raw materials.The chemical structure of Bala was confirmed by 1H nuclear magnetic resonance (1H-NMR).Ammonium polyphosphate (APP) microcapsules modified by polybenzoxazine (BMAPP) were prepared by in situ ring-opening polymerization of Bala on the surfaces of APP.Fourier transform infrared spectroscopy (FTIR) and static contact angle test showed that Bala polymerized successfully,and enhanced effectively the hydrophobicity of APP.The static contact angle of the BMAPP microcapsules increased to 71.3° from 10.8°.EP/BMAPP flame-retardant materials were prepared by adding BMAPP microcapsules into epoxy matrix (EP).Thermal properties and combustion performance of EP and its composites were investigated by thermogravimetric