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Sample records for blocks lipopolysaccharide-induced gene

  1. A novel podocyte gene, semaphorin 3G, protects glomerular podocyte from lipopolysaccharide-induced inflammation.

    Science.gov (United States)

    Ishibashi, Ryoichi; Takemoto, Minoru; Akimoto, Yoshihiro; Ishikawa, Takahiro; He, Peng; Maezawa, Yoshiro; Sakamoto, Kenichi; Tsurutani, Yuya; Ide, Shintaro; Ide, Kana; Kawamura, Harukiyo; Kobayashi, Kazuki; Tokuyama, Hirotake; Tryggvason, Karl; Betsholtz, Christer; Yokote, Koutaro

    2016-05-16

    Kidney diseases including diabetic nephropathy have become huge medical problems, although its precise mechanisms are still far from understood. In order to increase our knowledge about the patho-physiology of kidney, we have previously identified >300 kidney glomerulus-enriched transcripts through large-scale sequencing and microarray profiling of the mouse glomerular transcriptome. One of the glomerulus-specific transcripts identified was semaphorin 3G (Sema3G) which belongs to the semaphorin family. The aim of this study was to analyze both the in vivo and in vitro functions of Sema3G in the kidney. Sema3G was expressed in glomerular podocytes. Although Sema3G knockout mice did not show obvious glomerular defects, ultrastructural analyses revealed partially aberrant podocyte foot processes structures. When these mice were injected with lipopolysaccharide to induce acute inflammation or streptozotocin to induce diabetes, the lack of Sema3G resulted in increased albuminuria. The lack of Sema3G in podocytes also enhanced the expression of inflammatory cytokines including chemokine ligand 2 and interleukin 6. On the other hand, the presence of Sema3G attenuated their expression through the inhibition of lipopolysaccharide-induced Toll like receptor 4 signaling. Taken together, our results surmise that the Sema3G protein is secreted by podocytes and protects podocytes from inflammatory kidney diseases and diabetic nephropathy.

  2. Effects of lipopolysaccharide-induced inflammation on expression of growth-associated genes by corticospinal neurons

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    Lieberman AR

    2006-01-01

    Full Text Available Abstract Background Inflammation around cell bodies of primary sensory neurons and retinal ganglion cells enhances expression of neuronal growth-associated genes and stimulates axonal regeneration. We have asked if inflammation would have similar effects on corticospinal neurons, which normally show little response to spinal cord injury. Lipopolysaccharide (LPS was applied onto the pial surface of the motor cortex of adult rats with or without concomitant injury of the corticospinal tract at C4. Inflammation around corticospinal tract cell bodies in the motor cortex was assessed by immunohistochemistry for OX42 (a microglia and macrophage marker. Expression of growth-associated genes c-jun, ATF3, SCG10 and GAP-43 was investigated by immunohistochemistry or in situ hybridisation. Results Application of LPS induced a gradient of inflammation through the full depth of the motor cortex and promoted c-Jun and SCG10 expression for up to 2 weeks, and GAP-43 upregulation for 3 days by many corticospinal neurons, but had very limited effects on neuronal ATF3 expression. However, many glial cells in the subcortical white matter upregulated ATF3. LPS did not promote sprouting of anterogradely labelled corticospinal axons, which did not grow into or beyond a cervical lesion site. Conclusion Inflammation produced by topical application of LPS promoted increased expression of some growth-associated genes in the cell bodies of corticospinal neurons, but was insufficient to promote regeneration of the corticospinal tract.

  3. Cytokine and acute phase protein gene expression in liver biopsies from dairy cows with a lipopolysaccharide - induced mastitis

    DEFF Research Database (Denmark)

    Vels, J; Røntved, Christine M.; Bjerring, Martin

    2009-01-01

    A minimally invasive liver biopsy technique was tested for its applicability to study the hepatic acute phase response (APR) in dairy cows with Escherichia coli lipopolysaccharide (LPS)-induced mastitis. The hepatic mRNA expression profiles of the inflammatory cytokines, tumor necrosis factor (TNF......, a minimally invasive liver biopsy technique can be used for studying the hepatic APR in diseased cattle. Lipopolysaccharide-induced mastitis resulted in a time-dependent production of inflammatory cytokines and SAA and Hp in the liver of dairy cows.......- ), IL-1β, IL-6, and IL-10, and the acute phase proteins serum amyloid A isoform 3 (SAA3), haptoglobin (Hp), and 1-acid glycoprotein (AGP) were determined by real-time reverse transcription-PCR. Fourteen primiparous cows in mid lactation were challenged with 200 µg of LPS (n = 8) or NaCl solution (n = 6...

  4. Dynamic expression of leukocyte innate immune genes in whole blood from horses with lipopolysaccharide-induced acute systemic inflammation

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    Vinther, Anne Mette L.; Skovgaard, Kerstin; Heegaard, Peter M. H.

    2015-01-01

    Background: In horses, insights into the innate immune processes in acute systemic inflammation are limited even though these processes may be highly important for future diagnostic and therapeutic advances in high-mortality disease conditions as the systemic inflammatory response syndrome (SIRS......) and sepsis. Therefore, the aim of this study was to investigate the expression of 31 selected blood leukocyte immune genes in an equine model of acute systemic inflammation to identify significantly regulated genes and to describe their expression dynamics during a 24-h experimental period. Systemic...... were compared with baseline levels. Results: Systemic inflammation was confirmed by the presence of clinical and hematological changes which were consistent with SIRS. The clinical response to LPS was transient and brief as all horses except one showed unaltered general demeanor after 24 h. Twenty...

  5. Dynamic expression of leukocyte innate immune genes in whole blood from horses with lipopolysaccharide-induced acute systemic inflammation

    DEFF Research Database (Denmark)

    Vinther, Anne Mette L.; Skovgaard, Kerstin; Heegaard, Peter M. H.

    2015-01-01

    Background: In horses, insights into the innate immune processes in acute systemic inflammation are limited even though these processes may be highly important for future diagnostic and therapeutic advances in high-mortality disease conditions as the systemic inflammatory response syndrome (SIRS......) and sepsis. Therefore, the aim of this study was to investigate the expression of 31 selected blood leukocyte immune genes in an equine model of acute systemic inflammation to identify significantly regulated genes and to describe their expression dynamics during a 24-h experimental period. Systemic...... expressions in blood leukocytes during equine acute LPS-induced systemic inflammation thoroughly characterized a highly regulated and dynamic innate immune response. These results provide new insights into the molecular mechanisms of equine systemic inflammation....

  6. Neonatal manipulation of oxytocin prevents lipopolysaccharide-induced decrease in gene expression of growth factors in two developmental stages of the female rat.

    Science.gov (United States)

    Bakos, Jan; Lestanova, Zuzana; Strbak, Vladimir; Havranek, Tomas; Bacova, Zuzana

    2014-10-01

    Oxytocin production and secretion is important for early development of the brain. Long-term consequences of manipulation of oxytocin system might include changes in markers of brain plasticity - cytoskeletal proteins and neurotrophins. The aim of the present study was (1) to determine whether neonatal oxytocin administration affects gene expression of nestin, microtubule-associated protein-2 (MAP-2), brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in the brain of two developmental stages of rat and (2) to evaluate whether neonatal oxytocin administration protects against lipopolysaccharide (LPS) induced inflammation. Neonatal oxytocin did not prevent a decrease of body weight in the LPS treated animals. Oxytocin significantly increased gene expression of BDNF in the right hippocampus in 21-day and 2-month old rats of both sexes. Gene expression of NGF and MAP-2 significantly increased in males treated with oxytocin. Both, growth factors and intermediate filament-nestin mRNA levels, were reduced in females exposed to LPS. Oxytocin treatment prevented a decrease in the gene expression of only growth factors. In conclusion, neonatal manipulation of oxytocin has developmental and sex-dependent effect on markers of brain plasticity. These results also indicate, that oxytocin may be protective against inflammation particularly in females. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Reactive oxygen species are involved in lipopolysaccharide-induced intrauterine growth restriction and skeletal development retardation in mice.

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    Xu, De-Xiang; Chen, Yuan-Hua; Zhao, Lei; Wang, Hua; Wei, Wei

    2006-12-01

    Maternal infection is a cause of adverse developmental outcomes including embryonic resorption, intrauterine fetal death, and preterm labor. Lipopolysaccharide-induced developmental toxicity at early gestational stages has been well characterized. The purpose of the present study was to investigate the effects of maternal lipopolysaccharide exposure at late gestational stages on intrauterine fetal growth and skeletal development and to assess the potential role of reactive oxygen species in lipopolysaccharide-induced intrauterine fetal growth restriction and skeletal development retardation. The timed pregnant CD-1 mice were intraperitoneally injected with lipopolysaccharide (25 to 75 microg/kg per day) on gestational day 15 to 17. To investigate the role of reactive oxygen species on lipopolysaccharide-induced intrauterine fetal growth restriction and skeletal development retardation, the pregnant mice were injected with alpha-phenyl-N-t-butylnitrone (100 mg/kg, intraperitoneally) at 30 minutes before lipopolysaccharide (75 microg/kg per day, intraperitoneally), followed by an additional dose of alpha-phenyl-N-t-butylnitrone (50 mg/kg, intraperitoneally) at 3 hours after lipopolysaccharide. The number of live fetuses, dead fetuses, and resorption sites was counted on gestational day 18. Live fetuses in each litter were weighed. Crown-rump and tail lengths were examined and skeletal development was evaluated. Maternal lipopolysaccharide exposure significantly increased fetal mortality, reduced fetal weight and crown-rump and tail lengths of live fetuses, and retarded skeletal ossification in caudal vertebrae, anterior and posterior phalanges, and supraoccipital bone in a dose-dependent manner. Alpha-phenyl-N-t-butylnitrone, a free radical spin-trapping agent, almost completely blocked lipopolysaccharide-induced fetal death (63.2% in lipopolysaccharide group versus 6.5% in alpha-phenyl-N-t-butylnitrone + lipopolysaccharide group, P intrauterine growth restriction

  8. SIRT2 ameliorates lipopolysaccharide-induced inflammation in macrophages

    International Nuclear Information System (INIS)

    Lee, Ae Sin; Jung, Yu Jin; Kim, Dal; Nguyen-Thanh, Tung; Kang, Kyung Pyo; Lee, Sik; Park, Sung Kwang; Kim, Won

    2014-01-01

    Highlights: • Knockout of SIRT2 attenuates lipopolysaccharide-induced iNOS expression. • Lipopolysaccharide-induced NO production is decreased in SIRT2 KO macrophage. • SIRT2 deficiency suppresses lipopolysaccharide-induced ROS production in macrophage. • M1-macrophage related factors are decreased in SIRT2 deficient cells. • SIRT2 deficiency decreases lipopolysaccharide-induced activation of NFκB. - Abstract: Introduction: SIRT2 is a NAD(+)-dependent deacetylases and associated with numerous processes such as infection, carcinogenesis, DNA damage and cell cycle regulation. However, the role of SIRT2 in inflammatory process in macrophage remains unclear. Materials and methods: In the present study, we have evaluated the regulatory effects of SIRT2 in lipopolysaccharide (LPS)-stimulated macrophages isolated from SIRT2 knockout (KO) and wild type (WT) mice or Raw264.7 macrophage cells. As inflammatory parameters, expression of inducible nitric oxide synthase (iNOS), the productions of nitric oxide, reactive oxygen species (ROS) and M1-macrophage-related factors were evaluated. We also examined the effects of SIRT2 on activation of nuclear factor-kappaB (NFκB) signaling. Results: SIRT2 deficiency inhibits LPS-induced iNOS mRNA and protein expression in bone marrow derived macrophages. SIRT2-siRNA transfection also suppressed LPS-induced iNOS expression in Raw264.7 macrophage cells. Bone marrow derived macrophages isolated from SIRT2 KO mice produced lower nitric oxide and expressed lower levels of M1-macrophage related markers including iNOS and CD86 in response to LPS than WT mice. Decrease of SIRT2 reduced the LPS-induced reactive oxygen species production. Deficiency of SIRT2 resulted in inhibition of NFκB activation through reducing the phosphorylation and degradation of IκBα. The phosphorylation and nuclear translocation of p65 was significantly decreased in SIRT2-deficient macrophages after LPS stimulation. Discussion: Our data suggested that

  9. SIRT2 ameliorates lipopolysaccharide-induced inflammation in macrophages

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    Lee, Ae Sin; Jung, Yu Jin; Kim, Dal; Nguyen-Thanh, Tung [Department of Internal Medicine, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Kang, Kyung Pyo [Department of Internal Medicine, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Research Institute of Clinical Medicine of Chonbuk National University, Chonbuk National University Hospital, Jeonju (Korea, Republic of); Lee, Sik [Department of Internal Medicine, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Park, Sung Kwang [Department of Internal Medicine, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Research Institute of Clinical Medicine of Chonbuk National University, Chonbuk National University Hospital, Jeonju (Korea, Republic of); Kim, Won, E-mail: kwon@jbnu.ac.kr [Department of Internal Medicine, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Research Institute of Clinical Medicine of Chonbuk National University, Chonbuk National University Hospital, Jeonju (Korea, Republic of)

    2014-08-08

    Highlights: • Knockout of SIRT2 attenuates lipopolysaccharide-induced iNOS expression. • Lipopolysaccharide-induced NO production is decreased in SIRT2 KO macrophage. • SIRT2 deficiency suppresses lipopolysaccharide-induced ROS production in macrophage. • M1-macrophage related factors are decreased in SIRT2 deficient cells. • SIRT2 deficiency decreases lipopolysaccharide-induced activation of NFκB. - Abstract: Introduction: SIRT2 is a NAD(+)-dependent deacetylases and associated with numerous processes such as infection, carcinogenesis, DNA damage and cell cycle regulation. However, the role of SIRT2 in inflammatory process in macrophage remains unclear. Materials and methods: In the present study, we have evaluated the regulatory effects of SIRT2 in lipopolysaccharide (LPS)-stimulated macrophages isolated from SIRT2 knockout (KO) and wild type (WT) mice or Raw264.7 macrophage cells. As inflammatory parameters, expression of inducible nitric oxide synthase (iNOS), the productions of nitric oxide, reactive oxygen species (ROS) and M1-macrophage-related factors were evaluated. We also examined the effects of SIRT2 on activation of nuclear factor-kappaB (NFκB) signaling. Results: SIRT2 deficiency inhibits LPS-induced iNOS mRNA and protein expression in bone marrow derived macrophages. SIRT2-siRNA transfection also suppressed LPS-induced iNOS expression in Raw264.7 macrophage cells. Bone marrow derived macrophages isolated from SIRT2 KO mice produced lower nitric oxide and expressed lower levels of M1-macrophage related markers including iNOS and CD86 in response to LPS than WT mice. Decrease of SIRT2 reduced the LPS-induced reactive oxygen species production. Deficiency of SIRT2 resulted in inhibition of NFκB activation through reducing the phosphorylation and degradation of IκBα. The phosphorylation and nuclear translocation of p65 was significantly decreased in SIRT2-deficient macrophages after LPS stimulation. Discussion: Our data suggested that

  10. RNA interference prevents lipopolysaccharide-induced preprotachykinin gene expression

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    Lai, Y.-L.; Yu, S.C.; Chen, M.-J.

    2003-01-01

    We showed previously that lipopolysaccharide (LPS) induces noncholinergic airway hyperreactivity to capsaicin via an upregulation of tachykinin synthesis. This study was designed to test whether double-stranded preprotachykinin (ds PPT) RNA, RNA interference (RNAi), prevents the LPS-induced alterations. First, cultured primary nodose ganglial cells of newborn Brown-Norway rats were divided into four groups: control; LPS; LPS+RNAi; and LPS+RNAi+liposome. Second, young Brown-Norway rats for the in vivo study were divided into three groups (control; LPS; and LPS+RNAi), and ds PPT RNA was microinjected bilaterally into the nodose ganglia in the LPS+RNAi group. Then, ganglial cells were collected from the culture whereas the nodose ganglia and lungs were sampled from the animals, and PPT mRNA and substance P (SP) levels were analyzed. Also, airway reactivity to capsaicin was performed in vivo. LPS induced significant increases in PPT mRNA and SP levels in vitro and in vivo and an increase in airway reactivity to capsaicin in vivo. However, ds PPT RNA, but not scrambled RNA, prevented all LPS-induced alterations. The effect of ds PPT RNA was not enhanced by liposome in vitro. Therefore, we demonstrated that the local application of RNAi prevents effectively the activation of the noncholinergic system modulating the lungs/airways

  11. Murine P-glycoprotein deficiency alters intestinal injury repair and blunts lipopolysaccharide-induced radioprotection.

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    Staley, Elizabeth M; Yarbrough, Vanisha R; Schoeb, Trenton R; Daft, Joseph G; Tanner, Scott M; Steverson, Dennis; Lorenz, Robin G

    2012-09-01

    P-glycoprotein (P-gp) has been reported to increase stem cell proliferation and regulate apoptosis. Absence of P-gp results in decreased repair of intestinal epithelial cells after chemical injury. To further explore the mechanisms involved in the effects of P-gp on intestinal injury and repair, we used the well-characterized radiation injury model. In this model, injury repair is mediated by production of prostaglandins (PGE(2)) and lipopolysaccharide (LPS) has been shown to confer radioprotection. B6.mdr1a(-/-) mice and wild-type controls were subjected to 12 Gy total body X-ray irradiation and surviving crypts in the proximal jejunum and distal colon were evaluated 3.5 days after irradiation. B6.mdr1a(-/-) mice exhibited normal baseline stem cell proliferation and COX dependent crypt regeneration after irradiation. However, radiation induced apoptosis was increased and LPS-induced radioprotection was blunted in the C57BL6.mdr1a(-/-) distal colon, compared to B6 wild-type controls. The LPS treatment induced gene expression of the radioprotective cytokine IL-1α, in B6 wild-type controls but not in B6.mdr1a(-/-) animals. Lipopolysaccharid-induced radioprotection was absent in IL-1R1(-/-) animals, indicating a role for IL-1α in radioprotection, and demonstrating that P-gp deficiency interferes with IL-1α gene expression in response to systemic exposure to LPS.

  12. Carbachol ameliorates lipopolysaccharide-induced intestinal epithelial tight junction damage by down-regulating NF-{kappa}{beta} and myosin light-chain kinase pathways

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    Zhang, Ying [Department of Anesthesia, Critical Care Medicine and Emergency Medicine Center, Zhongnan Hospital, Wuhan University, Wuhan 430071, Hubei Province, People' s Republic of China (China); Li, Jianguo, E-mail: 2010lijianguo@sina.cn [Department of Anesthesia, Critical Care Medicine and Emergency Medicine Center, Zhongnan Hospital, Wuhan University, Wuhan 430071, Hubei Province, People' s Republic of China (China)

    2012-11-16

    Highlights: Black-Right-Pointing-Pointer Carbachol reduced the lipopolysaccharide-induced intestinal barrier breakdown. Black-Right-Pointing-Pointer Carbachol ameliorated the lipopolysaccharide-induced ileal tight junction damage. Black-Right-Pointing-Pointer Carbachol prevented the LPS-induced NF-{kappa}{beta} and myosin light-chain kinase activation. Black-Right-Pointing-Pointer Carbachol exerted its beneficial effects in an {alpha}7 nicotinic receptor-dependent manner. -- Abstract: Carbachol is a cholinergic agonist that protects the intestines after trauma or burn injury. The present study determines the beneficial effects of carbachol and the mechanisms by which it ameliorates the lipopolysaccharide (LPS)-induced intestinal barrier breakdown. Rats were injected intraperitoneally with 10 mg/kg LPS. Results showed that the gut barrier permeability was reduced, the ultrastructural disruption of tight junctions (TJs) was prevented, the redistribution of zonula occludens-1 and claudin-2 proteins was partially reversed, and the nuclear factor-kappa beta (NF-{kappa}{beta}) and myosin light-chain kinase (MLCK) activation in the intestinal epithelium were suppressed after carbachol administration in LPS-exposed rats. Pretreatment with the {alpha}7 nicotinic acetylcholine receptor ({alpha}7nAchR) antagonist {alpha}-bungarotoxin blocked the protective action of carbachol. These results suggested that carbachol treatment can protect LPS-induced intestinal barrier dysfunction. Carbachol exerts its beneficial effect on the amelioration of the TJ damage by inhibiting the NF-{kappa}{beta} and MLCK pathways in an {alpha}7nAchR-dependent manner.

  13. Riboflavin attenuates lipopolysaccharide-induced lung injury in rats.

    Science.gov (United States)

    Al-Harbi, Naif O; Imam, Faisal; Nadeem, Ahmed; Al-Harbi, Mohammed M; Korashy, Hesham M; Sayed-Ahmed, Mohammed M; Hafez, Mohamed M; Al-Shabanah, Othman A; Nagi, Mahmoud N; Bahashwan, Saleh

    2015-01-01

    Riboflavin (vitamin B2) is an easily absorbed micronutrient with a key role in maintaining health in humans and animals. It is the central component of the cofactors flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) and is therefore required by all flavoproteins. Riboflavin also works as an antioxidant by scavenging free radicals. The present study was designed to evaluate the effects of riboflavin against acute lungs injury induced by the administration of a single intranasal dose (20 μg/rat) of lipopolysaccharides (LPS) in experimental rats. Administration of LPS resulted in marked increase in malondialdehyde (MDA) level (p riboflavin in a dose-dependent manner (30 and 100 mg/kg, respectively). Riboflavin (100 mg/kg, p.o.) showed similar protective effects as dexamethasone (1 mg/kg, p.o.). Administration of LPS showed marked cellular changes including interstitial edema, hemorrhage, infiltration of PMNs, etc., which were reversed by riboflavin administration. Histopathological examinations showed normal morphological structures of lungs tissue in the control group. These biochemical and histopathological examination were appended with iNOS and CAT gene expression. The iNOS mRNA expression was increased significantly (p riboflavin significantly (p riboflavin caused a protective effect against LPS-induced ALI. These results suggest that riboflavin may be used to protect against toxic effect of LPS in lungs.

  14. Dynamic Regulation of Delta-Opioid Receptor in Rat Trigeminal Ganglion Neurons by Lipopolysaccharide-induced Acute Pulpitis.

    Science.gov (United States)

    Huang, Jin; Lv, Yiheng; Fu, Yunjie; Ren, Lili; Wang, Pan; Liu, Baozhu; Huang, Keqiang; Bi, Jing

    2015-12-01

    Delta-opioid receptor (DOR) and its endogenous ligands distribute in trigeminal system and play a very important role in modulating peripheral inflammatory pain. DOR activation can trigger p44/42 mitogen-activated protein kinase (ERK1/2) and Akt signaling pathways, which participate in anti-inflammatory and neuroprotective effects. In this study, our purpose was to determine the dynamic changes of DOR in trigeminal ganglion (TG) neurons during the process of acute dental pulp inflammation and elucidate its possible mechanism. Forty rats were used to generate lipopolysaccharide-induced acute pulpitis animal models at 6, 12, and 24 hours and sham-operated groups. Acute pulpitis was confirmed by hematoxylin-eosin staining, and TG neuron activation was determined by anti-c-Fos immunohistochemistry. DOR protein and gene expression in TG was investigated by immunohistochemistry, Western blotting, and real-time polymerase chain reaction, and DOR expression in trigeminal nerves and dental pulp was also determined by immunohistochemistry. To further investigate the mechanism of DOR modulating acute inflammation, the change of pErk1/2 and pAkt in TG was examined by immunohistochemistry. Lipopolysaccharide could successfully induce acute pulpitis and activated TG neurons. Acute pulpitis could dynamically increase DOR protein and gene expression at 6, 12, and 24 hours in TG, and DOR dimerization was significantly increased at 12 and 24 hours. Acute pulpitis also induced the dynamic change of DOR protein in trigeminal nerve and dental pulp. Furthermore, ERK1/2 and Akt signaling pathways were inhibited in TG after acute pulpitis. Increased DOR expression and dimerization may play important roles in peripheral acute inflammatory pain. Copyright © 2015 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  15. Paeonol attenuates lipopolysaccharide-induced depressive-like behavior in mice.

    Science.gov (United States)

    Tao, Weiwei; Wang, Hanqing; Su, Qiang; Chen, Yanyan; Xue, Wenda; Xia, Baomei; Duan, Jinao; Chen, Gang

    2016-04-30

    The present study was designed to detect the anti-depressant effects of paeonol and the possible mechanisms in the lipopolysaccharide-induced depressive-like behavior. Open-field test(OFT), tail suspension test(TST) and forced swimming test(FST) were used to evaluate the behavioral activity. The contents of 5-hydroxytryptamine (5-HT) and norepinephrine (NE) in mice hippocampus were determined by HPLC-ECD. Serum interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α levels were evaluated by enzyme-linked immunosorbent assay (ELISA). Our results showed that LPS significantly decreased the levels of 5-HT and NE in the hippocampus. LPS also reduced open-field activity, as well as increased immobility duration in FST and TST. Paeonol administration could effectively reverse the alterations in the concentrations of 5-HT, NE and reduce the IL-6 and TNF-α levels. Moreover, paeonol effectively downregulated brain-derived neurotrophic factor (BDNF), tropomyosin-related kinase B (TrkB) and Nuclear factor-κB (NF-κB) in hippocampal. In conclusion, paeonol administration exhibited significant antidepressant-like effects in mice with LPS-induced depression. Copyright © 2016. Published by Elsevier Ireland Ltd.

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

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    Hussain S

    2012-03-01

    were found either in vesicles or free in the cytoplasm. However, no significant differences in secreted cytokine profiles were observed between CeO2 nanoparticle-treated cells and control cells at noncytotoxic doses. No significant effects of CeO2 nanoparticle exposure subsequent to lipopolysaccharide priming was observed on cytokine secretion. Moreover, no significant difference in lipopolysaccharide-induced cytokine production was observed after exposure to CeO2 nanoparticles followed by lipopolysaccharide exposure.Conclusion: CeO2 nanoparticles at noncytotoxic concentrations neither modulate pre-existing inflammation nor prime for subsequent exposure to lipopolysaccharides in human monocytes from healthy subjects.Keywords: cerium dioxide, nanoparticle, nanomedicine, inflammation, human monocyte, lipopolysaccharides

  17. Amphiphilic block co-polymers: preparation and application in nanodrug and gene delivery.

    Science.gov (United States)

    Xiong, Xiao-Bing; Binkhathlan, Ziyad; Molavi, Ommoleila; Lavasanifar, Afsaneh

    2012-07-01

    Self-assembly of amphiphilic block co-polymers composed of poly(ethylene oxide) (PEO) as the hydrophilic block and poly(ether)s, poly(amino acid)s, poly(ester)s and polypropyleneoxide (PPO) as the hydrophobic block can lead to the formation of nanoscopic structures of different morphologies. These structures have been the subject of extensive research in the past decade as artificial mimics of lipoproteins and viral vectors for drug and gene delivery. The aim of this review is to provide an overview of the synthesis of commonly used amphiphilic block co-polymers. It will also briefly go over some pharmaceutical applications of amphiphilic block co-polymers as "nanodelivery systems" for small molecules and gene therapeutics. Copyright © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  18. DNMT1-interacting RNAs block gene specific DNA methylation

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    Di Ruscio, Annalisa; Ebralidze, Alexander K.; Benoukraf, Touati; Amabile, Giovanni; Goff, Loyal A.; Terragni, Joylon; Figueroa, Maria Eugenia; De Figureido Pontes, Lorena Lobo; Alberich-Jorda, Meritxell; Zhang, Pu; Wu, Mengchu; D’Alò, Francesco; Melnick, Ari; Leone, Giuseppe; Ebralidze, Konstantin K.; Pradhan, Sriharsa; Rinn, John L.; Tenen, Daniel G.

    2013-01-01

    Summary DNA methylation was described almost a century ago. However, the rules governing its establishment and maintenance remain elusive. Here, we present data demonstrating that active transcription regulates levels of genomic methylation. We identified a novel RNA arising from the CEBPA gene locus critical in regulating the local DNA methylation profile. This RNA binds to DNMT1 and prevents CEBPA gene locus methylation. Deep sequencing of transcripts associated with DNMT1 combined with genome-scale methylation and expression profiling extended the generality of this finding to numerous gene loci. Collectively, these results delineate the nature of DNMT1-RNA interactions and suggest strategies for gene selective demethylation of therapeutic targets in disease. PMID:24107992

  19. An allele of the crm gene blocks cyanobacterial circadian rhythms.

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    Boyd, Joseph S; Bordowitz, Juliana R; Bree, Anna C; Golden, Susan S

    2013-08-20

    The SasA-RpaA two-component system constitutes a key output pathway of the cyanobacterial Kai circadian oscillator. To date, rhythm of phycobilisome associated (rpaA) is the only gene other than kaiA, kaiB, and kaiC, which encode the oscillator itself, whose mutation causes completely arrhythmic gene expression. Here we report a unique transposon insertion allele in a small ORF located immediately upstream of rpaA in Synechococcus elongatus PCC 7942 termed crm (for circadian rhythmicity modulator), which results in arrhythmic promoter activity but does not affect steady-state levels of RpaA. The crm ORF complements the defect when expressed in trans, but only if it can be translated, suggesting that crm encodes a small protein. The crm1 insertion allele phenotypes are distinct from those of an rpaA null; crm1 mutants are able to grow in a light:dark cycle and have no detectable oscillations of KaiC phosphorylation, whereas low-amplitude KaiC phosphorylation rhythms persist in the absence of RpaA. Levels of phosphorylated RpaA in vivo measured over time are significantly altered compared with WT in the crm1 mutant as well as in the absence of KaiC. Taken together, these results are consistent with the hypothesis that the Crm polypeptide modulates a circadian-specific activity of RpaA.

  20. Transcriptional profiles of Rel/NF-κB, inhibitor of NF-κB (IκB), and lipopolysaccharide-induced TNF-α factor (LITAF) in the lipopolysaccharide (LPS) and two Vibrio sp.-exposed intertidal copepod, Tigriopus japonicus.

    Science.gov (United States)

    Kim, Bo-Mi; Jeong, Chang-Bum; Rhee, Jae-Sung; Lee, Jae-Seong

    2014-02-01

    The immune system and the role of immunity-related genes have rarely been studied in copepods, even though copepods have a primitive immune response system and also have a potential in pathogen transport higher trophic levels. In this study, we firstly cloned and characterized three core immune genes such as nuclear factor κB (NF-κB), inhibitor of NF-κB (IκB), and lipopolysaccharide-induced TNF-α factor (LITAF) genes in the intertidal copepod Tigriopus japonicus. Several in silico analyses based on conserved domains, motifs, and phylogenetic relationships were supporting their annotations. To investigate the immune-related role of three genes, we exposed lipopolysaccharide (LPS) and two Vibrio sp. to T. japonicus. After exposure of different concentrations of LPS and two Vibrio sp., transcripts of TJ-IκB and TJ-LITAF genes were significantly elevated during the time course in a dose-dependent manner, while TJ-NF-κB transcripts were not significantly changed during exposure. These findings demonstrated that the copepod T. japonicus has a conserved immunity against infection. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. Aloin Suppresses Lipopolysaccharide-Induced Inflammatory Response and Apoptosis by Inhibiting the Activation of NF-κB

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    Xuan Luo

    2018-02-01

    Full Text Available Numerous herbal-derived natural products are excellent anti-inflammatory agents. Several studies have reported that aloin, the major anthraquinone glycoside obtained from the Aloe species, exhibits anti-inflammatory activity. However, the molecular mechanism of this activity is not well understood. In this report, we found that aloin suppresses lipopolysaccharide-induced pro-inflammatory cytokine secretion and nitric oxide production, and downregulates the expression of tumor necrosis factor alpha (TNF-α, interleukin 6 (IL-6, inducible nitric oxide synthase (iNOS, and cyclooxygenase-2 (COX-2. Aloin inhibits the phosphorylation and acetylation of the NF-κB p65 subunit by suppressing the upstream kinases p38 and Msk1, preventing LPS-induced p65 translocation to the nucleus. We have also shown that aloin inhibits LPS-induced caspase-3 activation and apoptotic cell death. Collectively, these findings suggest that aloin effectively suppresses the inflammatory response, primarily through the inhibition of NF-κB signaling.

  2. Lipopolysaccharide induces a downregulation of adiponectin receptors in-vitro and in-vivo

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    Alison Hall

    2015-11-01

    Full Text Available Background. Adipose tissue contributes to the inflammatory response through production of cytokines, recruitment of macrophages and modulation of the adiponectin system. Previous studies have identified a down-regulation of adiponectin in pathologies characterised by acute (sepsis and endotoxaemia and chronic inflammation (obesity and type-II diabetes mellitus. In this study, we investigated the hypothesis that LPS would reduce adiponectin receptor expression in a murine model of endotoxaemia and in adipoocyte and myocyte cell cultures.Methods. 25 mg/kg LPS was injected intra-peritoneally into C57BL/6J mice, equivalent volumes of normal saline were used in control animals. Mice were killed at 4 or 24 h post injection and tissues harvested. Murine adipocytes (3T3-L1 and myocytes (C2C12 were grown in standard culture, treated with LPS (0.1 µg/ml–10 µg/ml and harvested at 4 and 24 h. RNA was extracted and qPCR was conducted according to standard protocols and relative expression was calculated.Results. After LPS treatment there was a significant reduction after 4 h in gene expression of adipo R1 in muscle and peri-renal fat and of adipo R2 in liver, peri-renal fat and abdominal wall subcutaneous fat. After 24 h, significant reductions were limited to muscle. Cell culture extracts showed varied changes with reduction in adiponectin and adipo R2 gene expression only in adipocytes.Conclusions. LPS reduced adiponectin receptor gene expression in several tissues including adipocytes. This reflects a down-regulation of this anti-inflammatory and insulin-sensitising pathway in response to LPS. The trend towards base line after 24 h in tissue depots may reflect counter-regulatory mechanisms. Adiponectin receptor regulation differs in the tissues investigated.

  3. Molecular evidence for the existence of lipopolysaccharide-induced TNF-alpha factor (LITAF) and Rel/NF-kB pathways in disk abalone (Haliotis discus discus).

    Science.gov (United States)

    De Zoysa, Mahanama; Nikapitiya, Chamilani; Oh, Chulhong; Whang, Ilson; Lee, Jae-Seong; Jung, Sung-Ju; Choi, Cheol Young; Lee, Jehee

    2010-01-01

    The lipopolysaccharide-induced TNF-alpha factor (LITAF) and Rel family nuclear factor kappaB (Rel/NF-kB) are two important transcription factors which play major roles in the regulating inflammatory cytokine, apoptosis and immune related genes. Here, we report the discovery of disk abalone LITAF (AbLITAF) and Rel/NF-kB (AbRel/NF-kB) homologues and their immune responses. Full-length cDNA of AbLITAF consists of 441 bp open reading frame (ORF) that translates into putative peptide of 147 aa. Analysis of AbLITAF sequence showed it has characteristic LITAF (Zn(+2)) binding domain with two CXXC motifs. Phylogenetic analysis results further revealed that AbLITAF is a member of LITAF family. AbRel/NF-kB is 584 aa protein that contains several characteristic motifs including Rel homology domain (RHD), Rel protein signature, DNA binding motif, nuclear localization signal (NLS) and transcription factor immunoglobulin - like fold (TIG) similar to their invertebrate and vertebrate counterparts. Tissue specific analysis results showed that both AbLITAF and AbRel/NF-kB mRNA was expressed ubiquitously in all selected tissues in constitutive manner. However, constitutive expression of AbLITAF was higher than AbRel/NF-kB in all tissues except mantle. Upon immune challenge by bacteria (Vibrio alginolyticus, Vibrio parahemolyticus and Lysteria monocytogenes) and viral hemoragic septicemia virus (VHSV), AbLITAF showed the significant up-regulation in gills while AbRel/NF-kB transcription was not change significantly. Based on transcriptional response against immune challenge, we could suggest that regulation of TNF-alpha expression may have occurred mainly by LITAF activation rather than NF-kB in disk abalone. The cumulative data from other molluscs and our data with reference to TNF-alpha, LITAF and Rel/NF-kB from disk abalone provide strong evidence that LITAF and NF-kB are independent pathways likely to occur throughout the Phylum mollusca. 2010 Elsevier Ltd. All rights reserved.

  4. Potential role of an antimicrobial peptide, KLK in inhibiting lipopolysaccharide-induced macrophage inflammation.

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    Pornpimon Jantaruk

    Full Text Available Antimicrobial peptides (AMPs are attractive alternatives to antibiotics. Due to their immune modulatory properties, AMPs are at present emerging as promising agents for controlling inflammatory-mediated diseases. In this study, anti-inflammatory potential of an antimicrobial peptide, KLK (KLKLLLLLKLK and its analogs was evaluated in lipopolysaccharide (LPS-induced RAW 264.7 macrophages. The results herein demonstrated that KLK peptide as well as its analogs significantly inhibited the pro-inflammatory mediator nitric oxide (NO, interleukin-1β (IL-1β and tumor necrosis factor-α (TNF-α production in LPS-stimulated RAW 264.7 macrophages in dose-dependent manners, and such inhibitory effects were not due to direct cytotoxicity. When considering inhibition potency, KLK among the test peptides exhibited the most effective activity. The inhibitory activity of KLK peptide also extended to include suppression of LPS-induced production of prostaglandin E2 (PGE2. KLK significantly decreased mRNA and protein expression of inducible nitric oxide synthase (iNOS and cyclooxygenase-2 (COX-2 as well as mRNA expression of IL-1β and TNF-α. Moreover, KLK inhibited nuclear translocation of nuclear factor-κB (NF-κB p65 and blocked degradation and phosphorylation of inhibitor of κB (IκB. Taken together, these results suggested that the KLK peptide inhibited inflammatory response through the down-regulation of NF-κB mediated activation in macrophages. Since peptide analogs with different amino acid sequences and arrangement were investigated for their anti-inflammatory activities, the residues/structures required for activity were also discussed. Our findings therefore proved anti-inflammatory potential of the KLK peptide and provide direct evidence for therapeutic application of KLK as a novel anti-inflammatory agent.

  5. Peripheral and central mediators of lipopolysaccharide induced suppression of defensive rage behavior in the cat.

    Science.gov (United States)

    Bhatt, S; Bhatt, R S; Zalcman, S S; Siegel, A

    2009-11-10

    Based upon recent findings in our laboratory that cytokines microinjected into the medial hypothalamus or periaqueductal gray (PAG) powerfully modulate defensive rage behavior in cat, the present study determined the effects of peripherally released cytokines following lipopolysaccharide (LPS) challenge upon defensive rage. The study involved initial identification of the effects of peripheral administration of LPS upon defensive rage by electrical stimulation from PAG and subsequent determination of the peripheral and central mechanisms governing this process. The results revealed significant elevation in response latencies for defensive rage from 60 to 300 min, post LPS injection, with no detectable signs of sickness behavior present at 60 min. In contrast, head turning behavior elicited by stimulation of adjoining midbrain sites was not affected by LPS administration, suggesting a specificity of the effects of LPS upon defensive rage. Direct administration of LPS into the medial hypothalamus had no effect on defensive rage, suggesting that the effects of LPS were mediated by peripheral cytokines rather than by any direct actions upon hypothalamic neurons. Complete blockade of the suppressive effects of LPS by peripheral pretreatment with an Anti-tumor necrosis factor-alpha (TNFalpha) antibody but not with an anti- interleukin-1 (IL-1) antibody demonstrated that the effects of LPS were mediated through TNF-alpha rather than through an IL-1 mechanism. A determination of the central mechanisms governing LPS suppression revealed that pretreatment of the medial hypothalamus with PGE(2) or 5-HT(1A) receptor antagonists each completely blocked the suppressive effects of LPS, while microinjections of a TNF-alpha antibody into the medial hypothalamus were ineffective. Microinjections of -Iodo-N-[2-[4-(methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) benzamide monohydrochloride (p-MPPI) into lateral hypothalamus (to test for anatomical specificity) had no effect upon

  6. A Fermented Whole Grain Prevents Lipopolysaccharides-Induced Dysfunction in Human Endothelial Progenitor Cells

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    Laura Giusti

    2017-01-01

    Full Text Available Endogenous and exogenous signals derived by the gut microbiota such as lipopolysaccharides (LPS orchestrate inflammatory responses contributing to development of the endothelial dysfunction associated with atherosclerosis in obesity, metabolic syndrome, and diabetes. Endothelial progenitor cells (EPCs, bone marrow derived stem cells, promote recovery of damaged endothelium playing a pivotal role in cardiovascular repair. Since healthy nutrition improves EPCs functions, we evaluated the effect of a fermented grain, Lisosan G (LG, on early EPCs exposed to LPS. The potential protective effect of LG against LPS-induced alterations was evaluated as cell viability, adhesiveness, ROS production, gene expression, and NF-kB signaling pathway activation. Our results showed that LPS treatment did not affect EPCs viability and adhesiveness but induced endothelial alterations via activation of NF-kB signaling. LG protects EPCs from inflammation as well as from LPS-induced oxidative and endoplasmic reticulum (ER stress reducing ROS levels, downregulating proinflammatory and proapoptotic factors, and strengthening antioxidant defense. Moreover, LG pretreatment prevented NF-kB translocation from the cytoplasm into the nucleus caused by LPS exposure. In human EPCs, LPS increases ROS and upregulates proinflammatory tone, proapoptotic factors, and antioxidants. LG protects EPCs exposed to LPS reducing ROS, downregulating proinflammatory and proapoptotic factors, and strengthening antioxidant defenses possibly by inhibiting NF-κB nuclear translocation.

  7. Valproic acid potentiates curcumin-mediated neuroprotection in Lipopolysaccharide induced rats

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    Amira eZaky

    2014-10-01

    Full Text Available The etiology of neuroinflammation is complex and comprises multifactorial, involving both genetic and environmental factors during which diverse genetic and epigenetic modulations are implicated. Curcumin (Cur, and valproic acid (VPA, histone deacetylase 1 inhibitor, have neuroprotective effects. The present study was designed with an aim to investigate the ability of co-treatment of both compounds (Cur or VPA (200mg/kg for four weeks to augment neuroprotection and enhance brain recovery from intra-peritoneal (IP injection of (250 µg/kg lipopolysaccharide (LPS-stimulated neuroinflammatory condition on rat brain cortex. Cortex activation and the effects of combined treatment and production of proinflammatory mediators, COX-2, APE1 and nitric oxide/iNOS were investigated. Neuroinflammation development was assessed by histological analyses and by investigating associated indices (BACE1, APP, PSEN-1 and PSEN-2. Furthermore we measured the expression profile of let-7 miRNAs members a, b, c, e and f in all groups, a highly abundant regulator of gene expression in the CNS. Protein and mRNA levels of neuroinflammation markers COX-2, BACE1, APP and iNOS were also attenuated by combined therapy. On the other hand, assessment of the indicated five let-7 members, showed distinct expression profile pattern in the different groups. Let-7 a, b and c disappeared in the induced group, an effect that was partially suppressed by co-addition of either Cur or VPA. These data suggest that the combined treatment induced significantly the expression of the five members when compared to rats treated with Cur or VPA only as well as to self-recovery group, which indicates a possible benefit from the synergistic effect of Cur-VPA combination as therapeutic agents for neuroinflammation and its associated disorders. The mechanism elucidated here highlights the particular drug-induced expression profile of let-7 family as new targets for future pharmacological development.

  8. DHA suppresses Prevotella intermedia lipopolysaccharide-induced production of proinflammatory mediators in murine macrophages.

    Science.gov (United States)

    Choi, Eun-Young; Jin, Ji-Young; Choi, Jeom-Il; Choi, In Soon; Kim, Sung-Jo

    2014-04-14

    Several reports have indicated that dietary intake of DHA is associated with lower prevalence of periodontitis. In the present study, we investigated the effect of DHA on the production of proinflammatory mediators in murine macrophage-like RAW264.7 cells stimulated with lipopolysaccharide (LPS) isolated from Prevotella intermedia, a pathogen implicated in inflammatory periodontal disease, and its mechanisms of action. LPS was isolated from lyophilised P. intermedia ATCC 25,611 cells using the standard hot-phenol-water protocol. Culture supernatants were collected and assayed for NO, IL-1β and IL-6. Real-time PCR analysis was carried out to detect the expression of inducible NO synthase (iNOS), IL-1β, IL-6 and haeme oxygenase-1 (HO-1) mRNA. Immunoblot analysis was carried out to quantify the expression of iNOS and HO-1 protein and concentrations of signalling proteins. DNA-binding activities of NF-κB subunits were determined using an ELISA-based assay kit. DHA significantly attenuated the production of NO, IL-1β and IL-6 at both gene transcription and translation levels in P. intermedia LPS-activated RAW264.7 cells. DHA induced the expression of HO-1 in cells treated with P. intermedia LPS. Selective inhibition of HO-1 activity by tin protoporphyrin IX significantly mitigated the inhibitory effects of DHA on LPS-induced NO production. DHA significantly attenuated the phosphorylation of c-Jun N-terminal kinase induced by LPS. In addition, DHA suppressed the transcriptional activity of NF-κB by regulating the nuclear translocation and DNA-binding activity of NF-κB p50 subunit and inhibited the phosphorylation of signal transducer and activator of transcription 1. Further in vivo studies are needed to better evaluate the potential of DHA in humans as a therapeutic agent to treat periodontal disease.

  9. Photodegradable neutral-cationic brush block copolymers for nonviral gene delivery.

    Science.gov (United States)

    Hu, Xianglong; Li, Yang; Liu, Tao; Zhang, Guoying; Liu, Shiyong

    2014-08-01

    We report on the fabrication of a photodegradable gene-delivery vector based on PEO-b-P(GMA-g-PDMAEMA) neutral-cationic brush block copolymers that possess cationic poly(N,N-dimethylaminoethyl methacrylate) (PDMAEMA) brushes for DNA compaction, poly(ethylene oxide) (PEO) as a hydrophilic block, and poly(glycidyl methacrylate) (PGMA) as the backbone. The PEO-b-P(GMA-g-PDMAEMA) copolymers were synthesized through the combination of reversible addition-fragmentation transfer (RAFT) polymerization and postmodification. A photocleavable PEO-based macroRAFT agent was first synthesized; next, the PEO-b-PGMA block copolymer was prepared by RAFT polymerization of GMA; this was followed by a click reaction to introduce the RAFT initiators on the side chains of the PGMA block; then, RAFT polymerization of DMAEMA afforded the PEO-b-P(GMA-g-PDMAEMA) copolymer. The obtained neutral-cationic brush block copolymer could effectively complex plasmid DNA (pDNA) into nanoparticles at an N/P ratio (i.e., the number of nitrogen residues per DNA phosphate) of 4. Upon UV irradiation, pDNA could be released owing to cleavage of the pDNA-binding cationic PDMAEMA side chains as well as the nitrobenzyl ester linkages at the diblock junction point. In addition, in vitro gene transfection results demonstrated that the polyplexes could be effectively internalized by cells with good transfection efficiency, and the UV irradiation protocol could considerably enhance the efficiency of gene transfection. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. κ-Carrageenan Enhances Lipopolysaccharide-Induced Interleukin-8 Secretion by Stimulating the Bcl10-NF-κB Pathway in HT-29 Cells and Aggravates C. freundii-Induced Inflammation in Mice

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    Wei Wu

    2017-01-01

    Full Text Available Background. The dietary usage of carrageenan as common food additive has increased observably over the last 50 years. But there is substantial controversy about its safety. Methods. We investigated whether the κ-carrageenan could enhance lipopolysaccharide-induced IL-8 expression by studying its actions on the TLR4-NF-κB pathway. The aggravating effect of κ-carrageenan on Citrobacter freundii DBS100-induced intestinal inflammation was also investigated in a mouse model. Results. Our data show that κ-carrageenan pretreatment promoted LPS-induced IL-8 expression in HT-29 cells. Although CD14, MD-2, and TLR4 were upregulated, the binding of LPS was not enhanced. However, the pathway of Bcl10-NF-κB was triggered. Interestingly, κ-carrageenan competitively blocked the binding of FITC-LPS. Furthermore, pretreatment with κ-carrageenan for one week previous to gavage with C. freundii DBS100 markedly aggravated weight loss, mortality, and colonic damage. The secretion of cytokines was unbalanced and the ratio of Tregs was decreased significantly. In addition, κ-carrageenan, together with C. freundii DBS100, enhanced the transcription and secretion of TLR4 and NF-κB. Conclusions. κ-Carrageenan can synergistically activate LPS-induced inflammatory through the Bcl10-NF-κB pathway, as indicated by its aggravation of C. freundii DBS100-induced colitis in mice. General Significance. Our results suggest that κ-carrageenan serves as a potential inflammatory agent that magnifies existing intestinal inflammation.

  11. Derepression of the Iroquois Homeodomain Transcription Factor Gene IRX3 Confers Differentiation Block in Acute Leukemia

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    Tim D.D. Somerville

    2018-01-01

    Full Text Available The Iroquois homeodomain transcription factor gene IRX3 is expressed in the developing nervous system, limb buds, and heart, and transcript levels specify obesity risk in humans. We now report a functional role for IRX3 in human acute leukemia. Although transcript levels are very low in normal human bone marrow cells, high IRX3 expression is found in ∼30% of patients with acute myeloid leukemia (AML, ∼50% with T-acute lymphoblastic leukemia, and ∼20% with B-acute lymphoblastic leukemia, frequently in association with high-level HOXA gene expression. Expression of IRX3 alone was sufficient to immortalize hematopoietic stem and progenitor cells (HSPCs in myeloid culture and induce lymphoid leukemias in vivo. IRX3 knockdown induced terminal differentiation of AML cells. Combined IRX3 and Hoxa9 expression in murine HSPCs impeded normal T-progenitor differentiation in lymphoid culture and substantially enhanced the morphologic and phenotypic differentiation block of AML in myeloid leukemia transplantation experiments through suppression of a terminal myelomonocytic program. Likewise, in cases of primary human AML, high IRX3 expression is strongly associated with reduced myelomonocytic differentiation. Thus, tissue-inappropriate derepression of IRX3 contributes significantly to the block in differentiation, which is the pathognomonic feature of human acute leukemias.

  12. Cytokinesis is blocked in mammalian cells transfected with Chlamydia trachomatis gene CT223

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    Weeks Sara K

    2009-01-01

    Full Text Available Abstract Background The chlamydiae alter many aspects of host cell biology, including the division process, but the molecular biology of these alterations remains poorly characterized. Chlamydial inclusion membrane proteins (Incs are likely candidates for direct interactions with host cell cytosolic proteins, as they are secreted to the inclusion membrane and exposed to the cytosol. The inc gene CT223 is one of a sequential set of orfs that encode or are predicted to encode Inc proteins. CT223p is localized to the inclusion membrane in all tested C. trachomatis serovars. Results A plasmid transfection approach was used to examine the function of the product of CT223 and other Inc proteins within uninfected mammalian cells. Fluorescence microscopy was used to demonstrate that CT223, and, to a lesser extent, adjacent inc genes, are capable of blocking host cell cytokinesis and facilitating centromere supranumeracy defects seen by others in chlamydiae-infected cells. Both phenotypes were associated with transfection of plasmids encoding the carboxy-terminal tail of CT223p, a region of the protein that is likely exposed to the cytosol in infected cells. Conclusion These studies suggest that certain Inc proteins block cytokinesis in C. trachomatis-infected cells. These results are consistent with the work of others showing chlamydial inhibition of host cell cytokinesis.

  13. Alternative splicing, a new target to block cellular gene expression by poliovirus 2A protease

    International Nuclear Information System (INIS)

    Alvarez, Enrique; Castello, Alfredo; Carrasco, Luis; Izquierdo, Jose M.

    2011-01-01

    Highlights: → Novel role for poliovirus 2A protease as splicing modulator. → Poliovirus 2A protease inhibits the alternative splicing of pre-mRNAs. → Poliovirus 2A protease blocks the second catalytic step of splicing. -- Abstract: Viruses have developed multiple strategies to interfere with the gene expression of host cells at different stages to ensure their own survival. Here we report a new role for poliovirus 2A pro modulating the alternative splicing of pre-mRNAs. Expression of 2A pro potently inhibits splicing of reporter genes in HeLa cells. Low amounts of 2A pro abrogate Fas exon 6 skipping, whereas higher levels of protease fully abolish Fas and FGFR2 splicing. In vitro splicing of MINX mRNA using nuclear extracts is also strongly inhibited by 2A pro , leading to accumulation of the first exon and the lariat product containing the unspliced second exon. These findings reveal that the mechanism of action of 2A pro on splicing is to selectively block the second catalytic step.

  14. Alternative splicing, a new target to block cellular gene expression by poliovirus 2A protease

    Energy Technology Data Exchange (ETDEWEB)

    Alvarez, Enrique, E-mail: ealvarez@cbm.uam.es [Centro de Biologia Molecular Severo Ochoa (CSIC-UAM), Nicolas Cabrera, 1 Universidad Autonoma de Madrid, Cantoblanco, 28049 Madrid (Spain); Castello, Alfredo; Carrasco, Luis; Izquierdo, Jose M. [Centro de Biologia Molecular Severo Ochoa (CSIC-UAM), Nicolas Cabrera, 1 Universidad Autonoma de Madrid, Cantoblanco, 28049 Madrid (Spain)

    2011-10-14

    Highlights: {yields} Novel role for poliovirus 2A protease as splicing modulator. {yields} Poliovirus 2A protease inhibits the alternative splicing of pre-mRNAs. {yields} Poliovirus 2A protease blocks the second catalytic step of splicing. -- Abstract: Viruses have developed multiple strategies to interfere with the gene expression of host cells at different stages to ensure their own survival. Here we report a new role for poliovirus 2A{sup pro} modulating the alternative splicing of pre-mRNAs. Expression of 2A{sup pro} potently inhibits splicing of reporter genes in HeLa cells. Low amounts of 2A{sup pro} abrogate Fas exon 6 skipping, whereas higher levels of protease fully abolish Fas and FGFR2 splicing. In vitro splicing of MINX mRNA using nuclear extracts is also strongly inhibited by 2A{sup pro}, leading to accumulation of the first exon and the lariat product containing the unspliced second exon. These findings reveal that the mechanism of action of 2A{sup pro} on splicing is to selectively block the second catalytic step.

  15. Histone deacetylase inhibitors restore IL-10 expression in lipopolysaccharide-induced cell inflammation and reduce IL-1β and IL-6 production in breast silicone implant in C57BL/6J wild-type murine model.

    Science.gov (United States)

    Di Liddo, Rosa; Valente, Sergio; Taurone, Samanta; Zwergel, Clemens; Marrocco, Biagina; Turchetta, Rosaria; Conconi, Maria Teresa; Scarpa, Carlotta; Bertalot, Thomas; Schrenk, Sandra; Mai, Antonello; Artico, Marco

    2016-01-20

    Among epigenetic enzymes, histone deacetylases (HDACs) are responsible for regulating the expression of an extensive array of genes by reversible deacetylation of nuclear histones as well as a large number of non-histone proteins. Initially proposed for cancer therapy, recently the interest for HDAC inhibitors (HDACi) as orally active, safe, and anti-inflammatory agents is rising due to their ability in reducing the severity of inflammatory and autoimmune diseases. In particular, selective HDAC3, HDAC6, and HDAC8 inhibitors have been described to downregulate the expression of pro-inflammatory cytokines (TNF-α, TGF-β, IL-1β, and IL-6). Herein, using KB31, C2C12, and 3T3-J2 cell lines, we demonstrated that, under lipopolysaccharide-induced in vitro inflammation, HDAC3/6/8 inhibitor MC2625 and HDAC6-selective inhibitor MC2780 were effective at a concentration of 30 ng/mL to downregulate mRNA expression of pro-inflammatory cytokines (IL-1β and IL-6) and to promote the transcription of IL-10 gene, without affecting the cell viability. Afterwards, we investigated by immunohistochemistry the activity of MC2625 and MC2780 at a concentration of 60 ng/kg animal weight to regulate silicone-triggered immune response in C57BL/6J female mice. Our findings evidenced the ability of such inhibitors to reduce host inflammation in silicone implants promoting a thickness reduction of peri-implant fibrous capsule, upregulating IL-10 expression, and reducing the production of both IL-1β and IL-6. These results underline the potential application of MC2625 and MC2780 in inflammation-related diseases.

  16. Senataxin Mutation Reveals How R-Loops Promote Transcription by Blocking DNA Methylation at Gene Promoters.

    Science.gov (United States)

    Grunseich, Christopher; Wang, Isabel X; Watts, Jason A; Burdick, Joshua T; Guber, Robert D; Zhu, Zhengwei; Bruzel, Alan; Lanman, Tyler; Chen, Kelian; Schindler, Alice B; Edwards, Nancy; Ray-Chaudhury, Abhik; Yao, Jianhua; Lehky, Tanya; Piszczek, Grzegorz; Crain, Barbara; Fischbeck, Kenneth H; Cheung, Vivian G

    2018-02-01

    R-loops are three-stranded nucleic acid structures found abundantly and yet often viewed as by-products of transcription. Studying cells from patients with a motor neuron disease (amyotrophic lateral sclerosis 4 [ALS4]) caused by a mutation in senataxin, we uncovered how R-loops promote transcription. In ALS4 patients, the senataxin mutation depletes R-loops with a consequent effect on gene expression. With fewer R-loops in ALS4 cells, the expression of BAMBI, a negative regulator of transforming growth factor β (TGF-β), is reduced; that then leads to the activation of the TGF-β pathway. We uncovered that genome-wide R-loops influence promoter methylation of over 1,200 human genes. DNA methyl-transferase 1 favors binding to double-stranded DNA over R-loops. Thus, in forming R-loops, nascent RNA blocks DNA methylation and promotes further transcription. Hence, our results show that nucleic acid structures, in addition to sequences, influence the binding and activity of regulatory proteins. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Bigelovii A Protects against Lipopolysaccharide-Induced Acute Lung Injury by Blocking NF-κB and CCAAT/Enhancer-Binding Protein δ Pathways

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    Chunguang Yan

    2016-01-01

    Full Text Available Optimal methods are applied to acute lung injury (ALI and the acute respiratory distress syndrome (ARDS, but the mortality rate is still high. Accordingly, further studies dedicated to identify novel therapeutic approaches to ALI are urgently needed. Bigelovii A is a new natural product and may exhibit anti-inflammatory activity. Therefore, we sought to investigate its effect on lipopolysaccharide- (LPS- induced ALI and the underlying mechanisms. We found that LPS-induced ALI was significantly alleviated by Bigelovii A treatment, characterized by reduction of proinflammatory mediator production, neutrophil infiltration, and lung permeability. Furthermore, Bigelovii A also downregulated LPS-stimulated inflammatory mediator expressions in vitro. Moreover, both NF-κB and CCAAT/enhancer-binding protein δ (C/EBPδ activation were obviously attenuated by Bigelovii A treatment. Additionally, phosphorylation of both p38 MAPK and ERK1/2 (upstream signals of C/EBPδ activation in response to LPS challenge was also inhibited by Bigelovii A. Therefore, Bigelovii A could attenuate LPS-induced inflammation by suppression of NF-κB, inflammatory mediators, and p38 MAPK/ERK1/2—C/EBPδ, inflammatory mediators signaling pathways, which provide a novel theoretical basis for the possible application of Bigelovii A in clinic.

  18. Production of Polyclonal Antiobies to a Recombinant Potato Mop-top Virus Non-structural Triple Gene Block Protein l

    Czech Academy of Sciences Publication Activity Database

    Čeřovská, Noemi; Filigarová, Marie; Pečenková, Tamara

    2006-01-01

    Roč. 154, - (2006), s. 422-427 ISSN 0931-1785 R&D Projects: GA ČR GA522/04/1329 Institutional research plan: CEZ:AV0Z50380511 Keywords : Potato mop-top virus * recombinant protein * triple gene block * polyclonal antibodies Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.817, year: 2006

  19. AWRK6, A Synthetic Cationic Peptide Derived from Antimicrobial Peptide Dybowskin-2CDYa, Inhibits Lipopolysaccharide-Induced Inflammatory Response

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    Qiuyu Wang

    2018-02-01

    Full Text Available Lipopolysaccharides (LPS are major outer membrane components of Gram-negative bacteria and produce strong inflammatory responses in animals. Most antibiotics have shown little clinical anti-endotoxin activity while some antimicrobial peptides have proved to be effective in blocking LPS. Here, the anti-LPS activity of the synthetic peptide AWRK6, which is derived from antimicrobial peptide dybowskin-2CDYa, has been investigated in vitro and in vivo. The positively charged α-helical AWRK6 was found to be effective in blocking the binding of LBP (LPS binding protein with LPS in vitro using ELISA. In a murine endotoxemia model, AWRK6 offered satisfactory protection efficiency against endotoxemia death, and the serum levels of LPS, IL-1β, IL-6, and TNF-α were found to be attenuated using ELISA. Further, histopathological analysis suggested that AWRK6 could improve the healing of liver and lung injury in endotoxemia mice. The results of real-time PCR and Western blotting showed that AWRK6 significantly reversed LPS-induced TLR4 overexpression and IκB depression, as well as the enhanced IκB phosphorylation. Additionally, AWRK6 did not produce any significant toxicity in vivo and in vitro. In summary, AWRK6 showed efficacious protection from LPS challenges in vivo and in vitro, by blocking LPS binding to LBP, without obvious toxicity, providing a promising strategy against LPS-induced inflammatory responses.

  20. Carbon monoxide induced PPARγ SUMOylation and UCP2 block inflammatory gene expression in macrophages.

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    Arvand Haschemi

    Full Text Available Carbon monoxide (CO dampens pro-inflammatory responses in a peroxisome proliferator-activated receptor-γ (PPARγ and p38 mitogen-activated protein kinase (MAPK dependent manner. Previously, we demonstrated that CO inhibits lipopolysaccharide (LPS-induced expression of the proinflammatory early growth response-1 (Egr-1 transcription factor in macrophages via activation of PPARγ. Here, we further characterize the molecular mechanisms by which CO modulates the activity of PPARγ and Egr-1 repression. We demonstrate that CO enhances SUMOylation of PPARγ which we find was attributed to mitochondrial ROS generation. Ectopic expression of a SUMOylation-defective PPARγ-K365R mutant partially abolished CO-mediated suppression of LPS-induced Egr-1 promoter activity. Expression of a PPARγ-K77R mutant did not impair the effect of CO. In addition to PPARγ SUMOylation, CO-activated p38 MAPK was responsible for Egr-1 repression. Blocking both CO-induced PPARγ SUMOylation and p38 activation, completely reversed the effects of CO on inflammatory gene expression. In primary macrophages isolated form C57/BL6 male mice, we identify mitochondrial ROS formation by CO as the upstream trigger for the observed effects on Egr-1 in part through uncoupling protein 2 (UCP2. Macrophages derived from bone marrow isolated from Ucp2 gene Knock-Out C57/BL6 mice (Ucp2(-/-, produced significantly less ROS with CO exposure versus wild-type macrophages. Moreover, absence of UCP2 resulted in a complete loss of CO mediated Egr-1 repression. Collectively, these results indentify p38 activation, PPARγ-SUMOylation and ROS formation via UCP2 as a cooperative system by which CO impacts the inflammatory response.

  1. Physiological Responses and Gene Expression in Ultrasound-Guided Supraclavicular Brachial Plexus Block: a Comparative Study

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    Hayam G Sayyed

    2018-05-01

    Full Text Available Background/Aims: Ultrasound-guided supraclavicular brachial plexus block (BPB has come into wider use as a regional anesthetic during upper limb operations. This study assessed the neurological and hemodynamic changes and gene expression after co-administration of midazolam or neostigmine with bupivacaine during supraclavicular BPB. Methods: The study involved 90 adults divided into three groups: control (bupivacaine, midazolam (bupivacaine plus midazolam, and neostigmine (bupivacaine plus neostigmine. Blood samples were taken and interleukin-6 (IL-6 and tumor necrosis factor-alpha (TNF-α mRNA levels were measured by real-time PCR, and oxidative stress markers were identified. In addition to the hemodynamic variables, the onset and duration of sensory and motor blockades, duration of analgesia, pain scores, time of first request for an analgesic, and amounts of analgesics ingested were evaluated. Results: Compared with the control and neostigmine groups, the midazolam group experienced longer sensory and motor blockades, prolonged analgesia, lower pain scores at 12 h and 24 h, and lower need for postoperative analgesics. Moreover, the midazolam group exhibited lower oxidative stress markers with a higher fold change in IL-6 and TNF-α mRNA levels. Conclusion: Midazolam co-administered with bupivacaine provided better analgesic quality than did neostigmine with bupivacaine. This might be due to its superior antioxidant and anti-inflammatory effects.

  2. Expression of macrophage migration inhibitory factor and CD74 in the inner ear and middle ear in lipopolysaccharide-induced otitis media.

    Science.gov (United States)

    Ishihara, Hisashi; Kariya, Shin; Okano, Mitsuhiro; Zhao, Pengfei; Maeda, Yukihide; Nishizaki, Kazunori

    2016-10-01

    Significant expression of macrophage migration inhibitory factor and its receptor (CD74) was observed in both the middle ear and inner ear in experimental otitis media in mice. Modulation of macrophage migration inhibitory factor and its signaling pathway might be useful in the management of inner ear inflammation due to otitis media. Inner ear dysfunction secondary to otitis media has been reported. However, the specific mechanisms involved are not clearly understood. The aim of this study is to investigate the expression of macrophage migration inhibitory factor and CD74 in the middle ear and inner ear in lipopolysaccharide-induced otitis media. BALB/c mice received a transtympanic injection of either lipopolysaccharide or phosphate-buffered saline (PBS). The mice were sacrificed 24 h after injection, and temporal bones were processed for polymerase chain reaction (PCR) analysis, histologic examination, and immunohistochemistry. PCR examination revealed that the lipopolysaccharide-injected mice showed a significant up-regulation of macrophage migration inhibitory factor in both the middle ear and inner ear as compared with the PBS-injected control mice. The immunohistochemical study showed positive reactions for macrophage migration inhibitory factor and CD74 in infiltrating inflammatory cells, middle ear mucosa, and inner ear in the lipopolysaccharide-injected mice.

  3. Evaluation of an Aqueous Extract from Horseradish Root (Armoracia rusticana Radix against Lipopolysaccharide-Induced Cellular Inflammation Reaction

    Directory of Open Access Journals (Sweden)

    Corinna Herz

    2017-01-01

    Full Text Available Horseradish (Armoracia rusticana is a perennial crop and its root is used in condiments. Traditionally, horseradish root is used to treat bacterial infections of the respiratory tract and urinary bladder. The antiphlogistic activity, determined in activated primary human peripheral blood mononuclear cells (PBMC, was evaluated for an aqueous extract and its subfractions, separated by HPLC. Compound analysis was done by UHPLC-QToF/MS and GC-MS. The aqueous extract concentration-dependently inhibited the anti-inflammatory response to lipopolysaccharide (LPS in terms of TNF-α release at ≥37 μg/mL. Further, the cyclooxygenase as well as lipoxygenase pathway was blocked by the extract as demonstrated by inhibition of COX-2 protein expression and PGE2 synthesis at ≥4 μg/mL and leukotriene LTB4 release. Mechanistic studies revealed that inhibition of ERK1/2 and c-Jun activation preceded COX-2 suppression upon plant extract treatment in the presence of LPS. Chemical analysis identified target compounds with a medium polarity as relevant for the observed bioactivity. Importantly, allyl isothiocyanate, which is quite well known for its anti-inflammatory capacity and as the principal pungent constituent in horseradish roots, was not relevant for the observations. The results suggest that horseradish root exerts an antiphlogistic activity in human immune cells by regulation of the COX and LOX pathway via MAPK signalling.

  4. Evaluation of an Aqueous Extract from Horseradish Root (Armoracia rusticana Radix) against Lipopolysaccharide-Induced Cellular Inflammation Reaction.

    Science.gov (United States)

    Herz, Corinna; Tran, Hoai Thi Thu; Márton, Melinda-Rita; Maul, Ronald; Baldermann, Susanne; Schreiner, Monika; Lamy, Evelyn

    2017-01-01

    Horseradish ( Armoracia rusticana ) is a perennial crop and its root is used in condiments. Traditionally, horseradish root is used to treat bacterial infections of the respiratory tract and urinary bladder. The antiphlogistic activity, determined in activated primary human peripheral blood mononuclear cells (PBMC), was evaluated for an aqueous extract and its subfractions, separated by HPLC. Compound analysis was done by UHPLC-QToF/MS and GC-MS. The aqueous extract concentration-dependently inhibited the anti-inflammatory response to lipopolysaccharide (LPS) in terms of TNF- α release at ≥37  μ g/mL. Further, the cyclooxygenase as well as lipoxygenase pathway was blocked by the extract as demonstrated by inhibition of COX-2 protein expression and PGE 2 synthesis at ≥4  μ g/mL and leukotriene LTB4 release. Mechanistic studies revealed that inhibition of ERK1/2 and c-Jun activation preceded COX-2 suppression upon plant extract treatment in the presence of LPS. Chemical analysis identified target compounds with a medium polarity as relevant for the observed bioactivity. Importantly, allyl isothiocyanate, which is quite well known for its anti-inflammatory capacity and as the principal pungent constituent in horseradish roots, was not relevant for the observations. The results suggest that horseradish root exerts an antiphlogistic activity in human immune cells by regulation of the COX and LOX pathway via MAPK signalling.

  5. TLR4-NOX4-AP-1 signaling mediates lipopolysaccharide-induced CXCR6 expression in human aortic smooth muscle cells

    International Nuclear Information System (INIS)

    Patel, Devang N.; Bailey, Steven R.; Gresham, John K.; Schuchman, David B.; Shelhamer, James H.; Goldstein, Barry J.; Foxwell, Brian M.; Stemerman, Michael B.; Maranchie, Jodi K.; Valente, Anthony J.; Mummidi, Srinivas; Chandrasekar, Bysani

    2006-01-01

    CXCL16 is a transmembrane non-ELR CXC chemokine that signals via CXCR6 to induce aortic smooth muscle cell (ASMC) proliferation. While bacterial lipopolysaccharide (LPS) has been shown to stimulate CXCL16 expression in SMC, its effects on CXCR6 are not known. Here, we demonstrate that LPS upregulates CXCR6 mRNA, protein, and surface expression in human ASMC. Inhibition of TLR4 with neutralizing antibodies or specific siRNA interference blocked LPS-mediated CXCR6 expression. LPS stimulated both AP-1 (c-Fos, c-Jun) and NF-κB (p50 and p65) activation, but only inhibition of AP-1 attenuated LPS-induced CXCR6 expression. Using dominant negative expression vectors and siRNA interference, we demonstrate that LPS induces AP-1 activation via MyD88, TRAF6, ERK1/2, and JNK signaling pathways. Furthermore, the flavoprotein inhibitor diphenyleniodonium chloride significantly attenuated LPS-mediated AP-1-dependent CXCR6 expression, as did inhibition of NOX4 NADPH oxidase by siRNA. Finally, CXCR6 knockdown inhibited CXCL16-induced ASMC proliferation. These results demonstrate that LPS-TLR4-NOX4-AP-1 signaling can induce CXCR6 expression in ASMC, and suggest that the CXCL16-CXCR6 axis may be an important proinflammatory pathway in the pathogenesis of atherosclerosis

  6. Porphyromonas endodontalis lipopolysaccharides induce RANKL by mouse osteoblast in a way different from that of Escherichia coli lipopolysaccharide.

    Science.gov (United States)

    Tang, Yin; Sun, Feifei; Li, Xiaoting; Zhou, Yuan; Yin, Shihai; Zhou, Xuedong

    2011-12-01

    Porphyromonas endodontalis lipopolysaccharide (LPS) has been shown to have a high positive rate in infected root canals and symptomatic apical periodontitis. It may play an integral role as a potent stimulator of inflammatory cytokines involved in apical lesions. The receptor activator of nuclear factor-κB ligand (RANKL) has been proven to be the key regulator of bone remodeling. This study investigated P. endodontalis LPS-induced RANKL production and LPS signaling in mouse osteoblasts. LPS-induced RANKL production in mouse osteoblast MC3T3-E1 cells was measured by Western blot and real-time polymerase chain reaction, and the Toll-like receptors (TLRs) were determined by the blocking test using anti-TLRs antibodies. In addition, specific inhibitors were used to analyze the intracellular signaling pathways. Escherichia coli LPS was used as the control. Both of the anti-TLR2 and anti-TLR4 antibodies significantly (P endodontalis LPS; only anti-TLR2 antibody had a significant (P endodontalis LPS-infected osteoblasts (P endodontalis LPS has the ability to promote the expression of RANKL in mouse osteoblasts, and this induction was mainly through the TLR2/4-JNK signaling pathway, a situation quite different from that of typical bacterial endotoxin (E. coli LPS). Copyright © 2011 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  7. Acanthopanax trifoliatus inhibits lipopolysaccharide-induced inflammatory response in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Tzu-Mei Chien

    2015-10-01

    Full Text Available Acanthopanax trifoliatus is a well-known herb that is used for the treatment of bruising, neuralgia, impotence, and gout in Taiwan. This herb exhibits multifunctional activities, including anticancer, anti-inflammation, and antioxidant effects. This paper investigated the in vitro and in vivo anti-inflammatory effect of A. trifoliatus. High-performance liquid chromatography analysis established the fingerprint chromatogram of the ethyl acetate fraction of A. trifoliatus (EAAT. The anti-inflammatory effect of EAAT was detected using lipopolysaccharide (LPS stimulation of the mouse macrophage cell line RAW264.7 in vitro and LPS-induced lung injury in vivo. The effects of EAAT on LPS-induced production of inflammatory mediators in RAW264.7 murine macrophages and the mouse model were measured using enzyme-linked immunosorbent assay and Western blot. EAAT attenuated the production of LPS-induced nitric oxide (NO, tumor necrosis factor-alpha, interleukin-1β (IL-1β, and IL-6 in vitro and in vivo. Pretreatment with EAAT markedly reduced LPS-induced histological alterations in lung tissues. Furthermore, EAAT significantly reduced the number of total cells and protein concentration levels in the bronchoalveolar lavage fluid. Western blotting test results revealed that EAAT blocked protein expression of inducible NO synthase, cyclooxygenase-2, phosphorylation of Nuclear factor-kappa-B Inhibitor alpha (IκB-α protein, and mitogen-activated protein kinases in LPS-stimulated RAW264.7 cells as well as LPS-induced lung injury. This study suggests that A. trifoliatus may be a potential therapeutic candidate for the treatment of inflammatory diseases.

  8. Effects of betaine on lipopolysaccharide-induced memory impairment in mice and the involvement of GABA transporter 2

    Directory of Open Access Journals (Sweden)

    Miwa Masaya

    2011-11-01

    Full Text Available Abstract Background Betaine (glycine betaine or trimethylglycine plays important roles as an osmolyte and a methyl donor in animals. While betaine is reported to suppress expression of proinflammatory molecules and reduce oxidative stress in aged rat kidney, the effects of betaine on the central nervous system are not well known. In this study, we investigated the effects of betaine on lipopolysaccharide (LPS-induced memory impairment and on mRNA expression levels of proinflammatory molecules, glial markers, and GABA transporter 2 (GAT2, a betaine/GABA transporter. Methods Mice were continuously treated with betaine for 13 days starting 1 day before they were injected with LPS, or received subacute or acute administration of betaine shortly before or after LPS injection. Then, their memory function was evaluated using Y-maze and novel object recognition tests 7 and 10-12 days after LPS injection (30 μg/mouse, i.c.v., respectively. In addition, mRNA expression levels in hippocampus were measured by real-time RT-PCR at different time points. Results Repeated administration of betaine (0.163 mmol/kg, s.c. prevented LPS-induced memory impairment. GAT2 mRNA levels were significantly increased in hippocampus 24 hr after LPS injection, and administration of betaine blocked this increase. However, betaine did not affect LPS-induced increases in levels of mRNA related to inflammatory responses. Both subacute administration (1 hr before, and 1 and 24 hr after LPS injection and acute administration (1 hr after LPS injection of betaine also prevented LPS-induced memory impairment in the Y-maze test. Conclusions These data suggest that betaine has protective effects against LPS-induced memory impairment and that prevention of LPS-induced changes in GAT2 mRNA expression is crucial to this ameliorating effect.

  9. Lipopolysaccharide induces the migration of human dental pulp cells by up-regulating miR-146a.

    Science.gov (United States)

    Wang, Min-Ching; Hung, Pei-Shih; Tu, Hsi-Feng; Shih, Wen-Yu; Li, Wan-Chun; Chang, Kuo-Wei

    2012-12-01

    MicroRNAs are small noncoding RNAs that play crucial roles in regulating normal and pathologic functions. Bacterial lipopolysaccharide (LPS) is one of the key regulators of pulpal pathogenesis. This study investigated how LPS regulates microRNA expression and affects the phenotype of human dental pulp cells (DPCs). Primary DPCs were established and immortalized to achieve immortalized DPCs (I-DPCs). DPCs and I-DPCs were treated with LPS and examined to identify changes in microRNA expression, cell proliferation, and cell migration. Quantitative reverse-transcriptase polymerase chain reaction was used to detect changes in gene expression. Exogenous miR-146a expression was performed transfection with pre-mir-146a mimic. Knockdown of interleukin receptor-associated kinase (IRAK1) and tumor necrosis factor receptor-associated factor 6 (TRAF6) expression was performed by small interference oligonucleotide transfection. Western blot analysis was used to detect changes in the expression of the IRAK1 and TRAF6 proteins. The differentiation of DPCs was induced by osteogenic medium. I-DPCs had a higher level of human telomerase reverse transcriptase gene than the parental DPCs. Up-regulation of miR-146a expression and an increase in migration was induced by LPS treatment of DPCs and I-DPCs. Exogenous miR-146a expression increased the migration of DPCs and I-DPCs and down-regulated the expression of IRAK1 and TRAF6. Knockdown of IRAK1 and/or TRAF6 increased the migration of DPCs. The results suggested that LPS is able to increase the migration of DPCs by modulating the miR-146a-TRAF6/IRAK1 regulatory cascade. Copyright © 2012 American Association of Endodontists. All rights reserved.

  10. Lipopolysaccharide-induced blood-brain barrier disruption: roles of cyclooxygenase, oxidative stress, neuroinflammation, and elements of the neurovascular unit.

    Science.gov (United States)

    Banks, William A; Gray, Alicia M; Erickson, Michelle A; Salameh, Therese S; Damodarasamy, Mamatha; Sheibani, Nader; Meabon, James S; Wing, Emily E; Morofuji, Yoichi; Cook, David G; Reed, May J

    2015-11-25

    Disruption of the blood-brain barrier (BBB) occurs in many diseases and is often mediated by inflammatory and neuroimmune mechanisms. Inflammation is well established as a cause of BBB disruption, but many mechanistic questions remain. We used lipopolysaccharide (LPS) to induce inflammation and BBB disruption in mice. BBB disruption was measured using (14)C-sucrose and radioactively labeled albumin. Brain cytokine responses were measured using multiplex technology and dependence on cyclooxygenase (COX) and oxidative stress determined by treatments with indomethacin and N-acetylcysteine. Astrocyte and microglia/macrophage responses were measured using brain immunohistochemistry. In vitro studies used Transwell cultures of primary brain endothelial cells co- or tri-cultured with astrocytes and pericytes to measure effects of LPS on transendothelial electrical resistance (TEER), cellular distribution of tight junction proteins, and permeability to (14)C-sucrose and radioactive albumin. In comparison to LPS-induced weight loss, the BBB was relatively resistant to LPS-induced disruption. Disruption occurred only with the highest dose of LPS and was most evident in the frontal cortex, thalamus, pons-medulla, and cerebellum with no disruption in the hypothalamus. The in vitro and in vivo patterns of LPS-induced disruption as measured with (14)C-sucrose, radioactive albumin, and TEER suggested involvement of both paracellular and transcytotic pathways. Disruption as measured with albumin and (14)C-sucrose, but not TEER, was blocked by indomethacin. N-acetylcysteine did not affect disruption. In vivo, the measures of neuroinflammation induced by LPS were mainly not reversed by indomethacin. In vitro, the effects on LPS and indomethacin were not altered when brain endothelial cells (BECs) were cultured with astrocytes or pericytes. The BBB is relatively resistant to LPS-induced disruption with some brain regions more vulnerable than others. LPS-induced disruption appears is

  11. Curcumin Attenuates Lipopolysaccharide-Induced Hepatic Lipid Metabolism Disorder by Modification of m6 A RNA Methylation in Piglets.

    Science.gov (United States)

    Lu, Na; Li, Xingmei; Yu, Jiayao; Li, Yi; Wang, Chao; Zhang, Lili; Wang, Tian; Zhong, Xiang

    2018-01-01

    N 6 -methyladenosine (m 6 A) regulates gene expression and affects cellular metabolism. In this study, we checked whether the regulation of lipid metabolism by curcumin is associated with m 6 A RNA methylation. We investigated the effects of dietary curcumin supplementation on lipopolysaccharide (LPS)-induced liver injury and lipid metabolism disorder, and on m 6 A RNA methylation in weaned piglets. A total of 24 Duroc × Large White × Landrace piglets were randomly assigned to control, LPS, and CurL (LPS challenge and 200 mg/kg dietary curcumin) groups (n = 8/group). The results showed that curcumin reduced the increase in relative liver weight as well as the concentrations of aspartate aminotransferase and lactate dehydrogenase induced by LPS injection in the plasma and liver of weaning piglets (p < 0.05). The amounts of total cholesterol and triacylglycerols were decreased by curcumin compared to that by the LPS injection (p < 0.05). Additionally, curcumin reduced the expression of Bcl-2 and Bax mRNA, whereas it increased the p53 mRNA level in the liver (p < 0.05). Curcumin inhibited the enhancement of SREBP-1c and SCD-1 mRNA levels induced by LPS in the liver. Notably, dietary curcumin affected the expression of METTL3, METTL14, ALKBH5, FTO, and YTHDF2 mRNA, and increased the abundance of m 6 A in the liver of piglets. In conclusion, the protective effect of curcumin in LPS-induced liver injury and hepatic lipid metabolism disruption might be due to the increase in m 6 A RNA methylation. Our study provides mechanistic insights into the effect of curcumin in protecting against hepatic injury during inflammation and metabolic diseases. © 2018 AOCS.

  12. Ginseng Berry Extract Prevents Atherogenesis via Anti-Inflammatory Action by Upregulating Phase II Gene Expression

    Directory of Open Access Journals (Sweden)

    Chun-Ki Kim

    2012-01-01

    Full Text Available Ginseng berry possesses higher ginsenoside content than its root, which has been traditionally used in herbal medicine for many human diseases, including atherosclerosis. We here examined the antiatherogenic effects of the Korean ginseng berry extract (KGBE and investigated its underlying mechanism of action in vitro and in vivo. Administration of KGBE decreased atherosclerotic lesions, which was inversely correlated with the expression levels of phase II genes to include heme oxygenase-1 (HO-1 and glutamine-cysteine ligase (GCL. Furthermore, KGBE administration suppressed NF-κB-mediated expression of atherogenic inflammatory genes (TNF-α, IL-1β, iNOS, COX-2, ICAM-1, and VCAM-1, without altering serum cholesterol levels, in ApoE-/- mice fed a high fat-diet. Treatment with KGBE increased phase II gene expression and suppressed lipopolysaccharide-induced reactive oxygen species production, NF-κB activation, and inflammatory gene expression in primary macrophages. Importantly, these cellular events were blocked by selective inhibitors of HO-1 and GCL. In addition, these inhibitors reversed the suppressive effect of KGBE on TNF-α-mediated induction of ICAM-1 and VCAM-1, resulting in decreased interaction between endothelial cells and monocytes. These results suggest that KGBE ameliorates atherosclerosis by inhibiting NF-κB-mediated expression of atherogenic genes via upregulation of phase II enzymes and thus has therapeutic or preventive potential for atherosclerosis.

  13. Horizontal gene transfer from macrophages to ischemic muscles upon delivery of naked DNA with Pluronic block copolymers.

    Science.gov (United States)

    Mahajan, Vivek; Gaymalov, Zagit; Alakhova, Daria; Gupta, Richa; Zucker, Irving H; Kabanov, Alexander V

    2016-01-01

    Intramuscular administration of plasmid DNA (pDNA) with non-ionic Pluronic block copolymers increases gene expression in injected muscles and lymphoid organs. We studied the role of immune cells in muscle transfection upon inflammation. Local inflammation in murine hind limb ischemia model (MHLIM) drastically increased DNA, RNA and expressed protein levels in ischemic muscles injected with pDNA/Pluronic. The systemic inflammation (MHLIM or peritonitis) also increased expression of pDNA/Pluronic in the muscles. When pDNA/Pluronic was injected in ischemic muscles the reporter gene, Green Fluorescent Protein (GFP) co-localized with desmin(+) muscle fibers and CD11b(+) macrophages (MØs), suggesting transfection of MØs along with the muscle cells. P85 enhanced (∼ 4 orders) transfection of MØs with pDNA in vitro. Moreover, adoptively transferred MØs were shown to pass the transgene to inflamed muscle cells in MHLIM. Using a co-culture of myotubes (MTs) and transfected MØs expressing a reporter gene under constitutive (cmv-luciferase) or muscle specific (desmin-luciferase) promoter we demonstrated that P85 enhances horizontal gene transfer from MØ to MTs. Therefore, MØs can play an important role in muscle transfection with pDNA/Pluronic during inflammation, with both inflammation and Pluronic contributing to the increased gene expression. pDNA/Pluronic has potential for therapeutic gene delivery in muscle pathologies that involve inflammation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Well-defined block copolymers for gene delivery to dendritic cells: probing the effect of polycation chain-length.

    Science.gov (United States)

    Tang, Rupei; Palumbo, R Noelle; Nagarajan, Lakshmi; Krogstad, Emily; Wang, Chun

    2010-03-03

    The development of safe and efficient polymer carriers for DNA vaccine delivery requires mechanistic understanding of structure-function relationship of the polymer carriers and their interaction with antigen-presenting cells. Here we have synthesized a series of diblock copolymers with well-defined chain-length using atom transfer radical polymerization and characterized the influence of polycation chain-length on the physico-chemical properties of the polymer/DNA complexes as well as the interaction with dendritic cells. The copolymers consist of a hydrophilic poly(ethylene glycol) block and a cationic poly(aminoethyl methacrylate) (PAEM) block. The average degree of polymerization (DP) of the PAEM block was varied among 19, 39, and 75, with nearly uniform distribution. With increasing PAEM chain-length, polyplexes formed by the diblock copolymers and plasmid DNA had smaller average particle size and showed higher stability against electrostatic destabilization by salt and heparin. The polymers were not toxic to mouse dendritic cells (DCs) and only displayed chain-length-dependent toxicity at a high concentration (1mg/mL). In vitro gene transfection efficiency and polyplex uptake in DCs were also found to correlate with chain-length of the PAEM block with the longer polymer chain favoring transfection and cellular uptake. The polyplexes induced a modest up-regulation of surface markers for DC maturation that was not significantly dependent on PAEM chain-length. Finally, the polyplex prepared from the longest PAEM block (DP of 75) achieved an average of 20% enhancement over non-condensed anionic dextran in terms of uptake by DCs in the draining lymph nodes 24h after subcutaneous injection into mice. Insights gained from studying such structurally well-defined polymer carriers and their interaction with dendritic cells may contribute to improved design of practically useful DNA vaccine delivery systems. Copyright 2009 Elsevier B.V. All rights reserved.

  15. Sensitivity of spiral ganglion neurons to damage caused by mobile phone electromagnetic radiation will increase in lipopolysaccharide-induced inflammation in vitro model.

    Science.gov (United States)

    Zuo, Wen-Qi; Hu, Yu-Juan; Yang, Yang; Zhao, Xue-Yan; Zhang, Yuan-Yuan; Kong, Wen; Kong, Wei-Jia

    2015-05-29

    .0 W/kg when cells are in fragile or micro-damaged condition. It seems that the sensitivity of SGN to damage caused by mobile phone electromagnetic radiation will increase in a lipopolysaccharide-induced inflammation in vitro model.

  16. Hap2, a novel gene in Babesia bigemina is expressed in tick stages, and specific antibodies block zygote formation

    Directory of Open Access Journals (Sweden)

    Minerva Camacho-Nuez

    2017-11-01

    Full Text Available Abstract Background Bovine babesiosis is a tick-borne disease caused by the protozoan parasites of the genus Babesia. In their host vector, Babesia spp. undergo sexual reproduction. Therefore, the development of sexual stages and the subsequent formation of the zygote are essential for the parasite to invade the intestinal cells of the vector tick and continue its life-cycle. HAP2/GCS1 is a protein identified in plants, protozoan parasites and other organisms that has an important role during membrane fusion in fertilization processes. The identification and characterization of HAP-2 protein in Babesia would be very significant to understand the biology of the parasite and to develop a transmission-blocking vaccine in the future. Results To isolate and sequence the hap2 gene DNA from an infected bovine with Babesia bigemina was purified. The hap2 gene was amplified, cloned and sequenced. The sequences of hap2 from four geographically different strains showed high conservation at the amino acid level, including the typical structure with a signal peptide and the HAP2/GSC domain. Antisera anti-HAP2 against the conserved extracellular region of the HAP2 amino acid sequence were obtained from rabbits. The expression of hap2 in the host and vector tissues was analyzed by using semi-quantitative RT-PCR, and the protein was examined by western blot and immunofluorescence. Based on the RT-PCR and WB results, HAP2 is expressed in both, sexual stages induced in vitro, and in infected ticks as well. We did not detect any expression in asexual erythrocytic stages of B. bigemina, relevantly anti-HAP2 specific antibodies were able to block zygotes formation in vitro. Conclusion Babesia bigemina HAP2 is expressed only in tick-infecting stages, and specific antibodies block zygote formation. Further studies regarding the function of HAP2 during tick infection may provide new insights into the molecular mechanisms of sexual reproduction of the parasite.

  17. Gene expression changes in rat prostate after activation or blocking of the androgen and estrogen receptor

    DEFF Research Database (Denmark)

    Nellemann, Christine Lydia; Dalgaard, Majken; Holst, Bjørn

    2005-01-01

    responsive genes (complement C3, ER alpha, ER beta, AR, TRPM-2, PBPC3, ODC, and IGF-1 mRNA) was analyzed in rat ventral prostate by real time RT-PCR. Administration of estradiol benzoate (EB) to castrated testosterone-treated rats had no effect on reproductive organ weights or gene expression levels...... reversed by ICI 182780, and affected TRPM-2, PBP C3, ODC, IGF-1, AR, and ERa mRNA levels. AR expression in the prostate seemed to be under regulation of both estrogens and androgens, as ICI 182780 inhibited the testosterone-induced AR expression, and flutamide inhibited the EB-induced AR expression...... administration abolished the effects of EB. First choice of gene expression profiles in the Hershberger assay to study androgenic or anti-androgenic effects would be the traditional, TRPNI-2 and PBP C3, supplemented with the new complement C3....

  18. Biofunctionalized nanoparticles with pH-responsive and cell penetrating blocks for gene delivery

    International Nuclear Information System (INIS)

    Gaspar, V M; Marques, J G; Sousa, F; Queiroz, J A; Correia, I J; Louro, R O

    2013-01-01

    Bridging the gap between nanoparticulate delivery systems and translational gene therapy is a long sought after requirement in nanomedicine-based applications. However, recent developments regarding nanoparticle functionalization have brought forward the ability to synthesize materials with biofunctional moieties that mimic the evolved features of viral particles. Herein we report the versatile conjugation of both cell penetrating arginine and pH-responsive histidine moieties into the chitosan polymeric backbone, to improve the physicochemical characteristics of the native material. Amino acid coupling was confirmed by 2D TOCSY NMR and Fourier transform infrared spectroscopy. The synthesized chitosan–histidine–arginine (CH–H–R) polymer complexed plasmid DNA biopharmaceuticals, and spontaneously assembled into stable 105 nm nanoparticles with spherical morphology and positive surface charge. The functionalized delivery systems were efficiently internalized into the intracellular compartment, and exhibited remarkably higher transfection efficiency than unmodified chitosan without causing any cytotoxic effect. Additional findings regarding intracellular trafficking events reveal their preferential escape from degradative lysosomal pathways and nuclear localization. Overall, this assembly of nanocarriers with bioinspired moieties provides the foundations for the design of efficient and customizable materials for cancer gene therapy. (paper)

  19. Methamphetamine blocks exercise effects on Bdnf and Drd2 gene expression in frontal cortex and striatum.

    Science.gov (United States)

    Thompson, Andrew B; Stolyarova, Alexandra; Ying, Zhe; Zhuang, Yumei; Gómez-Pinilla, Fernando; Izquierdo, Alicia

    2015-12-01

    Exposure to drugs of abuse can produce many neurobiological changes which may lead to increased valuation of rewards and decreased sensitivity to their costs. Many of these behavioral alterations are associated with activity of D2-expressing medium spiny neurons in the striatum. Additionally, Bdnf in the striatum has been shown to play a role in flexible reward-seeking behavior. Given that voluntary aerobic exercise can affect the expression of these proteins in healthy subjects, and that exercise has shown promise as an anti-addictive therapy, we set out to quantify changes in D2 and Bdnf expression in methamphetamine-exposed rats given access to running wheels. Sixty-four rats were treated for two weeks with an escalating dose of methamphetamine or saline, then either sacrificed, housed in standard cages, or given free access to a running wheel for 6 weeks prior to sacrifice. Rats treated with methamphetamine ran significantly greater distances than saline-treated rats, suggesting an augmentation in the reinforcement value of voluntary wheel running. Transcription of Drd2 and Bdnf was assessed via RT-qPCR. Protein expression levels of D2 and phosphorylation of the TrkB receptor were measured via western blot. Drd2 and Bdnf mRNA levels were impacted independently by exercise and methamphetamine, but exposure to methamphetamine prior to the initiation of exercise blocked the exercise-induced changes seen in rats treated with saline. Expression levels of both proteins were elevated immediately after methamphetamine, but returned to baseline after six weeks, regardless of exercise status. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Carbon monoxide-releasing molecule-3 suppresses Prevotella intermedia lipopolysaccharide-induced production of nitric oxide and interleukin-1β in murine macrophages.

    Science.gov (United States)

    Choi, Eun-Young; Choe, So-Hui; Hyeon, Jin-Yi; Choi, Jeom-Il; Choi, In Soon; Kim, Sung-Jo

    2015-10-05

    This study was performed to analyze the effect of carbon monoxide (CO)-releasing molecule-3 (CORM-3) in alleviating the production of proinflammatory mediators in macrophages treated with lipopolysaccharide (LPS) from Prevotella intermedia, a pathogen associated with periodontal disease, and its possible mechanisms of action. LPS was isolated using the hot phenol-water method. Culture supernatants were assayed for nitric oxide (NO) and interleukin-1β (IL-1β). Gene expression was quantified by real-time PCR, and protein expression by immunoblotting. DNA-binding activities of NF-κB subunits were determined using an ELISA-based kit. CORM-3 suppressed the production of inducible NO synthase (iNOS)-derived NO and IL-1β at both gene transcription and translation levels in P. intermedia LPS-activated RAW264.7 cells. CORM-3 enhanced heme oxygenase-1 (HO-1) expression in cells stimulated with P. intermedia LPS, and inhibition of HO-1 activity by SnPP notably reversed the suppressive effect of CORM-3 on LPS-induced production of NO. LPS-induced phosphorylation of p38 and JNK was not affected by CORM-3. CORM-3 did not influence P. intermedia LPS-induced degradation of IκB-α. Instead, nuclear translocation of NF-κB p65 and p50 subunits was blocked by CORM-3 in LPS-treated cells. In addition, CORM-3 reduced LPS-induced p65 and p50 binding to DNA. Besides, CORM-3 significantly suppressed P. intermedia LPS-induced phosphorylation of STAT1. Overall, this study indicates that CORM-3 suppresses the production of NO and IL-1β in P. intermedia LPS-activated murine macrophages via HO-1 induction and inhibition of NF-κB and STAT1 pathways. The modulation of host inflammatory response by CORM-3 would be an attractive therapeutic approach to attenuate the progression of periodontal disease. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. The inhibition of lactate dehydrogenase A hinders the transcription of histone 2B gene independently from the block of aerobic glycolysis

    International Nuclear Information System (INIS)

    Brighenti, Elisa; Carnicelli, Domenica; Brigotti, Maurizio; Fiume, Luigi

    2017-01-01

    Most cancer cells use aerobic glycolysis to fuel their growth and many efforts are made to selectively block this metabolic pathway in cancer cells by inhibiting lactate dehydrogenase A (LDHA). However, LDHA is a moonlighting protein which exerts functions also in the nucleus as a factor associated to transcriptional complexes. Here we found that two small molecules which inhibit the enzymatic activity of LDHA hinder the transcription of histone 2B gene independently from the block of aerobic glycolysis. Moreover, we observed that silencing this gene reduces cell replication, hence suggesting that the inhibition of LDHA can also affect the proliferation of normal non-glycolysing dividing cells. - Highlights: • Blocking aerobic glycolysis is an approach to impair proliferation of cancer cells. • Small inhibitors of LDHA block aerobic glycolysis. • LDHA is also involved in the transcription of histone 2B gene. • LDHA inhibitors block histone 2B transcription. • LDHA inhibitors can hinder the proliferation also of non-glycolysing normal cells.

  2. Bacterial lipopolysaccharide-induced systemic inflammation alters perfusion of white matter-rich regions without altering flow in brain-irrigating arteries: Relationship to blood-brain barrier breakdown?

    Science.gov (United States)

    Dhaya, Ibtihel; Griton, Marion; Raffard, Gérard; Amri, Mohamed; Hiba, Bassem; Konsman, Jan Pieter

    2018-01-15

    To better understand brain dysfunction during sepsis, cerebral arterial blood flow was assessed with Phase Contrast Magnetic Resonance Imaging, perfusion with Arterial Spin Labeling and structure with diffusion-weighted Magnetic Resonance Imaging in rats after intraperitoneal administration of bacterial lipopolysaccharides. Although cerebral arterial flow was not altered, perfusion of the corpus callosum region and diffusion parallel to its fibers were higher after lipopolysaccharide administration as compared to saline injection. In parallel, lipopolysaccharide induced perivascular immunoglobulin-immunoreactivity in white matter. These findings indicate that systemic inflammation can result in increased perfusion, blood-brain barrier breakdown and altered water diffusion in white matter. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Efficient bacterial expression of recombinant potato mop-top virus non-structural triple gene block protein 1 modified by progressive deletion of its N-terminus

    Czech Academy of Sciences Publication Activity Database

    Pečenková, Tamara; Filigarová, Marie; Čeřovská, Noemi

    2005-01-01

    Roč. 41, - (2005), s. 128-135 ISSN 1046-5928 R&D Projects: GA ČR GA522/04/1329 Institutional research plan: CEZ:AV0Z50380511 Keywords : Protein expression * Potato mop-top virus * Triple gene block Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.553, year: 2005

  4. Nerve Blocks

    Science.gov (United States)

    ... News Physician Resources Professions Site Index A-Z Nerve Blocks A nerve block is an injection to ... the limitations of Nerve Block? What is a Nerve Block? A nerve block is an anesthetic and/ ...

  5. Low Molecular Weight pDMAEMA-block-pHEMA Block-Copolymers Synthesized via RAFT-Polymerization: Potential Non-Viral Gene Delivery Agents?

    Directory of Open Access Journals (Sweden)

    Thomas Kissel

    2011-03-01

    Full Text Available The aim of this study was to investigate non-viral pDNA carriers based on diblock-copolymers consisting of poly(2-(dimethyl aminoethyl methacrylate (pDMAEMA and poly(2-hydroxyethyl methacrylate (pHEMA. Specifically the block-lengths and molecular weights were varied to determine the minimal requirements for transfection. Such vectors should allow better transfection at acceptable toxicity levels and the entire diblock-copolymer should be suitable for renal clearance. For this purpose, a library of linear poly(2-(dimethyl aminoethyl methacrylate-block-poly(2-hydroxyl methacrylate (pDMAEMA-block-pHEMA copolymers was synthesized via RAFT (reversible addition-fragmentation chain transfer polymerization in a molecular weight (Mw range of 17–35.7 kDa and analyzed using 1H and 13C NMR (nuclear magnetic resonance, ATR (attenuated total reflectance, GPC (gel permeation chromatography and DSC (differential scanning calorimetry. Copolymers possessing short pDMAEMA-polycation chains were 1.4–9.7 times less toxic in vitro than polyethylenimine (PEI 25 kDa, and complexed DNA into polyplexes of 100–170 nm, favorable for cellular uptake. The DNA-binding affinity and polyplex stability against competing polyanions was comparable with PEI 25 kDa. The zeta-potential of polyplexes of pDMAEMA-grafted copolymers remained positive (+15–30 mV. In comparison with earlier reported low molecular weight homo pDMAEMA vectors, these diblock-copolymers showed enhanced transfection efficacy under in vitro conditions due to their lower cytotoxicity, efficient cellular uptake and DNA packaging. The homo pDMAEMA115 (18.3 kDa self-assembled with DNA into small positively charged polyplexes, but was not able to transfect cells. The grafting of 6 and 57 repeating units of pHEMA (0.8 and 7.4 kDa to pDMAEMA115 increased the transfection efficacy significantly, implying a crucial impact of pHEMA on vector-cell interactions. The intracellular trafficking, in vivo transfection

  6. Homology blocks of Plasmodium falciparum var genes and clinically distinct forms of severe malaria in a local population.

    Science.gov (United States)

    Rorick, Mary M; Rask, Thomas S; Baskerville, Edward B; Day, Karen P; Pascual, Mercedes

    2013-11-06

    The primary target of the human immune response to the malaria parasite Plasmodium falciparum, P. falciparum erythrocyte membrane protein 1 (PfEMP1), is encoded by the members of the hyper-diverse var gene family. The parasite exhibits antigenic variation via mutually exclusive expression (switching) of the ~60 var genes within its genome. It is thought that different variants exhibit different host endothelial binding preferences that in turn result in different manifestations of disease. Var sequences comprise ancient sequence fragments, termed homology blocks (HBs), that recombine at exceedingly high rates. We use HBs to define distinct var types within a local population. We then reanalyze a dataset that contains clinical and var expression data to investigate whether the HBs allow for a description of sequence diversity corresponding to biological function, such that it improves our ability to predict disease phenotype from parasite genetics. We find that even a generic set of HBs, which are defined for a small number of non-local parasites: capture the majority of local sequence diversity; improve our ability to predict disease severity from parasite genetics; and reveal a previously hypothesized yet previously unobserved parasite genetic basis for two forms of severe disease. We find that the expression rates of some HBs correlate more strongly with severe disease phenotypes than the expression rates of classic var DBLα tag types, and principal components of HB expression rate profiles further improve genotype-phenotype models. More specifically, within the large Kenyan dataset that is the focus of this study, we observe that HB expression differs significantly for severe versus mild disease, and for rosetting versus impaired consciousness associated severe disease. The analysis of a second much smaller dataset from Mali suggests that these HB-phenotype associations are consistent across geographically distant populations, since we find evidence suggesting

  7. Identification of Putative Ortholog Gene Blocks Involved in Gestant and Lactating Mammary Gland Development: A Rodent Cross-Species Microarray Transcriptomics Approach

    Science.gov (United States)

    Rodríguez-Cruz, Maricela; Coral-Vázquez, Ramón M.; Hernández-Stengele, Gabriel; Sánchez, Raúl; Salazar, Emmanuel; Sanchez-Muñoz, Fausto; Encarnación-Guevara, Sergio; Ramírez-Salcedo, Jorge

    2013-01-01

    The mammary gland (MG) undergoes functional and metabolic changes during the transition from pregnancy to lactation, possibly by regulation of conserved genes. The objective was to elucidate orthologous genes, chromosome clusters and putative conserved transcriptional modules during MG development. We analyzed expression of 22,000 transcripts using murine microarrays and RNA samples of MG from virgin, pregnant, and lactating rats by cross-species hybridization. We identified 521 transcripts differentially expressed; upregulated in early (78%) and midpregnancy (89%) and early lactation (64%), but downregulated in mid-lactation (61%). Putative orthologous genes were identified. We mapped the altered genes to orthologous chromosomal locations in human and mouse. Eighteen sets of conserved genes associated with key cellular functions were revealed and conserved transcription factor binding site search entailed possible coregulation among all eight block sets of genes. This study demonstrates that the use of heterologous array hybridization for screening of orthologous gene expression from rat revealed sets of conserved genes arranged in chromosomal order implicated in signaling pathways and functional ontology. Results demonstrate the utilization power of comparative genomics and prove the feasibility of using rodent microarrays to identification of putative coexpressed orthologous genes involved in the control of human mammary gland development. PMID:24288657

  8. Amphiphilic star block copolymers as gene carrier Part I: Synthesis via ATRP using calix[4]resorcinarene-based initiators and characterization

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Anna; Xue, Yan; Wei, Dafu [Shanghai Key Laboratory of Advanced Polymeric Materials, Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237 (China); Guan, Yong, E-mail: yguan@ecust.edu.cn [Shanghai Key Laboratory of Advanced Polymeric Materials, Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237 (China); Xiao, Huining [Department of Chemical Engineering, University of New Brunswick, Fredericton, New Brunswick, Canada E3B 5A3 (Canada)

    2013-01-01

    In this work, a cationic star polymer [poly(2-dimethylamino)ethyl methacrylate (PDMAEMA)] was prepared via atom transfer radical polymerization (ATRP), using brominated calix[4]resorcinarene as an initiator. Hydrophobic moieties, methyl methacrylate (MMA) and butyl acrylate (BA), were further incorporated via 'one-pot' method. Well-defined eight-armed star block copolymers bearing hydrophilic blocks inside and hydrophobic blocks outside were synthesized. The molecular weight, particle size, electrophoretic mobility and apparent charge density were determined by gel permeation chromatography (GPC), dynamic light scattering (DLS), phase analysis light scattering (PALS) and colloidal titration, respectively. The zeta potentials and apparent charge densities of the products exhibited the characteristics of polyelectrolyte. The incorporation of hydrophobic moieties generated electrostatic screening effect. The as-synthesized amphiphilic star copolymer is promising as a thermo-sensitive gene carrier for gene therapy. Highlights: Black-Right-Pointing-Pointer Amphiphilic cationic star block copolymers with well-controlled structures were prepared via ATRP. Black-Right-Pointing-Pointer The molecular structures and properties of the initiator and copolymers were systematically characterized. Black-Right-Pointing-Pointer The products exhibited the positive charged character, and hydrophobic moieties generated electrostatic screening effect.

  9. Resolvin D1 and D2 Reverse Lipopolysaccharide-Induced Depression-Like Behaviors Through the mTORC1 Signaling Pathway.

    Science.gov (United States)

    Deyama, Satoshi; Ishikawa, Yuka; Yoshikawa, Kotomi; Shimoda, Kento; Ide, Soichiro; Satoh, Masamichi; Minami, Masabumi

    2017-07-01

    Resolvin D1 and D2 are bioactive lipid mediators that are generated from docosahexaenoic acid. Although recent preclinical studies suggest that these compounds have antidepressant effects, their mechanisms of action remain unclear. We investigated mechanisms underlying the antidepressant effects of resolvin D1 and resolvin D2 in lipopolysaccharide (0.8 mg/kg, i.p.)-induced depression model mice using a tail suspension test. I.c.v. infusion of resolvin D1 (10 ng) and resolvin D2 (10 ng) produced antidepressant effects; these effects were significantly blocked by a resolvin D1 receptor antagonist WRW4 (10 µg, i.c.v.) and a resolvin D2 receptor antagonist O-1918 (10 µg, i.c.v.), respectively. The mammalian target of rapamycin complex 1 inhibitor rapamycin (10 mg/kg, i.p.) and a mitogen-activated protein kinase kinase inhibitor U0126 (5 µg, i.c.v.) significantly blocked the antidepressant effects of resolvin D1 and resolvin D2. An AMPA receptor antagonist NBQX (10 mg/kg, i.p.) and a phosphoinositide 3-kinase inhibitor LY294002 (3 µg, i.c.v.) blocked the antidepressant effects of resolvin D1 significantly, but not of resolvin D2. Bilateral infusions of resolvin D1 (0.3 ng/side) or resolvin D2 (0.3 ng/side) into the medial prefrontal cortex or dentate gyrus of the hippocampus produced antidepressant effects. These findings demonstrate that resolvin D1 and resolvin D2 produce antidepressant effects via the mammalian target of rapamycin complex 1 signaling pathway, and that the medial prefrontal cortex and dentate gyrus are important brain regions for these antidepressant effects. These compounds and their receptors may be promising targets for the development of novel rapid-acting antidepressants, like ketamine and scopolamine. © The Author 2017. Published by Oxford University Press on behalf of CINP.

  10. Oleamide suppresses lipopolysaccharide-induced expression of iNOS and COX-2 through inhibition of NF-kappaB activation in BV2 murine microglial cells.

    Science.gov (United States)

    Oh, Young Taek; Lee, Jung Yeon; Lee, Jinhwa; Lee, Ju Hie; Kim, Ja-Eun; Ha, Joohun; Kang, Insug

    2010-05-03

    Oleamide (cis-9-octadecenamide) is an endogenous sleep-inducing fatty acid amide that accumulates in the cerebrospinal fluid of the sleep-deprived animals. Microglia are the major immune cells involved in neuroinflammation causing brain damage during infection, ischemia, and neurodegenerative disease. In this study, we examined the effects of oleamide on LPS-induced production of proinflammatory mediators and the mechanisms involved in BV2 microglia. Oleamide inhibited LPS-induced production of NO and prostaglandin E2 as well as expression of iNOS and COX-2. We showed that oleamide blocked LPS-induced NF-kappaB activation and phosphorylation of inhibitor kappaB kinase (IKK). We also showed that oleamide inhibited LPS-induced phosphorylation of Akt, p38 MAPK, and ERK, activation of PI 3-kinase, and accumulation of reactive oxygen species (ROS). Finally, we showed that a specific antagonist of the CB2 receptor, AM630, blocked the inhibitory effects of oleamide on LPS-induced production of proinflammatory mediators and activation of NF-kappaB. Taken together, our results suggest that oleamide shows an anti-inflammatory effect through inhibition of NF-kappaB activation in LPS-stimulated BV2 microglia. 2010 Elsevier Ireland Ltd. All rights reserved.

  11. Complex phenotype linked to a mutation in exon 11 of the lamin A/C gene: Hypertrophic cardiomyopathy, atrioventricular block, severe dyslipidemia and diabetes.

    Science.gov (United States)

    Francisco, Ana Rita G; Santos Gonçalves, Inês; Veiga, Fátima; Mendes Pedro, Mónica; Pinto, Fausto J; Brito, Dulce

    2017-09-01

    The lamin A/C (LMNA) gene encodes lamins A and C, which have an important role in nuclear cohesion and chromatin organization. Mutations in this gene usually lead to the so-called laminopathies, the primary cardiac manifestations of which are dilated cardiomyopathy and intracardiac conduction defects. Some mutations, associated with lipodystrophy but not cardiomyopathy, have been linked to metabolic abnormalities such as diabetes and severe dyslipidemia. Herein we describe a new phenotype associated with a mutation in exon 11 of the LMNA gene: hypertrophic cardiomyopathy, atrioventricular block, severe dyslipidemia and diabetes. A 64-year-old woman with hypertrophic cardiomyopathy and a point mutation in exon 11 of the LMNA gene (c.1718C>T, Ser573Leu) presented with severe symptomatic ventricular hypertrophy and left ventricular outflow tract obstruction. She underwent septal alcohol ablation, followed by Morrow myectomy. The patient was also diagnosed with severe dyslipidemia, diabetes and obesity, and fulfilled diagnostic criteria for metabolic syndrome. No other characteristics of LMNA mutation-related phenotypes were identified. The development of type III atrioventricular block with no apparent cause, and mildly depressed systolic function, prompted referral for cardiac resynchronization therapy. In conclusion, the association between LMNA mutations and different phenotypes is complex and not fully understood, and can present with a broad spectrum of severity. Copyright © 2017 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

  12. Side-chain amino-acid-based pH-responsive self-assembled block copolymers for drug delivery and gene transfer.

    Science.gov (United States)

    Kumar, Sonu; Acharya, Rituparna; Chatterji, Urmi; De, Priyadarsi

    2013-12-10

    Developing safe and effective nanocarriers for multitype of delivery system is advantageous for several kinds of successful biomedicinal therapy with the same carrier. In the present study, we have designed amino acid biomolecules derived hybrid block copolymers which can act as a promising vehicle for both drug delivery and gene transfer. Two representative natural chiral amino acid-containing (l-phenylalanine and l-alanine) vinyl monomers were polymerized via reversible addition-fragmentation chain transfer (RAFT) process in the presence of monomethoxy poly(ethylene glycol) based macro-chain transfer agents (mPEGn-CTA) for the synthesis of well-defined side-chain amino-acid-based amphiphilic block copolymers, monomethoxy poly(ethylene glycol)-b-poly(Boc-amino acid methacryloyloxyethyl ester) (mPEGn-b-P(Boc-AA-EMA)). The self-assembled micellar aggregation of these amphiphilic block copolymers were studied by fluorescence spectroscopy, atomic force microscopy (AFM) and scanning electron microscopy (SEM). Potential applications of these hybrid polymers as drug carrier have been demonstrated in vitro by encapsulation of nile red dye or doxorubicin drug into the core of the micellar nanoaggregates. Deprotection of side-chain Boc- groups in the amphiphilic block copolymers subsequently transformed them into double hydrophilic pH-responsive cationic block copolymers having primary amino groups in the side-chain terminal. The DNA binding ability of these cationic block copolymers were further investigated by using agarose gel retardation assay and AFM. The in vitro cytotoxicity assay demonstrated their biocompatible nature and these polymers can serve as "smart" materials for promising bioapplications.

  13. 5-Methoxyl Aesculetin Abrogates Lipopolysaccharide-Induced Inflammation by Suppressing MAPK and AP-1 Pathways in RAW 264.7 Cells

    Directory of Open Access Journals (Sweden)

    Lei Wu

    2016-03-01

    Full Text Available For the first time, a pale amorphous coumarin derivative, 5-methoxyl aesculetin (MOA, was isolated from the dried bark of Fraxinus rhynchophylla Hance (Oleaceae. MOA modulates cytokine expression in lipopolysaccharide (LPS-treated RAW 264.7 macrophages, but the precise mechanisms are still not fully understood. We determined the effects of MOA on the production of inflammatory mediators and pro-inflammatory cytokines in the LPS-induced inflammatory responses of RAW 264.7 macrophages. MOA significantly inhibited the LPS-induced production of nitric oxide (NO, prostaglandin E2 (PGE2, tumor necrosis factor-α (TNF-α, interleukin-6, and interleukin-1β. It also effectively attenuated inducible nitric oxide (NO synthase, cyclooxygenase-2, and TNF-α mRNA expression and significantly decreased the levels of intracellular reactive oxygen species. It inhibited phosphorylation of the extracellular signal-regulated kinase (ERK1/2, thus blocking nuclear translocation of activation protein (AP-1. In a molecular docking study, MOA was shown to target the binding site of ERK via the formation of three hydrogen bonds with two residues of the kinase, which is sufficient for the inhibition of ERK. These results suggest that the anti-inflammatory effects of MOA in RAW 264.7 macrophages derive from its ability to block both the activation of mitogen-activated protein kinases (MAPKs and one of their downstream transcription factors, activator protein-1 (AP-1. Our observations support the need for further research into MOA as a promising therapeutic agent in inflammatory diseases.

  14. 5-Methoxyl Aesculetin Abrogates Lipopolysaccharide-Induced Inflammation by Suppressing MAPK and AP-1 Pathways in RAW 264.7 Cells

    Science.gov (United States)

    Wu, Lei; Li, Xueqin; Wu, Haifeng; Long, Wei; Jiang, Xiaojian; Shen, Ting; Qiang, Qian; Si, Chuanling; Wang, Xinfeng; Jiang, Yunyao; Hu, Weicheng

    2016-01-01

    For the first time, a pale amorphous coumarin derivative, 5-methoxyl aesculetin (MOA), was isolated from the dried bark of Fraxinus rhynchophylla Hance (Oleaceae). MOA modulates cytokine expression in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages, but the precise mechanisms are still not fully understood. We determined the effects of MOA on the production of inflammatory mediators and pro-inflammatory cytokines in the LPS-induced inflammatory responses of RAW 264.7 macrophages. MOA significantly inhibited the LPS-induced production of nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), interleukin-6, and interleukin-1β. It also effectively attenuated inducible nitric oxide (NO) synthase, cyclooxygenase-2, and TNF-α mRNA expression and significantly decreased the levels of intracellular reactive oxygen species. It inhibited phosphorylation of the extracellular signal-regulated kinase (ERK1/2), thus blocking nuclear translocation of activation protein (AP)-1. In a molecular docking study, MOA was shown to target the binding site of ERK via the formation of three hydrogen bonds with two residues of the kinase, which is sufficient for the inhibition of ERK. These results suggest that the anti-inflammatory effects of MOA in RAW 264.7 macrophages derive from its ability to block both the activation of mitogen-activated protein kinases (MAPKs) and one of their downstream transcription factors, activator protein-1 (AP-1). Our observations support the need for further research into MOA as a promising therapeutic agent in inflammatory diseases. PMID:26938526

  15. Clinical significance of proliferation, apoptosis and senescence of nasopharyngeal cells by the simultaneously blocking EGF, IGF-1 receptors and Bcl-xl genes

    International Nuclear Information System (INIS)

    Dai, Guodong; Peng, Tao; Zhou, Xuhong; Zhu, Jun; Kong, Zhihua; Ma, Li; Xiong, Zhi; Yuan, Yulin

    2013-01-01

    Highlight: •Construction of shRNA segments expression vectors is valid by the investigation of RT-PCR for IGF1R, EGFR and Bcl-xl mRNA and protein expression. •Studies have suggested that the vectors in blocking these genes of the growth factor receptors and anti- apoptosis is capable of breaking the balance of tumor growth so that tumor trend apoptosis and senescence. •Simultaneously blocking multiple genes that are abnormally expressed may be more effective in treating cancer cells than silencing a single gene. -- Abstract: Background: In previous work, we constructed short hairpin RNA (shRNA) expression plasmids that targeted human EGF and IGF-1 receptors messenger RNA, respectively, and demonstrated that these vectors could induce apoptosis of human nasopharyngeal cell lines (CNE2) and inhibit ligand-induced pAkt and pErk activation. Method: We have constructed multiple shRNA expression vectors of targeting EGFR, IGF1R and Bcl-xl, which were transfected to the CNE2 cells. The mRNA expression was assessed by RT-PCR. The growth of the cells, cell cycle progression, apoptosis of the cells, senescent tumor cells and the proteins of EGFR, IGF1R and Bcl-xl were analyzed by MTT, flow cytometry, cytochemical therapy or Western blot. Results: In group of simultaneously blocking EGFR, IGF1R and Bcl-xl genes, the mRNA of EGFR, IGF1R and Bcl-xl expression was decreased by (66.66 ± 3.42)%, (73.97 ± 2.83)% and (64.79 ± 2.83)%, and the protein expressions was diminished to (67.69 ± 4.02)%, (74.32 ± 2.30)%, and (60.00 ± 3.34)%, respectively. Meanwhile, the cell apoptosis increased by 65.32 ± 0.18%, 65.16 ± 0.25% and 55.47 ± 0.45%, and senescent cells increased by 1.42 ± 0.15%, 2.26 ± 0.15% and 3.22 ± 0.15% in the second, third and fourth day cultures, respectively. Conclusions: Simultaneously blocking EGFR, IGF1R and Bcl-xl genes is capable of altering the balance between proliferating versus apoptotic and senescent cells in the favor of both of apoptosis and

  16. Clinical significance of proliferation, apoptosis and senescence of nasopharyngeal cells by the simultaneously blocking EGF, IGF-1 receptors and Bcl-xl genes

    Energy Technology Data Exchange (ETDEWEB)

    Dai, Guodong [Anatomy and Embryology, Wuhan University School of Medicine, Wuhan, Hubei 430071 (China); Peng, Tao; Zhou, Xuhong [Department of Otolaryngology-Head and Neck Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Zhu, Jun; Kong, Zhihua; Ma, Li; Xiong, Zhi [Anatomy and Embryology, Wuhan University School of Medicine, Wuhan, Hubei 430071 (China); Yuan, Yulin, E-mail: yuanyulin19620120@126.com [Anatomy and Embryology, Wuhan University School of Medicine, Wuhan, Hubei 430071 (China)

    2013-11-01

    Highlight: •Construction of shRNA segments expression vectors is valid by the investigation of RT-PCR for IGF1R, EGFR and Bcl-xl mRNA and protein expression. •Studies have suggested that the vectors in blocking these genes of the growth factor receptors and anti- apoptosis is capable of breaking the balance of tumor growth so that tumor trend apoptosis and senescence. •Simultaneously blocking multiple genes that are abnormally expressed may be more effective in treating cancer cells than silencing a single gene. -- Abstract: Background: In previous work, we constructed short hairpin RNA (shRNA) expression plasmids that targeted human EGF and IGF-1 receptors messenger RNA, respectively, and demonstrated that these vectors could induce apoptosis of human nasopharyngeal cell lines (CNE2) and inhibit ligand-induced pAkt and pErk activation. Method: We have constructed multiple shRNA expression vectors of targeting EGFR, IGF1R and Bcl-xl, which were transfected to the CNE2 cells. The mRNA expression was assessed by RT-PCR. The growth of the cells, cell cycle progression, apoptosis of the cells, senescent tumor cells and the proteins of EGFR, IGF1R and Bcl-xl were analyzed by MTT, flow cytometry, cytochemical therapy or Western blot. Results: In group of simultaneously blocking EGFR, IGF1R and Bcl-xl genes, the mRNA of EGFR, IGF1R and Bcl-xl expression was decreased by (66.66 ± 3.42)%, (73.97 ± 2.83)% and (64.79 ± 2.83)%, and the protein expressions was diminished to (67.69 ± 4.02)%, (74.32 ± 2.30)%, and (60.00 ± 3.34)%, respectively. Meanwhile, the cell apoptosis increased by 65.32 ± 0.18%, 65.16 ± 0.25% and 55.47 ± 0.45%, and senescent cells increased by 1.42 ± 0.15%, 2.26 ± 0.15% and 3.22 ± 0.15% in the second, third and fourth day cultures, respectively. Conclusions: Simultaneously blocking EGFR, IGF1R and Bcl-xl genes is capable of altering the balance between proliferating versus apoptotic and senescent cells in the favor of both of apoptosis and

  17. Extract of corn silk (stigma of Zea mays) inhibits the tumour necrosis factor-alpha- and bacterial lipopolysaccharide-induced cell adhesion and ICAM-1 expression.

    Science.gov (United States)

    Habtemariam, S

    1998-05-01

    Treatment of human endothelial cells with cytokines such as tumour necrosis factor-alpha (TNF) or E. coli lipopolysaccharide (LPS) induces the expression of several adhesion molecules and enhances leukocyte adhesion to endothelial cell surface. Interfering with this leukocyte adhesion or adhesion molecules upregulation is an important therapeutic target for the treatment of bacterial sepsis and various inflammatory diseases. In the course of screening marketed European anti-inflammatory herbal drugs for TNF antagonistic activity, a crude ethanolic extract of corn silk (stigma of Zea mays) exhibited significant activity. The extract at concentrations of 9-250 micrograms/ml effectively inhibited the TNF- and LPS-induced adhesiveness of EAhy 926 endothelial cells to monocytic U937 cells. Similar concentration ranges of corn silk extract did also block the TNF and LPS but not the phorbol 12-myristate 13-acetate-induced ICAM-1 expression on EAhy 926 endothelial cell surface. The extract did not alter the production of TNF by LPS-activated macrophages and failed to inhibit the cytotoxic activity of TNF. It is concluded that corn silk possesses important therapeutic potential for TNF- and LPS-mediated leukocyte adhesion and trafficking.

  18. Ulinastatin suppresses lipopolysaccharide induced neuro-inflammation through the downregulation of nuclear factor-κB in SD rat hippocampal astrocyte

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yuting; Zhao, Lei; Fu, Huiqun [Department of Anesthesiology, Xuanwu Hospital, Capital Medical University, 100053 Beijing (China); Wu, Yan [Department of Anatomy, Capital Medical University, 100069 Beijing (China); Wang, Tianlong, E-mail: litingliting258@163.com [Department of Anesthesiology, Xuanwu Hospital, Capital Medical University, 100053 Beijing (China)

    2015-03-20

    Astrocyte activation plays a pivotal role in neuroinflammation, which contributes to neuronal damage, so the inhibition of astrocyte activation may alleviate the progression of neurodegeneration. Recent studies have proved that urinary trypsin inhibitor ulinastatin could inhibit NF-kB activation. In our study, the inhibitory effects of ulinastatin on the production of pro-inflammatory mediators were investigated in lipopolysaccharide (LPS)-reduced primary astrocyte. Our results showed that ulinastatin significantly inhibited LPS-induced astrogliosis, which is measured by MTT and BrdU. Ulinastatin decreased the production of pro-inflammatory cytokines, such as TNF-α, IL-6, IL-1β, it significantly decreased both the mRNA and the protein levels of these pro-inflammatory cytokines and also increased the protein levels of IκB-α binded to NF-κB, which blocked NF-κB translocation to the nucleus and prevented its activity. Our results suggest that ulinastatin is able to inhibit neuroinflammation by interfering with NF-κB signaling. The study provides direct evidence of potential therapy methods of ulinastatin for the treatment of neuroinflammatory diseases. - Highlights: • The anti-inflammatory effect of UTI on hippocampal astrocyte. • UTI showed protective effect on neuroinflammation by the downregulation of NF-κB. • UTI led to expression of cytokines decreased in concentration and time dependence.

  19. Lipopolysaccharide-induced dopaminergic cell death in rat midbrain slice cultures: role of inducible nitric oxide synthase and protection by indomethacin.

    Science.gov (United States)

    Shibata, Haruki; Katsuki, Hiroshi; Nishiwaki, Mayumi; Kume, Toshiaki; Kaneko, Shuji; Akaike, Akinori

    2003-09-01

    Glial cell activation associated with inflammatory reaction may contribute to pathogenic processes of neurodegenerative disorders, through production of several cytotoxic molecules. We investigated the consequences of glial activation by interferon-gamma (IFN-gamma)/lipopolysaccharide (LPS) in rat midbrain slice cultures. Application of IFN-gamma followed by LPS caused dopaminergic cell death and accompanying increases in nitrite production and lactate dehydrogenase release. Aminoguanidine, an inhibitor of inducible nitric oxide synthase (iNOS), or SB203580, an inhibitor of p38 mitogen-activated protein kinase, prevented dopaminergic cell loss as well as nitrite production. SB203580 also suppressed expression of iNOS and cyclooxygenase-2 (COX-2) induced by IFN-gamma/LPS. A COX inhibitor indomethacin protected dopaminergic neurons from IFN-gamma/LPS-induced injury, whereas selective COX-2 inhibitors such as NS-398 and nimesulide did not. Notably, indomethacin was able to attenuate neurotoxicity of a nitric oxide (NO) donor. Neutralizing antibodies against tumour necrosis factor-alpha and interleukin-1beta did not inhibit dopaminergic cell death caused by IFN-gamma/LPS, although combined application of these antibodies blocked lactate dehydrogenase release and decrease in the number of non-dopaminergic neurons. These results indicate that iNOS-derived NO plays a crucial role in IFN-gamma/LPS-induced dopaminergic cell death, and that indomethacin exerts protective effect by mechanisms probably related to NO neurotoxicity rather than through COX inhibition.

  20. Protective role of benfotiamine, a fat-soluble vitamin B1 analogue, in lipopolysaccharide-induced cytotoxic signals in murine macrophages.

    Science.gov (United States)

    Yadav, Umesh C S; Kalariya, Nilesh M; Srivastava, Satish K; Ramana, Kota V

    2010-05-15

    This study was designed to investigate the molecular mechanisms by which benfotiamine, a lipid-soluble analogue of vitamin B1, affects lipopolysaccharide (LPS)-induced inflammatory signals leading to cytotoxicity in the mouse macrophage cell line RAW264.7. Benfotiamine prevented LPS-induced apoptosis, expression of the Bcl-2 family of proapoptotic proteins, caspase-3 activation, and PARP cleavage and altered mitochondrial membrane potential and release of cytochrome c and apoptosis-inducing factor and phosphorylation and subsequent activation of p38-MAPK, stress-activated kinases (SAPK/JNK), protein kinase C, and cytoplasmic phospholipase A2 in RAW cells. Further, phosphorylation and degradation of inhibitory kappaB and consequent activation and nuclear translocation of the redox-sensitive transcription factor NF-kappaB were significantly prevented by benfotiamine. The LPS-induced increased expression of cytokines and chemokines and the inflammatory marker proteins iNOS and COX-2 and their metabolic products NO and PGE(2) was also blocked significantly. Thus, our results elucidate the molecular mechanism of the anti-inflammatory action of benfotiamine in LPS-induced inflammation in murine macrophages. Benfotiamine suppresses oxidative stress-induced NF-kappaB activation and prevents bacterial endotoxin-induced inflammation, indicating that vitamin B1 supplementation could be beneficial in the treatment of inflammatory diseases. Copyright 2010 Elsevier Inc. All rights reserved.

  1. Ulinastatin suppresses lipopolysaccharide induced neuro-inflammation through the downregulation of nuclear factor-κB in SD rat hippocampal astrocyte

    International Nuclear Information System (INIS)

    Li, Yuting; Zhao, Lei; Fu, Huiqun; Wu, Yan; Wang, Tianlong

    2015-01-01

    Astrocyte activation plays a pivotal role in neuroinflammation, which contributes to neuronal damage, so the inhibition of astrocyte activation may alleviate the progression of neurodegeneration. Recent studies have proved that urinary trypsin inhibitor ulinastatin could inhibit NF-kB activation. In our study, the inhibitory effects of ulinastatin on the production of pro-inflammatory mediators were investigated in lipopolysaccharide (LPS)-reduced primary astrocyte. Our results showed that ulinastatin significantly inhibited LPS-induced astrogliosis, which is measured by MTT and BrdU. Ulinastatin decreased the production of pro-inflammatory cytokines, such as TNF-α, IL-6, IL-1β, it significantly decreased both the mRNA and the protein levels of these pro-inflammatory cytokines and also increased the protein levels of IκB-α binded to NF-κB, which blocked NF-κB translocation to the nucleus and prevented its activity. Our results suggest that ulinastatin is able to inhibit neuroinflammation by interfering with NF-κB signaling. The study provides direct evidence of potential therapy methods of ulinastatin for the treatment of neuroinflammatory diseases. - Highlights: • The anti-inflammatory effect of UTI on hippocampal astrocyte. • UTI showed protective effect on neuroinflammation by the downregulation of NF-κB. • UTI led to expression of cytokines decreased in concentration and time dependence

  2. Gomisin N ameliorates lipopolysaccharide-induced depressive-like behaviors by attenuating inflammation in the hypothalamic paraventricular nucleus and central nucleus of the amygdala in mice

    Directory of Open Access Journals (Sweden)

    Ryota Araki

    2016-10-01

    Full Text Available Emotional impairments such as depressive symptoms often develop in patients with sustained and systemic immune activation. The objective of this study is to investigate the effect of gomisin N, a dibenzocyclooctadiene lignan isolated from the dried fruits of Schisandra chinensis (Turcz. Baill., which exhibited inhibitory effects of the bacterial endotoxin lipopolysaccharide (LPS-induced NO production in a screening assay, on inflammation-induced depressive symptoms. We examined the effects of gomisin N on inflammation induced by LPS in murine microglial BV-2 cells and on LPS-induced behavioral changes in mice. Gomisin N inhibited LPS-induced expression of mRNAs for inflammation-related genes (inducible nitric oxide synthase (iNOS, cyclooxygenase (COX-2, interleukin (IL-1β, IL-6 and tumor necrosis factor (TNF-α in BV-2 cells. Administration of gomisin N attenuated LPS-induced expression of mRNAs for inflammation-related genes, increases in the number of c-Fos immunopositive cells in the hypothalamus and amygdala, depressive-like behavior in the forced swim test and exploratory behavior deficits 24 h after LPS administration in mice. These results suggest that gomisin N might ameliorate LPS-induced depressive-like behaviors through inhibition of inflammatory responses and neural activation in the hypothalamus and amygdala.

  3. A polysaccharide isolated from the liquid culture of Lentinus edodes (Shiitake) mushroom mycelia containing black rice bran protects mice against a Salmonella lipopolysaccharide-induced endotoxemia.

    Science.gov (United States)

    Kim, Sung Phil; Park, Sun Ok; Lee, Sang Jong; Nam, Seok Hyun; Friedman, Mendel

    2013-11-20

    Endotoxemia (sepsis, septic shock) is an inflammatory, virulent disease that results mainly from bacterial infection. The present study investigates the inhibitory effect of a bioprocessed polysaccharide (BPP) isolated from the edible Lentinus edodes liquid mycelial mushroom culture supplemented with black rice bran against murine endotoxemia induced by the Salmonella lipopolysaccharide and d-galactosamine (LPS/GalN). BPP was obtained after dialysis against water using a cellulose tube with a molecular weight cutoff of 10000. BPP eluted as a single peak on an HPLC chromatogram. Acid hydrolysis of BPP showed the presence of the following sugars: fucose, galactose, galactosamine, glucose, glucosamine, mannose, rhamnose, and xylose. Treatment of BPP with β-glucanase reduced its immunostimulating activity, suggesting that the polysaccharide has a β-glucan structure. Pretreatment of mice with BPP via oral or intraperitoneal (ip) administration for 2 weeks resulted in the suppression of LPS/GalN-induced catalase, superoxide dismutase (SOD), and transaminase (GOT/GPT) liver enzymes, amelioration of necrotic liver lesions, and reduction of tumor necrosis factor α (TNF-α) and nitrite serum levels as well as myeloperoxidase (MPO) activity, an index of necrotic injury. Immunostimulating macrophage activity was up to 5.4-fold greater than that observed with the culture without the rice bran. BPP also extended the lifespan of the toxemic mice. These positive results with inflammation biomarkers and lifespan studies suggest that the BPP can protect mice against LPS/GalN-induced liver, lung, and kidney injuries and inflammation by blocking oxidative stress and TNF-α production, thus increasing the survival of the toxic shock-induced mice. The polysaccharide has the potential to serve as a new functional food.

  4. Lipopolysaccharide induces VCAM-1 expression and neutrophil adhesion to human tracheal smooth muscle cells: Involvement of Src/EGFR/PI3-K/Akt pathway

    International Nuclear Information System (INIS)

    Lin, W.-N.; Luo, S.-F.; Wu, C.-B.; Lin, C.-C.; Yang, C.-M.

    2008-01-01

    In our previous study, LPS has been shown to induce vascular cell adhesion molecule-1(VCAM-1) expression through MAPKs and NF-κB in human tracheal smooth muscle cells (HTSMCs). In addition to these pathways, the non-receptor tyrosine kinases (Src), EGF receptor (EGFR), and phosphatidylinositol 3-kinase (PI3K) have been shown to be implicated in the expression of several inflammatory target proteins. Here, we reported that LPS-induced up-regulation of VCAM-1 enhanced the adhesion of neutrophils onto HTSMC monolayer, which was inhibited by LY294002 and wortmannin. LPS stimulated phosphorylation of protein tyrosine kinases including Src, PYK2, and EGFR, which were further confirmed using specific anti-phospho-Src, PYK2, or EGFR Ab, respectively, revealed by Western blotting. LPS-stimulated Src, PYK2, EGFR, and Akt phosphorylation and VCAM-1 expression were attenuated by the inhibitors of Src (PP1), EGFR (AG1478), PI3-K (LY294002 and wortmannin), and Akt (SH-5), respectively, or transfection with siRNAs of Src or Akt and shRNA of p110. LPS-induced VCAM-1 expression was also blocked by pretreatment with curcumin (a p300 inhibitor) or transfection with p300 siRNA. LPS-stimulated Akt activation translocated into nucleus and associated with p300 and VCAM-1 promoter region was further confirmed by immunofluorescence, immunoprecipitation, and chromatin immunoprecipitation assays. This association of Akt and p300 to VCAM-1 promoter was inhibited by pretreatment with PP1, AG1478, wortmannin, and SH-5. LPS-induced p300 activation enhanced VCAM-1 promoter activity and VCAM-1 mRNA expression. These results suggested that in HTSMCs, Akt phosphorylation mediated through transactivation of Src/PYK2/EGFR promoted the transcriptional p300 activity and eventually led to VCAM-1 expression induced by LPS

  5. Effect of nitric oxide-releasing derivative of indomethacin on Prevotella intermedia lipopolysaccharide-induced production of proinflammatory mediators in murine macrophages.

    Science.gov (United States)

    Choe, So-Hui; Choi, Eun-Young; Hyeon, Jin-Yi; Choi, In Soon; Kim, Sung-Jo

    2017-10-14

    The purpose of this study was to investigate the influences of NCX 2121, a nitric oxide (NO)-releasing derivative of indomethacin, upon the generation of proinflammatory mediators using murine macrophages activated by lipopolysaccharide (LPS) isolated from Prevotella intermedia, which is one of the pathogens implicated in periodontal diseases. Inducible NO synthase (iNOS)-derived NO, IL-1β and IL-6 as well as their relevant mRNA were significantly attenuated by NCX 2121 in RAW264.7 cells activated by P. intermedia LPS. NCX 2121 was much more effective than the parental compound indomethacin in reducing these proinflammatory mediators. NCX 2121 triggered induction of heme oxygenase-1 (HO-1) in cells exposed to P. intermedia LPS, and its inhibitory influence upon P. intermedia LPS-elicited NO generation was notably blocked by SnPP treatment. NCX 2121 attenuated NF-κB-dependent SEAP release induced by P. intermedia LPS. NCX 2121 did not display inhibitory action towards IκB-α degradation triggered by LPS. Instead, it significantly diminished nuclear translocation as well as DNA-binding action of NF-κB p50 subunit elicited by P. intermedia LPS. Further, NCX 2121 significantly up-regulated SOCS1 mRNA expression in cells challenged with P. intermedia LPS. In summary, NCX 2121 down-regulates P. intermedia LPS-elicited generation of NO, IL-1β and IL-6 in murine macrophages in a mechanism that involves anti-inflammatory HO-1 induction as well as decrement of NF-κB activation, which may be associated with SOCS1 expression. NCX 2121 may have potential benefits as a host immunomodulatory agent for the therapy of periodontal disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Resveratrol, an extract of red wine, inhibits lipopolysaccharide induced airway neutrophilia and inflammatory mediators through an NF-kappaB-independent mechanism.

    Science.gov (United States)

    Birrell, M A; McCluskie, K; Wong, S; Donnelly, L E; Barnes, P J; Belvisi, M G

    2005-05-01

    Consumption of a naturally occurring polyphenol, resveratrol, in particular through drinking moderate amounts of red wine, has been suggested to be beneficial to health. A plethora of in vitro studies published demonstrate various anti-inflammatory actions of resveratrol. The aim of this research was to determine whether any of these anti-inflammatory effects translate in vivo in a rodent model of LPS induced airway inflammation. Resveratrol reduced lung tissue neutrophilia to a similar magnitude as that achieved by treatment with budesonide. This was associated with a reduction in pro-inflammatory cytokines and prostanoid levels. Interestingly, the reduction did not appear to be due to an impact on NF-kappaB activation or the expression of the respective genes as suggested by various in vitro publications. These results suggest that resveratrol may possess anti-inflammatory properties via a novel mechanism. Elucidation of this mechanism may lead to potential new therapies for the treatment of chronic inflammation.

  7. Inhibition of Phosphodiesterase 4 by FCPR03 Alleviates Lipopolysaccharide-Induced Depressive-Like Behaviors in Mice: Involvement of p38 and JNK Signaling Pathways

    Directory of Open Access Journals (Sweden)

    Hui Yu

    2018-02-01

    Full Text Available Inflammatory responses induced by peripheral administration of lipopolysaccharide (LPS triggers depressive-like behavioral syndrome in rodents. Inhibition of phosphodiesterase 4 (PDE4 produces a robust anti-inflammatory effect in inflammatory cells. Unfortunately, archetypal PDE4 inhibitors cause intolerable gastrointestinal side-effects, such as vomiting and nausea. N-isopropyl-3-(cyclopropylmethoxy-4-difluoromethoxy benzamide (FCPR03 is a novel, selective PDE4 inhibitor with little, or no, emetic potency. Our previous studies show that FCPR03 is effective in attenuating neuroinflammation in mice treated with LPS. However, whether FCPR03 could exert antidepressant-like effect induced by LPS is largely unknown. In the present study, mice injected intraperitoneally (i.p. with LPS was established as an in vivo animal model of depression. The antidepressant-like activities of FCPR03 were evaluated using a tail suspension test, forced swimming test, and sucrose preference test. We demonstrated that administration of FCPR03 (1 mg/kg produced antidepressant-like effects in mice challenged by LPS, as evidenced by decreases in the duration of immobility in the forced swim and tail suspension tests, while no significant changes in locomotor activity were observed. FCPR03 also increased sucrose preference in mice treated with LPS. In addition, treatment with FCPR03 abolished the downregulation of brain-derived neurotrophic factor induced by LPS and decreased the level of corticosterone in plasma. Meanwhile, periphery immune challenge by LPS induced enhanced phosphorylation of p38-mitogen activated protein kinase (p38 and c-Jun N-terminal kinase (JNK in both the cerebral cortex and hippocampus in mice. Interestingly, treatment with FCPR03 significantly blocked the role of LPS and reduced the levels of phosphorylated p38 and JNK. Collectively, these results indicate that FCPR03 shows antidepressant-like effects in mice challenged by LPS, and the p38/JNK

  8. The Neurokinin-1 Receptor Contributes to the Early Phase of Lipopolysaccharide-Induced Fever via Stimulation of Peripheral Cyclooxygenase-2 Protein Expression in Mice

    Directory of Open Access Journals (Sweden)

    Eszter Pakai

    2018-02-01

    Full Text Available Neurokinin (NK signaling is involved in various inflammatory processes. A common manifestation of systemic inflammation is fever, which is usually induced in animal models with the administration of bacterial lipopolysaccharide (LPS. A role for the NK1 receptor was shown in LPS-induced fever, but the underlying mechanisms of how the NK1 receptor contributes to febrile response, especially in the early phase, have remained unknown. We administered LPS (120 µg/kg, intraperitoneally to mice with the Tacr1 gene, i.e., the gene encoding the NK1 receptor, either present (Tacr1+/+ or absent (Tacr1−/− and measured their thermoregulatory responses, serum cytokine levels, tissue cyclooxygenase-2 (COX-2 expression, and prostaglandin (PG E2 concentration. We found that the LPS-induced febrile response was attenuated in Tacr1−/− compared to their Tacr1+/+ littermates starting from 40 min postinfusion. The febrigenic effect of intracerebroventricularly administered PGE2 was not suppressed in the Tacr1−/− mice. Serum concentration of pyrogenic cytokines did not differ between Tacr1−/− and Tacr1+/+ at 40 min post-LPS infusion. Administration of LPS resulted in amplification of COX-2 mRNA expression in the lungs, liver, and brain of the mice, which was statistically indistinguishable between the genotypes. In contrast, the LPS-induced augmentation of COX-2 protein expression was attenuated in the lungs and tended to be suppressed in the liver of Tacr1−/− mice compared with Tacr1+/+ mice. The Tacr1+/+ mice responded to LPS with a significant surge of PGE2 production in the lungs, whereas Tacr1−/− mice did not. In conclusion, the NK1 receptor is necessary for normal fever genesis. Our results suggest that the NK1 receptor contributes to the early phase of LPS-induced fever by enhancing COX-2 protein expression in the periphery. These findings advance the understanding of the crosstalk between NK signaling and the “cytokine-COX-2

  9. Arctigenin inhibits lipopolysaccharide-induced iNOS expression in RAW264.7 cells through suppressing JAK-STAT signal pathway.

    Science.gov (United States)

    Kou, Xianjuan; Qi, Shimei; Dai, Wuxing; Luo, Lan; Yin, Zhimin

    2011-08-01

    Arctigenin has been demonstrated to have an anti-inflammatory function, but the precise mechanisms of its action remain to be fully defined. In the present study, we determined the effects of arctigenin on lipopolysaccharide (LPS)-induced production of proinflammatory mediators and the underlying mechanisms involved in RAW264.7 cells. Our results indicated that arctigenin exerted its anti-inflammatory effect by inhibiting ROS-dependent STAT signaling through its antioxidant activity. Arctigenin also significantly reduced the phosphorylation of STAT1 and STAT 3 as well as JAK2 in LPS-stimulated RAW264.7 cells. The inhibitions of STAT1 and STAT 3 by arctigenin prevented their translocation to the nucleus and consequently inhibited expression of iNOS, thereby suppressing the expression of inflammation-associated genes, such as IL-1β, IL-6 and MCP-1, whose promoters contain STAT-binding elements. However, COX-2 expression was slightly inhibited at higher drug concentrations (50 μM). Our data demonstrate that arctigenin inhibits iNOS expression via suppressing JAK-STAT signaling pathway in macrophages. Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.

  10. Dietary l-threonine supplementation attenuates lipopolysaccharide-induced inflammatory responses and intestinal barrier damage of broiler chickens at an early age.

    Science.gov (United States)

    Chen, Yueping; Zhang, Hao; Cheng, Yefei; Li, Yue; Wen, Chao; Zhou, Yanmin

    2018-06-01

    This study was conducted to investigate the protective effects of l-threonine (l-Thr) supplementation on growth performance, inflammatory responses and intestinal barrier function of young broilers challenged with lipopolysaccharide (LPS). A total of 144 1-d-old male chicks were allocated to one of three treatments: non-challenged broilers fed a basal diet (control group), LPS-challenged broilers fed a basal diet without l-Thr supplementation and LPS-challenged broilers fed a basal diet supplemented with 3·0 g/kg l-Thr. LPS challenge was performed intraperitoneally at 17, 19 and 21 d of age, whereas the control group received physiological saline injection. Compared with the control group, LPS challenge impaired growth performance of broilers, and l-Thr administration reversed LPS-induced increase in feed/gain ratio. LPS challenge elevated blood cell counts related to inflammation, and pro-inflammatory cytokine concentrations in serum (IL-1β and TNF-α), spleen (IL-1β and TNF-α) and intestinal mucosa (jejunal interferon-γ (IFN-γ) and ileal IL-1β). The concentrations of intestinal cytokines in LPS-challenged broilers were reduced by l-Thr supplementation. LPS administration increased circulating d-lactic acid concentration, whereas it reduced villus height, the ratio between villus height and crypt depth and goblet density in both jejunum and ileum. LPS-induced decreases in jejunal villus height, intestinal villus height:crypt depth ratio and ileal goblet cell density were reversed with l-Thr supplementation. Similarly, LPS-induced alterations in the intestinal mRNA abundances of genes related to intestinal inflammation and barrier function (jejunal toll-like receptor 4, IFN- γ and claudin-3, and ileal IL-1 β and zonula occludens-1) were normalised with l-Thr administration. It can be concluded that l-Thr supplementation could attenuate LPS-induced inflammatory responses and intestinal barrier damage of young broilers.

  11. Keap1 silencing boosts lipopolysaccharide-induced transcription of interleukin 6 via activation of nuclear factor κB in macrophages

    International Nuclear Information System (INIS)

    Lv, Peng; Xue, Peng; Dong, Jian; Peng, Hui; Clewell, Rebecca; Wang, Aiping; Wang, Yue; Peng, Shuangqing; Qu, Weidong; Zhang, Qiang; Andersen, Melvin E.; Pi, Jingbo

    2013-01-01

    Interleukin-6 (IL6) is a multifunctional cytokine that regulates immune and inflammatory responses. Multiple transcription factors, including nuclear factor κB (NF-κB) and nuclear factor E2-related factor 2 (Nrf2), regulate IL6 transcription. Kelch-like ECH-associated protein 1 (Keap1) is a substrate adaptor protein for the Cullin 3-dependent E3 ubiquitin ligase complex, which regulates the degradation of many proteins, including Nrf2 and IκB kinase β (IKKβ). Here, we found that stable knockdown of Keap1 (Keap1-KD) in RAW 264.7 (RAW) mouse macrophages and human monocyte THP-1 cells significantly increased expression of Il6, and Nrf2-target genes, under basal and lipopolysaccharide (LPS, 0.001–0.1 μg/ml)-challenged conditions. However, Nrf2 activation alone, by tert-butylhydroquinone treatment of RAW cells, did not increase expression of Il6. Compared to cells transduced with scrambled non-target negative control shRNA, Keap1-KD RAW cells showed enhanced protein levels of IKKβ and increased expression and phosphorylation of NF-κB p65 under non-stressed and LPS-treated conditions. Because the expression of Il6 in Keap1-KD RAW cells was significantly attenuated by silencing of Ikkβ, but not Nrf2, it appears that stabilized IKKβ is responsible for the enhanced transactivation of Il6 in Keap1-KD cells. This study demonstrated that silencing of Keap1 in macrophages boosts LPS-induced transcription of Il6 via NF-κB activation. Given the importance of IL6 in the inflammatory response, the Keap1–IKKβ–NF-κB pathway may be a novel target for treatment and prevention of inflammation and associated disorders. - Highlights: • Knockdown of Keap1 increases expression of Il6 in macrophages. • Silencing of Keap1 results in protein accumulation of IKKβ and NF-κB p65. • Induction of Il6 resulting from Keap1 silencing is attributed to NF-κB activation

  12. Keap1 silencing boosts lipopolysaccharide-induced transcription of interleukin 6 via activation of nuclear factor κB in macrophages

    Energy Technology Data Exchange (ETDEWEB)

    Lv, Peng [Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709 (United States); Xue, Peng; Dong, Jian [Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709 (United States); Peng, Hui [Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709 (United States); Evaluation and Research Center for Toxicology, Institute of Disease Control and Prevention, Academy of Military Medical Sciences (China); Clewell, Rebecca [Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709 (United States); Wang, Aiping [Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Wang, Yue [Institute for Medical Device Standardization Administration, National Institutes for Food and Drug Control, Beijing (China); Peng, Shuangqing [Evaluation and Research Center for Toxicology, Institute of Disease Control and Prevention, Academy of Military Medical Sciences (China); Qu, Weidong [Key Laboratory of the Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai (China); Zhang, Qiang; Andersen, Melvin E. [Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709 (United States); Pi, Jingbo, E-mail: jpi@thehamner.org [Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709 (United States)

    2013-11-01

    Interleukin-6 (IL6) is a multifunctional cytokine that regulates immune and inflammatory responses. Multiple transcription factors, including nuclear factor κB (NF-κB) and nuclear factor E2-related factor 2 (Nrf2), regulate IL6 transcription. Kelch-like ECH-associated protein 1 (Keap1) is a substrate adaptor protein for the Cullin 3-dependent E3 ubiquitin ligase complex, which regulates the degradation of many proteins, including Nrf2 and IκB kinase β (IKKβ). Here, we found that stable knockdown of Keap1 (Keap1-KD) in RAW 264.7 (RAW) mouse macrophages and human monocyte THP-1 cells significantly increased expression of Il6, and Nrf2-target genes, under basal and lipopolysaccharide (LPS, 0.001–0.1 μg/ml)-challenged conditions. However, Nrf2 activation alone, by tert-butylhydroquinone treatment of RAW cells, did not increase expression of Il6. Compared to cells transduced with scrambled non-target negative control shRNA, Keap1-KD RAW cells showed enhanced protein levels of IKKβ and increased expression and phosphorylation of NF-κB p65 under non-stressed and LPS-treated conditions. Because the expression of Il6 in Keap1-KD RAW cells was significantly attenuated by silencing of Ikkβ, but not Nrf2, it appears that stabilized IKKβ is responsible for the enhanced transactivation of Il6 in Keap1-KD cells. This study demonstrated that silencing of Keap1 in macrophages boosts LPS-induced transcription of Il6 via NF-κB activation. Given the importance of IL6 in the inflammatory response, the Keap1–IKKβ–NF-κB pathway may be a novel target for treatment and prevention of inflammation and associated disorders. - Highlights: • Knockdown of Keap1 increases expression of Il6 in macrophages. • Silencing of Keap1 results in protein accumulation of IKKβ and NF-κB p65. • Induction of Il6 resulting from Keap1 silencing is attributed to NF-κB activation.

  13. Epidural block

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/patientinstructions/000484.htm Epidural block - pregnancy To use the sharing features on this page, please enable JavaScript. An epidural block is a numbing medicine given by injection (shot) ...

  14. Expression of nodule-specific genes in alfalfa root nodules blocked at an early stage of development.

    NARCIS (Netherlands)

    Dickstein, R.; Bisseling, T.; Reinhold, V.N.; Ausubel, F.M.

    1988-01-01

    To help dissect the molecular basis of the Rhizobium-legume symbiosis, we used in vitro translation and Northern blot analysis of nodule RNA to examine alfalfa-specific genes (nodulins) expressed in two types of developmentally defective root nodules elicited by Rhizobium meliloti. Fix- nodules were

  15. Population Blocks.

    Science.gov (United States)

    Smith, Martin H.

    1992-01-01

    Describes an educational game called "Population Blocks" that is designed to illustrate the concept of exponential growth of the human population and some potential effects of overpopulation. The game material consists of wooden blocks; 18 blocks are painted green (representing land), 7 are painted blue (representing water); and the remaining…

  16. Lentiviral gene ontology (LeGO) vectors equipped with novel drug-selectable fluorescent proteins: new building blocks for cell marking and multi-gene analysis.

    Science.gov (United States)

    Weber, K; Mock, U; Petrowitz, B; Bartsch, U; Fehse, B

    2010-04-01

    Vector-encoded fluorescent proteins (FPs) facilitate unambiguous identification or sorting of gene-modified cells by fluorescence-activated cell sorting (FACS). Exploiting this feature, we have recently developed lentiviral gene ontology (LeGO) vectors (www.LentiGO-Vectors.de) for multi-gene analysis in different target cells. In this study, we extend the LeGO principle by introducing 10 different drug-selectable FPs created by fusing one of the five selection marker (protecting against blasticidin, hygromycin, neomycin, puromycin and zeocin) and one of the five FP genes (Cerulean, eGFP, Venus, dTomato and mCherry). All tested fusion proteins allowed both fluorescence-mediated detection and drug-mediated selection of LeGO-transduced cells. Newly generated codon-optimized hygromycin- and neomycin-resistance genes showed improved expression as compared with their ancestors. New LeGO constructs were produced at titers >10(6) per ml (for non-concentrated supernatants). We show efficient combinatorial marking and selection of various cells, including mesenchymal stem cells, simultaneously transduced with different LeGO constructs. Inclusion of the cytomegalovirus early enhancer/chicken beta-actin promoter into LeGO vectors facilitated robust transgene expression in and selection of neural stem cells and their differentiated progeny. We suppose that the new drug-selectable markers combining advantages of FACS and drug selection are well suited for numerous applications and vector systems. Their inclusion into LeGO vectors opens new possibilities for (stem) cell tracking and functional multi-gene analysis.

  17. CDKL5, a novel MYCN-repressed gene, blocks cell cycle and promotes differentiation of neuronal cells

    OpenAIRE

    Valli, Emanuele; Trazzi, Stefania; Fuchs, Claudia; Erriquez, Daniela; Bartesaghi, Renata; Perini, Giovanni; Ciani, Elisabetta

    2012-01-01

    Mutations in the CDKL5 (cyclin-dependent kinase-like 5) gene are associated with a severe epileptic encephalopathy (early infantile epileptic encephalopathy type 2, EIEE2) characterized by early-onset intractable seizures, infantile spasms, severe developmental delay, intellectual disability, and Rett syndrome (RTT)-like features. Despite the clear involvement of CDKL5 mutations in intellectual disability, the function of this protein during brain development and the molecular mechanisms invo...

  18. Suaeda japonica Makino Attenuates Lipopolysaccharide- Induced ...

    African Journals Online (AJOL)

    HP

    Tropical Journal of Pharmaceutical Research June 2013; 12 (3): 351-356 ... expression and production of inflammatory mediators determined by Western blot analysis. Results: SJE significantly ..... This work was supported by Business for.

  19. Hara on lipopolysaccharide-induced neuroinflammation

    African Journals Online (AJOL)

    read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. Tropical Journal of Pharmaceutical Research is indexed by Science Citation Index (SciSearch), Scopus,.

  20. Inhibition of Lipopolysaccharide-Induced Neuroinflammatory Events ...

    African Journals Online (AJOL)

    Tropical Journal of Pharmaceutical Research October 2014; 13 (10): 1615-1620. ISSN: 1596-5996 ... LPS-induced excessive production of inflammatory mediator such as iNOS was also ... several studies have reported antioxidant, antiallergic ...

  1. Oryza sativa (Rice) Hull Extract Inhibits Lipopolysaccharide-Induced Inflammatory Response in RAW264.7 Macrophages by Suppressing Extracellular Signal-regulated Kinase, c-Jun N-terminal Kinase, and Nuclear Factor-κB Activation.

    Science.gov (United States)

    Ha, Sang Keun; Sung, Jeehye; Choi, Inwook; Kim, Yoonsook

    2016-01-01

    Rice ( Oryza sativa ) is a major cereal crop in many Asian countries and an important staple food source. Rice hulls have been reported to possess antioxidant activities. In this study, we evaluated the antiinflammatory effects of rice hull extract and associated signal transduction mechanisms in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. We found that rice hull extract inhibited nitric oxide (NO) and prostaglandin E 2 by suppressing the expression of inducible NO synthase and cyclooxygenase-2, respectively. The release of interleukin-1β and tumor necrosis factor-α was also reduced in a dose-dependent manner. Furthermore, rice hull extract attenuated the activation of nuclear factor-kappa B (NF-κB), as well as the phosphorylation of mitogen-activated protein kinases, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK), in LPS-stimulated RAW264.7 cells. This suggests that rice hull extract decreases the production of inflammatory mediators by downregulating ERK and JNK and the NF-κB signal pathway in RAW 264.7 cells. Rice hull extract inhibits the lipopolysaccharide-induced inflammatory response in RAW264.7 macrophages.Rice hull extract inhibited nitric oxide and prostaglandin E 2 by suppressing the expression of inducible NO synthase and cyclooxygenase-2, respectively.Rice hull extract exerted anti-inflammatory effect through inhibition of nuclear factor-kappa B, extracellular signal-regulated kinase and c-Jun N-terminal kinase signaling pathways.Rice hull extract may provide a potential therapeutic approach for inflammatory diseases. Abbreviations used: COX-2: cyclooxygenase-2, ERK: extracellular signal-regulated kinase, IκB: inhibitory kappa B, IL-1β: interleukin-1β, iNOS: inducible NO synthase, JNK: c-Jun N-terminal kinase, LPS: lipopolysaccharide, MAPKs: mitogen-activated protein kinases, NF-κB: nuclear factor-κB, NO: nitric oxide, PGE2: prostaglandin E2, RHE: rice hull extract, ROS: reactive oxygen species

  2. Cardiac fibroblast transcriptome analyses support a role for interferogenic, profibrotic, and inflammatory genes in anti-SSA/Ro-associated congenital heart block.

    Science.gov (United States)

    Clancy, Robert M; Markham, Androo J; Jackson, Tanisha; Rasmussen, Sara E; Blumenberg, Miroslav; Buyon, Jill P

    2017-09-01

    The signature lesion of SSA/Ro autoantibody-associated congenital heart block (CHB) is fibrosis and a macrophage infiltrate, supporting an experimental focus on cues influencing the fibroblast component. The transcriptomes of human fetal cardiac fibroblasts were analyzed using two complementary approaches. Cardiac injury conditions were simulated in vitro by incubating human fetal cardiac fibroblasts with supernatants from macrophages transfected with the SSA/Ro-associated noncoding Y ssRNA. The top 10 upregulated transcripts in the stimulated fibroblasts reflected a type I interferon (IFN) response [e.g., IFN-induced protein 44-like (IFI44L), of MX dynamin-like GTPase (MX)1, MX2, and radical S -adenosyl methionine domain containing 2 (Rsad2)]. Within the fibrotic pathway, transcript levels of endothelin-1 (EDN1), phosphodiesterase (PDE)4D, chemokine (C-X-C motif) ligand (CXCL)2, and CXCL3 were upregulated, while others, including adenomedullin, RAP guanine nucleotide exchange factor 3 (RAPGEF3), tissue inhibitor of metalloproteinase (TIMP)1, TIMP3, and dual specificity phosphatase 1, were downregulated. Agnostic Database for Annotation, Visualization and Integrated Discovery analysis revealed a significant increase in inflammatory genes, including complement C3A receptor 1 (C3AR1), F2R-like thrombin/trypsin receptor 3, and neutrophil cytosolic factor 2. In addition, stimulated fibroblasts expressed high levels of phospho-MADS box transcription enhancer factor 2 [a substrate of MAPK5 (ERK5)], which was inhibited by BIX-02189, a specific inhibitor of ERK5. Translation to human disease leveraged an unprecedented opportunity to interrogate the transcriptome of fibroblasts freshly isolated and cell sorted without stimulation from a fetal heart with CHB and a matched healthy heart. Consistent with the in vitro data, five IFN response genes were among the top 10 most highly expressed transcripts in CHB fibroblasts. In addition, the expression of matrix-related genes

  3. CDKL5, a novel MYCN-repressed gene, blocks cell cycle and promotes differentiation of neuronal cells.

    Science.gov (United States)

    Valli, Emanuele; Trazzi, Stefania; Fuchs, Claudia; Erriquez, Daniela; Bartesaghi, Renata; Perini, Giovanni; Ciani, Elisabetta

    2012-01-01

    Mutations in the CDKL5 (cyclin-dependent kinase-like 5) gene are associated with a severe epileptic encephalopathy (early infantile epileptic encephalopathy type 2, EIEE2) characterized by early-onset intractable seizures, infantile spasms, severe developmental delay, intellectual disability, and Rett syndrome (RTT)-like features. Despite the clear involvement of CDKL5 mutations in intellectual disability, the function of this protein during brain development and the molecular mechanisms involved in its regulation are still unknown. Using human neuroblastoma cells as a model system we found that an increase in CDKL5 expression caused an arrest of the cell cycle in the G(0)/G(1) phases and induced cellular differentiation. Interestingly, CDKL5 expression was inhibited by MYCN, a transcription factor that promotes cell proliferation during brain development and plays a relevant role in neuroblastoma biology. Through a combination of different and complementary molecular and cellular approaches we could show that MYCN acts as a direct repressor of the CDKL5 promoter. Overall our findings unveil a functional axis between MYCN and CDKL5 governing both neuron proliferation rate and differentiation. The fact that CDKL5 is involved in the control of both neuron proliferation and differentiation may help understand the early appearance of neurological symptoms in patients with mutations in CDKL5. Copyright © 2012 Elsevier B.V. All rights reserved.

  4. Blocking signaling at the level of GLI regulates downstream gene expression and inhibits proliferation of canine osteosarcoma cells.

    Science.gov (United States)

    Shahi, Mehdi Hayat; Holt, Roseline; Rebhun, Robert B

    2014-01-01

    The Hedgehog-GLI signaling pathway is active in a variety of human malignancies and is known to contribute to the growth and survival of human osteosarcoma cells. In this study, we examined the expression and regulation of GLI transcription factors in multiple canine osteosarcoma cell lines and analyzed the effects of inhibiting GLI with GANT61, a GLI-specific inhibitor. Compared with normal canine osteoblasts, real-time PCR showed that GLI1 and GLI2 were highly expressed in two out of three cell lines and correlated with downstream target gene expression of PTCH1and PAX6. Treatment of canine osteosarcoma cells with GANT61 resulted in decreased expression of GLI1, GLI2, PTCH1, and PAX6. Furthermore, GANT61 inhibited proliferation and colony formation in all three canine osteosarcoma cell lines. The finding that GLI signaling activity is present and active in canine osteosarcoma cells suggests that spontaneously arising osteosarcoma in dogs might serve as a good model for future preclinical testing of GLI inhibitors.

  5. Blocking signaling at the level of GLI regulates downstream gene expression and inhibits proliferation of canine osteosarcoma cells.

    Directory of Open Access Journals (Sweden)

    Mehdi Hayat Shahi

    Full Text Available The Hedgehog-GLI signaling pathway is active in a variety of human malignancies and is known to contribute to the growth and survival of human osteosarcoma cells. In this study, we examined the expression and regulation of GLI transcription factors in multiple canine osteosarcoma cell lines and analyzed the effects of inhibiting GLI with GANT61, a GLI-specific inhibitor. Compared with normal canine osteoblasts, real-time PCR showed that GLI1 and GLI2 were highly expressed in two out of three cell lines and correlated with downstream target gene expression of PTCH1and PAX6. Treatment of canine osteosarcoma cells with GANT61 resulted in decreased expression of GLI1, GLI2, PTCH1, and PAX6. Furthermore, GANT61 inhibited proliferation and colony formation in all three canine osteosarcoma cell lines. The finding that GLI signaling activity is present and active in canine osteosarcoma cells suggests that spontaneously arising osteosarcoma in dogs might serve as a good model for future preclinical testing of GLI inhibitors.

  6. Novel Cocaine Vaccine Linked to a Disrupted Adenovirus Gene Transfer Vector Blocks Cocaine Psychostimulant and Reinforcing Effects

    Science.gov (United States)

    Wee, Sunmee; Hicks, Martin J; De, Bishnu P; Rosenberg, Jonathan B; Moreno, Amira Y; Kaminsky, Stephen M; Janda, Kim D; Crystal, Ronald G; Koob, George F

    2012-01-01

    Immunotherapy is a promising treatment for drug addiction. However, insufficient immune responses to vaccines in most subjects pose a challenge. In this study, we tested the efficacy of a new cocaine vaccine (dAd5GNE) in antagonizing cocaine addiction-related behaviors in rats. This vaccine used a disrupted serotype 5 adenovirus (Ad) gene transfer vector coupled to a third-generation cocaine hapten, termed GNE (6-(2R,3S)-3-(benzoyloxy)-8-methyl-8-azabicyclo [3.2.1] octane-2-carboxamido-hexanoic acid). Three groups of rats were immunized with dAd5GNE. One group was injected with 3H-cocaine, and radioactivity in the blood and brain was determined. A second group was tested for cocaine-induced locomotor sensitization. A third group was examined for cocaine self-administration, extinction, and reinstatement of responding for cocaine. Antibody titers were determined at various time-points. In each experiment, we added a control group that was immunized with dAd5 without a hapten. The vaccination with dAd5GNE produced long-lasting high titers (>105) of anti-cocaine antibodies in all of the rats. The vaccination inhibited cocaine-induced hyperlocomotor activity and sensitization. Vaccinated rats acquired cocaine self-administration, but they showed less motivation to self-administer cocaine under a progressive-ratio schedule than control rats. When cocaine was not available in a session, control rats exhibited ‘extinction burst' responding, whereas vaccinated rats did not. Moreover, when primed with cocaine, vaccinated rats did not reinstate responding, suggesting a blockade of cocaine-seeking behavior. These data strongly suggest that our dAd5GNE vector-based vaccine may be effective in treating cocaine abuse and addiction. PMID:21918504

  7. Transglutaminase 2 gene ablation protects against renal ischemic injury by blocking constant NF-κB activation

    International Nuclear Information System (INIS)

    Kim, Dae-Seok; Kim, Bora; Tahk, Hongmin; Kim, Dong-Hyun; Ahn, Eu-Ree; Choi, Changsun; Jeon, Yoon; Park, Seo Young; Lee, Ho; Oh, Seung Hyun; Kim, Soo-Youl

    2010-01-01

    Research highlights: → No acute renal tubular necrotic lesions were found in TGase2 -/- mice with ischemic kidney injury. → NF-κB activation is reduced in TGase2 -/- mice with ischemic kidney injury. → Hypoxic stress did not increase NF-κB activity in MEFs from TGase2 -/- mice. → COX-2 induction is suppressed in TGase2 -/- mice with ischemic kidney injury. -- Abstract: Transglutaminase 2 knockout (TGase2 -/- ) mice show significantly reduced inflammation with decreased myofibroblasts in a unilateral ureteral obstruction (UUO) model, but the mechanism remains to be clarified. Nuclear factor-κB (NF-κB) activation plays a major role in the progression of inflammation in an obstructive nephropathy model. However, the key factors extending the duration of NF-κB activation in UUO are not known. In several inflammatory diseases, we and others recently found that TGase 2 plays a key role in extending NF-κB activation, which contributes to the pathogenesis of disease. In the current study, we found that NF-κB activity in mouse embryogenic fibroblasts (MEFs) from TGase2 -/- mice remained at the control level while the NF-κB activity of wild-type (WT) MEFs was highly increased under hypoxic stress. Using the obstructive nephropathy model, we found that NF-κB activity remained at the control level in TGase2 -/- mouse kidney tissues, as measured by COX-2 expression, but was highly increased in WT tissues. We conclude that TGase 2 gene ablation reduces the duration of NF-κB activation in ischemic injury.

  8. Detection block

    International Nuclear Information System (INIS)

    Bezak, A.

    1987-01-01

    A diagram is given of a detection block used for monitoring burnup of nuclear reactor fuel. A shielding block is an important part of the detection block. It stabilizes the fuel assembly in the fixing hole in front of a collimator where a suitable gamma beam is defined for gamma spectrometry determination of fuel burnup. The detector case and a neutron source case are placed on opposite sides of the fixing hole. For neutron measurement for which the water in the tank is used as a moderator, the neutron detector-fuel assembly configuration is selected such that neutrons from spontaneous fission and neutrons induced with the neutron source can both be measured. The patented design of the detection block permits longitudinal travel and rotation of the fuel assembly to any position, and thus more reliable determination of nuclear fuel burnup. (E.S.). 1 fig

  9. Mutations that alter a conserved element upstream of the potato virus X triple block and coat protein genes affect subgenomic RNA accumulation.

    Science.gov (United States)

    Kim, K H; Hemenway, C

    1997-05-26

    The putative subgenomic RNA (sgRNA) promoter regions upstream of the potato virus X (PVX) triple block and coat protein (CP) genes contain sequences common to other potexviruses. The importance of these sequences to PVX sgRNA accumulation was determined by inoculation of Nicotiana tabacum NT1 cell suspension protoplasts with transcripts derived from wild-type and modified PVX cDNA clones. Analyses of RNA accumulation by S1 nuclease digestion and primer extension indicated that a conserved octanucleotide sequence element and the spacing between this element and the start-site for sgRNA synthesis are critical for accumulation of the two major sgRNA species. The impact of mutations on CP sgRNA levels was also reflected in the accumulation of CP. In contrast, genomic minus- and plus-strand RNA accumulation were not significantly affected by mutations in these regions. Studies involving inoculation of tobacco plants with the modified transcripts suggested that the conserved octanucleotide element functions in sgRNA accumulation and some other aspect of the infection process.

  10. Isorhamnetin inhibits Prevotella intermedia lipopolysaccharide-induced production of interleukin-6 in murine macrophages via anti-inflammatory heme oxygenase-1 induction and inhibition of nuclear factor-κB and signal transducer and activator of transcription 1 activation.

    Science.gov (United States)

    Jin, J Y; Choi, E Y; Park, H R; Choi, J I; Choi, I S; Kim, S J

    2013-12-01

    Interleukin-6 (IL-6) is a key proinflammatory cytokine that has been considered to be important in the pathogenesis of periodontal disease. Therefore, host-modulatory agents directed at inhibiting IL-6 appear to be beneficial in terms of attenuating periodontal disease progression and potentially improving disease susceptibility. In the current study, we investigated the effect of the flavonoid isorhamnetin on the production of IL-6 in murine macrophages stimulated with lipopolysaccharide (LPS) from Prevotella intermedia, a pathogen implicated in inflammatory periodontal disease, and its mechanisms of action. Lipopolysaccharide from P. intermedia ATCC 25611 was isolated using the standard hot phenol-water method. Culture supernatants were collected and assayed for IL-6. We used real-time PCR to quantify IL-6 and heme oxygenase-1 (HO-1) mRNA expression. The expression of HO-1 protein and the levels of signaling proteins were monitored using immunoblot analyses. The DNA-binding activity of nuclear factor-κB (NF-κB) was analyzed using ELISA-based assay kits. Isorhamnetin significantly down-regulated P. intermedia LPS-induced production of IL-6 as well as its mRNA expression in RAW264.7 cells. Isorhamnetin up-regulated the expression of HO-1 at both gene transcription and translation levels in cells stimulated with P. intermedia LPS. In addition, inhibition of HO-1 activity by tin protoporphyrin IX blocked the inhibitory effect of isorhamnetin on IL-6 production. Isorhamnetin failed to prevent LPS from activating either c-Jun N-terminal kinase or p38 pathways. Isorhamnetin did not inhibit NF-κB transcriptional activity at the level of inhibitory κB-α degradation. Isorhamnetin suppressed NF-κB signaling through inhibition of nuclear translocation and DNA binding activity of NF-κB p50 subunit and attenuated signal transducer and activator of transcription 1 signaling. Although further research is required to clarify the detailed mechanism of action, we propose

  11. An efficient, block-by-block algorithm for inverting a block tridiagonal, nearly block Toeplitz matrix

    International Nuclear Information System (INIS)

    Reuter, Matthew G; Hill, Judith C

    2012-01-01

    We present an algorithm for computing any block of the inverse of a block tridiagonal, nearly block Toeplitz matrix (defined as a block tridiagonal matrix with a small number of deviations from the purely block Toeplitz structure). By exploiting both the block tridiagonal and the nearly block Toeplitz structures, this method scales independently of the total number of blocks in the matrix and linearly with the number of deviations. Numerical studies demonstrate this scaling and the advantages of our method over alternatives.

  12. Analysis of Block OMP using Block RIP

    OpenAIRE

    Wang, Jun; Li, Gang; Zhang, Hao; Wang, Xiqin

    2011-01-01

    Orthogonal matching pursuit (OMP) is a canonical greedy algorithm for sparse signal reconstruction. When the signal of interest is block sparse, i.e., it has nonzero coefficients occurring in clusters, the block version of OMP algorithm (i.e., Block OMP) outperforms the conventional OMP. In this paper, we demonstrate that a new notion of block restricted isometry property (Block RIP), which is less stringent than standard restricted isometry property (RIP), can be used for a very straightforw...

  13. [Complete atrioventricular block in Duchenne muscular dystrophy].

    Science.gov (United States)

    Kuru, Satoshi; Tanahashi, Tamotsu; Matsumoto, Shinjirou; Kitamura, Tetsuya; Konagaya, Masaaki

    2012-01-01

    We report a case of complete atrioventricular (AV) block in a 40-year-old patient with Duchenne muscular dystrophy (DMD). While he was bed-ridden and required mechanical ventilation, his cardiac involvement was mild. He had the deletion of exon 45-52 in the dystrophin gene. He underwent transient complete AV block and came to require pacemaker implantation due to recurrence of complete AV block ten days after the first attack. Electrophysiological study revealed mild prolonged AH and HV interval. Although DMD patients with AV block have been rarely reported so far, attention should be paid to AV block for patients who prolonged their lives.

  14. Gene

    Data.gov (United States)

    U.S. Department of Health & Human Services — Gene integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes,...

  15. Anti-Inflammatory Effect of Methylpenicinoline from a Marine Isolate of Penicillium sp. (SF-5995: Inhibition of NF-κB and MAPK Pathways in Lipopolysaccharide-Induced RAW264.7 Macrophages and BV2 Microglia

    Directory of Open Access Journals (Sweden)

    Dong-Cheol Kim

    2014-11-01

    Full Text Available In the course of a search for anti-inflammatory metabolites from marine-derived fungi, methylpenicinoline (1 was isolated from a marine isolate of Penicillin sp. Compound 1 inhibited lipopolysaccharide (LPS-stimulated nitric oxide (NO production by suppressing the expression of inducible NO synthase (iNOS in RAW264.7 macrophages and BV2 microglia. It also attenuated prostaglandin E2 (PGE2 production by suppressing cyclooxygenase-2 (COX-2 expression in a concentration-dependent manner (from 10 μM to 80 μM without affecting cell viability. In addition, compound 1 reduced the production of the pro-inflammatory cytokine interleukin-1β (IL-1β. In a further study designed to elucidate the mechanism of its anti-inflammatory effects, compound 1 was shown to block nuclear factor-kappa B (NF-κB activation in LPS-induced RAW264.7 macrophages and BV2 microglia by inhibiting the phosphorylation of inhibitor kappa B-α (IκB-α, thereby suppressing the nuclear translocation of NF-κB dimers, namely p50 and p65, that are known to be crucial molecules associated with iNOS and COX-2 expression. In addition, compound 1 inhibited the activation of mitogen-activated protein kinase (MAPK pathways. Taken together, the results suggest that compound 1 might be a valuable therapeutic agent for the treatment of anti-inflammatory and anti-neuroinflammatory diseases.

  16. Preventive Effects of Velvet Antler (Cervus elaphus against Lipopolysaccharide-Induced Acute Lung Injury in Mice by Inhibiting MAPK/NF-κB Activation and Inducing AMPK/Nrf2 Pathways

    Directory of Open Access Journals (Sweden)

    Jui-Shu Chang

    2018-01-01

    Full Text Available Velvet antler (Cervus elaphus is a typical traditional animal medicine. It is considered to have various pharmacological effects including stimulation of the immune system, increase in the physical strength, and enhancement of sexual function. This paper aims to investigate the aqueous extract of velvet antler (AVA in the mouse models of LPS-induced ALI. Inhibition of NO, TNF-α, IL-1β, IL-6, and IL-10 productions contributes to the attenuation of LPS-induced lung inflammation by AVA. A 5-day pretreatment of AVA prevented histological alterations and enhanced antioxidant enzyme activity in lung tissues. AVA significantly reduced the material (total number of cells and proteins in the BALF. Western blot analysis revealed that the expression of iNOS and COX-2 and phosphorylation of IκB-α and MAPKs proteins are blocked in LPS-stimulated macrophages as well as LPS-induced lung injury in mice. Consistent with this concept, the phosphorylation of CaMKKβ, LKB1, AMPK, Nrf2, and HO-1 was activated after AVA treatment. The results from this study indicate AVA has anti-inflammatory effects in vivo and AVA is a potential model for the development of health food. In addition, its pathways may be at least partially associated with inhibiting MAPK/NF-κB activation and upregulating AMPK/Nrf2 pathways and the regulation of antioxidant enzyme activity.

  17. Ultrasound guided supraclavicular block.

    LENUS (Irish Health Repository)

    Hanumanthaiah, Deepak

    2013-09-01

    Ultrasound guided regional anaesthesia is becoming increasingly popular. The supraclavicular block has been transformed by ultrasound guidance into a potentially safe superficial block. We reviewed the techniques of performing supraclavicular block with special focus on ultrasound guidance.

  18. Brachypodium distachyon line Bd3-1 resistance is elicited by the barley stripe mosaic virus triple gene block 1 movement protein

    NARCIS (Netherlands)

    Lee, M.Y.; Yan, L.J.; Gorter, F.A.; Kim, B.Y.T.; Cui, Y.; Hu, Y.; Yuan, C.; Grindheim, J.; Ganesan, U.; Liu, Z.Y.; Han, C.G.; Yu, J.L.; Li, D.W.; Jackson, A.O.

    2012-01-01

    Barley stripe mosaic virus North Dakota 18 (ND18), Beijing (BJ), Xinjiang (Xi), Type (TY) and CV21 strains are unable to infect the Brachypodium distachyon Bd3-1 inbred line, which harbours a resistance gene designated Bsr1, but the Norwich (NW) strain is virulent on Bd3-1. Analysis of ND18 and NW

  19. Agomelatine, a MT1/MT2 melatonergic receptor agonist with serotonin 5-HT2C receptor antagonistic properties, suppresses Prevotella intermedia lipopolysaccharide-induced production of proinflammatory mediators in murine macrophages.

    Science.gov (United States)

    Hyeon, Jin-Yi; Choi, Eun-Young; Choe, So-Hui; Park, Hae Ryoun; Choi, Jeom-Il; Choi, In Soon; Kim, Sung-Jo

    2017-10-01

    This study was performed in an attempt to examine the influence of agomelatine in mitigating the generation of proinflammatory mediators in RAW264.7 murine macrophages exposed to lipopolysaccharide (LPS) obtained from Prevotella intermedia, a gram-negative anaerobic bacterium that is related with various types of periodontal diseases, and the molecular mechanisms behind its effects. LPS from P. intermedia strain ATCC 25611 was prepared employing the conventional phenol-water procedure. Conditioned culture media were analyzed for the levels of nitric oxide (NO), interleukin-1β (IL-1β) and IL-6. Real-time PCR analysis was carried out to determine the mRNA levels of inducible NO synthase (iNOS), IL-1β, IL-6 and SOCS1. Protein expression levels were evaluated by immunoblot test. NF-κB-dependent SEAP reporter assay was performed using a reporter cell line. DNA-binding activities of NF-κB subunits were analyzed utilizing the ELISA-based kits. Agomelatine was found to down-regulate significantly the generation of iNOS-derived NO, IL-1β and IL-6 as well as the expression of their mRNAs in cells activated with P. intermedia LPS. Agomelatine decreased NF-κB-dependent SEAP release caused by P. intermedia LPS. Agomelatine did not inhibit NF-κB transcription induced by LPS at the level of IκB-α degradation. Instead, LPS-induced nuclear translocation and DNA binding of NF-κB p50 subunit was blocked by agomelatine. P. intermedia LPS-elicited activation of STAT1 and STAT3 was reduced notably by co-treatment with agomelatine. Agomelatine showed a tendency to enhance mRNA level of SOCS1 in LPS-activated cells as well. Agomelatine merits further evaluation to reveal its usefulness on the host modulation of periodontal disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Glycyrrhetinic acid attenuates lipopolysaccharide-induced fulminant hepatic failure in D-galactosamine-sensitized mice by up-regulating expression of interleukin-1 receptor-associated kinase-M

    Energy Technology Data Exchange (ETDEWEB)

    Yin, Xinru [Department of Pharmacology, Chongqing Medical University, Chongqing 400016 (China); Gong, Xia [Department of Anatomy, Chongqing Medical University, Chongqing 400016 (China); Zhang, Li; Jiang, Rong [Laboratory of Stem Cell and Tissue Engineering, Chongqing Medical University, Chongqing 400016 (China); Kuang, Ge [Department of Pharmacology, Chongqing Medical University, Chongqing 400016 (China); Wang, Bin [Department of Anesthesiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016 (China); Chen, Xinyu [Chongqing Traditional Chinese Medicine Hospital, Chongqing 400021 (China); Wan, Jingyuan, E-mail: jywan@cqmu.edu.cn [Department of Pharmacology, Chongqing Medical University, Chongqing 400016 (China)

    2017-04-01

    Glycyrrhetinic acid (GA), the main active ingredient of licorice, reportedly has anti-inflammatory and hepatoprotective properties, but its molecular mechanisms remain be elusive. In the present study, Balb/c mice were pretreated with GA (10, 30, or 100 mg/kg) 1 h before lipopolysaccharide (LPS)/D-galactosamine (D-GalN) administration. In other in vitro experiment, RAW264.7 macrophages were pretreated with GA before LPS exposure. The mortality, hepatic tissue histology, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were analyzed. Toll like receptor 4 (TLR4), interleukin-1 receptor-associated kinases (IRAKs), activation of mitogen-activated protein kinases (MAPKs) and NF-κB, and production of TNF-α were assessed by flow cytometry, western blotting, and enzyme-linked immunosorbent assay (ELISA), respectively. Our results showed that pretreatment with GA protected mice against LPS/D-GalN-induced fulminant hepatic failure (FHF), including a dose-dependent alleviation of mortality and ALT/AST elevation, ameliorating hepatic pathological damage, and decreasing TNF-α release. Moreover, GA inhibited LPS-induced activation of MAPKs and NF-κB in response to LPS, but the expression of TLR4 was not affected in vivo and in vitro. Notably, GA pretreatment in vivo suppressed IRAK-1 activity while inducing IRAK-M expression. Silencing of IRAK-M expression with siRNA blocked these beneficial effects of GA on the activation of MAPKs and NF-κB as well as TNF-α production in LPS-primed macrophages. Taken together, we conclude that GA could prevent LPS/D-GalN-induced FHF. The underlying mechanisms may be related to up-regulation of IRAK-M, which in turn caused deactivation of IRAK-1 and subsequent MAPKs and NF-κB, resulting in inhibiting TNF-α production. - Highlights: • Glycyrrhetinic acid protected from LPS/D-GalN-induced liver injury in mice. • Glycyrrhetinic acid inhibited LPS-induced TNF-α production in vivo and in vitro. • Glycyrrhetinic

  1. Homogeneous bilateral block shifts

    Indian Academy of Sciences (India)

    Douglas class were classified in [3]; they are unilateral block shifts of arbitrary block size (i.e. dim H(n) can be anything). However, no examples of irreducible homogeneous bilateral block shifts of block size larger than 1 were known until now.

  2. Inhibition of lipopolysaccharide-induced proinflammatory responses by Buddleja officinalis extract in BV-2 microglial cells via negative regulation of NF-kB and ERK1/2 signaling.

    Science.gov (United States)

    Oh, Won-Jun; Jung, Uhee; Eom, Hyun-Soo; Shin, Hee-June; Park, Hae-Ran

    2013-07-31

    Buddleja officinalis has been traditionally used in the supportive treatment of inflammatory and neuronal diseases in Korea and China. Although several reports have shown the anti-inflammatory effects of Buddleja officinalis, the anti-neuroinflammatory effect has remained unclear. In this study, we aimed to investigate the inhibitory effects of flower buds of B. officinalis Maximowicz water extract (BOWE) on LPS-induced inflammatory processes in BV-2 microglial cells. BOWE dose-dependently inhibited the production of nitric oxide as well as iNOS mRNA expression. Moreover, BOWE prevented IL-1β and IL-6 mRNA expression. However, BOWE had no effect on LPS-induced COX-2 or TNF-a mRNA expression. The extract also had no effect on LPS-stimulated p38 MAPK, JNK, and c-Jun phosphorylation, whereas ERK1/2 phosphorylation was strongly inhibited by BOWE. BOWE also inhibited the LPS-induced degradation of IkB-α, and LPS-induced phosphorylation of p65 NF-kB protein. These data indicate that BOWE inhibited the nitric oxide production and pro-inflammatory gene expression in BV-2 microglial cells, possibly through a negative regulation of the NF-kB and ERK1/2 pathways. Further identification of the direct target molecule(s) of BOWE is required to support its use as an anti-neuroinflammatory agent against the neurodegenerative disorders.

  3. Inhibition of Lipopolysaccharide-Induced Proinflammatory Responses by Buddleja officinalis Extract in BV-2 Microglial Cells via Negative Regulation of NF-kB and ERK1/2 Signaling

    Directory of Open Access Journals (Sweden)

    Hae-Ran Park

    2013-07-01

    Full Text Available Buddleja officinalis has been traditionally used in the supportive treatment of inflammatory and neuronal diseases in Korea and China. Although several reports have shown the anti-inflammatory effects of Buddleja officinalis, the anti-neuroinflammatory effect has remained unclear. In this study, we aimed to investigate the inhibitory effects of flower buds of B. officinalis Maximowicz water extract (BOWE on LPS-induced inflammatory processes in BV-2 microglial cells. BOWE dose-dependently inhibited the production of nitric oxide as well as iNOS mRNA expression. Moreover, BOWE prevented IL-1β and IL-6 mRNA expression. However, BOWE had no effect on LPS-induced COX-2 or TNF-a mRNA expression. The extract also had no effect on LPS-stimulated p38 MAPK, JNK, and c-Jun phosphorylation, whereas ERK1/2 phosphorylation was strongly inhibited by BOWE. BOWE also inhibited the LPS-induced degradation of IkB-α, and LPS-induced phosphorylation of p65 NF-kB protein. These data indicate that BOWE inhibited the nitric oxide production and pro-inflammatory gene expression in BV-2 microglial cells, possibly through a negative regulation of the NF-kB and ERK1/2 pathways. Further identification of the direct target molecule(s of BOWE is required to support its use as an anti-neuroinflammatory agent against the neurodegenerative disorders.

  4. Chromogenic in situ hybridization to detect EGFR gene copy number in cell blocks from fine-needle aspirates of non small cell lung carcinomas and lung metastases from colo-rectal cancer

    Directory of Open Access Journals (Sweden)

    Terrenato Irene

    2010-09-01

    Full Text Available Abstract Background Several studies demonstrated that epidermal growth factor receptor (EGFR gene copy number (GCN correlates to the response to tyrosine kinase inhibitors in non small cell lung cancer (NSCLC and to anti-EGFR monoclonal antibodies (MoAbs in metastatic colorectal cancer (CRC. In the presence of lung nodules, cytology is often the only possible diagnostic approach. Chromogenic in situ hybridization (CISH is an alternative technique to fluorescence in situ hybridization (FISH, but its feasibility in detecting EGFR GCN in cell blocks from fine-needle aspiration cytology (FNAC of lung nodules has not yet been established. Methods We evaluated the feasibility of CISH on 33 FNAC from 20 primary NSCLC (5 squamous carcinomas, 8 large cell carcinomas and 7 adenocarcinomas and 13 lung metastases from CRC. Results Of the 33 FNAC analyzed by CISH, 27 (82% presented a balanced increase in EGFR gene and chromosome 7 number: 10 cases (30% showed a low polysomy, 15 (45% a high polysomy and 2 (6% NSCLC were amplified. No significant differences between NSCLC and CRC lung metastases were found in relation to disomic or polysomic status. In addition, no correlation between EGFR GCN and EGFR immunohistochemical overexpression was found. Furthermore, we compared CISH results with those obtained by FISH on the same samples and we found 97% overall agreement between the two assays (k = 0.78, p Conclusions Our study shows that CISH is a valid method to detect EGFR GCN in cell blocks from FNAC of primary NSCLC or metastatic CRC to the lung.

  5. Vitamin D inhibits the growth of and virulence factor gene expression by Porphyromonas gingivalis and blocks activation of the nuclear factor kappa B transcription factor in monocytes.

    Science.gov (United States)

    Grenier, D; Morin, M-P; Fournier-Larente, J; Chen, H

    2016-06-01

    Increasing evidence suggests that 1,25-dihydroxyvitamin D3 (1,25(OH)2 D3 ), a fat-soluble secosteroid hormone, has a positive impact on periodontal health through diverse mechanisms. The present study was aimed at investigating the effect of 1,25(OH)2 D3 on the growth of and virulence factor gene expression by the periodontopathogenic bacterium Porphyromonas gingivalis. The effect of 1,25(OH)2 D3 on P. gingivalis-mediated activation of nuclear factor kappa B (NF-κB) transcription factor in monocytes was also assessed. A broth microdilution assay was used to determine the antibacterial activity of 1,25(OH)2 D3 . The modulation of virulence factor gene expression in P. gingivalis was assessed by quantitative reverse transcription-polymerase chain reaction. NF-κB activation was assessed using a human monocytic cell line stably transfected with a luciferase reporter containing NF-κB binding sites. Minimal inhibitory concentrations of 1,25(OH)2 D3 against P. gingivalis ranged from 3.125 to 6.25 μg/mL. Moreover, a partial synergistic effect was observed when 1,25(OH)2 D3 was used in association with metronidazole. 1,25(OH)2 D3 attenuated the virulence of P. gingivalis by reducing the expression of genes coding for important virulence factors, including adhesins (fimA, hagA and hagB) and proteinases (rgpA, rgpB and kgp). 1,25(OH)2 D3 dose-dependently prevented P. gingivalis-induced NF-κB activation in a monocyte model. Our study suggested that 1,25(OH)2 D3 selectively inhibits the growth of and virulence factor gene expression by P. gingivalis, in addition to attenuating NF-κB activation by this periodontopathogen. This dual action on P. gingivalis and the inflammatory response of host cells may be of particular interest with a view to developing a novel and inexpensive preventive/therapeutic strategy. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Vitamin D inhibits lipopolysaccharide-induced inflammatory response potentially through the Toll-like receptor 4 signalling pathway in the intestine and enterocytes of juvenile Jian carp (Cyprinus carpio var. Jian).

    Science.gov (United States)

    Jiang, Jun; Shi, Dan; Zhou, Xiao-Qiu; Yin, Long; Feng, Lin; Jiang, Wei-Dan; Liu, Yang; Tang, Ling; Wu, Pei; Zhao, Ye

    2015-11-28

    The present study was conducted to investigate the anti-inflammatory effect of vitamin D both in juvenile Jian carp (Cyprinus carpio var. Jian) in vivo and in enterocytes in vitro. In primary enterocytes, exposure to 10 mg lipopolysaccharide (LPS)/l increased lactate dehydrogenase activity in the culture medium (P<0·05) and resulted in a significant loss of cell viability (P<0·05). LPS exposure increased (P<0·05) the mRNA expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6 and IL-8), which was decreased by pre-treatment with 1,25-dihydroxyvitamin D (1,25D3) in a dose-dependent manner (P<0·05). Further results showed that pre-treatment with 1,25D3 down-regulated Toll-like receptor 4 (TLR4), myeloid differentiation primary response gene 88 (Myd88) and NF-κB p65 mRNA expression (P<0·05), suggesting potential mechanisms against LPS-induced inflammatory response. In vivo, intraperitoneal injection of LPS significantly increased TNF-α, IL-1β, IL-6 and IL-8 mRNA expression in the intestine of carp (P<0·05). Pre-treatment of fish with vitamin D3 protected the fish intestine from the LPS-induced increase of TNF-α, IL-1β, IL-6 and IL-8 mainly by downregulating TLR4, Myd88 and NF-κB p65 mRNA expression (P<0·05). These observations suggest that vitamin D could inhibit LPS-induced inflammatory response in juvenile Jian carp in vivo and in enterocytes in vitro. The anti-inflammatory effect of vitamin D is mediated at least in part by TLR4-Myd88 signalling pathways in the intestine and enterocytes of juvenile Jian carp.

  7. Testing block subdivision algorithms on block designs

    Science.gov (United States)

    Wiseman, Natalie; Patterson, Zachary

    2016-01-01

    Integrated land use-transportation models predict future transportation demand taking into account how households and firms arrange themselves partly as a function of the transportation system. Recent integrated models require parcels as inputs and produce household and employment predictions at the parcel scale. Block subdivision algorithms automatically generate parcel patterns within blocks. Evaluating block subdivision algorithms is done by way of generating parcels and comparing them to those in a parcel database. Three block subdivision algorithms are evaluated on how closely they reproduce parcels of different block types found in a parcel database from Montreal, Canada. While the authors who developed each of the algorithms have evaluated them, they have used their own metrics and block types to evaluate their own algorithms. This makes it difficult to compare their strengths and weaknesses. The contribution of this paper is in resolving this difficulty with the aim of finding a better algorithm suited to subdividing each block type. The proposed hypothesis is that given the different approaches that block subdivision algorithms take, it's likely that different algorithms are better adapted to subdividing different block types. To test this, a standardized block type classification is used that consists of mutually exclusive and comprehensive categories. A statistical method is used for finding a better algorithm and the probability it will perform well for a given block type. Results suggest the oriented bounding box algorithm performs better for warped non-uniform sites, as well as gridiron and fragmented uniform sites. It also produces more similar parcel areas and widths. The Generalized Parcel Divider 1 algorithm performs better for gridiron non-uniform sites. The Straight Skeleton algorithm performs better for loop and lollipop networks as well as fragmented non-uniform and warped uniform sites. It also produces more similar parcel shapes and patterns.

  8. VCAM-1-targeted core/shell nanoparticles for selective adhesion and delivery to endothelial cells with lipopolysaccharide-induced inflammation under shear flow and cellular magnetic resonance imaging in vitro.

    Science.gov (United States)

    Yang, Hong; Zhao, Fenglong; Li, Ying; Xu, Mingming; Li, Li; Wu, Chunhui; Miyoshi, Hirokazu; Liu, Yiyao

    2013-01-01

    these VCAM-1-targeted Fe(3)O(4)@SiO2(FITC) nanoparticles targeted to inflammatory endothelial cells could be used in the transfer of therapeutic drugs/genes into these cells or for diagnosis of vascular disease at the molecular and cellular levels in the future.

  9. 14-3-3γ Regulates Lipopolysaccharide-Induced Inflammatory Responses and Lactation in Dairy Cow Mammary Epithelial Cells by Inhibiting NF-κB and MAPKs and Up-Regulating mTOR Signaling

    Directory of Open Access Journals (Sweden)

    Lixin Liu

    2015-07-01

    Full Text Available As a protective factor for lipopolysaccharide (LPS-induced injury, 14-3-3γ has been the subject of recent research. Nevertheless, whether 14-3-3γ can regulate lactation in dairy cow mammary epithelial cells (DCMECs induced by LPS remains unknown. Here, the anti-inflammatory effect and lactation regulating ability of 14-3-3γ in LPS-induced DCMECs are investigated for the first time, and the molecular mechanisms responsible for their effects are explored. The results of qRT-PCR showed that 14-3-3γ overexpression significantly inhibited the mRNA expression of tumor necrosis factor-α (TNF-α, interleukin-6 (IL-6, interleukin-1β (IL-1β and inducible nitric oxide synthase (iNOS. Enzyme-linked immunosorbent assay (ELISA analysis revealed that 14-3-3γ overexpression also suppressed the production of TNF-α and IL-6 in cell culture supernatants. Meanwhile, CASY-TT Analyser System showed that 14-3-3γ overexpression clearly increased the viability and proliferation of cells. The results of kit methods and western blot analysis showed that 14-3-3γ overexpression promoted the secretion of triglycerides and lactose and the synthesis of β-casein. Furthermore, the expression of genes relevant to nuclear factor-κB (NF-κB and mitogen-activated protein kinase (MAPKs and lactation-associated proteins were assessed by western blot, and the results suggested that 14-3-3γ overexpression inactivated the NF-κB and MAPK signaling pathways by down-regulating extracellular signal regulated protein kinase (ERK, p38 mitogen-activated protein kinase (p38MAPK and inhibitor of NF-κB (IκB phosphorylation levels, as well as by inhibiting NF-κB translocation. Meanwhile, 14-3-3γ overexpression enhanced the expression levels of β-casein, mammalian target of rapamycin (mTOR, ribosomal protein S6 kinase 1 (S6K1, serine/threonine protein kinase Akt 1 (AKT1, sterol regulatory element binding protein 1 (SREBP1 and peroxisome proliferator-activated receptor gamma

  10. Haplotype block structure study of the CFTR gene. Most variants are associated with the M470 allele in several European populations.

    Science.gov (United States)

    Pompei, Fiorenza; Ciminelli, Bianca Maria; Bombieri, Cristina; Ciccacci, Cinzia; Koudova, Monika; Giorgi, Silvia; Belpinati, Francesca; Begnini, Angela; Cerny, Milos; Des Georges, Marie; Claustres, Mireille; Ferec, Claude; Macek, Milan; Modiano, Guido; Pignatti, Pier Franco

    2006-01-01

    An average of about 1700 CFTR (cystic fibrosis transmembrane conductance regulator) alleles from normal individuals from different European populations were extensively screened for DNA sequence variation. A total of 80 variants were observed: 61 coding SNSs (results already published), 13 noncoding SNSs, three STRs, two short deletions, and one nucleotide insertion. Eight DNA variants were classified as non-CF causing due to their high frequency of occurrence. Through this survey the CFTR has become the most exhaustively studied gene for its coding sequence variability and, though to a lesser extent, for its noncoding sequence variability as well. Interestingly, most variation was associated with the M470 allele, while the V470 allele showed an 'extended haplotype homozygosity' (EHH). These findings make us suggest a role for selection acting either on the M470V itself or through an hitchhiking mechanism involving a second site. The possible ancient origin of the V allele in an 'out of Africa' time frame is discussed.

  11. Poly(ferrocenylsilane)-block-Polylactide Block Copolymers

    NARCIS (Netherlands)

    Roerdink, M.; van Zanten, Thomas S.; Hempenius, Mark A.; Zhong, Zhiyuan; Feijen, Jan; Vancso, Gyula J.

    2007-01-01

    A PFS/PLA block copolymer was studied to probe the effect of strong surface interactions on pattern formation in PFS block copolymer thin films. Successful synthesis of PFS-b-PLA was demonstrated. Thin films of these polymers show phase separation to form PFS microdomains in a PLA matrix, and

  12. Block That Pain!

    Science.gov (United States)

    Skip Navigation Bar Home Current Issue Past Issues Block That Pain! Past Issues / Fall 2007 Table of ... contrast, most pain relievers used for surgical procedures block activity in all types of neurons. This can ...

  13. Bundle Branch Block

    Science.gov (United States)

    ... known cause. Causes can include: Left bundle branch block Heart attacks (myocardial infarction) Thickened, stiffened or weakened ... myocarditis) High blood pressure (hypertension) Right bundle branch block A heart abnormality that's present at birth (congenital) — ...

  14. Generalized Block Failure

    DEFF Research Database (Denmark)

    Jönsson, Jeppe

    2015-01-01

    Block tearing is considered in several codes as a pure block tension or a pure block shear failure mechanism. However in many situations the load acts eccentrically and involves the transfer of a substantial moment in combination with the shear force and perhaps a normal force. A literature study...... shows that no readily available tests with a well-defined substantial eccentricity have been performed. This paper presents theoretical and experimental work leading towards generalized block failure capacity methods. Simple combination of normal force, shear force and moment stress distributions along...... yield lines around the block leads to simple interaction formulas similar to other interaction formulas in the codes....

  15. Effects of lidocaine on lipopolysaccharide-induced synovitis in horses

    OpenAIRE

    Campebell,R.C.; Peiró,J.R.; Valadão,C.A.A.; Santana,A.E.; Cunha,F.Q.

    2004-01-01

    Lidocaine (100mg 2%) injected into the carpal joint was used to evaluate the inflammatory response induced by injection (1.5ng) of intra-articular E. coli lipopolysaccharide (LPS) endotoxin. Seventeen male Mangalarga horses aged two to three years were divided into three groups and in all animals was injected 0.9% saline (SAL) in the left carpus (LC), and in the right carpus (RC) one of the following combinations were injected: group A (n=6) LPS plus SAL; group B (n=6) LPS plus lidocaine; gro...

  16. Allicin Protects against Lipopolysaccharide-Induced Acute Lung ...

    African Journals Online (AJOL)

    Purpose: To investigate the effect of allicin, an active component of garlic, on lipopolysaccharide (LPS)- induced acute lung injury. Methods: Wistar rats were subjected to LPS intravenous injection with or without allicin treatment to induce acute lung injury (ALI) model. Also, A549 cells were stimulated with LPS in the ...

  17. Lipopolysaccharide induces amyloid formation of antimicrobial peptide HAL-2.

    Science.gov (United States)

    Wang, Jiarong; Li, Yan; Wang, Xiaoming; Chen, Wei; Sun, Hongbin; Wang, Junfeng

    2014-11-01

    Lipopolysaccharide (LPS), the important component of the outer membrane of Gram-negative bacteria, contributes to the integrity of the outer membrane and protects the cell against bactericidal agents, including antimicrobial peptides. However, the mechanisms of interaction between antimicrobial peptides and LPS are not clearly understood. Halictines-2 (HAL-2), one of the novel antimicrobial peptides, was isolated from the venom of the eusocial bee Halictus sexcinctus. HAL-2 has exhibited potent antimicrobial activity against Gram-positive and Gram-negative bacteria and even against cancer cells. Here, we studied the interactions between HAL-2 and LPS to elucidate the antibacterial mechanism of HAL-2 in vitro. Our results show that HAL-2 adopts a significant degree of β-strand structure in the presence of LPS. LPS is capable of inducing HAL-2 amyloid formation, which may play a vital role in its antimicrobial activity. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Intermittent fasting attenuates lipopolysaccharide-induced neuroinflammation and memory impairment.

    Science.gov (United States)

    Vasconcelos, Andrea R; Yshii, Lidia M; Viel, Tania A; Buck, Hudson S; Mattson, Mark P; Scavone, Cristoforo; Kawamoto, Elisa M

    2014-05-06

    Systemic bacterial infections often result in enduring cognitive impairment and are a risk factor for dementia. There are currently no effective treatments for infection-induced cognitive impairment. Previous studies have shown that intermittent fasting (IF) can increase the resistance of neurons to injury and disease by stimulating adaptive cellular stress responses. However, the impact of IF on the cognitive sequelae of systemic and brain inflammation is unknown. Rats on IF for 30 days received 1 mg/kg of lipopolysaccharide (LPS) or saline intravenously. Half of the rats were subjected to behavioral tests and the other half were euthanized two hours after LPS administration and the hippocampus was dissected and frozen for analyses. Here, we report that IF ameliorates cognitive deficits in a rat model of sepsis by a mechanism involving NF-κB activation, suppression of the expression of pro-inflammatory cytokines, and enhancement of neurotrophic support. Treatment of rats with LPS resulted in deficits in cognitive performance in the Barnes maze and inhibitory avoidance tests, without changing locomotor activity, that were ameliorated in rats that had been maintained on the IF diet. IF also resulted in reduced levels of mRNAs encoding the LPS receptor TLR4 and inducible nitric oxide synthase (iNOS) in the hippocampus. Moreover, IF prevented LPS-induced elevation of IL-1α, IL-1β and TNF-α levels, and prevented the LPS-induced reduction of BDNF levels in the hippocampus. IF also significantly attenuated LPS-induced elevations of serum IL-1β, IFN-γ, RANTES, TNF-α and IL-6 levels. Taken together, our results suggest that IF induces adaptive responses in the brain and periphery that can suppress inflammation and preserve cognitive function in an animal model of systemic bacterial infection.

  19. Inhibitory Effects of Ketamine on Lipopolysaccharide-Induced Microglial Activation

    Directory of Open Access Journals (Sweden)

    Yi Chang

    2009-01-01

    Full Text Available Microglia activated in response to brain injury release neurotoxic factors including nitric oxide (NO and proinflammatory cytokines such as tumor necrosis factor-α (TNF-α and interleukin-1β (IL-1β. Ketamine, an anesthetic induction agent, is generally reserved for use in patients with severe hypotension or respiratory depression. In this study, we found that ketamine (100 and 250 μM concentration-dependently inhibited lipopolysaccharide (LPS-induced NO and IL-1β release in primary cultured microglia. However, ketamine (100 and 250 μM did not significantly inhibit the LPS-induced TNF-α production in microglia, except at the higher concentration (500 μM. Further study of the molecular mechanisms revealed that ketamine markedly inhibited extracellular signal-regulated kinase (ERK1/2 phosphorylation but not c-Jun N-terminal kinase or p38 mitogen-activated protein kinase stimulated by LPS in microglia. These results suggest that microglial inactivation by ketamine is at least partially due to inhibition of ERK1/2 phosphorylation.

  20. Agmatine attenuates stress- and lipopolysaccharide-induced fever in rats

    Science.gov (United States)

    Aricioglu, Feyza; Regunathan, Soundar

    2010-01-01

    Physiological stress evokes a number of responses, including a rise in body temperature, which has been suggested to be the result of an elevation in the thermoregulatory set point. This response seems to share similar mechanisms with infectious fever. The aim of the present study was to investigate the effect of agmatine on different models of stressors [(restraint and lipopolysaccaride (LPS)] on body temperature. Rats were either restrained for 4 h or injected with LPS, both of these stressors caused an increase in body temperature. While agmatine itself had no effect on body temperature, treatment with agmatine (20, 40, 80 mg/kg intraperitoneally) dose dependently inhibited stress- and LPS-induced hyperthermia. When agmatine (80 mg/kg) was administered 30 min later than LPS (500 μg/kg) it also inhibited LPS-induced hyperthermia although the effect became significant only at later time points and lower maximal response compared to simultaneous administration. To determine if the decrease in body temperature is associated with an anti-inflammatory effect of agmatine, the nitrite/nitrate levels in plasma was measured. Agmatine treatment inhibited LPS-induced production of nitrates dose dependently. As an endogenous molecule, agmatine has the capacity to inhibit stress- and LPS-induced increases in body temperature. PMID:15936786

  1. Minocycline protects against lipopolysaccharide-induced cognitive impairment in mice.

    Science.gov (United States)

    Hou, Yue; Xie, Guanbo; Liu, Xia; Li, Guoxun; Jia, Congcong; Xu, Jinghua; Wang, Bing

    2016-03-01

    The role of glial cells, especially microglia and astrocytes, in neuroinflammation and cognition has been studied intensively. Lipopolysaccharide (LPS), a commonly used inducer of neuroinflammation, can cause cognitive impairment. Minocycline is known to possess potent neuroprotective activity, but its effect on LPS-induced cognitive impairment is unknown. This study aims to investigate the effects of minocycline on LPS-induced cognitive impairment and glial cell activation in mice. Behavioral tests were conducted for cognitive function, immunohistochemistry for microglial and astrocyte response, and quantitative PCR for mRNA expression of proinflammatory cytokines. Minocycline significantly reversed the decreased spontaneous alternation induced by intrahippocampal administration of LPS in the Y-maze task. In the Morris water maze place navigation test, minocycline decreased the escape latency and distance traveled compared to LPS-treated mice. In the probe test, minocycline-treated mice spent more time in the target quadrant and crossed the platform area more frequently than animals in the LPS-treated group. Minocycline produced a significant decrease in the number of Iba-1- and GFAP-positive hippocampal cells compared to the LPS-treated group. Minocycline-treated mice had significantly reduced hippocampal TNF-α and IL-1β mRNA levels compared with LPS-treated animals. Minocycline caused a significant increase in hippocampal BDNF expression compared to the LPS-treated group. Minocycline can attenuate LPS-induced cognitive impairments in mice. This effect may be associated with its action to suppress the activation of microglia and astrocytes and to normalize BDNF expression. Since neuroinflammatory processes and cognitive impairments are implicated in neurodegenerative disorders, minocycline may be a promising candidate for treating such diseases.

  2. Inhibition of lipopolysaccharide induced acute inflammation in lung by chlorination

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Jinshan; Xue, Jinling; Xu, Bi; Xie, Jiani [Environmental Simulation and Pollution Control State Key Joint Laboratory, School of Environment, Tsinghua University, Beijing 100084 (China); Qiao, Juan, E-mail: qjuan@tsinghua.edu.cn [Department of Chemistry, Tsinghua University, Beijing 100084 (China); Lu, Yun, E-mail: luyun@tsinghua.edu.cn [Environmental Simulation and Pollution Control State Key Joint Laboratory, School of Environment, Tsinghua University, Beijing 100084 (China)

    2016-02-13

    Highlights: • Chlorination is effective to reduce the inflammation inducing capacity of LPS in lung. • LAL-detected endotoxin activity is not correlated to the potency of inflammation induction. • Alkyl chain of LPS was chlorinated in chlorination process. • LPS aggregate size decreases after chlorination. - Abstract: Lipopolysaccharide (LPS, also called endotoxin) is a pro-inflammatory constituent of gram negative bacteria and cyanobacteria, which causes a potential health risk in the process of routine urban application of reclaimed water, such as car wash, irrigation, scenic water refilling, etc. Previous studies indicated that the common disinfection treatment, chlorination, has little effect on endotoxin activity removal measured by Limulus amebocyte lysate (LAL) assay. However, in this study, significant decrease of acute inflammatory effects was observed in mouse lung, while LAL assay still presented a moderate increase of endotoxin activity. To explore the possible mechanisms, the nuclear magnetic resonance (NMR) results showed the chlorination happened in alkyl chain of LPS molecules, which could affect the interaction between LPS and LPS-binding protein. Also the size of LPS aggregates was found to drop significantly after treatment, which could be another results of chlorination caused polarity change. In conclusion, our observation demonstrated that chlorination is effective to reduce the LPS induced inflammation in lung, and it is recommended to use health effect-based methods to assess risk removal of water treatment technologies.

  3. Dexmedetomidine reduces lipopolysaccharide induced neuroinflammation, sickness behavior, and anhedonia.

    Directory of Open Access Journals (Sweden)

    Ching-Hua Yeh

    Full Text Available Peripheral innate immune response may induce sickness behavior through activating microglia, excessive cytokines production, and neuroinflammation. Dexmedetomidine (Dex has anti-inflammatory effect. We investigated the effects of Dex on lipopolysaccharide (LPS-induced neuroinflammation and sickness behavior in mice.BALB/c mice were intraperitoneally (i.p. injected with Dex (50 ug/kg or vehicle. One hour later, the mice were injected (i.p. with Escherichia coli LPS (0.33 mg/kg or saline (n = 6 in each group. We analyzed the food and water intake, body weight loss, and sucrose preference of the mice for 24h. We also determined microglia activation and cytokines expression in the brains of the mice. In vitro, we determine cytokines expression in LPS-treated BV-2 microglial cells with or without Dex treatment.In the Dex-pretreated mice, LPS-induced sickness behavior (anorexia, weight loss, and social withdrawal were attenuated and microglial activation was lower than vehicle control. The mRNA expression of TNF-α, MCP-1, indoleamine 2, 3 dioxygenase (IDO, caspase-3, and iNOS were increased in the brain of LPS-challenged mice, which were reduced by Dex but not vehicle.Dexmedetomidine diminished LPS-induced neuroinflammation in the mouse brain and modulated the cytokine-associated changes in sickness behavior.

  4. Calcium hydroxide suppresses Porphyromonas endodontalis lipopolysaccharide-induced bone destruction.

    Science.gov (United States)

    Guo, J; Yang, D; Okamura, H; Teramachi, J; Ochiai, K; Qiu, L; Haneji, T

    2014-05-01

    Porphyromonas endodontalis and its main virulence factor, lipopolysaccharide (LPS), are associated with the development of periapical diseases and alveolar bone loss. Calcium hydroxide is commonly used for endodontic therapy. However, the effects of calcium hydroxide on the virulence of P. endodontalis LPS and the mechanism of P. endodontalis LPS-induced bone destruction are not clear. Calcium hydroxide rescued the P. endodontalis LPS-suppressed viability of MC3T3-E1 cells and activity of nuclear factor-κB (NF-κB) in these cells, resulting in the reduced expression of interleukin-6 and tumor necrosis factor-α. In addition, calcium hydroxide inhibited P. endodontalis LPS-induced osteoclastogenesis by decreasing the activities of NF-κB, p38, and ERK1/2 and the expression of nuclear factor of activated T-cell cytoplasmic 1 in RAW264.7 cells. Calcium hydroxide also rescued the P. endodontalis LPS-induced osteoclastogenesis and bone destruction in mouse calvaria. Taken together, our present results indicate that calcium hydroxide suppressed bone destruction by attenuating the virulence of P. endodontalis LPS on bone cells.

  5. Inhibition of lipopolysaccharide induced acute inflammation in lung by chlorination.

    Science.gov (United States)

    Zhang, Jinshan; Xue, Jinling; Xu, Bi; Xie, Jiani; Qiao, Juan; Lu, Yun

    2016-02-13

    Lipopolysaccharide (LPS, also called endotoxin) is a pro-inflammatory constituent of gram negative bacteria and cyanobacteria, which causes a potential health risk in the process of routine urban application of reclaimed water, such as car wash, irrigation, scenic water refilling, etc. Previous studies indicated that the common disinfection treatment, chlorination, has little effect on endotoxin activity removal measured by Limulus amebocyte lysate (LAL) assay. However, in this study, significant decrease of acute inflammatory effects was observed in mouse lung, while LAL assay still presented a moderate increase of endotoxin activity. To explore the possible mechanisms, the nuclear magnetic resonance (NMR) results showed the chlorination happened in alkyl chain of LPS molecules, which could affect the interaction between LPS and LPS-binding protein. Also the size of LPS aggregates was found to drop significantly after treatment, which could be another results of chlorination caused polarity change. In conclusion, our observation demonstrated that chlorination is effective to reduce the LPS induced inflammation in lung, and it is recommended to use health effect-based methods to assess risk removal of water treatment technologies. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Inhibition of lipopolysaccharide induced acute inflammation in lung by chlorination

    International Nuclear Information System (INIS)

    Zhang, Jinshan; Xue, Jinling; Xu, Bi; Xie, Jiani; Qiao, Juan; Lu, Yun

    2016-01-01

    Highlights: • Chlorination is effective to reduce the inflammation inducing capacity of LPS in lung. • LAL-detected endotoxin activity is not correlated to the potency of inflammation induction. • Alkyl chain of LPS was chlorinated in chlorination process. • LPS aggregate size decreases after chlorination. - Abstract: Lipopolysaccharide (LPS, also called endotoxin) is a pro-inflammatory constituent of gram negative bacteria and cyanobacteria, which causes a potential health risk in the process of routine urban application of reclaimed water, such as car wash, irrigation, scenic water refilling, etc. Previous studies indicated that the common disinfection treatment, chlorination, has little effect on endotoxin activity removal measured by Limulus amebocyte lysate (LAL) assay. However, in this study, significant decrease of acute inflammatory effects was observed in mouse lung, while LAL assay still presented a moderate increase of endotoxin activity. To explore the possible mechanisms, the nuclear magnetic resonance (NMR) results showed the chlorination happened in alkyl chain of LPS molecules, which could affect the interaction between LPS and LPS-binding protein. Also the size of LPS aggregates was found to drop significantly after treatment, which could be another results of chlorination caused polarity change. In conclusion, our observation demonstrated that chlorination is effective to reduce the LPS induced inflammation in lung, and it is recommended to use health effect-based methods to assess risk removal of water treatment technologies.

  7. Evidence for lipopolysaccharide-induced differentiation of RAW264 ...

    Indian Academy of Sciences (India)

    Unknown

    2Analytical Services Branch, HELD, National Institute for Occupational Safety and Health,. Center of Disease ... cells increased in cell size and acquired distinct dendritic morphology. ..... ferentiation of macrophages into DCs, further work is.

  8. Lipopolysaccharide induces autotaxin expression in human monocytic THP-1 cells

    International Nuclear Information System (INIS)

    Li Song; Zhang Junjie

    2009-01-01

    Autotaxin (ATX) is a secreted enzyme with lysophospholipase D (lysoPLD) activity, which converts lysophosphatidylcholine (LPC) into lysophosphatidic acid (LPA), a bioactive phospholipid involved in numerous biological activities, including cell proliferation, differentiation, and migration. In the present study, we found that bacterial lipopolysaccharide (LPS), a well-known initiator of the inflammatory response, induced ATX expression in monocytic THP-1 cells. The activation of PKR, JNK, and p38 MAPK was required for the ATX induction. The LPS-induced ATX in THP-1 cells was characterized as the β isoform. In the presence of LPC, ATX could promote the migrations of THP-1 and Jurkat cells, which was inhibited by pertussis toxin (PTX), an inhibitor of Gi-mediated LPA receptor signaling. In summary, LPS induces ATX expression in THP-1 cells via a PKR, JNK and p38 MAPK-mediated mechanism, and the ATX induction is likely to enhance immune cell migration in proinflammatory response by regulating LPA levels in the microenvironment.

  9. Lipopolysaccharide-induced acute renal failure in conscious rats

    DEFF Research Database (Denmark)

    Jonassen, Thomas E N; Graebe, Martin; Promeneur, Dominique

    2002-01-01

    In conscious, chronically instrumented rats we examined 1) renal tubular functional changes involved in lipopolysaccharide (LPS)-induced acute renal failure; 2) the effects of LPS on the expression of selected renal tubular water and sodium transporters; and 3) effects of milrinone......-alpha and lactate, inhibited the LPS-induced tachycardia, and exacerbated the acute LPS-induced fall in GFR. Furthermore, Ro-20-1724-treated rats were unable to maintain MAP. We conclude 1) PDE3 or PDE4 inhibition exacerbates LPS-induced renal failure in conscious rats; and 2) LPS treated rats develop an escape......, a phosphodiesterase type 3 (PDE3) inhibitor, and Ro-20-1724, a PDE4 inhibitor, on LPS-induced changes in renal function. Intravenous infusion of LPS (4 mg/kg b.wt. over 1 h) caused an immediate decrease in glomerular filtration rate (GFR) and proximal tubular outflow without changes in mean arterial pressure (MAP...

  10. Benzoxazole derivatives suppress lipopolysaccharide-induced mast cell activation.

    Science.gov (United States)

    Cho, Kyung-Ah; Park, Minhwa; Kim, Yu-Hee; Choo, Hea-Young Park; Lee, Kyung Ho

    2018-05-01

    Mast cells are central regulators of allergic inflammation that function by releasing various proallergic inflammatory mediators, including histamine, eicosanoids and proinflammatory cytokines. Occasionally, bacterial infections may initiate or worsen allergic inflammation. A number of studies have indicated that activation of lipoxygenase in mast cells positive regulates allergic inflammatory responses by generating leukotrienes and proinflammatory cytokines. In the present study, the effects of benzoxazole derivatives on the lipopolysaccharide (LPS)‑induced expression of proinflammatory cytokines, production of histamine and surface expression of co‑stimulatory molecules on bone marrow-derived mast cells (BMMCs) were studied. The benzoxazole derivatives significantly reduced the expression of interleukin (IL)‑1β, IL‑6, IL‑13, tumor necrosis factor‑α, perilipin (PLIN) 2, and PLIN3 in BMMCs treated with LPS. Furthermore, histamine production was suppressed in BMMCs treated with LPS, or treated with phorbol-12-myristate-13-acetate/ionomycin. Benzoxazole derivatives marginally affected the surface expression of cluster of differentiation (CD)80 and CD86 on BMMCs in the presence of LPS, although LPS alone did not increase the expression of those proteins. Therefore, benzoxazole derivatives inhibited the secretion of proinflammatory cytokines in mast cells and may be potential candidate anti‑allergic agents to suppress mast cell activation.

  11. Blocked Randomization with Randomly Selected Block Sizes

    Directory of Open Access Journals (Sweden)

    Jimmy Efird

    2010-12-01

    Full Text Available When planning a randomized clinical trial, careful consideration must be given to how participants are selected for various arms of a study. Selection and accidental bias may occur when participants are not assigned to study groups with equal probability. A simple random allocation scheme is a process by which each participant has equal likelihood of being assigned to treatment versus referent groups. However, by chance an unequal number of individuals may be assigned to each arm of the study and thus decrease the power to detect statistically significant differences between groups. Block randomization is a commonly used technique in clinical trial design to reduce bias and achieve balance in the allocation of participants to treatment arms, especially when the sample size is small. This method increases the probability that each arm will contain an equal number of individuals by sequencing participant assignments by block. Yet still, the allocation process may be predictable, for example, when the investigator is not blind and the block size is fixed. This paper provides an overview of blocked randomization and illustrates how to avoid selection bias by using random block sizes.

  12. 31 CFR 595.301 - Blocked account; blocked property.

    Science.gov (United States)

    2010-07-01

    ... (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY TERRORISM SANCTIONS REGULATIONS General Definitions § 595.301 Blocked account; blocked property. The terms blocked account and blocked...

  13. Block Cipher Analysis

    DEFF Research Database (Denmark)

    Miolane, Charlotte Vikkelsø

    ensurethat no attack violatesthe securitybounds specifiedbygeneric attack namely exhaustivekey search and table lookup attacks. This thesis contains a general introduction to cryptography with focus on block ciphers and important block cipher designs, in particular the Advanced Encryption Standard(AES...... on small scale variants of AES. In the final part of the thesis we present a new block cipher proposal Present and examine its security against algebraic and differential cryptanalysis in particular....

  14. Related Drupal Nodes Block

    NARCIS (Netherlands)

    Van der Vegt, Wim

    2010-01-01

    Related Drupal Nodes Block This module exposes a block that uses Latent Semantic Analysis (Lsa) internally to suggest three nodes that are relevant to the node a user is viewing. This module performs three tasks. 1) It periodically indexes a Drupal site and generates a Lsa Term Document Matrix.

  15. Designers Block 2002

    DEFF Research Database (Denmark)

    Dickson, Thomas

    2002-01-01

    Artiklen indleder med: ved siden aaf Londons etablerede designmesse '100% Design', er der vokset et undergrundsmiljø af designudstillinger op. Det dominerende og mest kendte initiativ er Designers Block, der i år udstillede to steder i byen. Designers Block er et mere uformelt udstillingsforum...

  16. Predictability of blocking

    International Nuclear Information System (INIS)

    Tosi, E.; Ruti, P.; Tibaldi, S.; D'Andrea, F.

    1994-01-01

    Tibaldi and Molteni (1990, hereafter referred to as TM) had previously investigated operational blocking predictability by the ECMWF model and the possible relationships between model systematic error and blocking in the winter season of the Northern Hemisphere, using seven years of ECMWF operational archives of analyses and day 1 to 10 forecasts. They showed that fewer blocking episodes than in the real atmosphere were generally simulated by the model, and that this deficiency increased with increasing forecast time. As a consequence of this, a major contribution to the systematic error in the winter season was shown to derive from the inability of the model to properly forecast blocking. In this study, the analysis performed in TM for the first seven winter seasons of the ECMWF operational model is extended to the subsequent five winters, during which model development, reflecting both resolution increases and parametrisation modifications, continued unabated. In addition the objective blocking index developed by TM has been applied to the observed data to study the natural low frequency variability of blocking. The ability to simulate blocking of some climate models has also been tested

  17. 31 CFR 594.301 - Blocked account; blocked property.

    Science.gov (United States)

    2010-07-01

    ... (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY GLOBAL TERRORISM SANCTIONS REGULATIONS General Definitions § 594.301 Blocked account; blocked property. The terms blocked account and...

  18. RX for Writer's Block.

    Science.gov (United States)

    Tompkins, Gail E.; Camp, Donna J.

    1988-01-01

    Describes four prewriting techniques that elementary and middle grade students can use to gather and organize ideas for writing, and by so doing, cure writer's block. Techniques discussed are: (1) brainstorming; (2) clustering; (3) freewriting; and (4) cubing.

  19. Block copolymer battery separator

    Science.gov (United States)

    Wong, David; Balsara, Nitash Pervez

    2016-04-26

    The invention herein described is the use of a block copolymer/homopolymer blend for creating nanoporous materials for transport applications. Specifically, this is demonstrated by using the block copolymer poly(styrene-block-ethylene-block-styrene) (SES) and blending it with homopolymer polystyrene (PS). After blending the polymers, a film is cast, and the film is submerged in tetrahydrofuran, which removes the PS. This creates a nanoporous polymer film, whereby the holes are lined with PS. Control of morphology of the system is achieved by manipulating the amount of PS added and the relative size of the PS added. The porous nature of these films was demonstrated by measuring the ionic conductivity in a traditional battery electrolyte, 1M LiPF.sub.6 in EC/DEC (1:1 v/v) using AC impedance spectroscopy and comparing these results to commercially available battery separators.

  20. Blocking in Category Learning

    OpenAIRE

    Bott, Lewis; Hoffman, Aaron B.; Murphy, Gregory L.

    2007-01-01

    Many theories of category learning assume that learning is driven by a need to minimize classification error. When there is no classification error, therefore, learning of individual features should be negligible. We tested this hypothesis by conducting three category learning experiments adapted from an associative learning blocking paradigm. Contrary to an error-driven account of learning, participants learned a wide range of information when they learned about categories, and blocking effe...

  1. Single-chain antibody-based gene therapy: Inhibition of tumor growth by in situ production of phage-derived antibodies blocking functionally active sites of cell-associated matrices

    DEFF Research Database (Denmark)

    Sanz, Laura; Kristensen, Peter; Blanco, Belén

    2002-01-01

    Experimental evidence suggests that blocking the interactions between endothelial cells and extracellular matrix (ECM) components may provide a potent and general strategy to inhibit tumor neovascularization. Based on these considerations, we have focused our efforts on laminin, component of the ...

  2. Uniaxial backfill block compaction

    International Nuclear Information System (INIS)

    Koskinen, V.

    2012-05-01

    The main parts of the project were: to make a literature survey of the previous uniaxial compaction experiments; do uniaxial compaction tests in laboratory scale; and do industrial scale production tests. Object of the project was to sort out the different factors affecting the quality assurance chain of the backfill block uniaxial production and solve a material sticking to mould problem which appeared during manufacturing the blocks of bentonite and cruched rock mixture. The effect of mineralogical and chemical composition on the long term functionality of the backfill was excluded from the project. However, the used smectite-rich clays have been tested for mineralogical consistency. These tests were done in B and Tech OY according their SOPs. The objective of the Laboratory scale tests was to find right material- and compaction parameters for the industrial scale tests. Direct comparison between the laboratory scale tests and industrial scale tests is not possible because the mould geometry and compaction speed has a big influence for the compaction process. For this reason the selected material parameters were also affected by the previous compaction experiments. The industrial scale tests were done in summer of 2010 in southern Sweden. Blocks were done with uniaxial compaction. A 40 tons of the mixture of bentonite and crushed rock blocks and almost 50 tons of Friedland-clay blocks were compacted. (orig.)

  3. Impression block with orientator

    International Nuclear Information System (INIS)

    Brilin, V I; Ulyanova, O S

    2015-01-01

    Tool review, namely the impression block, applied to check the shape and size of the top of fish as well as to determine the appropriate tool for fishing operation was realized. For multiple application and obtaining of the impress depth of 3 cm and more, the standard volumetric impression blocks with fix rods are used. However, the registered impress of fish is not oriented in space and the rods during fishing are in the extended position. This leads to rods deformation and sinking due to accidental impacts of impression block over the borehole irregularity and finally results in faulty detection of the top end of fishing object in hole. The impression blocks with copy rods and fixed magnetic needle allow estimating the object configuration and fix the position of magnetic needle determining the position of the top end of object in hole. However, the magnetic needle fixation is realized in staged and the rods are in extended position during fishing operations as well as it is in standard design. The most efficient tool is the impression block with copy rods which directs the examined object in the borehole during readings of magnetic needles data from azimuth plate and averaging of readings. This significantly increases the accuracy of fishing toll direction. The rods during fishing are located in the body and extended only when they reach the top of fishing object

  4. Vagal Blocking for Obesity Control

    DEFF Research Database (Denmark)

    Johannessen, Helene; Revesz, David; Kodama, Yosuke

    2017-01-01

    : VBLOC reduced body weight and food intake, which was associated with increased satiety but not with decreased hunger. Brain activities in response to VBLOC included increased gene expression of leptin and CCKb receptors, interleukin-1β, tumor necrosis factor, and transforming growth factor β1......BACKGROUND: Recently, the US FDA has approved "vagal blocking therapy or vBLoc® therapy" as a new treatment for obesity. The aim of the present study was to study the mechanism-of-action of "VBLOC" in rat models. METHODS: Rats were implanted with VBLOC, an intra-abdominal electrical device...... with leads placed around gastric vagal trunks through an abdominal incision and controlled by wireless device. Body weight, food intake, hunger/satiety, and metabolic parameters were monitored by a comprehensive laboratory animal monitoring system. Brain-gut responses were analyzed physiologically. RESULTS...

  5. Amphiphilic block copolymers for drug delivery.

    Science.gov (United States)

    Adams, Monica L; Lavasanifar, Afsaneh; Kwon, Glen S

    2003-07-01

    Amphiphilic block copolymers (ABCs) have been used extensively in pharmaceutical applications ranging from sustained-release technologies to gene delivery. The utility of ABCs for delivery of therapeutic agents results from their unique chemical composition, which is characterized by a hydrophilic block that is chemically tethered to a hydrophobic block. In aqueous solution, polymeric micelles are formed via the association of ABCs into nanoscopic core/shell structures at or above the critical micelle concentration. Upon micellization, the hydrophobic core regions serve as reservoirs for hydrophobic drugs, which may be loaded by chemical, physical, or electrostatic means, depending on the specific functionalities of the core-forming block and the solubilizate. Although the Pluronics, composed of poly(ethylene oxide)-block-poly(propylene oxide)-block-poly(ethylene oxide), are the most widely studied ABC system, copolymers containing poly(L-amino acid) and poly(ester) hydrophobic blocks have also shown great promise in delivery applications. Because each ABC has unique advantages with respect to drug delivery, it may be possible to choose appropriate block copolymers for specific purposes, such as prolonging circulation time, introduction of targeting moieties, and modification of the drug-release profile. ABCs have been used for numerous pharmaceutical applications including drug solubilization/stabilization, alteration of the pharmacokinetic profile of encapsulated substances, and suppression of multidrug resistance. The purpose of this minireview is to provide a concise, yet detailed, introduction to the use of ABCs and polymeric micelles as delivery agents as well as to highlight current and past work in this area. Copyright 2003 Wiley-Liss, Inc. and the American Pharmacists Association

  6. Integral-fuel blocks

    International Nuclear Information System (INIS)

    Cunningham, C.; Simpkin, S.D.

    1975-01-01

    A prismatic moderator block is described which has fuel-containing channels and coolant channels disposed parallel to each other and to edge faces of the block. The coolant channels are arranged in rows on an equilateral triangular lattice pattern and the fuel-containing channels are disposed in a regular lattice pattern with one fuel-containing channel between and equidistant from each of the coolant channels in each group of three mutually adjacent coolant channels. The edge faces of the block are parallel to the rows of coolant channels and the channels nearest to each edge face are disposed in two rows parallel thereto, with one of the rows containing only coolant channels and the other row containing only fuel-containing channels. (Official Gazette)

  7. Right bundle branch block

    DEFF Research Database (Denmark)

    Bussink, Barbara E; Holst, Anders Gaarsdal; Jespersen, Lasse

    2013-01-01

    AimsTo determine the prevalence, predictors of newly acquired, and the prognostic value of right bundle branch block (RBBB) and incomplete RBBB (IRBBB) on a resting 12-lead electrocardiogram in men and women from the general population.Methods and resultsWe followed 18 441 participants included...... in the Copenhagen City Heart Study examined in 1976-2003 free from previous myocardial infarction (MI), chronic heart failure, and left bundle branch block through registry linkage until 2009 for all-cause mortality and cardiovascular outcomes. The prevalence of RBBB/IRBBB was higher in men (1.4%/4.7% in men vs. 0.......5%/2.3% in women, P block was associated with significantly...

  8. ["Habitual" left branch block alternating with 2 "disguised" bracnch block].

    Science.gov (United States)

    Lévy, S; Jullien, G; Mathieu, P; Mostefa, S; Gérard, R

    1976-10-01

    Two cases of alternating left bundle branch block and "masquerading block" (with left bundle branch morphology in the stnadard leads and right bundle branch block morphology in the precordial leads) were studied by serial tracings and his bundle electrocardiography. In case 1 "the masquerading" block was associated with a first degree AV block related to a prolongation of HV interval. This case is to our knowledge the first cas of alternating bundle branch block in which his bundle activity was recorded in man. In case 2, the patient had atrial fibrilation and His bundle recordings were performed while differents degrees of left bundle branch block were present: The mechanism of the alternation and the concept of "masquerading" block are discussed. It is suggested that this type of block represents a right bundle branch block associated with severe lesions of the "left system".

  9. E-Block: A Tangible Programming Tool with Graphical Blocks

    OpenAIRE

    Danli Wang; Yang Zhang; Shengyong Chen

    2013-01-01

    This paper designs a tangible programming tool, E-Block, for children aged 5 to 9 to experience the preliminary understanding of programming by building blocks. With embedded artificial intelligence, the tool defines the programming blocks with the sensors as the input and enables children to write programs to complete the tasks in the computer. The symbol on the programming block's surface is used to help children understanding the function of each block. The sequence information is transfer...

  10. Linoleum Block Printing Revisited.

    Science.gov (United States)

    Chetelat, Frank J.

    1980-01-01

    The author discusses practical considerations of teaching linoleum block printing in the elementary grades (tool use, materials, motivation) and outlines a sequence of design concepts in this area for the primary, intermediate and junior high grades. A short list of books and audiovisual aids is appended. (SJL)

  11. Spice Blocks Melanoma Growth

    Science.gov (United States)

    Science Teacher, 2005

    2005-01-01

    Curcumin, the pungent yellow spice found in both turmeric and curry powders, blocks a key biological pathway needed for development of melanoma and other cancers, according to a study that appears in the journal Cancer. Researchers from The University of Texas M. D. Anderson Cancer Center demonstrate how curcumin stops laboratory strains of…

  12. Contaminated soil concrete blocks

    NARCIS (Netherlands)

    de Korte, A.C.J.; Brouwers, Jos; Limbachiya, Mukesh C.; Kew, Hsein Y.

    2009-01-01

    According to Dutch law the contaminated soil needs to be remediated or immobilised. The main focus in this article is the design of concrete blocks, containing contaminated soil, that are suitable for large production, financial feasible and meets all technical and environmental requirements. In

  13. Abdominal wall blocks in adults

    DEFF Research Database (Denmark)

    Børglum, Jens; Gögenür, Ismail; Bendtsen, Thomas F

    2016-01-01

    been introduced with success. Future research should also investigate the effect of specific abdominal wall blocks on neuroendocrine and inflammatory stress response after surgery.  Summary USG abdominal wall blocks in adults are commonplace techniques today. Most abdominal wall blocks are assigned......Purpose of review Abdominal wall blocks in adults have evolved much during the last decade; that is, particularly with the introduction of ultrasound-guided (USG) blocks. This review highlights recent advances of block techniques within this field and proposes directions for future research.......  Recent findings Ultrasound guidance is now considered the golden standard for abdominal wall blocks in adults, even though some landmark-based blocks are still being investigated. The efficiency of USG transversus abdominis plane blocks in relation to many surgical procedures involving the abdominal wall...

  14. SNUPPS power block engineering

    Energy Technology Data Exchange (ETDEWEB)

    Thompson, C A [Bechtel Power Corp., San Francisco, Calif. (USA)

    1975-11-01

    The Standard Power Block is based on a modular concept and consists of the following: turbine building, auxiliary building, fuel building, control building, radwaste building, diesel generators building, and outside storage tanks and transformers. Each power block unit includes a Westinghouse pressurized water reactor and has a thermal power rating of 3425 MW(t). The corresponding General Electric turbine generator net electrical output is 1188 MW(e). This standardization approach results in not only a reduction in the costs of engineering, licensing, procurement, and project planning, but should also result in additional savings by the application of experience gained in the construction of the first unit to the following units and early input of construction data to design.

  15. Change Around the Block?

    Science.gov (United States)

    Berlin, Joey

    2017-04-01

    Proponents of a block grant or per-capita cap trumpet them as vehicles for the federal government to give the states a capped amount of funding for Medicaid that legislatures would effectively distribute how they see fit. Questions abound as to what capped Medicaid funding would look like, and what effect it would have on the current Medicaid-eligible population, covered services, and physician payments.

  16. SUPERFICIAL CERVICAL PLEXUS BLOCK

    Directory of Open Access Journals (Sweden)

    Komang Mega Puspadisari

    2014-01-01

    Full Text Available Superficial cervical plexus block is one of the regional anesthesia in  neck were limited to thesuperficial fascia. Anesthesia is used to relieve pain caused either during or after the surgery iscompleted. This technique can be done by landmark or with ultrasound guiding. The midpointof posterior border of the Sternocleidomastoid was identified and the prosedure done on thatplace or on the level of cartilage cricoid.

  17. E-Block: A Tangible Programming Tool with Graphical Blocks

    Directory of Open Access Journals (Sweden)

    Danli Wang

    2013-01-01

    Full Text Available This paper designs a tangible programming tool, E-Block, for children aged 5 to 9 to experience the preliminary understanding of programming by building blocks. With embedded artificial intelligence, the tool defines the programming blocks with the sensors as the input and enables children to write programs to complete the tasks in the computer. The symbol on the programming block's surface is used to help children understanding the function of each block. The sequence information is transferred to computer by microcomputers and then translated into semantic information. The system applies wireless and infrared technologies and provides user with feedbacks on both screen and programming blocks. Preliminary user studies using observation and user interview methods are shown for E-Block's prototype. The test results prove that E-Block is attractive to children and easy to learn and use. The project also highlights potential advantages of using single chip microcomputer (SCM technology to develop tangible programming tools for children.

  18. Block and sub-block boundary strengthening in lath martensite

    NARCIS (Netherlands)

    Du, C.; Hoefnagels, J.P.M.; Vaes, R.; Geers, M.G.D.

    2016-01-01

    Well-defined uniaxial micro-tensile tests were performed on lath martensite single block specimens and multi-block specimens with different number of block boundaries parallel to the loading direction. Detailed slip trace analyses consistently revealed that in the {110}<111> slip system with the

  19. Habitat Blocks and Wildlife Corridors

    Data.gov (United States)

    Vermont Center for Geographic Information — Habitat blocks are areas of contiguous forest and other natural habitats that are unfragmented by roads, development, or agriculture. Vermonts habitat blocks are...

  20. Atrioventricular block, ECG tracing (image)

    Science.gov (United States)

    ... an abnormal rhythm (arrhythmia) called an atrioventricular (AV) block. P waves show that the top of the ... wave (and heart contraction), there is an atrioventricular block, and a very slow pulse (bradycardia).

  1. Fermion-scalar conformal blocks

    Energy Technology Data Exchange (ETDEWEB)

    Iliesiu, Luca [Joseph Henry Laboratories, Princeton University,Washington Road, Princeton, NJ 08544 (United States); Kos, Filip [Department of Physics, Yale University,217 Prospect Street, New Haven, CT 06520 (United States); Poland, David [Department of Physics, Yale University,217 Prospect Street, New Haven, CT 06520 (United States); School of Natural Sciences, Institute for Advanced Study,1 Einstein Dr, Princeton, New Jersey 08540 (United States); Pufu, Silviu S. [Joseph Henry Laboratories, Princeton University,Washington Road, Princeton, NJ 08544 (United States); Simmons-Duffin, David [School of Natural Sciences, Institute for Advanced Study,1 Einstein Dr, Princeton, New Jersey 08540 (United States); Yacoby, Ran [Joseph Henry Laboratories, Princeton University,Washington Road, Princeton, NJ 08544 (United States)

    2016-04-13

    We compute the conformal blocks associated with scalar-scalar-fermion-fermion 4-point functions in 3D CFTs. Together with the known scalar conformal blocks, our result completes the task of determining the so-called ‘seed blocks’ in three dimensions. Conformal blocks associated with 4-point functions of operators with arbitrary spins can now be determined from these seed blocks by using known differential operators.

  2. Powder wastes confinement block and manufacturing process of this block

    International Nuclear Information System (INIS)

    Dagot, L.; Brunel, G.

    1996-01-01

    This invention concerns a powder wastes containment block and a manufacturing process of this block. In this block, the waste powder is encapsulated in a thermo hardening polymer as for example an epoxy resin, the encapsulated resin being spread into cement. This block can contain between 45 and 55% in mass of wastes, between 18 and 36% in mass of polymer and between 14 and 32% in mass of cement. Such a containment block can be used for the radioactive wastes storage. (O.M.). 4 refs

  3. Building Curriculum during Block Play

    Science.gov (United States)

    Andrews, Nicole

    2015-01-01

    Blocks are not just for play! In this article, Nicole Andrews describes observing the interactions of three young boys enthusiastically engaged in the kindergarten block center of their classroom, using blocks in a building project that displayed their ability to use critical thinking skills, physics exploration, and the development of language…

  4. Isotope heating block

    International Nuclear Information System (INIS)

    Wenk, E.

    1976-01-01

    A suggestion is made not to lead the separated nuclear 'waste' from spent nuclear fuel elements directly to end storage, but to make use of the heat produced from the remaining radiation, e.g. for seawater desalination. According to the invention, the activated fission products are to be processed, e.g. by calcination or vitrification, so that one can handle them. They should then be arranged in layers alternately with plate-shaped heat conducting pipes to form a homogeneous block; the heat absorbed by the thermal plates should be further passed on to evaporators or heat exchangers. (UWI) [de

  5. Blocking the Hawking radiation

    DEFF Research Database (Denmark)

    Autzen, M.; Kouvaris, C.

    2014-01-01

    grows after its formation (and eventually destroys the star) instead of evaporating. The fate of the black hole is dictated by the two opposite mechanics, i.e., accretion of nuclear matter from the center of the star and Hawking radiation that tends to decrease the mass of the black hole. We study how...... the assumptions for the accretion rate can in fact affect the critical mass beyond which a black hole always grows. We also study to what extent degenerate nuclear matter can impede Hawking radiation due to the fact that emitted particles can be Pauli blocked at the core of the star....

  6. Introgression of a Block of Genome Under Infinitesimal Selection.

    Science.gov (United States)

    Sachdeva, Himani; Barton, Nicholas H

    2018-06-12

    Adaptive introgression is common in nature and can be driven by selection acting on multiple, linked genes. We explore the effects of polygenic selection on introgression under the infinitesimal model with linkage. This model assumes that the introgressing block has an effectively infinite number of loci, each with an infinitesimal effect on the trait under selection. The block is assumed to introgress under directional selection within a native population that is genetically homogeneous. We use individual-based simulations and a branching process approximation to compute various statistics of the introgressing block, and explore how these depend on parameters such as the map length and initial trait value associated with the introgressing block, the genetic variability along the block, and the strength of selection. Our results show that the introgression dynamics of a block under infinitesimal selection are qualitatively different from the dynamics of neutral introgression. We also find that in the long run, surviving descendant blocks are likely to have intermediate lengths, and clarify how their length is shaped by the interplay between linkage and infinitesimal selection. Our results suggest that it may be difficult to distinguish the long-term introgression of a block of genome with a single strongly selected locus from the introgression of a block with multiple, tightly linked and weakly selected loci. Copyright © 2018, Genetics.

  7. A standard graphite block

    Energy Technology Data Exchange (ETDEWEB)

    Ivkovic, M; Zdravkovic, Z; Sotic, O [Department of Reactor Physics and Dynamics, Boris Kidric Institute of nuclear sciences Vinca, Belgrade (Yugoslavia)

    1966-04-15

    A graphite block was calibrated for the thermal neutron flux of the Ra-Be source using indium foils as detectors. Experimental values of the thermal neutron flux along the central vertical axis of the system were corrected for the self-shielding effect and depression of flux in the detector. The experimental values obtained were compared with the values calculated on the basis of solving the conservation neutron equation by the continuous slowing-down theory. In this theoretical calculation of the flux the Ra-Be source was divided into three resonance energy regions. The measurement of the thermal neutron diffusion length in the standard graphite block is described. The measurements were performed in the thermal neutron region of the system. The experimental results were interpreted by the diffusion theory for point thermal neutron source in the finite system. The thermal neutron diffusion length was calculated to be L= 50.9 {+-}3.1 cm for the following graphite characteristics: density = 1.7 g/cm{sup 3}; boron content = 0.1 ppm; absorption cross section = 3.7 mb.

  8. A standard graphite block

    International Nuclear Information System (INIS)

    Ivkovic, M.; Zdravkovic, Z.; Sotic, O.

    1966-04-01

    A graphite block was calibrated for the thermal neutron flux of the Ra-Be source using indium foils as detectors. Experimental values of the thermal neutron flux along the central vertical axis of the system were corrected for the self-shielding effect and depression of flux in the detector. The experimental values obtained were compared with the values calculated on the basis of solving the conservation neutron equation by the continuous slowing-down theory. In this theoretical calculation of the flux the Ra-Be source was divided into three resonance energy regions. The measurement of the thermal neutron diffusion length in the standard graphite block is described. The measurements were performed in the thermal neutron region of the system. The experimental results were interpreted by the diffusion theory for point thermal neutron source in the finite system. The thermal neutron diffusion length was calculated to be L= 50.9 ±3.1 cm for the following graphite characteristics: density = 1.7 g/cm 3 ; boron content = 0.1 ppm; absorption cross section = 3.7 mb

  9. The wild tapered block bootstrap

    DEFF Research Database (Denmark)

    Hounyo, Ulrich

    In this paper, a new resampling procedure, called the wild tapered block bootstrap, is introduced as a means of calculating standard errors of estimators and constructing confidence regions for parameters based on dependent heterogeneous data. The method consists in tapering each overlapping block...... of the series first, the applying the standard wild bootstrap for independent and heteroscedastic distrbuted observations to overlapping tapered blocks in an appropriate way. Its perserves the favorable bias and mean squared error properties of the tapered block bootstrap, which is the state-of-the-art block......-order asymptotic validity of the tapered block bootstrap as well as the wild tapered block bootstrap approximation to the actual distribution of the sample mean is also established when data are assumed to satisfy a near epoch dependent condition. The consistency of the bootstrap variance estimator for the sample...

  10. Cre-/IoxP-Mediated Recombination between the SIL and SCL Genes Leads to a Block in T-Cell Development at the CD4-CD8- to CD4+CD8+ Transition

    Directory of Open Access Journals (Sweden)

    Yue Cheng

    2007-04-01

    Full Text Available In the most common form of stem cell leukemia (SCL gene rearrangement, an interstitial deletion of 82 kb brings SCL under the control of regulatory elements that normally govern expression of the ubiquitously expressed SCL interrupting locus (SIL gene, which is located directly upstream of SCL. To investigate the effect of this fusion in a mouse model, a bacterial artificial chromosome (BAC clone containing both human SIL and SCL genes was isolated, and IoxP sites were inserted into intron 1 of both the SIL and SCL genes, corresponding to the sites at which recombination occurs in human T-cell acute lymphocytic leukemia patients. This BAC clone was used to generate transgenic SILIoxloxSCL mice. These transgenic mice were subsequently bred to Lck-Cre mice that express the Cre recombinase specifically in the thymus. The BAC transgene was recombined between the two IoxP sites in over 50% of the thymocytes from SILIoxloxSCL/Cre double-transgenic mice, bringing the SCL gene under the direct control of SIL regulatory elements. Aberrant SCL gene expression in the thymus was verified by reverse transcription- polymerase chain reaction. Using FACS analysis, we found that mice carrying both SILIoxloxSCL and Cre transgenes have increased CD4-/CD8- thymocytes compared with transgenenegative mice. In the spleen, these transgenic mice show a marked reduction in the number of mature CD4+ or CD8+ cells. These results demonstrate that conditional activation of SCL under control of SIL regulatory elements can impair normal T-cell development.

  11. Photovoltaic building blocks

    DEFF Research Database (Denmark)

    Hanberg, Peter Jesper; Jørgensen, Anders Michael

    2014-01-01

    efficiency of about 15% for commercial Silicon solar cells there is still much to gain. DTU Danchip provides research facilities, equipment and expertise for the building blocks that comprises fabricating the efficient solar cell. In order to get more of the sun light into the device we provide thin film......Photovoltaics (PV), better known as solar cells, are now a common day sight on many rooftops in Denmark.The installed capacity of PV systems worldwide is growing exponentially1 and is the third most importantrenewable energy source today. The cost of PV is decreasing fast with ~10%/year but to make...... it directcompetitive with fossil energy sources a further reduction is needed. By increasing the efficiency of the solar cells one gain an advantage through the whole chain of cost. So that per produced Watt of power less material is spent, installation costs are lower, less area is used etc. With an average...

  12. Celiac ganglia block

    International Nuclear Information System (INIS)

    Akinci, Devrim; Akhan, Okan

    2005-01-01

    Pain occurs frequently in patients with advanced cancers. Tumors originating from upper abdominal viscera such as pancreas, stomach, duodenum, proximal small bowel, liver and biliary tract and from compressing enlarged lymph nodes can cause severe abdominal pain, which do not respond satisfactorily to medical treatment or radiotherapy. Percutaneous celiac ganglia block (CGB) can be performed with high success and low complication rates under imaging guidance to obtain pain relief in patients with upper abdominal malignancies. A significant relationship between pain relief and degree of tumoral celiac ganglia invasion according to CT features was described in the literature. Performing the procedure in the early grades of celiac ganglia invasion on CT can increase the effectiveness of the CGB, which is contrary to World Health Organization criteria stating that CGB must be performed in patients with advanced stage cancer. CGB may also be effectively performed in patients with chronic pancreatitis for pain palliation

  13. Atomic Basic Blocks

    Science.gov (United States)

    Scheler, Fabian; Mitzlaff, Martin; Schröder-Preikschat, Wolfgang

    Die Entscheidung, einen zeit- bzw. ereignisgesteuerten Ansatz für ein Echtzeitsystem zu verwenden, ist schwierig und sehr weitreichend. Weitreichend vor allem deshalb, weil diese beiden Ansätze mit äußerst unterschiedlichen Kontrollflussabstraktionen verknüpft sind, die eine spätere Migration zum anderen Paradigma sehr schwer oder gar unmöglich machen. Wir schlagen daher die Verwendung einer Zwischendarstellung vor, die unabhängig von der jeweils verwendeten Kontrollflussabstraktion ist. Für diesen Zweck verwenden wir auf Basisblöcken basierende Atomic Basic Blocks (ABB) und bauen darauf ein Werkzeug, den Real-Time Systems Compiler (RTSC) auf, der die Migration zwischen zeit- und ereignisgesteuerten Systemen unterstützt.

  14. Some Blocks from Heliopolis

    Directory of Open Access Journals (Sweden)

    dr.Nageh Omar

    2005-01-01

    Full Text Available These group of Architectural Fragments have been discovered during Excavations at Souq el – Khamees Site at the end of Mostorod Street in el – Matarya Area by the Supreme Council of Antiquities Mission Season 2003 and none published before . The Site of Excavations is Situated about 500 metres to the west Obelisk of the King Senusert I According to the inscriptions on the block (pl.1.a,fig.1 represents the coronation name of the king Senusret III, the fifth king of the twelfth dynasty within the cartouche .Through This recent discover and his Sphinx statue we Suggest that the king Senusret III built a shrine or Temple at Heliopols which was possibly a part of the great Temple of the universal God of Heliopolis . For block dating to the king Akhenaten and many monuments are discovered in Heliopolis at the same period emphasized that the king Akhenaten built temple for the god Aten in Heliopolis and through Studies about the king Akhenaten, we suggest that the king Akhenaten take his new principles from Heliopolis . The king Ramesses II mentioned from stela which discovered at Manshyt el- Sader, in the second horizontal line that he erected oblesk and some statues at the great Temple in Heliopolis , this recent Discover about Statue of the king Ramesses II emphasized site of excavations perhaps a shrine or open court from temple of the king Ramesses II at the great Temple in Heliopolis For nbt – htpt, we could show that the goddess Hathor take a forward position in Heliopolis and become the Lady of Hetepet in Heliopolis since Eighteenth dynasty at least

  15. Small homologous blocks in phytophthora genomes do not point to an ancient whole-genome duplication.

    Science.gov (United States)

    van Hooff, Jolien J E; Snel, Berend; Seidl, Michael F

    2014-05-01

    Genomes of the plant-pathogenic genus Phytophthora are characterized by small duplicated blocks consisting of two consecutive genes (2HOM blocks) and by an elevated abundance of similarly aged gene duplicates. Both properties, in particular the presence of 2HOM blocks, have been attributed to a whole-genome duplication (WGD) at the last common ancestor of Phytophthora. However, large intraspecies synteny-compelling evidence for a WGD-has not been detected. Here, we revisited the WGD hypothesis by deducing the age of 2HOM blocks. Two independent timing methods reveal that the majority of 2HOM blocks arose after divergence of the Phytophthora lineages. In addition, a large proportion of the 2HOM block copies colocalize on the same scaffold. Therefore, the presence of 2HOM blocks does not support a WGD at the last common ancestor of Phytophthora. Thus, genome evolution of Phytophthora is likely driven by alternative mechanisms, such as bursts of transposon activity.

  16. Common blocks for ASQS(12

    Directory of Open Access Journals (Sweden)

    Lorenzo Milazzo

    1997-05-01

    Full Text Available An ASQS(v is a particular Steiner system featuring a set of v vertices and two separate families of blocks, B and G, whose elements have a respective cardinality of 4 and 6. It has the property that any three vertices of X belong either to a B-block or to a G-block. The parameter cb is the number of common blocks in two separate ASQSs, both defined on the same set of vertices X . In this paper it is shown that cb ≤ 29 for any pair of ASQSs(12.

  17. Adductor Canal Block versus Femoral Nerve Block and Quadriceps Strength

    DEFF Research Database (Denmark)

    Jæger, Pia Therese; Nielsen, Zbigniew Jerzy Koscielniak; Henningsen, Lene Marianne

    2013-01-01

    : The authors hypothesized that the adductor canal block (ACB), a predominant sensory blockade, reduces quadriceps strength compared with placebo (primary endpoint, area under the curve, 0.5-6 h), but less than the femoral nerve block (FNB; secondary endpoint). Other secondary endpoints were...

  18. The block transfer system

    International Nuclear Information System (INIS)

    Bradish, G.J. III; Reid, A.E.

    1986-01-01

    The central instrumentation control and data acquisition (CICADA) computer system is comprised of a functionally distributed hierarchical network of thirteen (13) 32-bit mini-computers that are the heart of the control, monitoring, data collection and data analysis for the tokamak fusion test reactor (TFTR). The CICADA system was designed with the goal of providing complete control, monitoring, and data acquisition for TFTR, which includes the acquisition and storage of 20M points of data within a five-minute shot cycle. It was realized early in the system design that in order to meet this goal an ancillary system would have to be provided to supplement the subsystem CAMAC systems that, due to the relatively slow throughput of the serial highways and the overhead of relaying data to the central facilities within a star network, would not provide the necessary throughput. The authors discuss how the block transfer system provided a means of moving data directly from the CAMAC crate to the application running on the central facility computers

  19. OPAL Various Lead Glass Blocks

    CERN Multimedia

    These lead glass blocks were part of a CERN detector called OPAL (one of the four experiments at the LEP particle detector). OPAL uses some 12 000 blocks of glass like this to measure particle energies in the electromagnetic calorimeter. This detector measured the energy deposited when electrons and photons were slowed down and stopped.

  20. Writing Blocks and Tacit Knowledge.

    Science.gov (United States)

    Boice, Robert

    1993-01-01

    A review of the literature on writing block looks at two kinds: inability to write in a timely, fluent fashion, and reluctance by academicians to assist others in writing. Obstacles to fluent writing are outlined, four historical trends in treating blocks are discussed, and implications are examined. (MSE)

  1. Block storage subsystem performance analysis

    CERN Multimedia

    CERN. Geneva

    2016-01-01

    You feel that your service is slow because of the storage subsystem? But there are too many abstraction layers between your software and the raw block device for you to debug all this pile... Let's dive on the platters and check out how the block storage sees your I/Os! We can even figure out what those patterns are meaning.

  2. Region 9 Census Block 2010

    Science.gov (United States)

    Geography:The TIGER Line Files are feature classes and related database files (.) that are an extract of selected geographic and cartographic information from the U.S. Census Bureau's Master Address File / Topologically Integrated Geographic Encoding and Referencing (MAF/TIGER) Database (MTDB). The MTDB represents a seamless national file with no overlaps or gaps between parts, however, each TIGER Line File is designed to stand alone as an independent data set, or they can be combined to cover the entire nation. Census Blocks are statistical areas bounded on all sides by visible features, such as streets, roads, streams, and railroad tracks, and/or by non visible boundaries such as city, town, township, and county limits, and short line-of-sight extensions of streets and roads. Census blocks are relatively small in area; for example, a block in a city bounded by streets. However, census blocks in remote areas are often large and irregular and may even be many square miles in area. A common misunderstanding is that data users think census blocks are used geographically to build all other census geographic areas, rather all other census geographic areas are updated and then used as the primary constraints, along with roads and water features, to delineate the tabulation blocks. As a result, all 2010 Census blocks nest within every other 2010 Census geographic area, so that Census Bureau statistical data can be tabulated at the block level and aggregated up t

  3. A pH and Redox Dual Responsive 4-Arm Poly(ethylene glycol-block-poly(disulfide histamine Copolymer for Non-Viral Gene Transfection in Vitro and in Vivo

    Directory of Open Access Journals (Sweden)

    Kangkang An

    2014-05-01

    Full Text Available A novel 4-arm poly(ethylene glycol-b-poly(disulfide histamine copolymer was synthesized by Michael addition reaction of poly(ethylene glycol (PEG vinyl sulfone and amine-capped poly(disulfide histamine oligomer, being denoted as 4-arm PEG-SSPHIS. This copolymer was able to condense DNA into nanoscale polyplexes (<200 nm in average diameter with almost neutral surface charge (+(5–10 mV. Besides, these polyplexes were colloidal stable within 4 h in HEPES buffer saline at pH 7.4 (physiological environment, but rapidly dissociated to liberate DNA in the presence of 10 mM glutathione (intracellular reducing environment. The polyplexes also revealed pH-responsive surface charges which markedly increased with reducing pH values from 7.4–6.3 (tumor microenvironment. In vitro transfection experiments showed that polyplexes of 4-arm PEG-SSPHIS were capable of exerting enhanced transfection efficacy in MCF-7 and HepG2 cancer cells under acidic conditions (pH 6.3–7.0. Moreover, intravenous administration of the polyplexes to nude mice bearing HepG2-tumor yielded high transgene expression largely in tumor rather other normal organs. Importantly, this copolymer and its polyplexes had low cytotoxicity against the cells in vitro and caused no death of the mice. The results of this study indicate that 4-arm PEG-SSPHIS has high potential as a dual responsive gene delivery vector for cancer gene therapy.

  4. Conformal Nets II: Conformal Blocks

    Science.gov (United States)

    Bartels, Arthur; Douglas, Christopher L.; Henriques, André

    2017-08-01

    Conformal nets provide a mathematical formalism for conformal field theory. Associated to a conformal net with finite index, we give a construction of the `bundle of conformal blocks', a representation of the mapping class groupoid of closed topological surfaces into the category of finite-dimensional projective Hilbert spaces. We also construct infinite-dimensional spaces of conformal blocks for topological surfaces with smooth boundary. We prove that the conformal blocks satisfy a factorization formula for gluing surfaces along circles, and an analogous formula for gluing surfaces along intervals. We use this interval factorization property to give a new proof of the modularity of the category of representations of a conformal net.

  5. Harmony of spinning conformal blocks

    Energy Technology Data Exchange (ETDEWEB)

    Schomerus, Volker [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany). Theory Group; Sobko, Evgeny [Stockholm Univ. (Sweden); Nordita, Stockholm (Sweden); Isachenkov, Mikhail [Weizmann Institute of Science, Rehovoth (Israel). Dept. of Particle Physics and Astrophysics

    2016-12-07

    Conformal blocks for correlation functions of tensor operators play an increasingly important role for the conformal bootstrap programme. We develop a universal approach to such spinning blocks through the harmonic analysis of certain bundles over a coset of the conformal group. The resulting Casimir equations are given by a matrix version of the Calogero-Sutherland Hamiltonian that describes the scattering of interacting spinning particles in a 1-dimensional external potential. The approach is illustrated in several examples including fermionic seed blocks in 3D CFT where they take a very simple form.

  6. Harmony of spinning conformal blocks

    Energy Technology Data Exchange (ETDEWEB)

    Schomerus, Volker [DESY Hamburg, Theory Group,Notkestraße 85, 22607 Hamburg (Germany); Sobko, Evgeny [Nordita and Stockholm University,Roslagstullsbacken 23, SE-106 91 Stockholm (Sweden); Isachenkov, Mikhail [Department of Particle Physics and Astrophysics, Weizmann Institute of Science,Rehovot 7610001 (Israel)

    2017-03-15

    Conformal blocks for correlation functions of tensor operators play an increasingly important role for the conformal bootstrap programme. We develop a universal approach to such spinning blocks through the harmonic analysis of certain bundles over a coset of the conformal group. The resulting Casimir equations are given by a matrix version of the Calogero-Sutherland Hamiltonian that describes the scattering of interacting spinning particles in a 1-dimensional external potential. The approach is illustrated in several examples including fermionic seed blocks in 3D CFT where they take a very simple form.

  7. Genes and Gene Therapy

    Science.gov (United States)

    ... correctly, a child can have a genetic disorder. Gene therapy is an experimental technique that uses genes to ... or prevent disease. The most common form of gene therapy involves inserting a normal gene to replace an ...

  8. Rolling block mazes are PSPACE-complete

    NARCIS (Netherlands)

    Buchin, K.; Buchin, M.

    2012-01-01

    In a rolling block maze, one or more blocks lie on a rectangular board with square cells. In most mazes, the blocks have size k × m × n where k, m, n are integers that determine the size of the block in terms of units of the size of the board cells. The task of a rolling block maze is to roll a

  9. Left bundle-branch block

    DEFF Research Database (Denmark)

    Risum, Niels; Strauss, David; Sogaard, Peter

    2013-01-01

    The relationship between myocardial electrical activation by electrocardiogram (ECG) and mechanical contraction by echocardiography in left bundle-branch block (LBBB) has never been clearly demonstrated. New strict criteria for LBBB based on a fundamental understanding of physiology have recently...

  10. Recursion Relations for Conformal Blocks

    CERN Document Server

    Penedones, João; Yamazaki, Masahito

    2016-09-12

    In the context of conformal field theories in general space-time dimension, we find all the possible singularities of the conformal blocks as functions of the scaling dimension $\\Delta$ of the exchanged operator. In particular, we argue, using representation theory of parabolic Verma modules, that in odd spacetime dimension the singularities are only simple poles. We discuss how to use this information to write recursion relations that determine the conformal blocks. We first recover the recursion relation introduced in 1307.6856 for conformal blocks of external scalar operators. We then generalize this recursion relation for the conformal blocks associated to the four point function of three scalar and one vector operator. Finally we specialize to the case in which the vector operator is a conserved current.

  11. Defying gravity using Jenga™ blocks

    Science.gov (United States)

    Tan, Yin-Soo; Yap, Kueh-Chin

    2007-11-01

    This paper describes how Jenga™ blocks can be used to demonstrate the physics of an overhanging tower that appears to defy gravity. We also propose ideas for how this demonstration can be adapted for the A-level physics curriculum.

  12. Microbial production of polyhydroxyalkanoate block copolymer by recombinant Pseudomonas putida.

    Science.gov (United States)

    Li, Shi Yan; Dong, Cui Ling; Wang, Shen Yu; Ye, Hai Mu; Chen, Guo-Qiang

    2011-04-01

    Polyhydroxyalkanoate (PHA) synthesis genes phaPCJ(Ac) cloned from Aeromonas caviae were transformed into Pseudomonas putida KTOY06ΔC, a mutant of P. putida KT2442, resulting in the ability of the recombinant P. putida KTOY06ΔC (phaPCJ(A.c)) to produce a short-chain-length and medium-chain-length PHA block copolymer consisting of poly-3-hydroxybutyrate (PHB) as one block and random copolymer of 3-hydroxyvalerate (3HV) and 3-hydroxyheptanoate (3HHp) as another block. The novel block polymer was studied by differential scanning calorimetry (DSC), nuclear magnetic resonance, and rheology measurements. DSC studies showed the polymer to possess two glass transition temperatures (T(g)), one melting temperature (T(m)) and one cool crystallization temperature (T(c)). Rheology studies clearly indicated a polymer chain re-arrangement in the copolymer; these studies confirmed the polymer to be a block copolymer, with over 70 mol% homopolymer (PHB) of 3-hydroxybutyrate (3HB) as one block and around 30 mol% random copolymers of 3HV and 3HHp as the second block. The block copolymer was shown to have the highest tensile strength and Young's modulus compared with a random copolymer with similar ratio and a blend of homopolymers PHB and PHVHHp with similar ratio. Compared with other commercially available PHA including PHB, PHBV, PHBHHx, and P3HB4HB, the short-chain- and medium-chain-length block copolymer PHB-b-PHVHHp showed differences in terms of mechanical properties and should draw more attentions from the PHA research community. © Springer-Verlag 2010

  13. Risking Aggression: Reply to Block

    Directory of Open Access Journals (Sweden)

    Kris Borer

    2010-05-01

    Full Text Available In his paper, “Is There an ‘Anomalous’ Section of the Laffer Curve?”, Walter Block describes some situations in which it appears that a libertarian should violate the non-aggression principle. To rectify this, Block proposes a different perspective on libertarianism which he calls punishment theory. This paper argues that no new theory is needed, as the non-aggression principle can be used to resolve theapparent conundrums.

  14. Risking Aggression: Reply to Block

    OpenAIRE

    Kris Borer

    2010-01-01

    In his paper, “Is There an ‘Anomalous’ Section of the Laffer Curve?”, Walter Block describes some situations in which it appears that a libertarian should violate the non-aggression principle. To rectify this, Block proposes a different perspective on libertarianism which he calls punishment theory. This paper argues that no new theory is needed, as the non-aggression principle can be used to resolve theapparent conundrums.

  15. A Novel Tetrathiafulvalene Building Block

    DEFF Research Database (Denmark)

    Jeppesen, Jan Oskar; Takimiya, Kazuo; Thorup, Niels

    1999-01-01

    Efficient synthesis of a novel tetrathiafulvalene building block. 2,3-bis(2-cyanoethylthio)-6,7-bis(thiocyanato-methyl)tetrathiafulv alene (7) useful for stepwise and asymmetrical bis-function-alization is reported.......Efficient synthesis of a novel tetrathiafulvalene building block. 2,3-bis(2-cyanoethylthio)-6,7-bis(thiocyanato-methyl)tetrathiafulv alene (7) useful for stepwise and asymmetrical bis-function-alization is reported....

  16. TMPyP4 porphyrin distorts RNA G-quadruplex structures of the disease-associated r(GGGGCC)n repeat of the C9orf72 gene and blocks interaction of RNA-binding proteins.

    Science.gov (United States)

    Zamiri, Bita; Reddy, Kaalak; Macgregor, Robert B; Pearson, Christopher E

    2014-02-21

    Certain DNA and RNA sequences can form G-quadruplexes, which can affect genetic instability, promoter activity, RNA splicing, RNA stability, and neurite mRNA localization. Amyotrophic lateral sclerosis and frontotemporal dementia can be caused by expansion of a (GGGGCC)n repeat in the C9orf72 gene. Mutant r(GGGGCC)n- and r(GGCCCC)n-containing transcripts aggregate in nuclear foci, possibly sequestering repeat-binding proteins such as ASF/SF2 and hnRNPA1, suggesting a toxic RNA pathogenesis, as occurs in myotonic dystrophy. Furthermore, the C9orf72 repeat RNA was recently demonstrated to undergo the noncanonical repeat-associated non-AUG translation (RAN translation) into pathologic dipeptide repeats in patient brains, a process that is thought to depend upon RNA structure. We previously demonstrated that the r(GGGGCC)n RNA forms repeat tract length-dependent G-quadruplex structures that bind the ASF/SF2 protein. Here we show that the cationic porphyrin (5,10,15,20-tetra(N-methyl-4-pyridyl) porphyrin (TMPyP4)), which can bind some G-quadruplex-forming sequences, can bind and distort the G-quadruplex formed by r(GGGGCC)8, and this ablates the interaction of either hnRNPA1 or ASF/SF2 with the repeat. These findings provide proof of concept that nucleic acid binding small molecules, such as TMPyP4, can distort the secondary structure of the C9orf72 repeat, which may beneficially disrupt protein interactions, which may ablate either protein sequestration and/or RAN translation into potentially toxic dipeptides. Disruption of secondary structure formation of the C9orf72 RNA repeats may be a viable therapeutic avenue, as well as a means to test the role of RNA structure upon RAN translation.

  17. Comparative study between ultrasound guided TAP block and paravertebral block in upper abdominal surgeries

    Directory of Open Access Journals (Sweden)

    Ruqaya M Elsayed Goda

    2017-01-01

    Conclusion: We concluded that ultrasound guided transverses abdominis plane block and thoracic paravertebral block were safe and effective anesthetic technique for upper abdominal surgery with longer and potent postoperative analgesia in thoracic paravertebral block than transverses abdominis block.

  18. Various semiclassical limits of torus conformal blocks

    Energy Technology Data Exchange (ETDEWEB)

    Alkalaev, Konstantin [I.E. Tamm Department of Theoretical Physics, P.N. Lebedev Physical Institute,Leninsky ave. 53, Moscow, 119991 (Russian Federation); Department of General and Applied Physics, Moscow Institute of Physics and Technology,Institutskiy per. 7, Dolgoprudnyi, Moscow region, 141700 (Russian Federation); Geiko, Roman [Mathematics Department, National Research University Higher School of Economics,Usacheva str. 6, Moscow, 119048 (Russian Federation); Rappoport, Vladimir [I.E. Tamm Department of Theoretical Physics, P.N. Lebedev Physical Institute,Leninsky ave. 53, Moscow, 119991 (Russian Federation); Department of Quantum Physics, Institute for Information Transmission Problems,Bolshoy Karetny per. 19, Moscow, 127994 (Russian Federation)

    2017-04-12

    We study four types of one-point torus blocks arising in the large central charge regime. There are the global block, the light block, the heavy-light block, and the linearized classical block, according to different regimes of conformal dimensions. It is shown that the blocks are not independent being connected to each other by various links. We find that the global, light, and heavy-light blocks correspond to three different contractions of the Virasoro algebra. Also, we formulate the c-recursive representation of the one-point torus blocks which is relevant in the semiclassical approximation.

  19. Calcitonin gene-related peptide promotes the wound healing of human bronchial epithelial cells via PKC and MAPK pathways.

    Science.gov (United States)

    Zhou, Yong; Zhang, Min; Sun, Guo-Ying; Liu, Yong-Ping; Ran, Wen-Zhuo; Peng, Li; Guan, Cha-Xiang

    2013-06-10

    Calcitonin gene-related peptide (CGRP) is a 37-amino acid neuropeptide derived from the calcitonin gene. CGRP is widely distributed in the central and peripheral neuronal systems. In the lung, CGRP could modulate dendritic cell function, stimulate proliferation of alveolar epithelial cells and mediate lung injury in mice. In this study, we investigated the effect of CGRP on the wound healing of human bronchial epithelial cells (HBECs) in vitro. The results showed that CGRP accelerated the recovery of wound area of monolayer HBECs in a dose-dependent manner. CGRP inhibited the lipopolysaccharide-induced apoptosis in HBECs. The percentage of S phase and G2/M phase was increased in HBECs after CGRP treatment. CGRP upregulated the expression of Ki67 in a dose-dependent manner. Some pathway inhibitors were used to investigate the signal pathway in which CGRP was involved. We found out that PKC pathway inhibitor (H-7) and MAPK pathway inhibitor (PD98059) could partially attenuate the effect of CGRP, which indicated that CGRP might promote the wound healing of HBECs via PKC and/or MAPK dependent pathway by accelerating migration and proliferation, and inhibiting apoptosis. Copyright © 2013 Elsevier B.V. All rights reserved.

  20. Mitogen activated protein kinases blockade improves lipopolysaccharide-induced ileal motor disturbances El bloqueo de las proteínas cinasas activadas por mitógenos mejora las alteraciones motoras inducidas por el lipopolisacárido en íleon

    Directory of Open Access Journals (Sweden)

    Sergio Gonzalo

    2012-06-01

    Full Text Available Background: several diseases such as sepsis can affect the ileum. Lipopolysaccharide (LPS, an endotoxin present in the cell wall of gram negative bacteria, is a causative agent of sepsis. Objectives: the aims of this study were: a to investigate the role of mitogen activated protein kinases (MAPKs in the effect of LPS on the acetylcholine-induced contractions of rabbit ileum; and b to study the localization of MAPKs in the ileum. Material and methods: ileal contractility was studied in an organ bath and MAPKs were localized by immunohistochemistry. Results: acetylcholine-induced contractions decreased with LPS. SB203580, SP600125 and U0126 blocked the effect of LPS on the acetylcholine-induced contractions. Phosphorylated p38 and ERK were detected in neurons of myenteric plexus and phosphorylated p38 and JNK in smooth muscle cells of ileum. Conclusion: we can suggest that p38, JNK, and ERK MAPKs are involved in the mechanism of action of LPS in the ileum.Introducción: varias enfermedades como la sepsis pueden afectar al íleon. El lipopolisacárido (LPS, una endotoxina presente en la pared celular de las bacterias gram-negativas, es un agente causal de la sepsis. Objetivos: los objetivos del presente estudio fueron: a investigar el papel de las proteína cinasas activadas por mitógenos (MAPKs en los efectos del LPS en las contracciones inducidas por acetilcolina en el íleon de conejo; y b estudiar la localización de las MAPKs en el íleon. Material y métodos: la contractilidad ileal se estudió en un baño de órganos y las MAPKs se localizaron mediante inmunohistoquímica. Resultados: el LPS disminuyó las contracciones inducidas por acetilcolina. El SB203580, el SP600125 y el U0126 bloquearon los efectos del LPS sobre las contracciones inducidas por acetilcolina. La p38 y la ERK fosforiladas se detectaron en las neuronas del plexo mientérico y la p38 y la JNK fosforiladas en las células del músculo liso del íleon. Conclusi

  1. Climatological features of blocking anticyclones

    International Nuclear Information System (INIS)

    Lupo, A.R.; Smith, P.J.; Oglesby, R.J.

    1994-01-01

    Several climatological studies have been previously performed using large observational data sets (i.e., 10 years or longer) in order to determine the predominant characteristics of blocking anticyclones, including favored development regions, duration, preferred seasonal occurrence, and frequency of occurrence. These studies have shown that blocking anticyclones occur most frequently from October to April over the eastern Atlantic and Pacific oceans downstream from both the North American and Asian continental regions and the storm track regions to the east of these continents. Some studies have also revealed the presence of a third region block formation in western Russia near 40 degrees E which is associated with another storm track region over the Mediterranean and western Asia

  2. Sulforaphane Inhibits Lipopolysaccharide-Induced Inflammation, Cytotoxicity, Oxidative Stress, and miR-155 Expression and Switches to Mox Phenotype through Activating Extracellular Signal-Regulated Kinase 1/2-Nuclear Factor Erythroid 2-Related Factor 2/Antioxidant Response Element Pathway in Murine Microglial Cells.

    Science.gov (United States)

    Eren, Erden; Tufekci, Kemal Ugur; Isci, Kamer Burak; Tastan, Bora; Genc, Kursad; Genc, Sermin

    2018-01-01

    Sulforaphane (SFN) is a natural product with cytoprotective, anti-inflammatory, and antioxidant effects. In this study, we evaluated the mechanisms of its effects on lipopolysaccharide (LPS)-induced cell death, inflammation, oxidative stress, and polarization in murine microglia. We found that SFN protects N9 microglial cells upon LPS-induced cell death and suppresses LPS-induced levels of secreted pro-inflammatory cytokines, tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6. SFN is also a potent inducer of redox sensitive transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2), which is responsible for the transcription of antioxidant, cytoprotective, and anti-inflammatory genes. SFN induced translocation of Nrf2 to the nucleus via extracellular signal-regulated kinase 1/2 (ERK1/2) pathway activation. siRNA-mediated knockdown study showed that the effects of SFN on LPS-induced reactive oxygen species, reactive nitrogen species, and pro-inflammatory cytokine production and cell death are partly Nrf2 dependent. Mox phenotype is a novel microglial phenotype that has roles in oxidative stress responses. Our results suggested that SFN induced the Mox phenotype in murine microglia through Nrf2 pathway. SFN also alleviated LPS-induced expression of inflammatory microRNA, miR-155. Finally, SFN inhibits microglia-mediated neurotoxicity as demonstrated by conditioned medium and co-culture experiments. In conclusion, SFN exerts protective effects on microglia and modulates the microglial activation state.

  3. Aconitum pseudo-laeve var. erectum Inhibits Receptor Activator of Nuclear Factor Kappa-B Ligand-Induced Osteoclastogenesis via the c-Fos/nuclear Factor of Activated T-Cells, Cytoplasmic 1 Signaling Pathway and Prevents Lipopolysaccharide-Induced Bone Loss in Mice

    Directory of Open Access Journals (Sweden)

    Jong Min Baek

    2014-08-01

    Full Text Available Aconitum pseudo-laeve var. erectum (APE has been widely shown in herbal medicine to have a therapeutic effect on inflammatory conditions. However, there has been no evidence on whether the extract of APE is involved in the biological bone metabolism process, particularly osteoclast-mediated bone resorption. In this study, we confirmed that the administration of APE could restore normal skeletal conditions in a murine model of lipopolysaccharide (LPS-induced bone loss via a decrease in the receptor activator of nuclear factor kappa-B ligand (RANKL/osteoprotegerin (OPG ratio and osteoclast number. We then investigated the effect of APE on the RANKL-induced formation and function of osteoclasts to elucidate its underlying molecular mechanisms. APE suppressed the formation of tartrate-resistant acid phosphatase (TRAP-positive cells, as well as the bone-resorbing activity of mature osteoclasts. Furthermore, APE attenuated nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1 and c-Fos without affecting any early signal pathway of osteoclastogenesis. Subsequently, APE significantly downregulated the expression of various genes exclusively expressed in osteoclasts. These results demonstrate that APE restores LPS-induced bone loss through a decrease of the serum RANKL/OPG ratio, and inhibits osteoclast differentiation and function, suggesting the promise of APE as a potential cure for various osteoclast-associated bone diseases.

  4. Block ground interaction of rockfalls

    Science.gov (United States)

    Volkwein, Axel; Gerber, Werner; Kummer, Peter

    2016-04-01

    During a rockfall the interaction of the falling block with the ground is one of the most important factors that define the evolution of a rockfall trajectory. It steers the rebound, the rotational movement, possibly brake effects, friction losses and damping effects. Therefore, if most reliable rockfall /trajectory simulation software is sought a good understanding of the block ground interaction is necessary. Today's rockfall codes enable the simulation of a fully 3D modelled block within a full 3D surface . However, the details during the contact, i.e. the contact duration, the penetration depth or the dimension of the marks in the ground are usually not part of the simulation. Recent field tests with rocks between 20 and 80 kg have been conducted on a grassy slope in 2014 [1]. A special rockfall sensor [2] within the blocks measured the rotational velocity and the acting accelerations during the tests. External video records and a so-called LocalPositioningSystem deliver information on the travel velocity. With these data not only the flight phases of the trajectories but also the contacts with the ground can be analysed. During the single jumps of a block the flight time, jump length, the velocity, and the rotation are known. During the single impacts their duration and the acting accelerations are visible. Further, the changes of rotational and translational velocity influence the next jump of the block. The change of the rotational velocity over the whole trajectory nicely visualizes the different phases of a rockfall regarding general acceleration and deceleration in respect to the inclination and the topography of the field. References: [1] Volkwein A, Krummenacher B, Gerber W, Lardon J, Gees F, Brügger L, Ott T (2015) Repeated controlled rockfall trajectory testing. [Abstract] Geophys. Res. Abstr. 17: EGU2015-9779. [2] Volkwein A, Klette J (2014) Semi-Automatic Determination of Rockfall Trajectories. Sensors 14: 18187-18210.

  5. Cryptanalysis of Selected Block Ciphers

    DEFF Research Database (Denmark)

    Alkhzaimi, Hoda A.

    , pseudorandom number generators, and authenticated encryption designs. For this reason a multitude of initiatives over the years has been established to provide a secure and sound designs for block ciphers as in the calls for Data Encryption Standard (DES) and Advanced Encryption Standard (AES), lightweight...... ciphers initiatives, and the Competition for Authenticated Encryption: Security, Applicability, and Robustness (CAESAR). In this thesis, we first present cryptanalytic results on different ciphers. We propose attack named the Invariant Subspace Attack. It is utilized to break the full block cipher...

  6. Congenital and childhood atrioventricular blocks: pathophysiology and contemporary management.

    Science.gov (United States)

    Baruteau, Alban-Elouen; Pass, Robert H; Thambo, Jean-Benoit; Behaghel, Albin; Le Pennec, Solène; Perdreau, Elodie; Combes, Nicolas; Liberman, Leonardo; McLeod, Christopher J

    2016-09-01

    Atrioventricular block is classified as congenital if diagnosed in utero, at birth, or within the first month of life. The pathophysiological process is believed to be due to immune-mediated injury of the conduction system, which occurs as a result of transplacental passage of maternal anti-SSA/Ro-SSB/La antibodies. Childhood atrioventricular block is therefore diagnosed between the first month and the 18th year of life. Genetic variants in multiple genes have been described to date in the pathogenesis of inherited progressive cardiac conduction disorders. Indications and techniques of cardiac pacing have also evolved to allow safe permanent cardiac pacing in almost all patients, including those with structural heart abnormalities. Early diagnosis and appropriate management are critical in many cases in order to prevent sudden death, and this review critically assesses our current understanding of the pathogenetic mechanisms, clinical course, and optimal management of congenital and childhood AV block. • Prevalence of congenital heart block of 1 per 15,000 to 20,000 live births. AV block is defined as congenital if diagnosed in utero, at birth, or within the first month of life, whereas childhood AV block is diagnosed between the first month and the 18th year of life. As a result of several different etiologies, congenital and childhood atrioventricular block may occur in an entirely structurally normal heart or in association with concomitant congenital heart disease. Cardiac pacing is indicated in symptomatic patients and has several prophylactic indications in asymptomatic patients to prevent sudden death. • Autoimmune, congenital AV block is associated with a high neonatal mortality rate and development of dilated cardiomyopathy in 5 to 30 % cases. What is New: • Several genes including SCN5A have been implicated in autosomal dominant forms of familial progressive cardiac conduction disorders. • Leadless pacemaker technology and gene therapy for

  7. Asymmetric PS-block-(PS-co-PB)-block-PS block copolymers: morphology formation and deformation behaviour

    International Nuclear Information System (INIS)

    Adhikari, Rameshwar; Huy, Trinh An; Buschnakowski, Matthias; Michler, Goerg H; Knoll, Konrad

    2004-01-01

    Morphology formation and deformation behaviour of asymmetric styrene/butadiene triblock copolymers (total polystyrene (PS) content ∼70%) consisting of PS outer blocks held apart by a styrene-co-butadiene random copolymer block (PS-co-PB) each were investigated. The techniques used were differential scanning calorimetry, transmission electron microscopy, uniaxial tensile testing and Fourier-transform infrared spectroscopy. A significant shift of the phase behaviour relative to that of a neat symmetric triblock copolymer was observed, which can be attributed to the asymmetric architecture and the presence of PS-co-PB as a soft block. The mechanical properties and the microdeformation phenomena were mainly controlled by the nature of their solid-state morphology. Independent of morphology type, the soft phase was found to deform to a significantly higher degree of orientation when compared with the hard phase

  8. Main-chain supramolecular block copolymers.

    Science.gov (United States)

    Yang, Si Kyung; Ambade, Ashootosh V; Weck, Marcus

    2011-01-01

    Block copolymers are key building blocks for a variety of applications ranging from electronic devices to drug delivery. The material properties of block copolymers can be tuned and potentially improved by introducing noncovalent interactions in place of covalent linkages between polymeric blocks resulting in the formation of supramolecular block copolymers. Such materials combine the microphase separation behavior inherent to block copolymers with the responsiveness of supramolecular materials thereby affording dynamic and reversible materials. This tutorial review covers recent advances in main-chain supramolecular block copolymers and describes the design principles, synthetic approaches, advantages, and potential applications.

  9. Smart ampholytic ABC block copolypeptide

    Czech Academy of Sciences Publication Activity Database

    Schlaad, H.; Sun, J.; Černoch, Peter; Ruokolainen, J.

    2017-01-01

    Roč. 254, 20 August (2017), s. 79 ISSN 0065-7727. [ACS National Meeting & Exposition /254./. 20.08.2017-24.08.2017, Washington] Institutional support: RVO:61389013 Keywords : block copolypeptide * smart ampholytic Subject RIV: CD - Macromolecular Chemistry OBOR OECD: Polymer science

  10. First Degree Pacemaker Exit Block

    Directory of Open Access Journals (Sweden)

    Johnson Francis

    2016-10-01

    Full Text Available Usually atrial and ventricular depolarizations follow soon after the pacemaker stimulus (spike on the ECG. But there can be an exit block due to fibrosis at the electrode - tissue interface at the lead tip. This can increase the delay between the spike and atrial or ventricular depolarization.

  11. Building Blocks for Personal Brands

    Science.gov (United States)

    Thomas, Lisa Carlucci

    2011-01-01

    In this article, the author discusses the four essential building blocks for personal brands: (1) name; (2) message; (3) channels; and (4) bridges. However, outstanding building materials can only take a person so far. The author emphasizes that vision, determination, faith, a sense of humor, and humility are also required.

  12. Thermo-responsive block copolymers

    NARCIS (Netherlands)

    Mocan Cetintas, Merve

    2017-01-01

    Block copolymers (BCPs) are remarkable materials because of their self-assembly behavior into nano-sized regular structures and high tunable properties. BCPs are in used various applications such as surfactants, nanolithography, biomedicine and nanoporous membranes. In these thesis, we aimed to

  13. Cervical plexus block for thyroidectomy

    African Journals Online (AJOL)

    Adele

    RESEARCH. Southern African Journal of Anaesthesia & Analgesia - November 2003 ... Cervical plexus block has also been found useful for thy- .... lar, transverse cervical and supraclavicular nerves. ... administration of midazolam and pentazocine as required. ... find out if there were postoperative complications specific to.

  14. Blocking sets in Desarguesian planes

    NARCIS (Netherlands)

    Blokhuis, A.; Miklós, D.; Sós, V.T.; Szönyi, T.

    1996-01-01

    We survey recent results concerning the size of blocking sets in desarguesian projective and affine planes, and implications of these results and the technique to prove them, to related problemis, such as the size of maximal partial spreads, small complete arcs, small strong representative systems

  15. Cutaneous Sensory Block Area, Muscle-Relaxing Effect, and Block Duration of the Transversus Abdominis Plane Block

    DEFF Research Database (Denmark)

    Støving, Kion; Rothe, Christian; Rosenstock, Charlotte V

    2015-01-01

    BACKGROUND AND OBJECTIVES: The transversus abdominis plane (TAP) block is a widely used nerve block. However, basic block characteristics are poorly described. The purpose of this study was to assess the cutaneous sensory block area, muscle-relaxing effect, and block duration. METHODS: Sixteen...... healthy volunteers were randomized to receive an ultrasound-guided unilateral TAP block with 20 mL 7.5 mg/mL ropivacaine and placebo on the contralateral side. Measurements were performed at baseline and 90 minutes after performing the block. Cutaneous sensory block area was mapped and separated...... into a medial and lateral part by a vertical line through the anterior superior iliac spine. We measured muscle thickness of the 3 lateral abdominal muscle layers with ultrasound in the relaxed state and during maximal voluntary muscle contraction. The volunteers reported the duration of the sensory block...

  16. MicroRNA mimicry blocks pulmonary fibrosis

    Science.gov (United States)

    Montgomery, Rusty L; Yu, Guoying; Latimer, Paul A; Stack, Christianna; Robinson, Kathryn; Dalby, Christina M; Kaminski, Naftali; van Rooij, Eva

    2014-01-01

    Over the last decade, great enthusiasm has evolved for microRNA (miRNA) therapeutics. Part of the excitement stems from the fact that a miRNA often regulates numerous related mRNAs. As such, modulation of a single miRNA allows for parallel regulation of multiple genes involved in a particular disease. While many studies have shown therapeutic efficacy using miRNA inhibitors, efforts to restore or increase the function of a miRNA have been lagging behind. The miR-29 family has gained a lot of attention for its clear function in tissue fibrosis. This fibroblast-enriched miRNA family is downregulated in fibrotic diseases which induces a coordinate increase of many extracellular matrix genes. Here, we show that intravenous injection of synthetic RNA duplexes can increase miR-29 levels in vivo for several days. Moreover, therapeutic delivery of these miR-29 mimics during bleomycin-induced pulmonary fibrosis restores endogenous miR-29 function whereby decreasing collagen expression and blocking and reversing pulmonary fibrosis. Our data support the feasibility of using miRNA mimics to therapeutically increase miRNAs and indicate miR-29 to be a potent therapeutic miRNA for treating pulmonary fibrosis. PMID:25239947

  17. DNMT1-interacting RNAs block gene-specific DNA methylation

    Czech Academy of Sciences Publication Activity Database

    Di Ruscio, A.; Ebralidze, A.; Benoukraf, T.; Amabile, G.; Goff, L.A.; Terragni, J.; Figueroa, M.E.; Pontes, L.L.D.; Alberich-Jorda, Meritxell; Zhang, P.; Wu, M.C.; D´Alo, F.; Melnick, A.; Leone, G.; Ebralidze, K.K.; Pradhan, S.; Rinn, J.L.; Tenen, D.G.

    2013-01-01

    Roč. 503, č. 7476 (2013), s. 371-376 ISSN 0028-0836 R&D Projects: GA MŠk LK21307 Institutional support: RVO:68378050 Keywords : DNA methylation * non-coding RNA * DNMT1 Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 42.351, year: 2013

  18. On the Eigenvalues and Eigenvectors of Block Triangular Preconditioned Block Matrices

    KAUST Repository

    Pestana, Jennifer

    2014-01-01

    Block lower triangular matrices and block upper triangular matrices are popular preconditioners for 2×2 block matrices. In this note we show that a block lower triangular preconditioner gives the same spectrum as a block upper triangular preconditioner and that the eigenvectors of the two preconditioned matrices are related. © 2014 Society for Industrial and Applied Mathematics.

  19. Curcumin blocks interleukin-1 signaling in chondrosarcoma cells.

    Directory of Open Access Journals (Sweden)

    Thomas Kalinski

    Full Text Available Interleukin (IL-1 signaling plays an important role in inflammatory processes, but also in malignant processes. The essential downstream event in IL-1 signaling is the activation of nuclear factor (NF-κB, which leads to the expression of several genes that are involved in cell proliferation, invasion, angiogenesis and metastasis, among them VEGF-A. As microenvironment-derived IL-1β is required for invasion and angiogenesis in malignant tumors, also in chondrosarcomas, we investigated IL-1β-induced signal transduction and VEGF-A expression in C3842 and SW1353 chondrosarcoma cells. We additionally performed in vitro angiogenesis assays and NF-κB-related gene expression analyses. Curcumin is a substance which inhibits IL-1 signaling very early by preventing the recruitment of IL-1 receptor associated kinase (IRAK to the IL-1 receptor. We demonstrate that IL-1 signaling and VEGF-A expression are blocked by Curcumin in chondrosarcoma cells. We further show that Curcumin blocks IL-1β-induced angiogenesis and NF-κB-related gene expression. We suppose that IL-1 blockade is an additional treatment option in chondrosarcoma, either by Curcumin, its derivatives or other IL-1 blocking agents.

  20. Emplacement of small and large buffer blocks

    International Nuclear Information System (INIS)

    Saari, H.; Nikula, M.; Suikki, M.

    2010-05-01

    The report describes emplacement of a buffer structure encircling a spent fuel canister to be deposited in a vertical hole. The report deals with installability of various size blocks and with an emplacement gear, as well as evaluates the achieved quality of emplacement and the time needed for installing the buffer. Two block assembly of unequal size were chosen for examination. A first option involved small blocks, the use of which resulted in a buffer structure consisting of small sector blocks 200 mm in height. A second option involved large blocks, resulting in a buffer structure which consists of eight blocks. In these tests, the material chosen for both block options was concrete instead of bentonite. The emplacement test was a three-phase process. A first phase included stacking a two meter high buffer structure with small blocks for ensuring the operation of test equipment and blocks. A second phase included installing buffer structures with both block options to a height matching that of a canister-encircling cylindrical component. A third phase included testing also the installability of blocks to be placed above the canister by using small blocks. In emplacement tests, special attention was paid to the installability of blocks as well as to the time required for emplacement. Lifters for both blocks worked well. Due to the mass to be lifted, the lifter for large blocks had a more heavy-duty frame structure (and other lifting gear). The employed lifters were suspended in the tests on a single steel wire rope. Stacking was managed with both block sizes at adequate precision and stacked-up towers were steady. The stacking of large blocks was considerably faster. Therefore it is probably that the overall handling of the large blocks will be more convenient at a final disposal site. From the standpoint of reliability in lifting, the small blocks were safer to install above the canister. In large blocks, there are strict shape-related requirements which are

  1. UAV PHOTOGRAMMETRY: BLOCK TRIANGULATION COMPARISONS

    Directory of Open Access Journals (Sweden)

    R. Gini

    2013-08-01

    Full Text Available UAVs systems represent a flexible technology able to collect a big amount of high resolution information, both for metric and interpretation uses. In the frame of experimental tests carried out at Dept. ICA of Politecnico di Milano to validate vector-sensor systems and to assess metric accuracies of images acquired by UAVs, a block of photos taken by a fixed wing system is triangulated with several software. The test field is a rural area included in an Italian Park ("Parco Adda Nord", useful to study flight and imagery performances on buildings, roads, cultivated and uncultivated vegetation. The UAV SenseFly, equipped with a camera Canon Ixus 220HS, flew autonomously over the area at a height of 130 m yielding a block of 49 images divided in 5 strips. Sixteen pre-signalized Ground Control Points, surveyed in the area through GPS (NRTK survey, allowed the referencing of the block and accuracy analyses. Approximate values for exterior orientation parameters (positions and attitudes were recorded by the flight control system. The block was processed with several software: Erdas-LPS, EyeDEA (Univ. of Parma, Agisoft Photoscan, Pix4UAV, in assisted or automatic way. Results comparisons are given in terms of differences among digital surface models, differences in orientation parameters and accuracies, when available. Moreover, image and ground point coordinates obtained by the various software were independently used as initial values in a comparative adjustment made by scientific in-house software, which can apply constraints to evaluate the effectiveness of different methods of point extraction and accuracies on ground check points.

  2. [THE TECHNOLOGY "CELL BLOCK" IN CYTOLOGICAL PRACTICE].

    Science.gov (United States)

    Volchenko, N N; Borisova, O V; Baranova, I B

    2015-08-01

    The article presents summary information concerning application of "cell block" technology in cytological practice. The possibilities of implementation of various modern techniques (immune cytochemnical analysis. FISH, CISH, polymerase chain reaction) with application of "cell block" method are demonstrated. The original results of study of "cell block" technology made with gelatin, AgarCyto and Shadon Cyoblock set are presented. The diagnostic effectiveness of "cell block" technology and common cytological smear and also immune cytochemical analysis on samples of "cell block" technology and fluid cytology were compared. Actually application of "cell block" technology is necessary for ensuring preservation of cell elements for subsequent immune cytochemical and molecular genetic analysis.

  3. Minimum description length block finder, a method to identify haplotype blocks and to compare the strength of block boundaries.

    Science.gov (United States)

    Mannila, H; Koivisto, M; Perola, M; Varilo, T; Hennah, W; Ekelund, J; Lukk, M; Peltonen, L; Ukkonen, E

    2003-07-01

    We describe a new probabilistic method for finding haplotype blocks that is based on the use of the minimum description length (MDL) principle. We give a rigorous definition of the quality of a segmentation of a genomic region into blocks and describe a dynamic programming algorithm for finding the optimal segmentation with respect to this measure. We also describe a method for finding the probability of a block boundary for each pair of adjacent markers: this gives a tool for evaluating the significance of each block boundary. We have applied the method to the published data of Daly and colleagues. The results expose some problems that exist in the current methods for the evaluation of the significance of predicted block boundaries. Our method, MDL block finder, can be used to compare block borders in different sample sets, and we demonstrate this by applying the MDL-based method to define the block structure in chromosomes from population isolates.

  4. Adductor canal block versus femoral nerve block for analgesia after total knee arthroplasty

    DEFF Research Database (Denmark)

    Jaeger, Pia; Zaric, Dusanka; Fomsgaard, Jonna Storm

    2013-01-01

    Femoral nerve block (FNB), a commonly used postoperative pain treatment after total knee arthroplasty (TKA), reduces quadriceps muscle strength essential for mobilization. In contrast, adductor canal block (ACB) is predominately a sensory nerve block. We hypothesized that ACB preserves quadriceps...

  5. Blocking device especially for circulating pumps

    International Nuclear Information System (INIS)

    Susil, J.; Vychodil, V.; Lorenc, P.

    1976-01-01

    The claim of the invention is a blocking device which blocks reverse flow occurring after the shutdown of circulating pumps, namely in the operation of nuclear power plants or in pumps with a high delivery head. (F.M.)

  6. Reversible chronic acquired complete atrioventricular block.

    Science.gov (United States)

    Rakovec, P; Milcinski, G; Voga, G; Korsic, L

    1982-01-01

    The return of atrioventricular conduction is reported in a case after nearly four years of complete acquired heart block. After recovery from atrioventricular block, right bundle branch block persisted, but P-R interval and H-V interval were normal. Three months later a relapse of second degree infranodal atrioventricular block was noted. A short review of similar cases from the literature is given.

  7. Escitalopram block of hERG potassium channels.

    Science.gov (United States)

    Chae, Yun Ju; Jeon, Ji Hyun; Lee, Hong Joon; Kim, In-Beom; Choi, Jin-Sung; Sung, Ki-Wug; Hahn, Sang June

    2014-01-01

    Escitalopram, a selective serotonin reuptake inhibitor, is the pharmacologically active S-enantiomer of the racemic mixture of RS-citalopram and is widely used in the treatment of depression. The effects of escitalopram and citalopram on the human ether-a-go-go-related gene (hERG) channels expressed in human embryonic kidney cells were investigated using voltage-clamp and Western blot analyses. Both drugs blocked hERG currents in a concentration-dependent manner with an IC50 value of 2.6 μM for escitalopram and an IC50 value of 3.2 μM for citalopram. The blocking of hERG by escitalopram was voltage-dependent, with a steep increase across the voltage range of channel activation. However, voltage independence was observed over the full range of activation. The blocking by escitalopram was frequency dependent. A rapid application of escitalopram induced a rapid and reversible blocking of the tail current of hERG. The extent of the blocking by escitalopram during the depolarizing pulse was less than that during the repolarizing pulse, suggesting that escitalopram has a high affinity for the open state of the hERG channel, with a relatively lower affinity for the inactivated state. Both escitalopram and citalopram produced a reduction of hERG channel protein trafficking to the plasma membrane but did not affect the short-term internalization of the hERG channel. These results suggest that escitalopram blocked hERG currents at a supratherapeutic concentration and that it did so by preferentially binding to both the open and the inactivated states of the channels and by inhibiting the trafficking of hERG channel protein to the plasma membrane.

  8. MARINE BOTTOM COMMUNITIES OF BLOCK ISLAND WATERS

    Science.gov (United States)

    The sea has long been an integral part of Block Island's natural history, beginning when the rising sea surrounded the high spot on a Pleistocene terminal moraine that became Block Island. The southern New England continental shelf, which lies around Block Island, and the Great S...

  9. Encoders for block-circulant LDPC codes

    Science.gov (United States)

    Divsalar, Dariush (Inventor); Abbasfar, Aliazam (Inventor); Jones, Christopher R. (Inventor); Dolinar, Samuel J. (Inventor); Thorpe, Jeremy C. (Inventor); Andrews, Kenneth S. (Inventor); Yao, Kung (Inventor)

    2009-01-01

    Methods and apparatus to encode message input symbols in accordance with an accumulate-repeat-accumulate code with repetition three or four are disclosed. Block circulant matrices are used. A first method and apparatus make use of the block-circulant structure of the parity check matrix. A second method and apparatus use block-circulant generator matrices.

  10. Bullet-Block Science Video Puzzle

    Science.gov (United States)

    Shakur, Asif

    2015-01-01

    A science video blog, which has gone viral, shows a wooden block shot by a vertically aimed rifle. The video shows that the block hit dead center goes exactly as high as the one shot off-center. (Fig. 1). The puzzle is that the block shot off-center carries rotational kinetic energy in addition to the gravitational potential energy. This leads a…

  11. 49 CFR 236.708 - Block.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Block. 236.708 Section 236.708 Transportation... OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Definitions § 236.708 Block. A length of track of defined limits, the use of which by trains is governed by block signals, cab signals, or both. ...

  12. 49 CFR 236.804 - Signal, block.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Signal, block. 236.804 Section 236.804 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION... Signal, block. A roadway signal operated either automatically or manually at the entrance to a block. ...

  13. Block Play: Practical Suggestions for Common Dilemmas

    Science.gov (United States)

    Tunks, Karyn Wellhousen

    2009-01-01

    Learning materials and teaching methods used in early childhood classrooms have fluctuated greatly over the past century. However, one learning tool has stood the test of time: Wood building blocks, often called unit blocks, continue to be a source of pleasure and learning for young children at play. Wood blocks have the unique capacity to engage…

  14. Naming Block Structures: A Multimodal Approach

    Science.gov (United States)

    Cohen, Lynn; Uhry, Joanna

    2011-01-01

    This study describes symbolic representation in block play in a culturally diverse suburban preschool classroom. Block play is "multimodal" and can allow children to experiment with materials to represent the world in many forms of literacy. Combined qualitative and quantitative data from seventy-seven block structures were collected and analyzed.…

  15. 21 CFR 882.5070 - Bite block.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Bite block. 882.5070 Section 882.5070 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Therapeutic Devices § 882.5070 Bite block. (a) Identification. A bite block...

  16. Large block test status report

    International Nuclear Information System (INIS)

    Wilder, D.G.; Lin, W.; Blair, S.C.

    1997-01-01

    This report is intended to serve as a status report, which essentially transmits the data that have been collected to date on the Large Block Test (LBT). The analyses of data will be performed during FY98, and then a complete report will be prepared. This status report includes introductory material that is not needed merely to transmit data but is available at this time and therefore included. As such, this status report will serve as the template for the future report, and the information is thus preserved

  17. Block-conjugate-gradient method

    International Nuclear Information System (INIS)

    McCarthy, J.F.

    1989-01-01

    It is shown that by using the block-conjugate-gradient method several, say s, columns of the inverse Kogut-Susskind fermion matrix can be found simultaneously, in less time than it would take to run the standard conjugate-gradient algorithm s times. The method improves in efficiency relative to the standard conjugate-gradient algorithm as the fermion mass is decreased and as the value of the coupling is pushed to its limit before the finite-size effects become important. Thus it is potentially useful for measuring propagators in large lattice-gauge-theory calculations of the particle spectrum

  18. Cordycepin alleviates lipopolysaccharide-induced acute lung injury via Nrf2/HO-1 pathway.

    Science.gov (United States)

    Qing, Rui; Huang, Zezhi; Tang, Yufei; Xiang, Qingke; Yang, Fan

    2018-04-24

    The present study is to investigate the protective effect of cordycepin on inflammatory reactions in rats with acute lung injury (ALI) induced by lipopolysaccharide (LPS), as well as the underlying mechanism. Wistar rat model of ALI was induced by intravenous injection of LPS (30 mg/kg body weight). One hour later, intravenous injection of cordycepin (1, 10 or 30 mg/kg body weight) was administered. The wet-to-dry weight ratio of lung tissues and myeloperoxidase activity in the lung tissues were measured. The contents of nitrite and nitrate were measured by reduction method, while chemiluminescence was used to determine the content of superoxide. Quantitative real-time polymerase chain reaction and Western blotting were used to determine the expression of mRNA and protein, respectively. Colorimetry was performed to determine the enzymatic activity of heme oxygenase-1 (HO-1). Nuclear translocation of Nrf2 was identified by Western blotting. The plasma contents of cytokines were measured by enzyme-linked immunosorbent assay. Cordycepin enhanced the expression and enzymatic activity of HO-1 in ALI rats, and activated Nrf2 by inducing the translocation of Nrf2 from cytoplasm to nucleus. In addition, cordycepin regulated the secretion of TNF-α, IL-6 and IL-10 via HO-1, and suppressed inflammation in lung tissues of ALI rats by inducing the expression of HO-1. HO-1 played important roles in the down-regulation of superoxide levels in lung tissues by cordycepin, and HO-1 expression induced by cordycepin affected nitrite and nitrate concentrations in plasma and iNOS protein expression in lung tissues. Cordycepin showed protective effect on injuries in lung tissues. The present study demonstrates that cordycepin alleviates inflammation induced by LPS via the activation of Nrf2 and up-regulation of HO-1 expression. Copyright © 2018. Published by Elsevier B.V.

  19. Spred-2 deficiency exacerbates lipopolysaccharide-induced acute lung inflammation in mice.

    Directory of Open Access Journals (Sweden)

    Yang Xu

    Full Text Available BACKGROUND: Acute respiratory distress syndrome (ARDS is a severe and life-threatening acute lung injury (ALI that is caused by noxious stimuli and pathogens. ALI is characterized by marked acute inflammation with elevated alveolar cytokine levels. Mitogen-activated protein kinase (MAPK pathways are involved in cytokine production, but the mechanisms that regulate these pathways remain poorly characterized. Here, we focused on the role of Sprouty-related EVH1-domain-containing protein (Spred-2, a negative regulator of the Ras-Raf-extracellular signal-regulated kinase (ERK-MAPK pathway, in lipopolysaccharide (LPS-induced acute lung inflammation. METHODS: Wild-type (WT mice and Spred-2(-/- mice were exposed to intratracheal LPS (50 µg in 50 µL PBS to induce pulmonary inflammation. After LPS-injection, the lungs were harvested to assess leukocyte infiltration, cytokine and chemokine production, ERK-MAPK activation and immunopathology. For ex vivo experiments, alveolar macrophages were harvested from untreated WT and Spred-2(-/- mice and stimulated with LPS. In in vitro experiments, specific knock down of Spred-2 by siRNA or overexpression of Spred-2 by transfection with a plasmid encoding the Spred-2 sense sequence was introduced into murine RAW264.7 macrophage cells or MLE-12 lung epithelial cells. RESULTS: LPS-induced acute lung inflammation was significantly exacerbated in Spred-2(-/- mice compared with WT mice, as indicated by the numbers of infiltrating leukocytes, levels of alveolar TNF-α, CXCL2 and CCL2 in a later phase, and lung pathology. U0126, a selective MEK/ERK inhibitor, reduced the augmented LPS-induced inflammation in Spred-2(-/- mice. Specific knock down of Spred-2 augmented LPS-induced cytokine and chemokine responses in RAW264.7 cells and MLE-12 cells, whereas Spred-2 overexpression decreased this response in RAW264.7 cells. CONCLUSIONS: The ERK-MAPK pathway is involved in LPS-induced acute lung inflammation. Spred-2 controls the development of LPS-induced lung inflammation by negatively regulating the ERK-MAPK pathway. Thus, Spred-2 may represent a therapeutic target for the treatment of ALI.

  20. Role for macrophage inflammatory protein-2 in lipopolysaccharide-induced lung injury in rats

    DEFF Research Database (Denmark)

    Schmal, H; Shanley, T P; Jones, M L

    1996-01-01

    Macrophage inflammatory protein-2 (MIP-2) is a C-X-C chemokine that possesses chemotactic activity for neutrophils. Rat MIP-2 was cloned and expressed as a 7.9-kDa peptide that exhibited dose-dependent neutrophil chemotactic activity at concentrations from 10 to 250 nM. Rabbit polyclonal Ab to th...... instillation of LPS was found to be MIP-2-dependent. These data indicate that MIP-2 plays a significant role in LPS-induced inflammatory response in rat lungs and is required for the full recruitment of neutrophils....

  1. The effects of a novel botanical agent on lipopolysaccharide-induced alveolar bone loss in rats.

    Science.gov (United States)

    Lee, Bo-Ah; Lee, Hwa-Sun; Jung, Young-Suk; Kim, Se-Won; Lee, Yong-Wook; Chang, Sun-Hwa; Chung, Hyun-Ju; Kim, Ok-Su; Kim, Young-Joon

    2013-08-01

    The development of host-modulatory agents with low risk of adverse effects has been needed to treat periodontitis, a chronic inflammatory disease. A botanical mixture of extracts from two natural substances, Panax notoginseng and Rehmannia glutinosa Libosch, was developed as a novel botanical agent synthesized with anti-inflammatory effect. The aim of this study is to evaluate the effects of the botanical mixture on the release of inflammatory cytokines and its inhibitory effect on lipopolysaccharide (LPS)-induced alveolar bone loss (ABL) in a rat model. Cytotoxicity was assessed by 3-(4,5-dimethylthiazol-2yl)-5(3-carboxymethoxyphenol)-2-(4-sulfophenyl)-2H-tetrazolium assay using human gingival fibroblast (hGF) and human periodontal ligament (hPDL) cells. Human acute monocytic leukemia cell line and hGF cells were cultured to assay tumor necrosis factor (TNF)-α and interleukin (IL)-6, respectively. Microcomputed tomography analysis and immunofluoresence analysis were performed to evaluate the efficacy of the botanical mixture to inhibit the destruction of alveolar bone and connective tissue in a rat model. The botanical mixture is cytotoxic at concentrations exceeding 2.5 mg/mL (P botanical mixture to be used in all subsequent in vitro and in vivo experiments. The botanical mixture reduced the release of TNF-α and IL-6 from human monocytic cells and hGF cells in a dose-dependent manner (P botanical mixture significantly reduced the alveolar bone loss in a rat model (P botanical mixture, matrix metalloproteinase (MMP)-9 was detected along the alveolar bone crest (ABC), but not around the gingival connective tissue, while in the group with LPS-induced ABL, pronounced expression of MMP-9 around the ABC, periodontal ligament, and gingival connective tissue was found. The botanical mixture showed a potential adjunctive effect in the treatment of periodontitis. However, the present findings are obtained in vitro and in a rat model, so further clinical study is needed for its clinical application.

  2. Antioxidant properties of lutein contribute to the protection against lipopolysaccharide-induced uveitis in mice

    Directory of Open Access Journals (Sweden)

    Yao Xin-Sheng

    2011-10-01

    Full Text Available Abstract Background Lutein is an important eye-protective nutrient. This study investigates the protective effects and mechanisms of lutein on lipopolysaccharides (LPS-induced uveitis in mice. Methods Lutein, suspended in drinking water at a final concentration of 12.5 and 25 mg/mL, was administered to mice at 0.1 mL/10 g body weight for five consecutive days. Control and model group received drinking water only. Uveitis was induced by injecting LPS (100 mg per mouse into the footpad in the model and lutein groups on day 5 after the last drug administration. Eyes of the mice were collected 24 hours after the LPS injection for the detection of indicators using commercial kits and reverse transcription-polymerase chain reaction. Results LPS-induced uveitis was confirmed by significant pathological damage and increased the nitric oxide level in eye tissue of BALB/C mice 24 hours after the footpad injection. The elevated nitric oxide level was significantly reduced by oral administration of lutein (125 and 500 mg/kg/d for five days before LPS injection. Moreover, lutein decreased the malondialdehyde content, increased the oxygen radical absorbance capacity level, glutathione, the vitamin C contents and total superoxide dismutase (SOD and glutathione peroxidase (GPx activities. Lutein further increased expressions of copper-zinc SOD, manganese SOD and GPx mRNA. Conclusion The antioxidant properties of lutein contribute to the protection against LPS-induced uveitis, partially through the intervention of inflammation process.

  3. Static Magnetic Field Attenuates Lipopolysaccharide-Induced Inflammation in Pulp Cells by Affecting Cell Membrane Stability

    Directory of Open Access Journals (Sweden)

    Sung-Chih Hsieh

    2015-01-01

    Full Text Available One of the causes of dental pulpitis is lipopolysaccharide- (LPS- induced inflammatory response. Following pulp tissue inflammation, odontoblasts, dental pulp cells (DPCs, and dental pulp stem cells (DPSCs will activate and repair damaged tissue to maintain homeostasis. However, when LPS infection is too serious, dental repair is impossible and disease may progress to irreversible pulpitis. Therefore, the aim of this study was to examine whether static magnetic field (SMF can attenuate inflammatory response of dental pulp cells challenged with LPS. In methodology, dental pulp cells were isolated from extracted teeth. The population of DPSCs in the cultured DPCs was identified by phenotypes and multilineage differentiation. The effects of 0.4 T SMF on DPCs were observed through MTT assay and fluorescent anisotropy assay. Our results showed that the SMF exposure had no effect on surface markers or multilineage differentiation capability. However, SMF exposure increases cell viability by 15%. In addition, SMF increased cell membrane rigidity which is directly related to higher fluorescent anisotropy. In the LPS-challenged condition, DPCs treated with SMF demonstrated a higher tolerance to LPS-induced inflammatory response when compared to untreated controls. According to these results, we suggest that 0.4 T SMF attenuates LPS-induced inflammatory response to DPCs by changing cell membrane stability.

  4. Ficolins do not alter host immune responses to lipopolysaccharide-induced inflammation in vivo

    DEFF Research Database (Denmark)

    Genster, Ninette; Østrup, Olga; Schjalm, Camilla

    2017-01-01

    . Yet, the contribution of ficolins to inflammatory disease processes remains elusive. To address this, we investigated ficolin deficient mice during a lipopolysaccharide (LPS)-induced model of systemic inflammation. Although murine serum ficolin was shown to bind LPS in vitro, there was no difference...... an unaltered spleen transcriptome profile in ficolin deficient mice compared to wildtype mice. Collectively, results from this study demonstrate that ficolins are not involved in host response to LPS-induced systemic inflammation.......Ficolins are a family of pattern recognition molecules that are capable of activating the lectin pathway of complement. A limited number of reports have demonstrated a protective role of ficolins in animal models of infection. In addition, an immune modulatory role of ficolins has been suggested...

  5. Resveratrol protects from lipopolysaccharide-induced inflammation in the uterus and prevents experimental preterm birth.

    Science.gov (United States)

    Bariani, María Victoria; Correa, Fernando; Leishman, Emma; Domínguez Rubio, Ana Paula; Arias, Andreína; Stern, Aníbal; Bradshaw, Heather B; Franchi, Ana María

    2017-08-01

    Is resveratrol able to prevent the lipopolysaccharide (LPS)-induced preterm labor in 15-day pregnant BALB/c mice? Resveratrol prevented the LPS-induced onset of preterm labor in 64% of the cases and showed anti-inflammatory and tocolytic effects by downregulating COX-2 and iNOS expression and NOS activity, and by changing the uterine prostaglandin and endocannabinoid profiling. Genital tract infections by Gram-negative bacteria are a common complication in human pregnancy and have been shown to increase risk of preterm delivery. Bacterial LPS elicits a strong maternal inflammatory response that results in preterm delivery and fetal death in a murine model endotoxin-induced preterm labor. An in vivo animal study was conducted. On Day 15 of pregnancy, mice received at 8:00 h a dose of vehicle (40% ethanol in saline solution) or resveratrol (3 mg/kg in vehicle) via oral gavage followed by two doses of LPS or vehicle administered intraperitoneally (i.p.), the first one at 10:00 h (0.17 mg/kg in 0.1 ml of sterile saline solution) and the second at 13:00 h (0.5 mg/kg in 0.1 ml of sterile saline solution). The mice were closely observed for any signs of morbidity (piloerection, decreased movement, and diarrhea), vaginal bleeding or preterm delivery. The beginning of preterm delivery was defined by early delivery of the first pup. Normal term labor occurs on Day 19 of gestation. Time of labor, pregnancy outcome and morphological features were evaluated after LPS and/or resveratrol administration. Uterine stripes were collected 5 h after the last LPS injection and prostaglandin and endocannabinoid profiling was analyzed by mass spectrometry. Nitric oxide synthase (NOS) activity was measured by radioconversion assay. Cyclooxygenase-2 (Cox-2) and 15-hydroxyprostaglandin dehydrogenase (15-Pgdh) mRNA levels were analyzed by RT-PCR whilst the protein expression of inducible nitric oxide synthase (iNOS), COX-1 and COX-2 were studied by western blot. In vivo treatment of 15-day pregnant BALB/c mice with resveratrol prevented the LPS-induced preterm birth in 64% of the cases, whereas only 15% of mice with LPS alone escaped preterm birth. Treatment with resveratrol resulted in a reduced NOS activity (P resveratrol reduced the expression of LPS-induced pro-inflammatory agents such as iNOS (P resveratrol administration resulted in changes in the uterine endocannabinoid profiling altered by LPS. N/A. Since our experimental design involves the use of mice, the extrapolation of the results presented here to humans is limited. Our findings provide evidence for the tocolytic effects of resveratrol. Dr Ana María Franchi was funded by Agencia Nacional para la Promoción Científica y Tecnológica (PICT 2013/0097) and by Consejo Nacional de Investigaciones Científicas y Técnicas (PIP 2012/0061). Dr Heather B. Bradshaw was funded by NIH (DA006668). The authors have no competing interests. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  6. OPTICAL IMAGING OF LIPOPOLYSACCHARIDE-INDUCED OXIDATIVE STRESS IN ACUTE LUNG INJURY FROM HYPEROXIA AND SEPSIS

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    REYHANEH SEPEHR

    2013-07-01

    Full Text Available Reactive oxygen species (ROS have been implicated in the pathogenesis of many acute and chronic pulmonary disorders such as acute lung injury (ALI in adults and bronchopulmonary dysplasia (BPD in premature infants. Bacterial infection and oxygen toxicity, which result in pulmonary vascular endothelial injury, contribute to impaired vascular growth and alveolar simplification seen in the lungs of premature infants with BPD. Hyperoxia induces ALI, reduces cell proliferation, causes DNA damage and promotes cell death by causing mitochondrial dysfunction. The objective of this study was to use an optical imaging technique to evaluate the variations in fluorescence intensities of the auto-fluorescent mitochondrial metabolic coenzymes, NADH and FAD in four different groups of rats. The ratio of these fluorescence signals (NADH/FAD, referred to as NADH redox ratio (NADH RR has been used as an indicator of tissue metabolism in injuries. Here, we investigated whether the changes in metabolic state can be used as a marker of oxidative stress caused by hyperoxia and bacterial lipopolysaccharide (LPS exposure in neonatal rat lungs. We examined the tissue redox states of lungs from four groups of rat pups: normoxic (21% O2 pups, hyperoxic (90% O2 pups, pups treated with LPS (normoxic + LPS, and pups treated with LPS and hyperoxia (hyperoxic + LPS. Our results show that hyperoxia oxidized the respiratory chain as reflected by a ~ 31% decrease in lung tissue NADH RR as compared to that for normoxic lungs. LPS treatment alone or with hyperoxia had no significant effect on lung tissue NADH RR as compared to that for normoxic or hyperoxic lungs, respectively. Thus, NADH RR serves as a quantitative marker of oxidative stress level in lung injury caused by two clinically important conditions: hyperoxia and LPS exposure.

  7. Early Effects of Lipopolysaccharide-Induced Inflammation on Foetal Brain Development in Rat

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    Cristina A Ghiani

    2011-10-01

    Full Text Available Studies in humans and animal models link maternal infection and imbalanced levels of inflammatory mediators in the foetal brain to the aetiology of neuropsychiatric disorders. In a number of animal models, it was shown that exposure to viral or bacterial agents during a period that corresponds to the second trimester in human gestation triggers brain and behavioural abnormalities in the offspring. However, little is known about the early cellular and molecular events elicited by inflammation in the foetal brain shortly after maternal infection has occurred. In this study, maternal infection was mimicked by two consecutive intraperitoneal injections of 200 μg of LPS (lipopolysaccharide/kg to timed-pregnant rats at GD15 (gestational day 15 and GD16. Increased thickness of the CP (cortical plate and hippocampus together with abnormal distribution of immature neuronal markers and decreased expression of markers for neural progenitors were observed in the LPS-exposed foetal forebrains at GD18. Such effects were accompanied by decreased levels of reelin and the radial glial marker GLAST (glial glutamate transporter, and elevated levels of pro-inflammatory cytokines in maternal serum and foetal forebrains. Foetal inflammation elicited by maternal injections of LPS has discrete detrimental effects on brain development. The early biochemical and morphological changes described in this work begin to explain the sequelae of early events that underlie the neurobehavioural deficits reported in humans and animals exposed to prenatal insults.

  8. Acrolein inhalation suppresses lipopolysaccharide-induced inflammatory cytokine production but does not affect acute airways neutrophilia.

    Science.gov (United States)

    Kasahara, David Itiro; Poynter, Matthew E; Othman, Ziryan; Hemenway, David; van der Vliet, Albert

    2008-07-01

    Acrolein is a reactive unsaturated aldehyde that is produced during endogenous oxidative processes and is a major bioactive component of environmental pollutants such as cigarette smoke. Because in vitro studies demonstrate that acrolein can inhibit neutrophil apoptosis, we evaluated the effects of in vivo acrolein exposure on acute lung inflammation induced by LPS. Male C57BL/6J mice received 300 microg/kg intratracheal LPS and were exposed to acrolein (5 parts per million, 6 h/day), either before or after LPS challenge. Exposure to acrolein either before or after LPS challenge did not significantly affect the overall extent of LPS-induced lung inflammation, or the duration of the inflammatory response, as observed from recovered lung lavage leukocytes and histology. However, exposure to acrolein after LPS instillation markedly diminished the LPS-induced production of several inflammatory cytokines, specifically TNF-alpha, IL-12, and the Th1 cytokine IFN-gamma, which was associated with reduction in NF-kappaB activation. Our data demonstrate that acrolein exposure suppresses LPS-induced Th1 cytokine responses without affecting acute neutrophilia. Disruption of cytokine signaling by acrolein may represent a mechanism by which smoking contributes to chronic disease in chronic obstructive pulmonary disease and asthma.

  9. Docosahexaenoic acid ester of phloridzin inhibit lipopolysaccharide-induced inflammation in THP-1 differentiated macrophages.

    Science.gov (United States)

    Sekhon-Loodu, Satvir; Ziaullah; Rupasinghe, H P Vasantha

    2015-03-01

    Phloridzin or phlorizin (PZ) is a predominant phenolic compound found in apple and also used in various natural health products. Phloridzin shows poor absorption and cellular uptake due to its hydrophilic nature. The aim was to investigate and compare the effect of docosahexaenoic acid (DHA) ester of PZ (PZ-DHA) and its parent compounds (phloridzin and DHA), phloretin (the aglycone of PZ) and cyclooxygenase inhibitory drugs (diclofenac and nimesulide) on production of pro-inflammatory biomarkers in inflammation-induced macrophages by lipopolysaccharide (LPS)-stimulation. Human THP-1 monocytes were seeded in 24-well plates (5×10(5)/well) and treated with phorbol 12-myristate 13-acetate (PMA, 0.1μg/mL) for 48h to induce macrophage differentiation. After 48h, the differentiated macrophages were washed with Hank's buffer and treated with various concentrations of test compounds for 4h, followed by the LPS-stimulation (18h). Pre-exposure of PZ-DHA ester was more effective in reducing tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2) protein levels compared to DHA and nimesulide. However, diclofenac was the most effective in reducing prostaglandin (PGE2) level by depicting a dose-dependent response. However, PZ-DHA ester and DHA were the most effective in inhibiting the activation of nuclear factor-kappa B (NF-κB) among other test compounds. Our results suggest that PZ-DHA ester might possess potential therapeutic activity to treat inflammation related disorders such as type 2 diabetes, asthma, atherosclerosis and inflammatory bowel disease. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Atorvastatin reduces lipopolysaccharide-induced expression of cyclooxygenase-2 in human pulmonary epithelial cells

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    Chen Ping

    2005-04-01

    Full Text Available Abstract Objective To explore the effects of atorvastatin on expression of cyclooxygenase-2 (COX-2 in human pulmonary epithelial cells (A549. Methods A549 cells were incubated in DMEM medium containing lipopolysaccharide (LPS in the presence or absence of atorvastatin. After incubation, the medium was collected and the amount of prostaglandin E2 (PGE2 was measured by enzyme-linked immunosorbent assay (ELISA. The cells were harvested, and COX-2 mRNA and protein were analyzed by RT-PCR and western-blot respectively. Results LPS increased the expression of COX-2 mRNA and production of PGE2 in a dose- and time-dependent manner in A549. Induction of COX-2 mRNA and protein by LPS were inhibited by atorvastatin in a dose-dependent manner. Atorvastatin also significantly decreased LPS-induced production of PGE2. There was a positive correlation between reduced of COX-2 mRNA and decreased of PGE2 (r = 0.947, P Conclusion Atorvastatin down-regulates LPS-induced expression of the COX-2 and consequently inhibits production of PGE2 in cultured A549 cells.

  11. Modulation of lipopolysaccharide-induced chorioamnionitis in fetal sheep by maternal betamethasone.

    Science.gov (United States)

    Wolfe, Katherine B; Snyder, Candice C; Gisslen, Tate; Kemp, Matthew W; Newnham, John P; Kramer, Boris W; Jobe, Alan H; Kallapur, Suhas

    2013-12-01

    We tested the hypothesis that the order of exposure to maternal betamethasone and intra-amniotic (IA) lipopolysaccharide (LPS) will differentially modulate inflammation in the chorioamnion. Time-mated Merino ewes with singleton fetuses received saline alone, IA LPS alone, maternal betamethasone before LPS, or betamethasone after LPS. We assessed inflammatory markers in the chorioamnion and the amniotic fluid. Inflammatory cell infiltration, expression of myeloperoxidase, serum amyloid A3 (acute phase reactant) in the chorioamnion, and levels of interleukin (IL)-8 in the amniotic fluid increased 7 days after LPS exposure. Betamethasone prior to LPS decreased infiltration of the inflammatory cells, CD3+ T cells, and decreased the levels of IL-1β and IL-8 in the amniotic fluid. Betamethasone 7 days prior to LPS exposure suppressed LPS-induced inflammation. The markers of inflammation largely had returned to the baseline 14 days after LPS exposure.

  12. Modulation of lipopolysaccharide-induced chorioamnionitis by Ureaplasma parvum in sheep.

    Science.gov (United States)

    Snyder, Candice C; Wolfe, Katherine B; Gisslen, Tate; Knox, Christine L; Kemp, Matthew W; Kramer, Boris W; Newnham, John P; Jobe, Alan H; Kallapur, Suhas G

    2013-05-01

    Ureaplasma colonization in the setting of polymicrobial flora is common in women with chorioamnionitis, and is a risk factor for preterm delivery and neonatal morbidity. We hypothesized that Ureaplasma colonization of amniotic fluid would modulate chorioamnionitis induced by Escherichia coli lipopolysaccharide (LPS). Sheep received intraamniotic (IA) injections of media (control) or live Ureaplasma either 7 or 70 days before delivery. Another group received IA LPS 2 days before delivery. To test for interactions, U parvum-exposed animals were challenged with IA LPS, and delivered 2 days later. All animals were delivered preterm at 125 ± 1 day of gestation. Both IA Ureaplasma and LPS induced leukocyte infiltration of chorioamnion. LPS greatly increased the expression of proinflammatory cytokines and myeloperoxidase in leukocytes, while Ureaplasma alone caused modest responses. Interestingly, 7-day but not 70-day Ureaplasma exposure significantly down-regulated LPS-induced proinflammatory cytokines and myeloperoxidase expression in the chorioamnion. Acute (7-day) U parvum exposure can suppress LPS-induced chorioamnionitis. Copyright © 2013 Mosby, Inc. All rights reserved.

  13. Activation of PPARα by Wy-14643 ameliorates systemic lipopolysaccharide-induced acute lung injury

    International Nuclear Information System (INIS)

    Yoo, Seong Ho; Abdelmegeed, Mohamed A.; Song, Byoung-Joon

    2013-01-01

    Highlights: •Activation of PPARα attenuated LPS-mediated acute lung injury. •Pretreatment with Wy-14643 decreased the levels of IFN-γ and IL-6 in ALI. •Nitrosative stress and lipid peroxidation were downregulated by PPARα activation. •PPARα agonists may be potential therapeutic targets for acute lung injury. -- Abstract: Acute lung injury (ALI) is a major cause of mortality and morbidity worldwide. The activation of peroxisome proliferator-activated receptor-α (PPARα) by its ligands, which include Wy-14643, has been implicated as a potential anti-inflammatory therapy. To address the beneficial efficacy of Wy-14643 for ALI along with systemic inflammation, the in vivo role of PPARα activation was investigated in a mouse model of lipopolysaccharide (LPS)-induced ALI. Using age-matched Ppara-null and wild-type mice, we demonstrate that the activation of PPARα by Wy-14643 attenuated LPS-mediated ALI. This was evidenced histologically by the significant alleviation of inflammatory manifestations and apoptosis observed in the lung tissues of wild-type mice, but not in the corresponding Ppara-null mice. This protective effect probably resulted from the inhibition of LPS-induced increases in pro-inflammatory cytokines and nitroxidative stress levels. These results suggest that the pharmacological activation of PPARα might have a therapeutic effect on LPS-induced ALI

  14. Equine colostral carbohydrates reduce lipopolysaccharide-induced inflammatory responses in equine peripheral blood mononuclear cells.

    Science.gov (United States)

    Vendrig, J C; Coffeng, L E; Fink-Gremmels, J

    2012-12-01

    Increasing evidence suggests that reactions to lipopolysaccharide (LPS), particularly in the gut, can be partly or completely mitigated by colostrum- and milk-derived oligosaccharides. Confirmation of this hypothesis could lead to the development of new therapeutic concepts. To demonstrate the influence of equine colostral carbohydrates on the inflammatory response in an in vitro model with equine peripheral blood mononuclear cells (PBMCs). Carbohydrates were extracted from mare colostrum, and then evaluated for their influence on LPS-induced inflammatory responses in PBMCs isolated from the same mares, mRNA expression of tumour necrosis factor-alpha, interleukin-6 and interleukin-10 was measured as well as the protein levels of tumour necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10). Equine colostral carbohydrates significantly reduced LPS-induced TNF-alpha protein at both times measured and significantly reduced LPS-induced TNF-alpha, IL-6 and IL-10 mRNA expression by PBMCs. Moreover, cell viability significantly increased in the presence of high concentrations of colostral carbohydrates. Carbohydrates derived from equine colostrum reduce LPS-induced inflammatory responses of equine PBMCs. Colostrum and milk-derived carbohydrates are promising candidates for new concepts in preventive and regenerative medicine.

  15. Interleukin-10 Protection against Lipopolysaccharide-Induced Neuro-Inflammation and Neurotoxicity in Ventral Mesencephalic Cultures

    OpenAIRE

    Yan Zhu; Xiao Chen; Zhan Liu; Yu-Ping Peng; Yi-Hua Qiu

    2015-01-01

    Interleukin (IL)-10, an anti-inflammatory cytokine, is expressed in the brain and can inhibit microglial activation. Herein, we utilized lipopolysaccharide (LPS)-induced inflammatory Parkinson?s disease (PD) cell model to determine whether microglia and astrocytes are necessary targets for IL-10 neuroprotection. Primary ventral mesencephalic (VM) cultures with different composition of neurons, microglia and astrocytes were prepared. The cells were exposed to IL-10 (15, 50 or 150 ng/mL) 1 h pr...

  16. Interleukin-10 Protection against Lipopolysaccharide-Induced Neuro-Inflammation and Neurotoxicity in Ventral Mesencephalic Cultures

    Directory of Open Access Journals (Sweden)

    Yan Zhu

    2015-12-01

    Full Text Available Interleukin (IL-10, an anti-inflammatory cytokine, is expressed in the brain and can inhibit microglial activation. Herein, we utilized lipopolysaccharide (LPS-induced inflammatory Parkinson’s disease (PD cell model to determine whether microglia and astrocytes are necessary targets for IL-10 neuroprotection. Primary ventral mesencephalic (VM cultures with different composition of neurons, microglia and astrocytes were prepared. The cells were exposed to IL-10 (15, 50 or 150 ng/mL 1 h prior to LPS (50 ng/mL treatment. LPS induced dopaminergic and non-dopaminergic neuronal loss in VM cultures, VM neuron-enriched cultures, and neuron-microglia co-cultures, but not in neuron-astrocyte co-cultures. IL-10 reduced LPS-induced neuronal loss particularly in single VM neuron cultures. Pro-inflammatory mediators (TNF-α, IL-1β, inducible nitric oxide synthase and cyclooxygenase-2 were upregulated in both neuron-microglia and neuron-astrocyte co-cultures by LPS. In contrast, neurotrophic factors (brain-derived neurotrophic factor, insulin-like growth factor-1 or glial cell-derived neurotrophic factor were downregulated in neuron-microglia co-cultures, but upregulated in neuron-astrocyte co-cultures by LPS. IL-10 reduced both the increase in production of the pro-inflammatory mediators and the decrease in production of the neurotrophic factors induced by LPS. These results suggest that astrocytes can balance LPS neurotoxicity by releasing more neurotrophic factors and that IL-10 exerts neuroprotective property by an extensive action including direct on neurons and indirect via inhibiting microglial activation.

  17. Resveratrol Protects Dopamine Neurons Against Lipopolysaccharide-Induced Neurotoxicity through Its Anti-Inflammatory Actions

    Science.gov (United States)

    Zhang, Feng; Shi, Jing-Shan; Zhou, Hui; Wilson, Belinda; Hong, Jau-Shyong

    2010-01-01

    Parkinson's disease (PD) is the second most common neurodegenerative disease characterized by a progressive loss of dopamine (DA) neurons in the substantia nigra. Accumulating evidence indicates that inhibition of microglia-mediated neuroinflammation may become a reliable protective strategy for PD. Resveratrol, a nonflavonoid polyphenol naturally found in red wine and grapes, has been known to possess antioxidant, anticancer, and anti-inflammatory properties. Although recent studies have shown that resveratrol provided neuroprotective effects against ischemia, seizure, and neurodegenerative disorders, the mechanisms underlying its beneficial effects on dopaminergic neurodegeneration are poorly defined. In this study, rat primary midbrain neuron-glia cultures were used to elucidate the molecular mechanisms underlying resveratrol-mediated neuroprotection. The results clearly demonstrated that resveratrol protected DA neurons against lipopolysaccharide (LPS)-induced neurotoxicity in concentration- and time-dependent manners through the inhibition of microglial activation and the subsequent reduction of proinflammatory factor release. Mechanistically, resveratrol-mediated neuroprotection was attributed to the inhibition of NADPH oxidase. This conclusion is supported by the following observations. First, resveratrol reduced NADPH oxidase-mediated generation of reactive oxygen species. Second, LPS-induced translocation of NADPH oxidase cytosolic subunit p47 to the cell membrane was significantly attenuated by resveratrol. Third and most importantly, resveratrol failed to exhibit neuroprotection in cultures from NADPH oxidase-deficient mice. Furthermore, this neuroprotection was also related to an attenuation of the activation of mitogen-activated protein kinases and nuclear factor-κB signaling pathways in microglia. These findings suggest that resveratrol exerts neuroprotection against LPS-induced dopaminergic neurodegeneration, and NADPH oxidase may be a major player in resveratrol-mediated neuroprotection. PMID:20554604

  18. Aspirin reduces lipopolysaccharide-induced pulmonary inflammation in human models of ARDS.

    Science.gov (United States)

    Hamid, U; Krasnodembskaya, A; Fitzgerald, M; Shyamsundar, M; Kissenpfennig, A; Scott, C; Lefrancais, E; Looney, M R; Verghis, R; Scott, J; Simpson, A J; McNamee, J; McAuley, D F; O'Kane, C M

    2017-11-01

    Platelets play an active role in the pathogenesis of acute respiratory distress syndrome (ARDS). Animal and observational studies have shown aspirin's antiplatelet and immunomodulatory effects may be beneficial in ARDS. To test the hypothesis that aspirin reduces inflammation in clinically relevant human models that recapitulate pathophysiological mechanisms implicated in the development of ARDS. Healthy volunteers were randomised to receive placebo or aspirin 75  or 1200 mg (1:1:1) for seven days prior to lipopolysaccharide (LPS) inhalation, in a double-blind, placebo-controlled, allocation-concealed study. Bronchoalveolar lavage (BAL) was performed 6 hours after inhaling 50 µg of LPS. The primary outcome measure was BAL IL-8. Secondary outcome measures included markers of alveolar inflammation (BAL neutrophils, cytokines, neutrophil proteases), alveolar epithelial cell injury, systemic inflammation (neutrophils and plasma C-reactive protein (CRP)) and platelet activation (thromboxane B2, TXB2). Human lungs, perfused and ventilated ex vivo (EVLP) were randomised to placebo or 24 mg aspirin and injured with LPS. BAL was carried out 4 hours later. Inflammation was assessed by BAL differential cell counts and histological changes. In the healthy volunteer (n=33) model, data for the aspirin groups were combined. Aspirin did not reduce BAL IL-8. However, aspirin reduced pulmonary neutrophilia and tissue damaging neutrophil proteases (Matrix Metalloproteinase (MMP)-8/-9), reduced BAL concentrations of tumour necrosis factor α and reduced systemic and pulmonary TXB2. There was no difference between high-dose and low-dose aspirin. In the EVLP model, aspirin reduced BAL neutrophilia and alveolar injury as measured by histological damage. These are the first prospective human data indicating that aspirin inhibits pulmonary neutrophilic inflammation, at both low and high doses. Further clinical studies are indicated to assess the role of aspirin in the prevention and treatment of ARDS. NCT01659307 Results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  19. Pseudomonas aeruginosa lipopolysaccharide induces CF-like alteration of protein secretion by human tracheal gland cells.

    Science.gov (United States)

    Kammouni, W; Figarella, C; Baeza, N; Marchand, S; Merten, M D

    1997-12-18

    Human tracheal gland (HTG) serous cells are now believed to play a major role in the physiopathology of cystic fibrosis. Because of the persistent inflammation and the specific infection by Pseudomonas aeruginosa in the lung, we looked for the action of the lipopolysaccharide (LPS) of this bacteria on human tracheal gland cells in culture by studying the secretion of the secretory leukocyte proteinase inhibitor (SLPI) which is a specific serous secretory marker of these cells. Treatment with Pseudomonas aeruginosa LPS resulted in a significant dose-dependent increase in the basal production of SLPI (+ 250 +/- 25%) whilst the SLPI transcript mRNA levels remained unchanged. This LPS-induced increase in secretion was inhibited by glucocorticoides. Furthermore, LPS treatment of HTG cells induces a loss of responsiveness to carbachol and isoproterenol but not to adenosine triphosphate. These findings indicate that HTG cells treated by Pseudomonas aeruginosa LPS have the same behavior as those previously observed with CF-HTG cells. Exploration by using reverse transcriptase polymerase chain reaction amplification showed that LPS downregulated cystic fibrosis transmembrane conductance regulator (CFTR) mRNA expression in HTG cells indicative of a link between CFTR function and consequent CF-like alteration in protein secretory process.

  20. LIPOPOLYSACCHARIDE INDUCES THE PRODUCTION OF DIAGNOSTIC MONOCLONAL ANTIBODY BY HYBRIDOMA CELLS AGAINST CONGENITAL ADRENAL HYPERPLASIA

    Directory of Open Access Journals (Sweden)

    GEK KEE CHUA

    2017-11-01

    Full Text Available The purpose of this research is to screen and identify the potential inducers in maximizing the production of monoclonal antibody by hybridoma 192 cell line for Congenital Adrenal Hyperplasia diagnostic. There are nine inducers used in this research, namely lysozyme, aldolase, sodium butyrate, sodium phosphate, potassium phosphate, dimethyl sulfoxide, lipopolysaccharide, essential amino acids, and nonessential amino acids. Hybridoma 192 cell was cultured in 5% CO2 incubator at 37°C and ˃80% humidity in the medium with different concentrations of inducer agents. The inducers were added at the beginning of the culture and the samples were taken after 72 h of culture. The performance of these inducer agents was assessed based on the maximum monoclonal antibody titer achieved using Enzyme-linked Immunosorbent Assay. Lipopolysaccharide was found to increase the maximum monoclonal antibody titer when supplemented at 8 to 12 µg/mL. After optimization using one-factor central composite design at this range, the optimum point was determined to be 8 µg/mL. Verification experiments shows that lipopolysaccharide enhanced the average specific monoclonal antibody production rate by 56% relative to control. In conclusion, lipopolysaccharide at 8 µg/mL is able to increase the monoclonal antibody specific production of hybridoma 192 cell line.

  1. Activation of PPARα by Wy-14643 ameliorates systemic lipopolysaccharide-induced acute lung injury

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Seong Ho, E-mail: yoosh@snu.ac.kr [Seoul National University Hospital, Biomedical Research Institute and Institute of Forensic Medicine, Seoul National University College of Medicine, Seoul (Korea, Republic of); Abdelmegeed, Mohamed A. [Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD (United States); Song, Byoung-Joon, E-mail: bj.song@nih.gov [Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD (United States)

    2013-07-05

    Highlights: •Activation of PPARα attenuated LPS-mediated acute lung injury. •Pretreatment with Wy-14643 decreased the levels of IFN-γ and IL-6 in ALI. •Nitrosative stress and lipid peroxidation were downregulated by PPARα activation. •PPARα agonists may be potential therapeutic targets for acute lung injury. -- Abstract: Acute lung injury (ALI) is a major cause of mortality and morbidity worldwide. The activation of peroxisome proliferator-activated receptor-α (PPARα) by its ligands, which include Wy-14643, has been implicated as a potential anti-inflammatory therapy. To address the beneficial efficacy of Wy-14643 for ALI along with systemic inflammation, the in vivo role of PPARα activation was investigated in a mouse model of lipopolysaccharide (LPS)-induced ALI. Using age-matched Ppara-null and wild-type mice, we demonstrate that the activation of PPARα by Wy-14643 attenuated LPS-mediated ALI. This was evidenced histologically by the significant alleviation of inflammatory manifestations and apoptosis observed in the lung tissues of wild-type mice, but not in the corresponding Ppara-null mice. This protective effect probably resulted from the inhibition of LPS-induced increases in pro-inflammatory cytokines and nitroxidative stress levels. These results suggest that the pharmacological activation of PPARα might have a therapeutic effect on LPS-induced ALI.

  2. Impact of lipopolysaccharide-induced acute inflammation on baroreflex-controlled sympathetic arterial pressure regulation.

    Directory of Open Access Journals (Sweden)

    Takeshi Tohyama

    Full Text Available Lipopolysaccharide (LPS induces acute inflammation, activates sympathetic nerve activity (SNA and alters hemodynamics. Since the arterial baroreflex is a negative feedback system to stabilize arterial pressure (AP, examining the arterial baroreflex function is a prerequisite to understanding complex hemodynamics under LPS challenge. We investigated the impact of LPS-induced acute inflammation on SNA and AP regulation by performing baroreflex open-loop analysis.Ten anesthetized Sprague-Dawley rats were used. Acute inflammation was induced by an intravenous injection of LPS (60 μg/kg. We isolated the carotid sinuses from the systemic circulation and controlled carotid sinus pressure (CSP by a servo-controlled piston pump. We matched CSP to AP to establish the baroreflex closed-loop condition, whereas we decoupled CSP from AP to establish the baroreflex open-loop condition and changed CSP stepwise to evaluate the baroreflex open-loop function. We recorded splanchnic SNA and hemodynamic parameters under baroreflex open- and closed-loop conditions at baseline and at 60 and 120 min after LPS injection.In the baroreflex closed-loop condition, SNA continued to increase after LPS injection, reaching three-fold the baseline value at 120 min (baseline: 94.7 ± 3.6 vs. 120 min: 283.9 ± 31.9 a.u.. In contrast, AP increased initially (until 75 min, then declined to the baseline level. In the baroreflex open-loop condition, LPS reset the neural arc (CSP-SNA relationship upward to higher SNA, while shifted the peripheral arc (SNA-AP relationship downward at 120 min after the injection. As a result, the operating point determined by the intersection between function curves of neural arc and peripheral arc showed marked sympatho-excitation without substantial changes in AP.LPS-induced acute inflammation markedly increased SNA via resetting of the baroreflex neural arc, and suppressed the peripheral arc. The balance between the augmented neural arc and suppressed peripheral arc determines SNA and hemodynamics in LPS-induced acute inflammation.

  3. Impact of lipopolysaccharide-induced acute inflammation on baroreflex-controlled sympathetic arterial pressure regulation.

    Science.gov (United States)

    Tohyama, Takeshi; Saku, Keita; Kawada, Toru; Kishi, Takuya; Yoshida, Keimei; Nishikawa, Takuya; Mannoji, Hiroshi; Kamada, Kazuhiro; Sunagawa, Kenji; Tsutsui, Hiroyuki

    2018-01-01

    Lipopolysaccharide (LPS) induces acute inflammation, activates sympathetic nerve activity (SNA) and alters hemodynamics. Since the arterial baroreflex is a negative feedback system to stabilize arterial pressure (AP), examining the arterial baroreflex function is a prerequisite to understanding complex hemodynamics under LPS challenge. We investigated the impact of LPS-induced acute inflammation on SNA and AP regulation by performing baroreflex open-loop analysis. Ten anesthetized Sprague-Dawley rats were used. Acute inflammation was induced by an intravenous injection of LPS (60 μg/kg). We isolated the carotid sinuses from the systemic circulation and controlled carotid sinus pressure (CSP) by a servo-controlled piston pump. We matched CSP to AP to establish the baroreflex closed-loop condition, whereas we decoupled CSP from AP to establish the baroreflex open-loop condition and changed CSP stepwise to evaluate the baroreflex open-loop function. We recorded splanchnic SNA and hemodynamic parameters under baroreflex open- and closed-loop conditions at baseline and at 60 and 120 min after LPS injection. In the baroreflex closed-loop condition, SNA continued to increase after LPS injection, reaching three-fold the baseline value at 120 min (baseline: 94.7 ± 3.6 vs. 120 min: 283.9 ± 31.9 a.u.). In contrast, AP increased initially (until 75 min), then declined to the baseline level. In the baroreflex open-loop condition, LPS reset the neural arc (CSP-SNA relationship) upward to higher SNA, while shifted the peripheral arc (SNA-AP relationship) downward at 120 min after the injection. As a result, the operating point determined by the intersection between function curves of neural arc and peripheral arc showed marked sympatho-excitation without substantial changes in AP. LPS-induced acute inflammation markedly increased SNA via resetting of the baroreflex neural arc, and suppressed the peripheral arc. The balance between the augmented neural arc and suppressed peripheral arc determines SNA and hemodynamics in LPS-induced acute inflammation.

  4. Glucocorticoid inhibition of leptin- and lipopolysaccharide-induced interleukin-6 production in obesity.

    Science.gov (United States)

    Huang, Chun-Jung; Acevedo, Edmund O; Mari, David C; Randazzo, Christopher; Shibata, Yoshimi

    2014-01-01

    Obesity is considered a chronic inflammatory condition that enhances the risk of numerous inflammatory diseases, including diabetes and cardiovascular disease. Glucocorticoids (GCs) and synthetic therapeutic GCs are anti-inflammatory agents, but the exact functions of GCs in obesity-related inflammation are unknown. Therefore, the objective of this study was to examine the inhibitory effect of an exogenous GC (dexamethasone, DEX) on leptin- and lipopolysaccharide (LPS)-induced IL-6 production by peripheral blood mononuclear cells (PBMCs) ex vivo in obese subjects compared to normal-weight subjects. Blood samples were drawn from 14 obese (BMI>30 kg/m(2)) and 14 normal-weight (BMIobese subjects showed greater leptin- and LPS-induced IL-6 production compared to normal-weight subjects. The suppressive effect of DEX on leptin- and LPS-induced IL-6 production (IC50) was not different between the two groups. However, the IC50 of DEX for LPS-induced was correlated with BMI, waist circumference, and hip circumference. These findings suggest that reduced GC sensitivity may be an important mechanism in the up-regulation of selected obese inflammation. Published by Elsevier Inc.

  5. Lipopolysaccharide-induced Pulpitis Up-regulates TRPV1 in Trigeminal Ganglia

    Science.gov (United States)

    Chung, M.-K.; Lee, J.; Duraes, G.; Ro, J.Y.

    2011-01-01

    Tooth pain often accompanies pulpitis. Accumulation of lipopolysaccharides (LPS), a product of Gram-negative bacteria, is associated with painful clinical symptoms. However, the mechanisms underlying LPS-induced tooth pain are not clearly understood. TRPV1 is a capsaicin- and heat-gated nociceptive ion channel implicated in thermosensation and hyperalgesia under inflammation or injury. Although TRPV1 is expressed in pulpal afferents, it is not known whether the application of LPS to teeth modulates TRPV1 in trigeminal nociceptors. By assessing the levels of protein and transcript of TRPV1 in mouse trigeminal ganglia, we demonstrate that dentinal application of LPS increases the expression of TRPV1. Our results suggest that the up-regulation of TRPV1 in trigeminal nociceptors following bacterial infection could contribute to hyperalgesia under pulpitis conditions. PMID:21712529

  6. Bacterial lipopolysaccharide induces osteoclast formation in RAW 264.7 macrophage cells

    International Nuclear Information System (INIS)

    Islam, Shamima; Hassan, Ferdaus; Tumurkhuu, Gantsetseg; Dagvadorj, Jargalsaikhan; Koide, Naoki; Naiki, Yoshikazu; Mori, Isamu; Yoshida, Tomoaki; Yokochi, Takashi

    2007-01-01

    Lipopolysaccharide (LPS) is a potent bone resorbing factor. The effect of LPS on osteoclast formation was examined by using murine RAW 264.7 macrophage cells. LPS-induced the formation of multinucleated giant cells (MGC) in RAW 264.7 cells 3 days after the exposure. MGCs were positive for tartrate-resistant acid phosphatase (TRAP) activity. Further, MGC formed resorption pits on calcium-phosphate thin film that is a substrate for osteoclasts. Therefore, LPS was suggested to induce osteoclast formation in RAW 264.7 cells. LPS-induced osteoclast formation was abolished by anti-tumor necrosis factor (TNF)-α antibody, but not antibodies to macrophage-colony stimulating factor (M-CSF) and receptor activator of nuclear factor (NF)-κB ligand (RANKL). TNF-α might play a critical role in LPS-induced osteoclast formation in RAW 264.7 cells. Inhibitors of NF-κB and stress activated protein kinase (SAPK/JNK) prevented the LPS-induced osteoclast formation. The detailed mechanism of LPS-induced osteoclast formation is discussed

  7. Effect of methanolic extract of Asparagus racemosus Willd. on lipopolysaccharide induced-oxidative stress in rats.

    Science.gov (United States)

    Ahmad, Mohammad Parwez; Hussain, Arshad; Siddiqui, Hefazat Hussain; Wahab, Shadma; Adak, Manoranjan

    2015-03-01

    Lipopolysaccharide (LPS) induced oxidative stress and impairment of normal physiological function generally categorized by increased anxiety and reduced mobility. Therefore, the present study was to find out the effect Methanolic extract of Asparagus racemosus (MEAR ) in lipopolysaccharide (LPS)-induced oxidative stress in rats . LPS-induced oxidative stress in rats was measured by locomotor activity by photoactometer test, anxiety with elevated plus maze test and also studied the oxidative stress markers, nitric oxide and cytokines. The obtained data shows that LPS markedly exhausted (pAsparagus racemosus Willd. is a functionally newer type of cerebroprotective agent.

  8. Chondroitin Sulfate-Rich Extract of Skate Cartilage Attenuates Lipopolysaccharide-Induced Liver Damage in Mice.

    Science.gov (United States)

    Song, Yeong Ok; Kim, Mijeong; Woo, Minji; Baek, Jang-Mi; Kang, Keon-Hee; Kim, Sang-Ho; Roh, Seong-Soo; Park, Chan Hum; Jeong, Kap-Seop; Noh, Jeong-Sook

    2017-06-15

    The protective effects of a chondroitin sulfate-rich extract (CSE) from skate cartilage against lipopolysaccharide (LPS)-induced hepatic damage were investigated, and its mechanism of action was compared with that of chondroitin sulfate (CS) from shark cartilage. ICR mice were orally administrated 200 mg/kg body weight (BW) of CS or 400 mg/kg BW of CSE for 3 consecutive days, followed by a one-time intraperitoneal injection of LPS (20 mg/kg BW). The experimental groups were vehicle treatment without LPS injection (NC group), vehicle treatment with LPS injection (LPS group), CS pretreatment with LPS injection (CS group), and CSE pretreatment with LPS injection (CSE group). Hepatic antioxidant enzyme expression levels in the CS and CSE groups were increased relative to those in the LPS group. In LPS-insulted hepatic tissue, inflammatory factors were augmented relative to those in the NC group, but were significantly suppressed by pretreatment with CS or CSE. Moreover, CS and CSE alleviated the LPS-induced apoptotic factors and mitogen-activated protein kinase (MAPK). In addition, CS and CSE effectively decreased the serum lipid concentrations and downregulated hepatic sterol regulatory element-binding proteins expression. In conclusion, the skate CSE could protect against LPS-induced hepatic dyslipidemia, oxidative stress, inflammation, and apoptosis, probably through the regulation of MAPK signaling.

  9. Effect of anti-podoplanin antibody administration during lipopolysaccharide-induced lung injury in mice.

    Science.gov (United States)

    Lax, Sian; Rayes, Julie; Thickett, David R; Watson, Steve P

    2017-01-01

    Acute respiratory distress syndrome (ARDS) is a devastating pulmonary condition in the critically ill patient. A therapeutic intervention is yet to be found that can prevent progression to ARDS. We recently demonstrated that the interaction between podoplanin expressed on inflammatory alveolar macrophages (iAMs) and its endogenous ligand, platelet C-type lectin-like 2 (CLEC-2), protects against exaggerated lung inflammation during a mouse model of ARDS. In this study, we aim to investigate the therapeutic use of a crosslinking/activating anti-podoplanin antibody (α-PDPN, clone 8.1.1) during lipopolysaccharide (LPS)-induced lung inflammation in mice. Intravenous administration of α-PDPN was performed 6 hours after intratracheal LPS in wildtype, C57Bl/6 mice. Lung function decline was measured by pulse oximetry as well as markers of local inflammation including bronchoalveolar lavage neutrophilia and cytokine/chemokine expression. In parallel, alveolar macrophages were isolated and cultured in vitro from haematopoietic-specific podoplanin-deficient mice (Pdpn fl/fl VAV1cre + ) and floxed-only controls treated with or without LPS in the presence or absence of α-PDPN. Lung function decline as well as alveolar neutrophil recruitment was significantly decreased in mice treated with the crosslinking/activating α-PDPN in vivo. Furthermore, we demonstrate that, in vitro, activation of podoplanin on iAMs regulates their secretion of proinflammatory cytokines and chemokines. These data confirm the importance of the CLEC-2-podoplanin pathway during intratracheal (IT)-LPS and demonstrate the beneficial effect of targeting podoplanin during IT-LPS in mice possibly via modulation of local cytokine/chemokine expression. Moreover, these data suggest that podoplanin-targeted therapies may have a beneficial effect in patients at risk of developing ARDS.

  10. Rabdosia japonica var. glaucocalyx Flavonoids Fraction Attenuates Lipopolysaccharide-Induced Acute Lung Injury in Mice

    Directory of Open Access Journals (Sweden)

    Chun-jun Chu

    2014-01-01

    Full Text Available Rabdosia japonica var. glaucocalyx (Maxim. Hara, belonging to the Labiatae family, is widely used as an anti-inflammatory and antitumor drug for the treatment of different inflammations and cancers. Aim of the Study. To investigate therapeutic effects and possible mechanism of the flavonoids fraction of Rabdosia japonica var. glaucocalyx (Maxim. Hara (RJFs in acute lung injury (ALI mice induced by lipopolysaccharide (LPS. Materials and Methods. Mice were orally administrated with RJFs (6.4, 12.8, and 25.6 mg/kg per day for 7 days, consecutively, before LPS challenge. Lung specimens and the bronchoalveolar lavage fluid (BALF were isolated for histopathological examinations and biochemical analysis. The level of complement 3 (C3 in serum was quantified by a sandwich ELISA kit. Results. RJFs significantly attenuated LPS-induced ALI via reducing productions of the level of inflammatory mediators (TNF-α, IL-6, and IL-1β, and significantly reduced complement deposition with decreasing the level of C3 in serum, which was exhibited together with the lowered myeloperoxidase (MPO activity and nitric oxide (NO and protein concentration in BALF. Conclusions. RJFs significantly attenuate LPS-induced ALI via reducing productions of proinflammatory mediators, decreasing the level of complement, and reducing radicals.

  11. Interleukin-10 Protection against Lipopolysaccharide-Induced Neuro-Inflammation and Neurotoxicity in Ventral Mesencephalic Cultures.

    Science.gov (United States)

    Zhu, Yan; Chen, Xiao; Liu, Zhan; Peng, Yu-Ping; Qiu, Yi-Hua

    2015-12-28

    Interleukin (IL)-10, an anti-inflammatory cytokine, is expressed in the brain and can inhibit microglial activation. Herein, we utilized lipopolysaccharide (LPS)-induced inflammatory Parkinson's disease (PD) cell model to determine whether microglia and astrocytes are necessary targets for IL-10 neuroprotection. Primary ventral mesencephalic (VM) cultures with different composition of neurons, microglia and astrocytes were prepared. The cells were exposed to IL-10 (15, 50 or 150 ng/mL) 1 h prior to LPS (50 ng/mL) treatment. LPS induced dopaminergic and non-dopaminergic neuronal loss in VM cultures, VM neuron-enriched cultures, and neuron-microglia co-cultures, but not in neuron-astrocyte co-cultures. IL-10 reduced LPS-induced neuronal loss particularly in single VM neuron cultures. Pro-inflammatory mediators (TNF-α, IL-1β, inducible nitric oxide synthase and cyclooxygenase-2) were upregulated in both neuron-microglia and neuron-astrocyte co-cultures by LPS. In contrast, neurotrophic factors (brain-derived neurotrophic factor, insulin-like growth factor-1 or glial cell-derived neurotrophic factor) were downregulated in neuron-microglia co-cultures, but upregulated in neuron-astrocyte co-cultures by LPS. IL-10 reduced both the increase in production of the pro-inflammatory mediators and the decrease in production of the neurotrophic factors induced by LPS. These results suggest that astrocytes can balance LPS neurotoxicity by releasing more neurotrophic factors and that IL-10 exerts neuroprotective property by an extensive action including direct on neurons and indirect via inhibiting microglial activation.

  12. Pharmacologic studies on ET-26 hydrochloride in a rat model of lipopolysaccharide-induced sepsis.

    Science.gov (United States)

    Wang, Bin; Jiang, Junli; Yang, Jun; Chen, Jun; Zhu, Zhaoqiong; Liu, Jin; Zhang, Wensheng

    2017-11-15

    ET-26 hydrochloride (ET-26 HCl) is a promising sedation-hypnotic compound with stable hemodynamic features that elicits virtually no adrenocortical suppression. However, whether it preserves better pharmacologic characteristics in a rat model of sepsis is not known. This study compared the survival rate, levels of corticosterone and pro-inflammatory cytokines, and histologic injury in the lungs and kidneys of rats suffering from sepsis treated with ET-26 HCl, etomidate, or normal saline (NS). Rats were given lipopolysaccharide (1mg/kg body weight, i.v.) to establish a sepsis model. Thirty minutes after lipopolysaccharide administration, ET-26 HCl, etomidate or NS were given as a bolus injection at equivalent doses. Plasma levels of corticosterone, interleukin-1β, interleukin-6, interleukin-10, and tumor necrosis factor-α were measured 1, 2, 4, 6 and 24h after administration. Histologic injury was observed at the time of death or 24h after drug administration. The survival rate for rats in the etomidate, ET-26 HCl and NS groups was 40%, 90% and 90%, respectively. Corticosterone concentrations in the etomidate group were lower than those in the other groups 1h after administration of hypnotic compounds. Concentrations of pro-inflammatory cytokines in the ET-26 HCl group and NS group were not significantly different, but were significantly lower than those in the etomidate group. The injury scores of kidneys and lungs in the etomidate group were higher than those in ET-26 HCl and NS groups. ET-26 HCl showed virtually no suppression of corticosterone synthesis, lower concentrations of pro-inflammatory cytokines, higher survival rate, and less organ injury in rats suffering from sepsis compared with the etomidate group. It may be safer to induce anesthesia using ET-26 HCl, rather than etomidate, in patients suffering from sepsis. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. The effects of fisetin on lipopolysaccharide-induced depressive-like behavior in mice.

    Science.gov (United States)

    Yu, Xuefeng; Jiang, Xi; Zhang, Xiangming; Chen, Ziwei; Xu, Lexing; Chen, Lei; Wang, Guokang; Pan, Jianchun

    2016-10-01

    Major depressive disorder (MDD) involves a series of pathological changes including the inflammation and increased cytokine levels. Fisetin, a natural flavonoid, has anti-inflammatory and antioxidant, and also has been shown in our previous studies to exert anti-depressant-like properties. The present study aimed to investigate the effect of fisetin on lipopolysaccharide (LPS)-induced depressive-like behavior and inflammation in mice. The results suggested that the immobility time in the forced swimming test (FST) and tail suspension test (TST) were increased at 6 h, 12 h and 24 h after LPS injection (0.83 mg/kg). However, only the group of 24 h treatment did not show any effect on locomotion counts. Pretreatment with fisetin at doses of 20, 40 and 80 mg/kg (p.o.) for 7 days reversed LPS-induced alterations of the immobility time in both of these two tests. Further neurochemical assays suggested that pretreatment with fisetin reversed LPS-induced overexpression of pro-inflammatory cytokine (IL-1β, IL-6 and TNF-α) in the hippocampus and the prefrontal cortex (PFC). Moreover, higher dose of fisetin effectively antagonized iNOS mRNA expression and nitrite levels via the modulation of NF-κB in the hippocampus and PFC. Taken together, fisetin may be an effective therapeutic agent for LPS-induced depressive-like behaviors, which is due to its anti-inflammatory property.

  14. Obeticholic acid protects mice against lipopolysaccharide-induced liver injury and inflammation.

    Science.gov (United States)

    Xiong, Xi; Ren, Yuqian; Cui, Yun; Li, Rui; Wang, Chunxia; Zhang, Yucai

    2017-12-01

    Cholestasis, as a main manifestation, induces liver injury during sepsis. The farnesoid X receptor (FXR) plays an important role in regulating bile acid homeostasis. Whether FXR activation by its agonist obeticholic acid (OCA) is contributed to improve sepsis-induced liver injury remains unknown. The aim of the present study was to investigate the effect of OCA on lipopolysaccharide (LPS)-induced acute liver injury in mice. 8-week old male C57BL/6J mice were randomly divided into control group, LPS group, oral OCA group and LPS plus oral OCA (LPS + OCA) group. The serum and livers were collected for further analysis. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bile acid (TBA) and total bilirubin (TBIL) were measured at indicated time after LPS administration. Liver sections were stained with hematoxylin & eosin (H&E). Orally OCA pretreatment stimulated the expression of FXR and BSEP in livers and protected mice from LPS-induced hepatocyte apoptosis and inflammatory infiltration. Consistently, LPS-induced higher serum levels of ALT, AST, TBA and TBIL were significantly reversed by OCA administration. Meanwhile, the mRNA levels of interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α) and IL-6 were decreased in livers of mice in LPS + OCA group compared with LPS group. Further investigation indicated that the higher expression of ATF4 and LC3II/I were associated with the protective effect of OCA on LPS-induced liver injury. Orally OCA pretreatment protects mice from LPS-induced liver injury possibly contributed by improved bile acid homeostasis, decreased inflammatory factors and ATF4-mediated autophagy activity in hepatocytes. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  15. Fatty Acid Oxidation Compensates for Lipopolysaccharide-Induced Warburg Effect in Glucose-Deprived Monocytes

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    Nora Raulien

    2017-05-01

    Full Text Available Monocytes enter sites of microbial or sterile inflammation as the first line of defense of the immune system and initiate pro-inflammatory effector mechanisms. We show that activation with bacterial lipopolysaccharide (LPS induces them to undergo a metabolic shift toward aerobic glycolysis, similar to the Warburg effect observed in cancer cells. At sites of inflammation, however, glucose concentrations are often drastically decreased, which prompted us to study monocyte function under conditions of glucose deprivation and abrogated Warburg effect. Experiments using the Seahorse Extracellular Flux Analyzer revealed that limited glucose supply shifts monocyte metabolism toward oxidative phosphorylation, fueled largely by fatty acid oxidation at the expense of lipid droplets. While this metabolic state appears to provide sufficient energy to sustain functional properties like cytokine secretion, migration, and phagocytosis, it cannot prevent a rise in the AMP/ATP ratio and a decreased respiratory burst. The molecular trigger mediating the metabolic shift and the functional consequences is activation of AMP-activated protein kinase (AMPK. Taken together, our results indicate that monocytes are sufficiently metabolically flexible to perform pro-inflammatory functions at sites of inflammation despite glucose deprivation and inhibition of the LPS-induced Warburg effect. AMPK seems to play a pivotal role in orchestrating these processes during glucose deprivation in monocytes.

  16. Dietary Supplementation with Lactobacillus casei Alleviates Lipopolysaccharide-Induced Liver Injury in a Porcine Model

    Directory of Open Access Journals (Sweden)

    Di Zhao

    2017-11-01

    Full Text Available This study aims to determine whether Lactobacillus casei (L. casei could relieve liver injury in piglets challenged with lipopolysaccharide (LPS. Piglets were randomly allocated into one of the three groups: control, LPS, and L. casei. The control and LPS groups were fed a corn- and soybean meal-based diet, whereas the L. casei group was fed the basal diet supplemented with 6 × 106 cfu/g L. casei. On Day 31 of the trial, piglets in the LPS and L. casei groups received intraperitoneal administration of LPS (100 µg/kg body weight, while the control group received the same volume of saline. Blood and liver samples were collected for analysis. Results showed that L. casei supplementation decreased the feed/gain ratio (p = 0.027 and diarrhea incidence (p < 0.001, and attenuated LPS-induced liver histomorphological abnormalities. Compared with the control group, LPS challenge dramatically increased glutamyl transpeptidase activity (p = 0.001 in plasma as well as the concentrations of Interleukin 6 (IL-6 (p = 0.048, Tumor necrosis factor-alpha (TNF-α (p = 0.041, and Malondialdehyde (MDA (p = 0.001 in the liver, while decreasing the hepatic SOD activity. LPS also increased (p < 0.05 the mRNA levels for IL-6, IL-8, TNF-α, Toll-like receptors 4 (TLR4, Nuclear factor κB (NF-κB and Heat shock protein 70 (HSP70 in the liver. The adverse effects of LPS challenge were ameliorated by L. casei supplementation. In conclusion, dietary L. casei alleviates LPS-induced liver injury via reducing pro-inflammatory cytokines and increasing anti-oxidative capacity.

  17. Cardiac-specific overexpression of catalase attenuates lipopolysaccharide-induced myocardial contractile dysfunction: role of autophagy.

    Science.gov (United States)

    Turdi, Subat; Han, Xuefeng; Huff, Anna F; Roe, Nathan D; Hu, Nan; Gao, Feng; Ren, Jun

    2012-09-15

    Lipopolysaccharide (LPS) from gram-negative bacteria is a major initiator of sepsis, leading to cardiovascular collapse. Accumulating evidence has indicated a role of reactive oxygen species (ROS) in cardiovascular complications in sepsis. This study was designed to examine the effect of cardiac-specific overexpression of catalase in LPS-induced cardiac contractile dysfunction and the underlying mechanism(s) with a focus on autophagy. Catalase transgenic and wild-type FVB mice were challenged with LPS (6 mg/kg) and cardiac function was evaluated. Levels of oxidative stress, autophagy, apoptosis, and protein damage were examined using fluorescence microscopy, Western blot, TUNEL assay, caspase-3 activity, and carbonyl formation. A Kaplan-Meier curve was constructed for survival after LPS treatment. Our results revealed a lower mortality in catalase mice compared with FVB mice after LPS challenge. LPS injection led to depressed cardiac contractile capacity as evidenced by echocardiography and cardiomyocyte contractile function, the effect of which was ablated by catalase overexpression. LPS treatment induced elevated TNF-α level, autophagy, apoptosis (TUNEL, caspase-3 activation, cleaved caspase-3), production of ROS and O(2)(-), and protein carbonyl formation, the effects of which were significantly attenuated by catalase overexpression. Electron microscopy revealed focal myocardial damage characterized by mitochondrial injury after LPS treatment, which was less severe in catalase mice. Interestingly, LPS-induced cardiomyocyte contractile dysfunction was prevented by the antioxidant N-acetylcysteine and the autophagy inhibitor 3-methyladenine. Taken together, our data revealed that catalase protects against LPS-induced cardiac dysfunction and mortality, which may be associated with inhibition of oxidative stress and autophagy. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Cardiac-Specific Overexpression of Catalase Attenuates Lipopolysaccharide-Induced Myocardial Contractile Dysfunction: Role of Autophagy

    OpenAIRE

    Turdi, Subat; Han, Xuefeng; Huff, Anna F.; Roe, Nathan D.; Hu, Nan; Gao, Feng; Ren, Jun

    2012-01-01

    Lipopolysaccharide (LPS) from Gram-negative bacteria is a major initiator of sepsis, leading to cardiovascular collapse. Accumulating evidence has indicated a role of reactive oxygen species (ROS) in cardiovascular complication in sepsis. This study was designed to examine the effect of cardiac-specific overexpression of catalase in LPS-induced cardiac contractile dysfunction and the underlying mechanism(s) with a focus on autophagy. Catalase transgenic and wild-type FVB mice were challenged ...

  19. Improved Hepatoprotective Effect of Liposome-Encapsulated Astaxanthin in Lipopolysaccharide-Induced Acute Hepatotoxicity

    Directory of Open Access Journals (Sweden)

    Chun-Hung Chiu

    2016-07-01

    Full Text Available Lipopolysaccharide (LPS-induced acute hepatotoxicity is significantly associated with oxidative stress. Astaxanthin (AST, a xanthophyll carotenoid, is well known for its potent antioxidant capacity. However, its drawbacks of poor aqueous solubility and low bioavailability have limited its utility. Liposome encapsulation is considered as an effective alternative use for the improvement of bioavailability of the hydrophobic compound. We hypothesized that AST encapsulated within liposomes (LA apparently shows improved stability and transportability compared to that of free AST. To investigate whether LA administration can efficiently prevent the LPS-induced acute hepatotoxicity, male Sprague-Dawley rats (n = six per group were orally administered liposome-encapsulated AST at 2, 5 or 10 mg/kg-day (LA-2, LA-5, and LA-10 for seven days and then were LPS-challenged (i.p., 5 mg/kg. The LA-10 administered group, but not the other groups, exhibited a significant amelioration of serum glutamic pyruvic transaminase (GPT, glutamic oxaloacetic transaminase (GOT, blood urea nitrogen (BUN, creatinine (CRE, hepatic malondialdehyde (MDA and glutathione peroxidase (GSH-Px, IL-6, and hepatic nuclear NF-κB and inducible nitric oxide synthase (iNOS, suggesting that LA at a 10 mg/kg-day dosage renders hepatoprotective effects. Moreover, the protective effects were even superior to that of positive control N-acetylcysteine (NAC, 200 mg/kg-day. Histopathologically, NAC, free AST, LA-2 and LA-5 partially, but LA-10 completely, alleviated the acute inflammatory status. These results indicate that hydrophobic AST after being properly encapsulated by liposomes improves bioavailability and can also function as potential drug delivery system in treating hepatotoxicity.

  20. Protective effects of kaempferol on lipopolysaccharide-induced mastitis in mice.

    Science.gov (United States)

    Cao, Rongfeng; Fu, Kaiqiang; Lv, Xiaopei; Li, Weishi; Zhang, Naisheng

    2014-10-01

    Kaempferol isolated from the root of Zingiberaceae plants galangal and other Chinese herbal medicines have been reported to have anti-inflammatory properties. However, the anti-inflammatory effects of kaempferol on lipopolysaccharide (LPS)-induced mastitis are unknown and their underlying molecular mechanisms remain to be explored. The aim of this study was to evaluate the effects of kaempferol on LPS-induced mouse mastitis. The mouse model of mastitis was induced by injection of LPS through the duct of mammary gland. Kaempferol was injected 1 h before and 12 h after induction of LPS intraperitoneally. The present results showed that kaempferol markedly reduced infiltration of neutrophilic granulocyte, activation of myeloperoxidase (MPO), expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in a dose-dependent manner, which were increased in LPS-induced mouse mastitis. Furthermore, kaempferol suppressed the phosphorylation of nuclear factor-κB (NF-κB) p65 subunit and the degradation of its inhibitor IκBα. All results suggest that anti-inflammatory effects of kaempferol against the LPS-induced mastitis possibly through inhibition of the NF-κB signaling pathway. Kaempferol may be a potential therapeutic agent for mastitis.

  1. Magnesium Isoglycyrrhizinate attenuates lipopolysaccharide-induced depressive-like behavior in mice.

    Science.gov (United States)

    Jiang, Wenjiao; Chen, Qianying; Li, Peijin; Lu, Qianfeng; Pei, Xue; Sun, Yilin; Wang, Guangji; Hao, Kun

    2017-02-01

    Magnesium Isoglycyrrhizinate (MI) is a magnesium salt of 18α-GA stereoisomer which has been reported to exert hepatoprotective activity. The aim of the present study was to ascertain the underlying mechanisms behind the action of Magnesium Isoglycyrrhizinate on neuroinflammatation and oxidative stress in LPS-stimulated mice. Mice were pretreated with Magnesium Isoglycyrrhizinate (MI, 25, 50mg/kg) as well as fluoxetine (Flu, positive control, 20mg/kg) once daily for one week before intraperitoneal injection of LPS (0.83mg/kg). Pretreatments with MI and Flu significantly improved immobility time in tail suspension test (TST) and forced swim test (FST) as well as locomotor activity in open-field test (OFT). In addition, the levels of pro-inflammatory cytokines and oxidative stress in serum and hippocampus were also suppressed effectively by MI and Flu administrations. Western blot analysis showed the up-regulated levels of p-Jak3, p-STAT3, p-NF-κBp65, and p-IκBα in mice exposed to LPS, while different degrees of down-regulation in these expression were observed in MI (25, 50mg/kg) and Flu (20mg/kg) groups respectively. Taken together, our obtained results demonstrated that Magnesium Isoglycyrrhizinate (MI) exhibited an antidepressant-like effect in LPS-induced mice, which might be mediated by JAK/STAT/NF-κB signaling pathway. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  2. Beneficial effect of honokiol on lipopolysaccharide induced anxiety-like behavior and liver damage in mice.

    Science.gov (United States)

    Sulakhiya, Kunjbihari; Kumar, Parveen; Gurjar, Satendra S; Barua, Chandana C; Hazarika, Naba K

    2015-02-26

    Anxiety disorders are commonly occurring co-morbid neuropsychiatric disorders with chronic inflammatory conditions such as live damage. Numerous studies revealed that peripheral inflammation, oxidative stress and brain derived neurotrophic factor (BDNF) play important roles in the pathophysiology of anxiety disorders. Honokiol (HNK) is a polyphenol, possessing multiple biological activities including antioxidant, anti-inflammatory, anxiolytic, antidepressant and hepatoprotection. The present study was designed to investigate the effect of HNK, in lipopolysaccharide (LPS)-induced anxiety-like behavior and liver damage in mice. Mice (n=6-10/group) were pre-treated with different doses of HNK (2.5 and 5mg/kg; i.p.) for two days, and challenged with saline or LPS (0.83mg/kg; i.p.) on third day. Anxiety-like behavior was monitored using elevated plus maze (EPM) and open field test (OFT). Animals were sacrificed to evaluate various biochemical parameters in plasma and liver. HNK pre-treatment provided significant (P<0.01) protection against LPS-induced reduction in body weight, food and water intake in mice. HNK at higher dose significantly (P<0.05) attenuated LPS-induced anxiety-like behavior by increasing the number of entries and time spent in open arm in EPM test, and by increasing the frequency in central zone in OFT. HNK pre-treatment ameliorated LPS-induced peripheral inflammation by reducing plasma IL-1β, IL-6, TNF-α level, and also improved the plasma BDNF level, prevented liver damage via attenuating transaminases (AST, ALT), liver oxidative stress and TNF-α activity in LPS challenged mice. In conclusion, the current investigation suggests that HNK provided beneficial effect against LPS-induced anxiety-like behavior and liver damage which may be governed by inhibition of cytokines production, oxidative stress and depletion of plasma BDNF level. Our result suggests that HNK could be a therapeutic approach for the treatment of anxiety and other neuropsychiatric disorders associated with inflammation and oxidative stress. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Lipopolysaccharide-induced metabolome signature in Arabidopsis thaliana reveals dynamic reprogramming of Phytoalexin and Phytoanticipin pathways

    CSIR Research Space (South Africa)

    Finnegan, T

    2016-09-01

    Full Text Available tentatively identified. These include the phytohormones salicylic acid and jasmonic acid, and also the associated methyl esters and sugar conjugates. The induced defensive state resulted in increases in indoleÐand other glucosinolates, indole derivatives...

  4. Enriched dairy fat matrix diet prevents early life lipopolysaccharide-induced spatial memory impairment at adulthood.

    Science.gov (United States)

    Dinel, A L; Rey, C; Baudry, C; Fressange-Mazda, C; Le Ruyet, P; Nadjar, A; Pallet, P; Joffre, C; Layé, S

    2016-10-01

    Polyunsaturated fatty acids (PUFAs) are essential fatty acids, which are critical for brain development and later life cognitive functions. The main brain PUFAs are docosahexaenoic acid (DHA) for the n-3 family and arachidonic acid (ARA) for the n-6 family, which are provided to the post-natal brain by breast milk or infant formula. Recently, the use of dairy lipids (DL) in replacement of vegetable lipids (VL) was revealed to potently promote the accretion of DHA in the developing brain. Brain DHA, in addition to be a key component of brain development, display potent anti-inflammatory activities, which protect the brain from adverse inflammatory events. In this work, we evaluated the protective effect of partial replacement of VL by DL, supplemented or not with DHA and ARA, on post-natal inflammation and its consequence on memory. Mice were fed with diets poor in vegetal n-3 PUFA (Def VL), balanced in vegetal n-3/n-6 PUFA (Bal VL), balanced in dairy lipids (Bal DL) or enriched in DHA and ARA (Supp VL; Supp DL) from the first day of gestation until adulthood. At post-natal day 14 (PND14), pups received a single administration of the endotoxin lipopolysaccharide (LPS) and brain cytokine expression, microglia phenotype and neurogenesis were measured. In a second set of experiments, memory and neurogenesis were measured at adulthood. Overall, our data showed that lipid quality of the diet modulates early life LPS effect on microglia phenotype, brain cytokine expression and neurogenesis at PND14 and memory at adulthood. In particular, Bal DL diet protects from the adverse effect of early life LPS exposure on PND14 neurogenesis and adult spatial memory. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Cardiac-Specific Overexpression of Catalase Attenuates Lipopolysaccharide-Induced Myocardial Contractile Dysfunction: Role of Autophagy

    Science.gov (United States)

    Turdi, Subat; Han, Xuefeng; Huff, Anna F.; Roe, Nathan D.; Hu, Nan; Gao, Feng; Ren, Jun

    2012-01-01

    Lipopolysaccharide (LPS) from Gram-negative bacteria is a major initiator of sepsis, leading to cardiovascular collapse. Accumulating evidence has indicated a role of reactive oxygen species (ROS) in cardiovascular complication in sepsis. This study was designed to examine the effect of cardiac-specific overexpression of catalase in LPS-induced cardiac contractile dysfunction and the underlying mechanism(s) with a focus on autophagy. Catalase transgenic and wild-type FVB mice were challenged with LPS (6 mg/kg) and cardiac function was evaluated. Levels of oxidative stress, autophagy, apoptosis and protein damage were examined using fluorescence microscopy, Western blot, TUNEL assay, caspase-3 activity and carbonyl formation. Kaplan-Meier curve was constructed for survival following LPS treatment. Our results revealed a lower mortality in catalase mice compared with FVB mice following LPS challenge. LPS injection led to depressed cardiac contractile capacity as evidenced by echocardiography and cardiomyocyte contractile function, the effect of which was ablated by catalase overexpression. LPS treatment induced elevated TNF-α level, autophagy, apoptosis (TUNEL, caspase-3 activation, cleaved caspase-3), production of ROS and O2−, and protein carbonyl formation, the effects of which were significantly attenuated by catalase overexpression. Electron microscopy revealed focal myocardial damage characterized by mitochondrial injury following LPS treatment, which was less severe in catalase mice. Interestingly, LPS-induced cardiomyocyte contractile dysfunction was prevented by antioxidant NAC and the autophagy inhibitor 3-methyladenine. Taken together, our data revealed that catalase protects against LPS-induced cardiac dysfunction and mortality, which may be associated with inhibition of oxidative stress and autophagy. PMID:22902401

  6. Effect of azithromycin on Prevotella intermedia lipopolysaccharide-induced production of interleukin-6 in murine macrophages.

    Science.gov (United States)

    Choi, Eun-Young; Jin, Ji-Young; Choi, Jeom-Il; Choi, In Soon; Kim, Sung-Jo

    2014-04-15

    Interleukin-6 (IL-6) is a key proinflammatory cytokine which plays a central role in the pathogenesis of periodontal disease. Host modulatory agents targeting at inhibiting IL-6, therefore, appear to be beneficial in slowing the progression of periodontal disease and potentially reducing destructive aspects of the host response. The present study was designed to investigate the effect of the macrolide antibiotic azithromycin on IL-6 generation in murine macrophages treated with lipopolysaccharide (LPS) from Prevotella intermedia, a pathogen implicated in inflammatory periodontal disease, and its mechanisms of action. Azithromycin significantly suppressed IL-6 production as well as its mRNA expression in P. intermedia LPS-activated RAW264.7 cells. LPS-induced activation of JNK and p38 was not affected by azithromycin treatment. Azithromycin failed to prevent P. intermedia LPS from degrading IκB-α. Instead, azithromycin significantly diminished nuclear translocation and DNA binding activity of NF-κB p50 subunit induced with LPS. Azithromycin inhibited P. intermedia LPS-induced STAT1 and STAT3 phosphorylation. In addition, azithromycin up-regulated the mRNA level of SOCS1 in cells treated with LPS. In conclusion, azithromycin significantly attenuated P. intermedia LPS-induced production of IL-6 in murine macrophages via inhibition of NF-κB, STAT1 and STAT3 activation, which is possibly related to the activation of SOCS1 signaling. Further in vivo studies are required to better evaluate the potential of azithromycin in the treatment of periodontal disease. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Saccharomyces boulardii inhibits lipopolysaccharide-induced activation of human dendritic cells and T cell proliferation

    Science.gov (United States)

    Thomas, S; Przesdzing, I; Metzke, D; Schmitz, J; Radbruch, A; Baumgart, D C

    2009-01-01

    Saccharomyces boulardii (Sb) is a probiotic yeast preparation that has demonstrated efficacy in inflammatory and infectious disorders of the gastrointestinal tract in controlled clinical trials. Although patients clearly benefit from treatment with Sb, little is known on how Sb unfolds its anti-inflammatory properties in humans. Dendritic cells (DC) balance tolerance and immunity and are involved critically in the control of T cell activation. Thus, they are believed to have a pivotal role in the initiation and perpetuation of chronic inflammatory disorders, not only in the gut. We therefore decided to investigate if Sb modulates DC function. Culture of primary (native, non-monocyte-derived) human myeloid CD1c+CD11c+CD123– DC (mDC) in the presence of Sb culture supernatant (active component molecular weight < 3 kDa, as evaluated by membrane partition chromatography) reduced significantly expression of the co-stimulatory molecules CD40 and CD80 (P < 0·01) and the DC mobilization marker CC-chemokine receptor CCR7 (CD197) (P < 0·001) induced by the prototypical microbial antigen lipopolysaccharide (LPS). Moreover, secretion of key proinflammatory cytokines such as tumour necrosis factor-α and interleukin (IL)-6 were notably reduced, while the secretion of anti-inflammatory IL-10 increased. Finally, Sb supernatant inhibited the proliferation of naive T cells in a mixed lymphocyte reaction with mDC. In summary, our data suggest that Sb may exhibit part of its anti-inflammatory potential through modulation of DC phenotype, function and migration by inhibition of their immune response to bacterial microbial surrogate antigens such as LPS. PMID:19161443

  8. Atomic force microscopy observation of lipopolysaccharide-induced cardiomyocyte cytoskeleton reorganization.

    Science.gov (United States)

    Wang, Liqun; Chen, Tangting; Zhou, Xiang; Huang, Qiaobing; Jin, Chunhua

    2013-08-01

    We applied atomic force microscopy (AFM) to observe lipopolysaccharide (LPS)-induced intracellular cytoskeleton reorganization in primary cardiomyocytes from neonatal mouse. The nonionic detergent Triton X-100 was used to remove the membrane, soluble proteins, and organelles from the cell. The remaining cytoskeleton can then be directly visualized by AFM. Using three-dimensional technique of AFM, we were able to quantify the changes of cytoskeleton by the "density" and total "volume" of the cytoskeleton fibers. Compared to the control group, the density of cytoskeleton was remarkably decreased and the volume of cytoskeleton was significantly increased after LPS treatment, which suggests that LPS may induce the cytoskeleton reorganization and change the cardiomyocyte morphology. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Alpha-lipoic acid protects mitochondrial enzymes and attenuates lipopolysaccharide-induced hypothermia in mice

    Science.gov (United States)

    Abstract: Hypothermia is a key symptom of sepsis and the mechanism(s) leading to hypothermia during sepsis is largely unknown. To investigate a potential mechanism and find an effective treatment for hypothermia in sepsis, we induced hypothermia in mice by lipopolysaccharide (LP...

  10. Effects of propofol on lipopolysaccharide-induced expression and release of HMGB1 in macrophages

    Energy Technology Data Exchange (ETDEWEB)

    Wang, T.; Wei, X.Y.; Liu, B.; Wang, L.J.; Jiang, L.H. [Department of Anesthesiology, the Third Affiliated Hospital, Zhengzhou University, Zhengzhou (China)

    2015-02-24

    This study aimed to determine the effects of different concentrations of propofol (2,6-diisopropylphenol) on lipopolysaccharide (LPS)-induced expression and release of high-mobility group box 1 protein (HMGB1) in mouse macrophages. Mouse macrophage cell line RAW264.7 cells were randomly divided into 5 treatment groups. Expression levels of HMGB1 mRNA were detected using RT-PCR, and cell culture supernatant HMGB1 protein levels were detected using enzyme-linked immunosorbent assay (ELISA). Translocation of HMGB1 from the nucleus to the cytoplasm in macrophages was observed by Western blotting and activity of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in the nucleus was detected using ELISA. HMGB1 mRNA expression levels increased significantly in the cell culture supernatant and in cells after 24 h of stimulating RAW264.7 cells with LPS (500 ng/mL). However, HMGB1 mRNA expression levels in the P2 and P3 groups, which received 500 ng/mL LPS with 25 or 50 μmol/mL propofol, respectively, were significantly lower than those in the group receiving LPS stimulation (P<0.05). After stimulation by LPS, HMGB1 protein levels were reduced significantly in the nucleus but were increased in the cytoplasm (P<0.05). Simultaneously, the activity of NF-κB was enhanced significantly (P<0.05). After propofol intervention, HMGB1 translocation from the nucleus to the cytoplasm and NF-κB activity were inhibited significantly (each P<0.05). Thus, propofol can inhibit the LPS-induced expression and release of HMGB1 by inhibiting HMGB1 translocation and NF-κB activity in RAW264.7 cells, suggesting propofol may be protective in patients with sepsis.

  11. RGD-tagged helical rosette nanotubes aggravate acute lipopolysaccharide-induced lung inflammation

    Directory of Open Access Journals (Sweden)

    Suri SS

    2011-12-01

    Full Text Available Sarabjeet Singh Suri1, Steven Mills1, Gurpreet Kaur Aulakh1, Felaniaina Rakotondradany2, Hicham Fenniri2, Baljit Singh11Department of Veterinary Biomedical Sciences, University of Saskatchewan, Saskatoon; 2National Institute for Nanotechnology and Department of Chemistry, Edmonton, CanadaAbstract: Rosette nanotubes (RNT are a novel class of self-assembled biocompatible nanotubes that offer a built-in strategy for engineering structure and function through covalent tagging of synthetic self-assembling modules (G∧C motif. In this report, the G∧C motif was tagged with peptide Arg-Gly-Asp-Ser-Lys (RGDSK-G∧C and amino acid Lys (K-G∧C which, upon co-assembly, generate RNTs featuring RGDSK and K on their surface in predefined molar ratios. These hybrid RNTs, referred to as Kx/RGDSKy-RNT, where x and y refer to the molar ratios of K-G∧C and RGDSK–G∧C, were designed to target neutrophil integrins. A mouse model was used to investigate the effects of intravenous Kx/RGDSKy-RNT on acute lipopolysaccharide (LPS-induced lung inflammation. Healthy male C57BL/6 mice were treated intranasally with Escherichia coli LPS 80 µg and/or intravenously with K90/RGDSK10-RNT. Here we provide the first evidence that intravenous administration of K90/RGDSK10-RNT aggravates the proinflammatory effect of LPS in the mouse. LPS and K90/RGDSK10-RNT treatment groups showed significantly increased infiltration of polymorphonuclear cells in bronchoalveolar lavage fluid at all time points compared with the saline control. The combined effect of LPS and K90/RGDSK10-RNT was more pronounced than LPS alone, as shown by a significant increase in the expression of interleukin-1ß, MCP-1, MIP-1, and KC-1 in the bronchoalveolar lavage fluid and myeloperoxidase activity in the lung tissues. We conclude that K90/RGDSK10-RNT promotes acute lung inflammation, and when used along with LPS, leads to exaggerated immune response in the lung.Keywords: RGD peptide, helical rosette nanotubes, neutrophils, macrophages, chemokines, inflammation

  12. Possible Mechanisms Involved in Attenuation of Lipopolysaccharide-Induced Memory Deficits by Methyl Jasmonate in Mice.

    Science.gov (United States)

    Eduviere, Anthony Taghogho; Umukoro, Solomon; Adeoluwa, Olusegun A; Omogbiya, Itivere Adrian; Aluko, Oritoke Modupe

    2016-12-01

    This present study was carried out to investigate the likely mechanisms by which methyl jasmonate (MJ), 'an agent widely used in aromatherapy for neurological disorders, attenuates lipopolysaccharide (LPS)-induced memory deficits in mice. Mice were given intraperitoneal administration of LPS (250 µg/kg) alone or in combination with MJ (10-40 mg/kg), donepezil, DP (1 mg/kg), or vehicle for 7 successive days. Thereafter, memory was assessed using object recognition test (ORT). Acetylcholinesterase and myeloperoxidase activities were estimated in brain tissue homogenates. Brain levels of nitric oxide and markers of oxidative stress as well as histopathologic changes of the prefrontal cortex and cornu ammonis 1 (CA1) of the hippocampal region were also assessed. MJ (10-40 mg/kg) attenuated LPS-induced memory impairment in ORT. Moreover, the increased brain activities of acetylcholinesterase and myeloperoxidase enzymes were suppressed by MJ when compared with control (p memory deficits via mechanisms related to inhibition of acetylcholinesterase, myeloperoxidase, oxidative stress and neuronal degeneration.

  13. Methyl jasmonate attenuated lipopolysaccharide-induced depressive-like behaviour in mice.

    Science.gov (United States)

    Adebesin, Adaeze; Adeoluwa, Olusegun A; Eduviere, Anthony T; Umukoro, Solomon

    2017-11-01

    Depression is a recurrent neuropsychiatric disorder that affects millions of individuals worldwide and impact negatively on the patients' social functions and quality of life. Studies have shown that i.p injection of lipopolysaccharide (LPS) induces depressive-like behavior in rodents via induction of oxidative stress and neuroinflammation. Methyl jasmonate (MJ), an isolated compound from jasmine plant has gained reputation in aromatherapy for treatment of depression, nervousness and memory deficits. This study was designed to evaluate the effects of MJ on LPS-induced depressive-like behavior in mice. Mice were given MJ (5-20 mg/kg), imipramine (10 mg/kg) or vehicle (10 mL/kg) intraperitoneally for 7 consecutive days. On day 7, treatment was carried out 30 min prior to i.p injection of LPS (830 μg/kg). Twenty four hours after LPS administration, tail suspension, forced swim and sucrose preference tests were carried out. Thereafter, serum corticosterone levels were determined using ELISA. The levels of malondialdehyde (MDA), glutathione (GSH) and tumor necrosis factor-alpha (TNF-α) were determined in brain tissue homogenates. LPS significantly increased immobility time in the tail suspension and forced swim tests when compared with vehicle (p < 0.05), which indicates depressive-like syndromes. However, the increased immobility time was significantly reduced by MJ (5-20 mg/kg) when compared with LPS-treated group. LPS administration also altered the levels of MDA, GSH, corticosterone and TNF alpha in mice, which was significantly reversed by MJ. These findings suggest that attenuation of LPS-induced depressive-like behavior by MJ may be related to suppression of oxidative stress and release of TNF alpha. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Lipopolysaccharide-induced neuronal activation in the paraventricular and dorsomedial hypothalamus depends on ambient temperature.

    Directory of Open Access Journals (Sweden)

    Samuel P Wanner

    Full Text Available Systemic inflammatory response syndrome is associated with either fever or hypothermia, but the mechanisms responsible for switching from one to the other are unknown. In experimental animals, systemic inflammation is often induced by bacterial lipopolysaccharide (LPS. To identify the diencephalic and brainstem structures involved in the fever-hypothermia switch, we studied the expression of c-Fos protein, a marker of neuronal activation, in rats treated with the same high dose of LPS (0.5 mg/kg, intravenously either in a thermoneutral (30 °C or cool (24 °C environment. At 30 °C, LPS caused fever; at 24 °C, the same dose caused profound hypothermia. Both fever and hypothermia were associated with the induction of c-Fos in many brain areas, including several structures of the anterior preoptic, paraventricular, lateral, and dorsal hypothalamus, the bed nucleus of the stria terminalis, the posterior pretectal nucleus, ventrolateral periaqueductal gray, lateral parabrachial nucleus, area postrema, and nucleus of the solitary tract. Every brain area studied showed a comparable response to LPS at the two different ambient temperatures used, with the exception of two areas: the dorsomedial hypothalamic nucleus (DMH, which we studied together with the adjacent dorsal hypothalamic area (DA, and the paraventricular hypothalamic nucleus (PVH. Both structures had much stronger c-Fos expression during LPS hypothermia than during fever. We propose that PVH and DMH/DA neurons are involved in a circuit, which - depending on the ambient temperature - determines whether the thermoregulatory response to bacterial LPS will be fever or hypothermia.

  15. Deer Bone Oil Extract Suppresses Lipopolysaccharide-Induced Inflammatory Responses in RAW264.7 Cells.

    Science.gov (United States)

    Choi, Hyeon-Son; Im, Suji; Park, Yooheon; Hong, Ki-Bae; Suh, Hyung Joo

    2016-01-01

    The aim of this study was to investigate the effect of deer bone oil extract (DBOE) on lipopolysaccharide (LPS)-induced inflammatory responses in RAW264.7 cells. DBOE was fractionated by liquid-liquid extraction to obtain two fractions: methanol fraction (DBO-M) and hexane fraction (DBO-H). TLC showed that DBO-M had relatively more hydrophilic lipid complexes, including unsaturated fatty acids, than DBOE and DBO-H. The relative compositions of tetradecenoyl carnitine, α-linoleic acid, and palmitoleic acid increased in the DBO-M fraction by 61, 38, and 32%, respectively, compared with DBOE. The concentration of sugar moieties was 3-fold higher in the DBO-M fraction than DBOE and DBO-H. DBO-M significantly decreased LPS-induced nitric oxide (NO) production in RAW264.7 cells in a dose-dependent manner. This DBO-M-mediated decrease in NO production was due to downregulation of mRNA and protein levels of inducible nitric oxide synthase (iNOS). In addition, mRNA expression of pro-inflammatory mediators, such as cyclooxygenase (COX-2), interleukin (IL)-1β, and IL-12β, was suppressed by DBO-M. Our data showed that DBO-M, which has relatively higher sugar content than DBOE and DBO-H, could play an important role in suppressing inflammatory responses by controlling pro-inflammatory cytokines and mediators.

  16. Computational Topology Based Quantification Of Hepatocytes Nuclei In Lipopolysaccharide-Induced Liver Injury In Mice

    Directory of Open Access Journals (Sweden)

    Rodrigo Rojas Moraleda

    2016-06-01

    The computational topology approach proposed successfully detected hepatocyte cells under several natural variations. We evaluated on a per-pixel basis how the segmentation performs on: i all nuclei in the images, ii big round nuclei considered belonging to hepatocytes cells (accuracy 87.2%, recall 80.3%, and iii nuclei regarded to non-parenchymal cells.  

  17. Differential Involvement of the Suprachiasmatic Nucleus in Lipopolysaccharide-Induced Plasma Glucose and Corticosterone Responses

    NARCIS (Netherlands)

    Kalsbeek, Andries; Liu, Ji; Lei, Jun; Timmermans, Loes; Foppen, Ewout; Cailotto, Cathy; Fliers, Eric

    2012-01-01

    The hypothalamic suprachiasmatic nucleus (SCN) is an essential component of the circadian timing system, and an important determinant of neuroendocrine and metabolic regulation. Recent data indicate a modulatory role for the immune system on the circadian timing system. The authors investigated how

  18. Bursopentin (BP5 protects dendritic cells from lipopolysaccharide-induced oxidative stress for immunosuppression.

    Directory of Open Access Journals (Sweden)

    Tao Qin

    Full Text Available Dendritic cells (DCs play a vital role in the regulation of immune-mediated inflammatory diseases. Thus, DCs have been regarded as a major target for the development of immunomodulators. However, oxidative stress could disturb inflammatory regulation in DCs. Here, we examined the effect of bursopentine (BP5, a novel pentapeptide isolated from chicken bursa of fabricius, on the protection of DCs against oxidative stress for immunosuppression. BP5 showed potent protective effects against the lipopolysaccharide (LPS-induced oxidative stress in DCs, including nitric oxide, reactive oxygen species and lipid peroxidation. Furthermore, BP5 elevated the level of cellular reductive status through increasing the reduced glutathione (GSH and the GSH/GSSG ratio. Concomitant with these, the activities of several antioxidative redox enzymes, including glutathione peroxidase (GPx, catalase (CAT and superoxide dismutase (SOD, were obviously enhanced. BP5 also suppressed submucosal DC maturation in the LPS-stimulated intestinal epithelial cells (ECs/DCs coculture system. Finally, we found that heme oxygenase 1 (HO-1 was remarkably upregulated by BP5 in the LPS-induced DCs, and played an important role in the suppression of oxidative stress and DC maturation. These results suggested that BP5 could protect the LPS-activated DCs against oxidative stress and have potential applications in DC-related inflammatory responses.

  19. Isostatic compression of buffer blocks. Middle scale

    International Nuclear Information System (INIS)

    Ritola, J.; Pyy, E.

    2012-01-01

    Manufacturing of buffer components using isostatic compression method has been studied in small scale in 2008 (Laaksonen 2010). These tests included manufacturing of buffer blocks using different bentonite materials and different compression pressures. Isostatic mould technology was also tested, along with different methods to fill the mould, such as vibration and partial vacuum, as well as a stepwise compression of the blocks. The development of manufacturing techniques has continued with small-scale (30 %) blocks (diameter 600 mm) in 2009. This was done in a separate project: Isostatic compression, manufacturing and testing of small scale (D = 600 mm) buffer blocks. The research on the isostatic compression method continued in 2010 in a project aimed to test and examine the isostatic manufacturing process of buffer blocks at 70 % scale (block diameter 1200 to 1300 mm), and the aim was to continue in 2011 with full-scale blocks (diameter 1700 mm). A total of nine bentonite blocks were manufactured at 70 % scale, of which four were ring-shaped and the rest were cylindrical. It is currently not possible to manufacture full-scale blocks, because there is no sufficiently large isostatic press available. However, such a compression unit is expected to be possible to use in the near future. The test results of bentonite blocks, produced with an isostatic pressing method at different presses and at different sizes, suggest that the technical characteristics, for example bulk density and strength values, are somewhat independent of the size of the block, and that the blocks have fairly homogenous characteristics. Water content and compression pressure are the two most important properties determining the characteristics of the compressed blocks. By adjusting these two properties it is fairly easy to produce blocks at a desired density. The commonly used compression pressure in the manufacturing of bentonite blocks is 100 MPa, which compresses bentonite to approximately

  20. Isostatic compression of buffer blocks. Middle scale

    Energy Technology Data Exchange (ETDEWEB)

    Ritola, J.; Pyy, E. [VTT Technical Research Centre of Finland, Espoo (Finland)

    2012-01-15

    Manufacturing of buffer components using isostatic compression method has been studied in small scale in 2008 (Laaksonen 2010). These tests included manufacturing of buffer blocks using different bentonite materials and different compression pressures. Isostatic mould technology was also tested, along with different methods to fill the mould, such as vibration and partial vacuum, as well as a stepwise compression of the blocks. The development of manufacturing techniques has continued with small-scale (30 %) blocks (diameter 600 mm) in 2009. This was done in a separate project: Isostatic compression, manufacturing and testing of small scale (D = 600 mm) buffer blocks. The research on the isostatic compression method continued in 2010 in a project aimed to test and examine the isostatic manufacturing process of buffer blocks at 70 % scale (block diameter 1200 to 1300 mm), and the aim was to continue in 2011 with full-scale blocks (diameter 1700 mm). A total of nine bentonite blocks were manufactured at 70 % scale, of which four were ring-shaped and the rest were cylindrical. It is currently not possible to manufacture full-scale blocks, because there is no sufficiently large isostatic press available. However, such a compression unit is expected to be possible to use in the near future. The test results of bentonite blocks, produced with an isostatic pressing method at different presses and at different sizes, suggest that the technical characteristics, for example bulk density and strength values, are somewhat independent of the size of the block, and that the blocks have fairly homogenous characteristics. Water content and compression pressure are the two most important properties determining the characteristics of the compressed blocks. By adjusting these two properties it is fairly easy to produce blocks at a desired density. The commonly used compression pressure in the manufacturing of bentonite blocks is 100 MPa, which compresses bentonite to approximately

  1. Coastal protection using topological interlocking blocks

    Science.gov (United States)

    Pasternak, Elena; Dyskin, Arcady; Pattiaratchi, Charitha; Pelinovsky, Efim

    2013-04-01

    The coastal protection systems mainly rely on the self-weight of armour blocks to ensure its stability. We propose a system of interlocking armour blocks, which form plate-shape assemblies. The shape and the position of the blocks are chosen in such a way as to impose kinematic constraints that prevent the blocks from being removed from the assembly. The topological interlocking shapes include simple convex blocks such as platonic solids, the most practical being tetrahedra, cubes and octahedra. Another class of topological interlocking blocks is so-called osteomorphic blocks, which form plate-like assemblies tolerant to random block removal (almost 25% of blocks need to be removed for the assembly to loose integrity). Both classes require peripheral constraint, which can be provided either by the weight of the blocks or post-tensioned internal cables. The interlocking assemblies provide increased stability because lifting one block involves lifting (and bending) the whole assembly. We model the effect of interlocking by introducing an equivalent additional self-weight of the armour blocks. This additional self-weight is proportional to the critical pressure needed to cause bending of the interlocking assembly when it loses stability. Using beam approximation we find an equivalent stability coefficient for interlocking. It is found to be greater than the stability coefficient of a structure with similar blocks without interlocking. In the case when the peripheral constraint is provided by the weight of the blocks and for the slope angle of 45o, the effective stability coefficient for a structure of 100 blocks is 33% higher than the one for a similar structure without interlocking. Further increase in the stability coefficient can be reached by a specially constructed peripheral constraint system, for instance by using post-tension cables.

  2. Ganglion block. When and how?

    International Nuclear Information System (INIS)

    Bale, R.

    2015-01-01

    Increasing understanding of the anatomy and physiology of neural structures has led to the development of surgical and percutaneous neurodestructive methods in order to target and destroy various components of afferent nociceptive pathways. The dorsal root ganglia and in particular the ganglia of the autonomous nervous system are targets for radiological interventions. The autonomous nervous system is responsible for the regulation of organ functions, sweating, visceral and blood vessel-associated pain. Ganglia of the sympathetic chain and non-myelinized autonomous nerves can be irreversibly destroyed by chemical and thermal ablation. Computed tomography (CT)-guided sympathetic nerve blocks are well established interventional radiological procedures which lead to vasodilatation, reduction of sweating and reduction of pain associated with the autonomous nervous system. Sympathetic blocks are applied for the treatment of various vascular diseases including critical limb ischemia. Other indications for thoracic and lumbar sympathectomy include complex regional pain syndrome (CRPS), chronic tumor associated pain and hyperhidrosis. Neurolysis of the celiac plexus is an effective palliative pain treatment particularly in patients suffering from pancreatic cancer. Percutaneous dorsal root ganglion rhizotomy can be performed in selected patients with radicular pain that is resistant to conventional pharmacological and interventional treatment. (orig.) [de

  3. Randomized Block Cubic Newton Method

    KAUST Repository

    Doikov, Nikita; Richtarik, Peter

    2018-01-01

    We study the problem of minimizing the sum of three convex functions: a differentiable, twice-differentiable and a non-smooth term in a high dimensional setting. To this effect we propose and analyze a randomized block cubic Newton (RBCN) method, which in each iteration builds a model of the objective function formed as the sum of the natural models of its three components: a linear model with a quadratic regularizer for the differentiable term, a quadratic model with a cubic regularizer for the twice differentiable term, and perfect (proximal) model for the nonsmooth term. Our method in each iteration minimizes the model over a random subset of blocks of the search variable. RBCN is the first algorithm with these properties, generalizing several existing methods, matching the best known bounds in all special cases. We establish ${\\cal O}(1/\\epsilon)$, ${\\cal O}(1/\\sqrt{\\epsilon})$ and ${\\cal O}(\\log (1/\\epsilon))$ rates under different assumptions on the component functions. Lastly, we show numerically that our method outperforms the state-of-the-art on a variety of machine learning problems, including cubically regularized least-squares, logistic regression with constraints, and Poisson regression.

  4. Randomized Block Cubic Newton Method

    KAUST Repository

    Doikov, Nikita

    2018-02-12

    We study the problem of minimizing the sum of three convex functions: a differentiable, twice-differentiable and a non-smooth term in a high dimensional setting. To this effect we propose and analyze a randomized block cubic Newton (RBCN) method, which in each iteration builds a model of the objective function formed as the sum of the natural models of its three components: a linear model with a quadratic regularizer for the differentiable term, a quadratic model with a cubic regularizer for the twice differentiable term, and perfect (proximal) model for the nonsmooth term. Our method in each iteration minimizes the model over a random subset of blocks of the search variable. RBCN is the first algorithm with these properties, generalizing several existing methods, matching the best known bounds in all special cases. We establish ${\\\\cal O}(1/\\\\epsilon)$, ${\\\\cal O}(1/\\\\sqrt{\\\\epsilon})$ and ${\\\\cal O}(\\\\log (1/\\\\epsilon))$ rates under different assumptions on the component functions. Lastly, we show numerically that our method outperforms the state-of-the-art on a variety of machine learning problems, including cubically regularized least-squares, logistic regression with constraints, and Poisson regression.

  5. Thyroid blocking after nuclear accidents

    International Nuclear Information System (INIS)

    Rendl, J.; Reiners, C.

    1999-01-01

    Following the Chernobyl accident a marked increase in thyroid cancer incidence among the children in Belarus, the Ukraine and Russia has been detected, strongly suggesting a causal relationship to the large amounts of radioactive iodine isotopes in the resulting fallout. Taking into account the Chernobyl experience the German Committee on Radiation Protection decided to reduce the intervention levels on the basis of the 1989 WHO recommendations and adopted a new concept concerning thyroid blocking in response to nuclear power plant accidents. Experimental animal studies and theoretical considerations show that thyroid blocking with potassium iodide (KI) in a dose of about 1.4 mg per kg body weight is most effective in reducing irradiation to the thyroid from the intake of radioiodine nuclides, provided KI is given within 2 hours after exposure. According to the new concept, persons over 45 years of age should not take iodine tablets because the drug could cause a greater health risk due to prevalent functional thyroid autonomy in this age group than the radioactive iodine averted by KI. On the basis of accident analysis and the new philosophy suitable distribution strategies and logistics are proposed and discussed. (orig.) [de

  6. ALS insertion device block measurement and inspection

    International Nuclear Information System (INIS)

    Marks, S.; Carrieri, J.; Cook, C.; Hassenzahl, W.V.; Hoyer, E.; Plate, D.

    1991-05-01

    The performance specifications for ALS insertion devices require detailed knowledge and strict control of the Nd-Fe-B permanent magnet blocks incorporated in these devices. This paper describes the measurement and inspection apparatus and the procedures designed to qualify and characterize these blocks. A detailed description of a new, automated Helmholtz coil facility for measurement of the three components of magnetic moment is included. Physical block inspection and magnetic moment measurement procedures are described. Together they provide a basis for qualifying blocks and for specifying placement of blocks within an insertion devices' magnetic structures. 1 ref., 4 figs

  7. How to block and tackle the face.

    Science.gov (United States)

    Zide, B M; Swift, R

    1998-03-01

    Regional blocking techniques as noted in dentistry, anesthesia, and anatomy texts may result in inconsistent and imperfect analgesia when needed for facial aesthetic surgery. The advent of laser facial surgery and more complicated aesthetic facial procedures has thus increased the demand for anesthesia support. Surgeons should know a fail-safe method of nerve blocks. Fresh cadaver dissections are used to demonstrate a series of eight regional nerve-blocking routes. This sequence of bilateral blocks will routinely provide profound full facial anesthesia. Certain groupings of blocks are effective for perioral or periorbital laser surgery.

  8. High-Throughput Block Optical DNA Sequence Identification.

    Science.gov (United States)

    Sagar, Dodderi Manjunatha; Korshoj, Lee Erik; Hanson, Katrina Bethany; Chowdhury, Partha Pratim; Otoupal, Peter Britton; Chatterjee, Anushree; Nagpal, Prashant

    2018-01-01

    Optical techniques for molecular diagnostics or DNA sequencing generally rely on small molecule fluorescent labels, which utilize light with a wavelength of several hundred nanometers for detection. Developing a label-free optical DNA sequencing technique will require nanoscale focusing of light, a high-throughput and multiplexed identification method, and a data compression technique to rapidly identify sequences and analyze genomic heterogeneity for big datasets. Such a method should identify characteristic molecular vibrations using optical spectroscopy, especially in the "fingerprinting region" from ≈400-1400 cm -1 . Here, surface-enhanced Raman spectroscopy is used to demonstrate label-free identification of DNA nucleobases with multiplexed 3D plasmonic nanofocusing. While nanometer-scale mode volumes prevent identification of single nucleobases within a DNA sequence, the block optical technique can identify A, T, G, and C content in DNA k-mers. The content of each nucleotide in a DNA block can be a unique and high-throughput method for identifying sequences, genes, and other biomarkers as an alternative to single-letter sequencing. Additionally, coupling two complementary vibrational spectroscopy techniques (infrared and Raman) can improve block characterization. These results pave the way for developing a novel, high-throughput block optical sequencing method with lossy genomic data compression using k-mer identification from multiplexed optical data acquisition. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Influence of anchor block size on the thickness of adsorbed block copolymer layers

    NARCIS (Netherlands)

    Belder, G.F; ten Brinke, G.; Hadziioannou, G

    1997-01-01

    We present surface force data on three different polystyrene/poly(2-vinylpyridine) block copolymers (PS/P2VP) with a fixed size of the nonadsorbing PS block but widely varying sizes of the adsorbing P2VP block. With respect to the sizes of the two blocks, they range from moderately to highly

  10. Backfilling of deposition tunnels, block alternative

    International Nuclear Information System (INIS)

    Keto, P.; Roennqvist, P.-E.

    2007-03-01

    This report presents a preliminary process description of backfilling the deposition tunnels with pre-compacted blocks consisting of a mixture of bentonite and ballast (30:70). The process was modified for the Finnish KBS-3V type repository assuming that the amount of spent fuel canisters disposed of yearly is 40. Backfilling blocks (400 x 300 x 300 mm) are prepared in a block production plant with a hydraulic press with an estimated production capacity of 840 blocks per day. Some of the blocks are modified further to fit the profile of the tunnel roof. Prior to the installation of the blocks, the deposition tunnel floor is levelled with a mixture of bentonite and ballast (15:85). The blocks are placed in the tunnel with a modified reach truck. Centrifugal pellet throwing equipment is used to fill the gap between the blocks and the rock surface with bentonite pellets. Based on a preliminary assessment, the average dry density achieved with block backfill is sufficient to fulfil the criteria set for the backfill in order to ensure long-term safety and radiation protection. However, there are uncertainties concerning saturation, homogenisation, erosion, piping and self-healing of the block backfill that need to be studied further with laboratory and field tests. In addition, development efforts and testing concerning block manufacturing and installation are required to verify the technical feasibility of the concept. (orig.)

  11. Exercising with blocked muscle glycogenolysis

    DEFF Research Database (Denmark)

    Nielsen, Tue L; Pinós, Tomàs; Brull, Astrid

    2018-01-01

    BACKGROUND: McArdle disease (glycogen storage disease type V) is an inborn error of skeletal muscle metabolism, which affects glycogen phosphorylase (myophosphorylase) activity leading to an inability to break down glycogen. Patients with McArdle disease are exercise intolerant, as muscle glycogen......-derived glucose is unavailable during exercise. Metabolic adaptation to blocked muscle glycogenolysis occurs at rest in the McArdle mouse model, but only in highly glycolytic muscle. However, it is unknown what compensatory metabolic adaptations occur during exercise in McArdle disease. METHODS: In this study, 8......-week old McArdle and wild-type mice were exercised on a treadmill until exhausted. Dissected muscles were compared with non-exercised, age-matched McArdle and wild-type mice for histology and activation and expression of proteins involved in glucose uptake and glycogenolysis. RESULTS: Investigation...

  12. Used, Blocking and Sleeping Patents

    DEFF Research Database (Denmark)

    Torrisi, Salvatore; Gambardella, Alfonso; Giuri, Paola

    2016-01-01

    This paper employs data from a large-scale survey (InnoS&T) of inventors in Europe, the USA, and Japan who were listed in patent applications filed at the European Patent Office with priority years between 2003 and 2005. We provide evidence regarding the reasons for patenting and the ways in which...... patents are being utilized. A substantial share of patents is neither used internally nor for market transactions, which confirms the importance of strategic patenting and inefficiency in the management of intellectual property. We investigate different types of unused patents—unused blocking patents...... and sleeping patents. We also examine the association between used and unused patents and their characteristics such as family size, scope, generality and overlapping claims, technology area, type of applicant, and the competitive environment from where these patents originate. We discuss our results...

  13. LARGE BLOCK TEST STATUS REPORT

    International Nuclear Information System (INIS)

    D.G. WILDER, W. LIN, S.C. BLAIR, T. BUSCHECK, R.C. CARLSON, K. LEE, A. MEIKE, A.L. RAMIREZ, J.L. WAGONER, AND J. WANG

    1997-01-01

    This report is intended to serve as a status report, which essentially transmits the data that have been collected to date on the Large Block Test (LBT). The analyses of data will be performed during FY98, and then a complete report will be prepared. This status report includes introductory material that is not needed merely to transmit data but is available at this time and therefore included. As such, this status report will serve as the template for the future report, and the information is thus preserved. The United States Department of Energy (DOE) is investigatinq the suitability of Yucca Mountain (YM) as a potential site for the nation's first high-level nuclear waste repository. As shown in Fig. 1-1, the site is located about 120 km northwest of Las Vegas, Nevada, in an area of uninhabited desert

  14. Minimum Description Length Block Finder, a Method to Identify Haplotype Blocks and to Compare the Strength of Block Boundaries

    OpenAIRE

    Mannila, H.; Koivisto, M.; Perola, M.; Varilo, T.; Hennah, W.; Ekelund, J.; Lukk, M.; Peltonen, L.; Ukkonen, E.

    2003-01-01

    We describe a new probabilistic method for finding haplotype blocks that is based on the use of the minimum description length (MDL) principle. We give a rigorous definition of the quality of a segmentation of a genomic region into blocks and describe a dynamic programming algorithm for finding the optimal segmentation with respect to this measure. We also describe a method for finding the probability of a block boundary for each pair of adjacent markers: this gives a tool for evaluating the ...

  15. A functional SNP in the regulatory region of the decay-accelerating factor gene associates with extraocular muscle pareses in myasthenia gravis

    KAUST Repository

    Heckmann, J M

    2009-08-13

    Complement activation in myasthenia gravis (MG) may damage muscle endplate and complement regulatory proteins such as decay-accelerating factor (DAF) or CD55 may be protective. We hypothesize that the increased prevalence of severe extraocular muscle (EOM) dysfunction among African MG subjects reported earlier may result from altered DAF expression. To test this hypothesis, we screened the DAF gene sequences relevant to the classical complement pathway and found an association between myasthenics with EOM paresis and the DAF regulatory region c.-198CG SNP (odds ratio8.6; P0.0003). This single nucleotide polymorphism (SNP) results in a twofold activation of a DAF 5?-flanking region luciferase reporter transfected into three different cell lines. Direct matching of the surrounding SNP sequence within the DAF regulatory region with the known transcription factor-binding sites suggests a loss of an Sp1-binding site. This was supported by the observation that the c.-198CG SNP did not show the normal lipopolysaccharide-induced DAF transcriptional upregulation in lymphoblasts from four patients. Our findings suggest that at critical periods during autoimmune MG, this SNP may result in inadequate DAF upregulation with consequent complement-mediated EOM damage. Susceptible individuals may benefit from anti-complement therapy in addition to immunosuppression. © 2010 Macmillan Publishers Limited. All rights reserved.

  16. A PMT-Block test bench

    International Nuclear Information System (INIS)

    Adragna, P.; Antonaki, A.

    2006-01-01

    The front-end electronics of the ATLAS hadronic calorimeter (Tile Cal) is housed in a unit, called PMT-Block. The PMT-Block is a compact instrument comprising a light mixer, a PMT together with its divider and a 3-in-1 card, which provides shaping, amplification and integration for the signals. This instrument needs to be qualified before being assembled on the detector. A PMT-Block test bench has been developed for this purpose. This test bench is a system which allows fast, albeit accurate enough, measurements of the main properties of a complete PMT-Block. The system, both hardware and software, and the protocol used for the PMT-Blocks characterization are described in detail in this report. The results obtained in the test of about 10 000 PMT-Blocks needed for the instrumentation of the ATLAS (LHC-CERN) hadronic Tile Calorimeter are also reported

  17. A PMT-Block test bench

    Energy Technology Data Exchange (ETDEWEB)

    Adragna, P [Dipartimento di Fisica ' E.Fermi' , Universita di Pisa and Istituto Nazionale di Fisica Nucleare, Sezione di Pisa, Largo B. Pontecorvo 3, Pisa 56127 (Italy); Universita degli studi di Siena, via Roma 56, 53100 Siena (Italy); Antonaki, A [Institute of Accelerating Systems and Applications, P.O. Box 17214, Athens 10024 (Greece); National Capodistrian University of Athens, 30 Panepistimiou st., Athens 10679 (Greece)] (and others)

    2006-08-01

    The front-end electronics of the ATLAS hadronic calorimeter (Tile Cal) is housed in a unit, called PMT-Block. The PMT-Block is a compact instrument comprising a light mixer, a PMT together with its divider and a 3-in-1 card, which provides shaping, amplification and integration for the signals. This instrument needs to be qualified before being assembled on the detector. A PMT-Block test bench has been developed for this purpose. This test bench is a system which allows fast, albeit accurate enough, measurements of the main properties of a complete PMT-Block. The system, both hardware and software, and the protocol used for the PMT-Blocks characterization are described in detail in this report. The results obtained in the test of about 10 000 PMT-Blocks needed for the instrumentation of the ATLAS (LHC-CERN) hadronic Tile Calorimeter are also reported.

  18. Inferior alveolar nerve block: Alternative technique

    OpenAIRE

    Thangavelu, K.; Kannan, R.; Kumar, N. Senthil

    2012-01-01

    Background: Inferior alveolar nerve block (IANB) is a technique of dental anesthesia, used to produce anesthesia of the mandibular teeth, gingivae of the mandible and lower lip. The conventional IANB is the most commonly used the nerve block technique for achieving local anesthesia for mandibular surgical procedures. In certain cases, however, this nerve block fails, even when performed by the most experienced clinician. Therefore, it would be advantageous to find an alternative simple techni...

  19. A MAC Mode for Lightweight Block Ciphers

    DEFF Research Database (Denmark)

    Luykx, Atul; Preneel, Bart; Tischhauser, Elmar Wolfgang

    2016-01-01

    Lightweight cryptography strives to protect communication in constrained environments without sacrificing security. However, security often conflicts with efficiency, shown by the fact that many new lightweight block cipher designs have block sizes as low as 64 or 32 bits. Such low block sizes lead...... no effect on the security bound, allowing an order of magnitude more data to be processed per key. Furthermore, LightMAC is incredibly simple, has almost no overhead over the block cipher, and is parallelizable. As a result, LightMAC not only offers compact authentication for resource-constrained platforms...

  20. Using Interference to Block RFID Tags

    DEFF Research Database (Denmark)

    Krigslund, Rasmus; Popovski, Petar; Pedersen, Gert Frølund

    We propose a novel method to block RFID tags from responding, using intentional interference. We focus on the experimental evaluation, where we impose interference on the download and uplink, respectively. The results are positive, where modulated CCI shows most effective to block a tag.......We propose a novel method to block RFID tags from responding, using intentional interference. We focus on the experimental evaluation, where we impose interference on the download and uplink, respectively. The results are positive, where modulated CCI shows most effective to block a tag....

  1. Gene Therapy

    Science.gov (United States)

    Gene therapy Overview Gene therapy involves altering the genes inside your body's cells in an effort to treat or stop disease. Genes contain your ... that don't work properly can cause disease. Gene therapy replaces a faulty gene or adds a new ...

  2. CAPTURING REALITY AT CENTRE BLOCK

    Directory of Open Access Journals (Sweden)

    C. Boulanger

    2017-08-01

    Full Text Available The Centre Block of Canada’s Parliament buildings, National Historic Site of Canada is set to undergo a major rehabilitation project that will take approximately 10 years to complete. In preparation for this work, Heritage Conservation Services (HCS of Public Services and Procurement Canada has been completing heritage documentation of the entire site which includes laser scanning of all interior rooms and accessible confined spaces such as attics and other similar areas. Other documentation completed includes detailed photogrammetric documentation of rooms and areas of high heritage value. Some of these high heritage value spaces present certain challenges such as accessibility due to the height and the size of the spaces. Another challenge is the poor lighting conditions, requiring the use of flash or strobe lighting to either compliment or completely eliminate the available ambient lighting. All the spaces captured at this higher level of detail were also captured with laser scanning. This allowed the team to validate the information and conduct a quality review of the photogrammetric data. As a result of this exercise, the team realized that in most, if not all cases, the photogrammetric data was more detailed and at a higher quality then the terrestrial laser scanning data. The purpose and motivation of this paper is to present these findings, as well provide the advantages and disadvantages of the two methods and data sets.

  3. Capturing Reality at Centre Block

    Science.gov (United States)

    Boulanger, C.; Ouimet, C.; Yeomans, N.

    2017-08-01

    The Centre Block of Canada's Parliament buildings, National Historic Site of Canada is set to undergo a major rehabilitation project that will take approximately 10 years to complete. In preparation for this work, Heritage Conservation Services (HCS) of Public Services and Procurement Canada has been completing heritage documentation of the entire site which includes laser scanning of all interior rooms and accessible confined spaces such as attics and other similar areas. Other documentation completed includes detailed photogrammetric documentation of rooms and areas of high heritage value. Some of these high heritage value spaces present certain challenges such as accessibility due to the height and the size of the spaces. Another challenge is the poor lighting conditions, requiring the use of flash or strobe lighting to either compliment or completely eliminate the available ambient lighting. All the spaces captured at this higher level of detail were also captured with laser scanning. This allowed the team to validate the information and conduct a quality review of the photogrammetric data. As a result of this exercise, the team realized that in most, if not all cases, the photogrammetric data was more detailed and at a higher quality then the terrestrial laser scanning data. The purpose and motivation of this paper is to present these findings, as well provide the advantages and disadvantages of the two methods and data sets.

  4. Building blocks of the universe

    International Nuclear Information System (INIS)

    Malamud, E.; O'Connor, C.; Cooper, A.

    1990-01-01

    COSI [Ohio's Center for Science and Industry], a well established science center, and SciTech, an emerging one, have formed a collaboration to develop a group of original interactive exhibits conveying to a wide audience the nature of the most fundamental features of the Universe, as revealed in the fascinating world of nuclear and particle science. These new exhibits will add to, and be supported by, the basic science exhibits which have already attracted large numbers of visitors to both centers. The new project, called Building Blocks of the Universe, aims to foster an appreciation of the way all features of the Universe arise from simple, basic rules and to lead the visitor from the perceived complexities of our surroundings, to the unperceived, but simpler features of the sub-nuclear world. It has already become apparent from individual prototypes that these simple but immensely far-reaching ideas can indeed be conveyed by hands-on exhibits. These exhibits will be linked and enhanced by an effective museum environment, using pictorial diagrams, accurate non-technical text, and artistic displays to create an atmosphere in which visitors can learn about phenomena beyond the range of direct perception. This paper describes the goals, content and organization of the exhibition. The authors also outline their experience with prototype exhibits, and thereby invite additional input into the development process

  5. Comparative study between ultrasound guided tap block and paravertebral block in upper abdominal surgeries. Randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Ruqaya M. Elsayed

    2017-01-01

    Conclusion: We concluded that ultrasound guided transversus abdominis plane block and thoracic paravertebral block were safe and effective anesthetic technique for upper abdominal surgery with longer and potent postoperative analgesia in thoracic paravertebral block than transversus abdominis block.

  6. Ionization of amphiphilic acidic block copolymers.

    Science.gov (United States)

    Colombani, Olivier; Lejeune, Elise; Charbonneau, Céline; Chassenieux, Christophe; Nicolai, Taco

    2012-06-28

    The ionization behavior of an amphiphilic diblock copolymer poly(n-butyl acrylate(50%)-stat-acrylic acid(50%))(100)-block-poly(acrylic acid)(100) (P(nBA(50%)-stat-AA(50%))(100)-b-PAA(100), DH50) and of its equivalent triblock copolymer P(nBA(50%)-stat-AA(50%))(100)-b-PAA(200)-b-P(nBA(50%)-stat-AA(50%))(100) (TH50) were studied by potentiometric titration either in pure water or in 0.5 M NaCl. These polymers consist of a hydrophilic acidic block (PAA) connected to a hydrophobic block, P(nBA(50%)-stat-AA(50%))(100), whose hydrophobic character has been mitigated by copolymerization with hydrophilic units. We show that all AA units, even those in the hydrophobic block could be ionized. However, the AA units within the hydrophobic block were less acidic than those in the hydrophilic block, resulting in the preferential ionization of the latter block. The preferential ionization of PAA over that of P(nBA(50%)-stat-AA(50%))(100) was stronger at higher ionic strength. Remarkably, the covalent bonds between the PAA and P(nBA(50%)-stat-AA(50%))(100) blocks in the diblock or the triblock did not affect the ionization of each block, although the self-association of the block copolymers into spherical aggregates modified the environment of the PAA blocks compared to when PAA was molecularly dispersed.

  7. Proteins mediating DNA loops effectively block transcription.

    Science.gov (United States)

    Vörös, Zsuzsanna; Yan, Yan; Kovari, Daniel T; Finzi, Laura; Dunlap, David

    2017-07-01

    Loops are ubiquitous topological elements formed when proteins simultaneously bind to two noncontiguous DNA sites. While a loop-mediating protein may regulate initiation at a promoter, the presence of the protein at the other site may be an obstacle for RNA polymerases (RNAP) transcribing a different gene. To test whether a DNA loop alters the extent to which a protein blocks transcription, the lac repressor (LacI) was used. The outcome of in vitro transcription along templates containing two LacI operators separated by 400 bp in the presence of LacI concentrations that produced both looped and unlooped molecules was visualized with scanning force microscopy (SFM). An analysis of transcription elongation complexes, moving for 60 s at an average of 10 nt/s on unlooped DNA templates, revealed that they more often surpassed LacI bound to the lower affinity O2 operator than to the highest affinity Os operator. However, this difference was abrogated in looped DNA molecules where LacI became a strong roadblock independently of the affinity of the operator. Recordings of transcription elongation complexes, using magnetic tweezers, confirmed that they halted for several minutes upon encountering a LacI bound to a single operator. The average pause lifetime is compatible with RNAP waiting for LacI dissociation, however, the LacI open conformation visualized in the SFM images also suggests that LacI could straddle RNAP to let it pass. Independently of the mechanism by which RNAP bypasses the LacI roadblock, the data indicate that an obstacle with looped topology more effectively interferes with transcription. © 2017 The Authors Protein Science published by Wiley Periodicals, Inc. on behalf of The Protein Society.

  8. Micellar aggregates of amylose-block-polystyrene rod-coil block copolymers in water and THF

    NARCIS (Netherlands)

    Loos, Katja; Böker, Alexander; Zettl, Heiko; Zhang, Mingfu; Krausch, Georg; Müller, Axel H.E.; Boker, A.; Zhang, A.F.

    2005-01-01

    Amylose-block-polystyrenes with various block copolymer compositions were investigated in water and in THF solution. Fluorescence correlation spectroscopy, dynamic light, scattering (DLS), and asymmetric flow field-flow fractionation with multiangle light scattering detection indicate the presence

  9. Approximate design theory for a simple block design with random block effects

    OpenAIRE

    Christof, Karin

    1985-01-01

    Approximate design theory for a simple block design with random block effects / K. Christof ; F. Pukelsheim. - In: Linear statistical inference / ed. by T. Calinski ... - Berlin u. a. : Springer, 1985. - S. 20-28. - (Lecture notes in statistics ; 35)

  10. Distribution of short block copolymer chains in Binary Blends of Block Copolymers Having Hydrogen Bonding

    Science.gov (United States)

    Kwak, Jongheon; Han, Sunghyun; Kim, Jin Kon

    2014-03-01

    A binary mixture of two block copolymers whose blocks are capable of forming the hydrogen bonding allows one to obtain various microdomains that could not be expected for neat block copolymer. For instance, the binary blend of symmetric polystyrene-block-poly(2-vinylpyridine) copolymer (PS-b-P2VP) and polystyrene-block-polyhydroxystyrene copolymer (PS-b-PHS) blends where the hydrogen bonding occurred between P2VP and PHS showed hexagonally packed (HEX) cylindrical and body centered cubic (BCC) spherical microdomains. To know the exact location of short block copolymer chains at the interface, we synthesized deuterated polystyrene-block-polyhydroxystyrene copolymer (dPS-b-PHS) and prepared a binary mixture with PS-b-P2VP. We investigate, via small angle X-ray scattering (SAXS) and neutron reflectivity (NR), the exact location of shorter dPS block chain near the interface of the microdomains.

  11. Block Gas Sol Unit in Haderslev

    DEFF Research Database (Denmark)

    Vejen, Niels Kristian

    2000-01-01

    Investigation of a SDHW system based on a Block Gas Sol Unit from Baxi A/S installed by a consumer i Haderslev, Denmark.......Investigation of a SDHW system based on a Block Gas Sol Unit from Baxi A/S installed by a consumer i Haderslev, Denmark....

  12. Ground reaction curve based upon block theory

    International Nuclear Information System (INIS)

    Yow, J.L. Jr.; Goodman, R.E.

    1985-09-01

    Discontinuities in a rock mass can intersect an excavation surface to form discrete blocks (keyblocks) which can be unstable. Once a potentially unstable block is identified, the forces affecting it can be calculated to assess its stability. The normal and shear stresses on each block face before displacement are calculated using elastic theory and are modified in a nonlinear way by discontinuity deformations as the keyblock displaces. The stresses are summed into resultant forces to evaluate block stability. Since the resultant forces change with displacement, successive increments of block movement are examined to see whether the block ultimately becomes stable or fails. Two-dimensional (2D) and three-dimensional (3D) analytic models for the stability of simple pyramidal keyblocks were evaluated. Calculated stability is greater for 3D analyses than for 2D analyses. Calculated keyblock stability increases with larger in situ stress magnitudes, larger lateral stress ratios, and larger shear strengths. Discontinuity stiffness controls blocks displacement more strongly than it does stability itself. Large keyblocks are less stable than small ones, and stability increases as blocks become more slender

  13. Light extraction block with curved surface

    Science.gov (United States)

    Levermore, Peter; Krall, Emory; Silvernail, Jeffrey; Rajan, Kamala; Brown, Julia J.

    2016-03-22

    Light extraction blocks, and OLED lighting panels using light extraction blocks, are described, in which the light extraction blocks include various curved shapes that provide improved light extraction properties compared to parallel emissive surface, and a thinner form factor and better light extraction than a hemisphere. Lighting systems described herein may include a light source with an OLED panel. A light extraction block with a three-dimensional light emitting surface may be optically coupled to the light source. The three-dimensional light emitting surface of the block may includes a substantially curved surface, with further characteristics related to the curvature of the surface at given points. A first radius of curvature corresponding to a maximum principal curvature k.sub.1 at a point p on the substantially curved surface may be greater than a maximum height of the light extraction block. A maximum height of the light extraction block may be less than 50% of a maximum width of the light extraction block. Surfaces with cross sections made up of line segments and inflection points may also be fit to approximated curves for calculating the radius of curvature.

  14. On multiple blocking sets in Galois planes

    NARCIS (Netherlands)

    Blokhuis, A.; Lovász, L.; Storme, L.; Szönyi, T.

    2007-01-01

    This article continues the study of multiple blocking sets in PG(2, q). In [A. Blokhuis, L. Storme, T. Szonyi, Lacunary polynomials, multiple blocking sets and Baer subplanes. J. London Math. Soc. (2) 60 (1999), 321–332. MR1724814 (2000j:05025) Zbl 0940.51007], using lacunary polynomials, it was

  15. CONJUGATED BLOCK-COPOLYMERS FOR ELECTROLUMINESCENT DIODES

    NARCIS (Netherlands)

    Hilberer, A; Gill, R.E; Herrema, J.K; Malliaras, G.G; Wildeman, J.; Hadziioannou, G

    In this article we review results obtained in our laboratory on the design and study of new light-emitting polymers. We are interested in the synthesis and characterisation of block copolymers with regularly alternating conjugated and non conjugated sequences. The blocks giving rise to luminescence

  16. Programs for the calculi of blocks permeabilities

    International Nuclear Information System (INIS)

    Gomez Hernandez, J.J.; Sovero Sovero, H.F.

    1993-01-01

    This report studies the stochastic analysis of radionuclide transport. The permeability values of blocks are necessary to do a numeric model for the flux and transport problems in ground soils. The determination of block value by function on grill value is the objective of this program

  17. Substrate tolerant direct block copolymer nanolithography

    DEFF Research Database (Denmark)

    Li, Tao; Wang, Zhongli; Schulte, Lars

    2016-01-01

    Block copolymer (BC) self-assembly constitutes a powerful platform for nanolithography. However, there is a need for a general approach to BC lithography that critically considers all the steps from substrate preparation to the final pattern transfer. We present a procedure that significantly sim...... plasma treatment enables formation of the oxidized PDMS hard mask, PS block removal and polymer or graphene substrate patterning....

  18. Benchmarking Block Ciphers for Wireless Sensor Networks

    NARCIS (Netherlands)

    Law, Y.W.; Doumen, J.M.; Hartel, Pieter H.

    2004-01-01

    Choosing the most storage- and energy-efficient block cipher specifically for wireless sensor networks (WSNs) is not as straightforward as it seems. To our knowledge so far, there is no systematic evaluation framework for the purpose. We have identified the candidates of block ciphers suitable for

  19. Block Study: Learning About Your Local Community.

    Science.gov (United States)

    Eckbreth, Catherine

    Designed for 7th- and 8th-grade students, five lessons using a block of houses in an urban neighborhood help students learn about the history of a neighborhood, the owners of the houses, and the style and architectural features of the homes. Although this unit has been developed for a specific neighborhood, a similar block study could be conducted…

  20. Metallo-supramolecular block copolymer micelles

    NARCIS (Netherlands)

    Gohy, J.M.W.

    2009-01-01

    Supramolecular copolymers have become of increasing interest in recent years in the search for new materials with tunable properties. In particular, metallo-supramolecular block copolymers in which metal-ligand complexes are introduced in block copolymer architectures, have known important progress,

  1. Heuristic algorithms for feature selection under Bayesian models with block-diagonal covariance structure.

    Science.gov (United States)

    Foroughi Pour, Ali; Dalton, Lori A

    2018-03-21

    Many bioinformatics studies aim to identify markers, or features, that can be used to discriminate between distinct groups. In problems where strong individual markers are not available, or where interactions between gene products are of primary interest, it may be necessary to consider combinations of features as a marker family. To this end, recent work proposes a hierarchical Bayesian framework for feature selection that places a prior on the set of features we wish to select and on the label-conditioned feature distribution. While an analytical posterior under Gaussian models with block covariance structures is available, the optimal feature selection algorithm for this model remains intractable since it requires evaluating the posterior over the space of all possible covariance block structures and feature-block assignments. To address this computational barrier, in prior work we proposed a simple suboptimal algorithm, 2MNC-Robust, with robust performance across the space of block structures. Here, we present three new heuristic feature selection algorithms. The proposed algorithms outperform 2MNC-Robust and many other popular feature selection algorithms on synthetic data. In addition, enrichment analysis on real breast cancer, colon cancer, and Leukemia data indicates they also output many of the genes and pathways linked to the cancers under study. Bayesian feature selection is a promising framework for small-sample high-dimensional data, in particular biomarker discovery applications. When applied to cancer data these algorithms outputted many genes already shown to be involved in cancer as well as potentially new biomarkers. Furthermore, one of the proposed algorithms, SPM, outputs blocks of heavily correlated genes, particularly useful for studying gene interactions and gene networks.

  2. The undesirable effects of neuromuscular blocking drugs

    DEFF Research Database (Denmark)

    Claudius, C; Garvey, L H; Viby-Mogensen, J

    2009-01-01

    Neuromuscular blocking drugs are designed to bind to the nicotinic receptor at the neuromuscular junction. However, they also interact with other acetylcholine receptors in the body. Binding to these receptors causes adverse effects that vary with the specificity for the cholinergic receptor...... in question. Moreover, all neuromuscular blocking drugs may cause hypersensitivity reactions. Often the symptoms are mild and self-limiting but massive histamine release can cause systematic reactions with circulatory and respiratory symptoms and signs. At the end of anaesthesia, no residual effect...... of a neuromuscular blocking drug should be present. However, the huge variability in response to neuromuscular blocking drugs makes it impossible to predict which patient will suffer postoperative residual curarization. This article discusses the undesirable effects of the currently available neuromuscular blocking...

  3. Functional Nanoporous Polymers from Block Copolymer Precursors

    DEFF Research Database (Denmark)

    Guo, Fengxiao

    Abstract Self-assembly of block copolymers provides well-defined morphologies with characteristic length scales in the nanometer range. Nanoporous polymers prepared by selective removal of one block from self-assembled block copolymers offer great technological promise due to their many potential...... functionalities remains a great challenge due to the limitation of available polymer synthesis and the nanoscale confinement of the porous cavities. The main topic of this thesis is to develop methods for fabrication of functional nanoporous polymers from block copolymer precursors. A method has been developed......, where living anionic polymerization and atom transfer radical polymerization (ATRP) are combined to synthesize a polydimethylsiloxane-b-poly(tert-butyl acrylate)-b-polystyrene (PDMS-b-PtBA-b-PS) triblock copolymer precursor. By using either anhydrous hydrogen fluoride or trifluoroacetic acid, PtBA block...

  4. Thinking Outside the Block: An Innovative Alternative to 4X4 Block Scheduling.

    Science.gov (United States)

    Frank, Myra

    2002-01-01

    Introduces a 4x1 block scheduling method that was developed as an alternative to 4x4 block scheduling. Schedules Fridays for summer school, test preparation, and enrichment and elective courses. Includes suggestions on how to alleviate drawbacks of the 4x1 block schedule. (YDS)

  5. Traveling Rocky Roads: The Consequences of Transcription-Blocking DNA Lesions on RNA Polymerase II.

    Science.gov (United States)

    Steurer, Barbara; Marteijn, Jurgen A

    2017-10-27

    The faithful transcription of eukaryotic genes by RNA polymerase II (RNAP2) is crucial for proper cell function and tissue homeostasis. However, transcription-blocking DNA lesions of both endogenous and environmental origin continuously challenge the progression of elongating RNAP2. The stalling of RNAP2 on a transcription-blocking lesion triggers a series of highly regulated events, including RNAP2 processing to make the lesion accessible for DNA repair, R-loop-mediated DNA damage signaling, and the initiation of transcription-coupled DNA repair. The correct execution and coordination of these processes is vital for resuming transcription following the successful repair of transcription-blocking lesions. Here, we outline recent insights into the molecular consequences of RNAP2 stalling on transcription-blocking DNA lesions and how these lesions are resolved to restore mRNA synthesis. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  6. Paravertebral Block Plus Thoracic Wall Block versus Paravertebral Block Alone for Analgesia of Modified Radical Mastectomy: A Retrospective Cohort Study.

    Directory of Open Access Journals (Sweden)

    Nai-Liang Li

    Full Text Available Paravertebral block placement was the main anesthetic technique for modified radical mastectomy in our hospital until February 2014, when its combination with blocks targeting the pectoral musculature was initiated. We compared the analgesic effects of paravertebral blocks with or without blocks targeting the pectoral musculature for modified radical mastectomy.We retrospectively collected data from a single surgeon and anesthesiologist from June 1, 2012, to May 31, 2015. Intraoperative sedatives and analgesic requirements, time to the first analgesic request, postoperative analgesic doses, patient satisfaction, and complications were compared.Fifty-four patients received a paravertebral block alone (PECS 0, and 46 received a paravertebral block combined with blocks targeting the pectoral musculature (PECS 1. The highest intraoperative effect-site concentration of propofol was significantly lower in the PECS 1 group than in the PECS 0 group [2.3 (1.5, 2.8 vs 2.5 (1.5, 4 μg/mL, p = 0.0014]. The intraoperative rescue analgesic dose was significantly lower in the PECS 1 group [0 (0, 25 vs 0 (0, 75 mg of ketamine, p = 0.0384]. Furthermore, the PECS 1 group had a significantly longer time to the first analgesic request [636.5 (15, 720 vs 182.5 (14, 720 min, p = 0.0001]. After further adjustment for age, body mass index, American Society of Anesthesiologists Physical Status classification, chronic pain history, incidence of a superficial cervical plexus block placement, and operation duration, blocks targeting the pectoral musculature were determined to be the only significant factor (hazard ratio, 0.36; 95% confidence interval, 0.23-0.58; p < 0.0001. Very few patients used potent analgesics including morphine and ketorolac; the cumulative use of morphine or ketorolac was similar in the study groups. However, the incidence of all analgesic use, namely morphine, ketorolac, acetaminophen, and celecoxib, was significantly lower in the PECS 1 group [3

  7. Traveling Rocky Roads: The Consequences of Transcription-Blocking DNA Lesions on RNA Polymerase II

    NARCIS (Netherlands)

    B. Steurer (Barbara); J.A. Marteijn (Jurgen)

    2016-01-01

    textabstractThe faithful transcription of eukaryotic genes by RNA polymerase II (RNAP2) is crucial for proper cell function and tissue homeostasis. However, transcription-blocking DNA lesions of both endogenous and environmental origin continuously challenge the progression of elongating RNAP2. The

  8. Block Copolymers: Synthesis and Applications in Nanotechnology

    Science.gov (United States)

    Lou, Qin

    This study is focused on the synthesis and study of (block) copolymers using reversible deactivation radical polymerizations (RDRPs), including atom transfer radical polymerization (ATRP) and reversible addition-fragmentation chain transfer (RAFT) polymerization. In particular, two primary areas of study are undertaken: (1) a proof-of-concept application of lithographic block copolymers, and (2) the mechanistic study of the deposition of titania into block copolymer templates for the production of well-ordered titania nanostructures. Block copolymers have the ability to undergo microphase separation, with an average size of each microphase ranging from tens to hundreds of nanometers. As such, block copolymers have been widely considered for nanotechnological applications over the past two decades. The development of materials for various nanotechnologies has become an increasingly studied area as improvements in many applications, such as those found in the semiconductor and photovoltaic industries are constantly being sought. Significant growth in developments of new synthetic methods ( i.e. RDRPs) has allowed the production of block copolymers with molecular (and sometimes atomic) definition. In turn, this has greatly expanded the use of block copolymers in nanotechnology. Herein, we describe the synthesis of statistical and block copolymers of 193 nm photolithography methacrylate and acrylate resist monomers with norbornyl and adamantyl moieties using RAFT polymerization.. For these resist (block) copolymers, the phase separation behaviors were examined by atomic force microscopy (AFM). End groups were removed from the polymers to avoid complications during the photolithography since RAFT end groups absorb visible light. Poly(glycidyl methacrylate-block-polystyrene) (PGMA-b-PS) was synthesize by ATRP and demonstrated that this block copolymer acts as both a lithographic UV (365 nm) photoresist and a self-assembly material. The PGMA segments can undergo cationic

  9. Masquerading bundle branch block as a presenting manifestation of complete atrioventricular block that caused syncope.

    Science.gov (United States)

    Jiao, Zhenyu; Tian, Ying; Yang, Xinchun; Liu, Xingpeng

    2017-10-01

    A 59-year-old male patient was admitted with the main complaints of stuffiness and shortness of breath. An ECG from precordial leads on admission showed masquerading bundle branch block. Syncope frequently occurred after admission. During syncope episodes, ECG telemetry showed that the syncope was caused by intermittent complete atrioventricular block, with the longest RR interval lasting for 4.36 s. At the gap of syncope, ECG showed complete right bundle branch block accompanied by alternation of left anterior fascicular block and left posterior fascicular block. The patient was implanted with a dual-chamber permanent pacemaker. Follow-up of 9 months showed no reoccurrence of syncope.

  10. Toward Composable Hardware Agnostic Communications Blocks Lessons Learned

    Science.gov (United States)

    2016-11-01

    block-by-block level or on a multi- block level. In the block-by-block pushback approach, queues between each block are small and blocks processing data...medium access, and physical layers of the waveform has limited our ability to take advantage of technology advances in signal processing , rate...pro- cessing functions, and application processing functions as shown in Figure 1 [1]. Transceiver functions are functions associated with transmitting

  11. Inferior alveolar nerve block: Alternative technique.

    Science.gov (United States)

    Thangavelu, K; Kannan, R; Kumar, N Senthil

    2012-01-01

    Inferior alveolar nerve block (IANB) is a technique of dental anesthesia, used to produce anesthesia of the mandibular teeth, gingivae of the mandible and lower lip. The conventional IANB is the most commonly used the nerve block technique for achieving local anesthesia for mandibular surgical procedures. In certain cases, however, this nerve block fails, even when performed by the most experienced clinician. Therefore, it would be advantageous to find an alternative simple technique. The objective of this study is to find an alternative inferior alveolar nerve block that has a higher success rate than other routine techniques. To this purpose, a simple painless inferior alveolar nerve block was designed to anesthetize the inferior alveolar nerve. This study was conducted in Oral surgery department of Vinayaka Mission's dental college Salem from May 2009 to May 2011. Five hundred patients between the age of 20 years and 65 years who required extraction of teeth in mandible were included in the study. Out of 500 patients 270 were males and 230 were females. The effectiveness of the IANB was evaluated by using a sharp dental explorer in the regions innervated by the inferior alveolar, lingual, and buccal nerves after 3, 5, and 7 min, respectively. This study concludes that inferior alveolar nerve block is an appropriate alternative nerve block to anesthetize inferior alveolar nerve due to its several advantages.

  12. [Conduction block: a notion to let through].

    Science.gov (United States)

    Fournier, E

    2012-12-01

    Historical study of electrodiagnosis indicates that nerve conduction block is an old notion, used as early as the second century by Galien and then early in the 19th by physiologists such as Müller and Mateucci. Although introduced into the field of human pathology by Mitchell in 1872, who used it to study nerve injuries, and then by Erb in 1874 to study radial palsy, the contribution of nerve conduction blocks to electrodiagnosis was not exploited until the 1980s. At that time, attempts to improve early diagnosis of Guillain-Barré syndrome showed that among the electrophysiological consequences of demyelination, conduction block was the most appropriate to account for the paralysis. At the same time, descriptions of neuropathies characterized by conduction blocks led to considering conduction block as a major electrophysiological sign. Why was it so difficult for this sign to be retained for electrodiagnosis? Since the notion is not always associated with anatomical lesions, it doesn't fit easily into anatomoclinical reasoning, but has to be thought of in functional terms. Understanding how an uninjured axon could fail to conduct action potentials leads to an examination of the intimate consequences of demyelinations and axonal dysfunctions. But some of the difficulty encountered in adding this new old sign to the armamentarium of electrophysiological diagnosis was related to the technical precautions required to individualize a block. Several pitfalls have to be avoided if a conduction block is to be afforded real diagnostic value. Similar precautions and discussions are also needed to establish an opposing sign, the "excitability block" or "inverse block". Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  13. CT and fluoroscopy guided celiac ganglion block

    International Nuclear Information System (INIS)

    Lim, Sun Kyung; Kwon, Dae Ik; Ahn, Hyup; Kim, Jong Il; Kim, Byung Young; Lee, Jong Gil

    1994-01-01

    To evaluate the effects and usefulness of fluoroscopy guided celiac ganglion block after marking of needle path with CT scan. Celiac ganglion block with 100% ethyl alcohol was performed in 50 cancer patients who were inoperable and had intractable abdominal pain. Duration and degree of pain relief after the procedure and its complication were analyzed. Early pain relief was observed in 98% and long term relief in 68% without serious complication. Fluoroscopy guided celiac ganglion block after marking of needle path with CT scan was a safe and valuable procedure in relieving intractable pain in terminal cancer patients and reduced the time in the CT room

  14. Measurement of soil moisture using gypsum blocks

    DEFF Research Database (Denmark)

    Friis Dela, B.

    the building. Consequently, measuring the moisture of the surrounding soil is of great importance for detecting the source of moisture in a building. Up till now, information has been needed to carry out individual calibrations for the different types of gypsum blocks available on the market and to account......For the past 50 years, gypsum blocks have been used to determine soil moisture content. This report describes a method for calibrating gypsum blocks for soil moisture measurements. Moisture conditions inside a building are strongly influenced by the moisture conditions in the soil surrounding...

  15. Evaluative Conditioning is Insensitive to Blocking

    Directory of Open Access Journals (Sweden)

    Tom Beckers

    2009-01-01

    Full Text Available Evaluative conditioning has been claimed to have a number of functional characteristics that set it apart from other forms of associative learning in humans, such as insensitivity to extinction and contingency, independence of contingency awareness, and insensitivity to modulation. Despite its potential theoretical importance, until now few data are available concerning the susceptibility of evaluative conditioning to cue competition effects such as blocking. In the present study, we assessed the susceptibility of acquired preferences and evaluations to blocking in a candy game. Results suggest that evaluative conditioning is not susceptible to blocking. We discuss this observation in the light of theoretical accounts of evaluative conditioning and associative learning in humans.

  16. Blocks and families for cyclotomic Hecke algebras

    CERN Document Server

    Chlouveraki, Maria

    2009-01-01

    The definition of Rouquier for the families of characters introduced by Lusztig for Weyl groups in terms of blocks of the Hecke algebras has made possible the generalization of this notion to the case of complex reflection groups. The aim of this book is to study the blocks and to determine the families of characters for all cyclotomic Hecke algebras associated to complex reflection groups. This volume offers a thorough study of symmetric algebras, covering topics such as block theory, representation theory and Clifford theory, and can also serve as an introduction to the Hecke algebras of complex reflection groups.

  17. Theory of circuit block switch-off

    Directory of Open Access Journals (Sweden)

    S. Henzler

    2004-01-01

    Full Text Available Switching-off unused circuit blocks is a promising approach to supress static leakage currents in ultra deep sub-micron CMOS digital systems. Basic performance parameters of Circuit Block Switch-Off (CBSO schemes are defined and their dependence on basic circuit parameters is estimated. Therefore the design trade-off between strong leakage suppression in idle mode and adequate dynamic performance in active mode can be supported by simple analytic investigations. Additionally, a guideline for the estimation of the minimum time for which a block deactivation is useful is derived.

  18. Superintegrability of d-dimensional conformal blocks

    International Nuclear Information System (INIS)

    Isachenkov, Mikhail

    2016-02-01

    We observe that conformal blocks of scalar 4-point functions in a d-dimensional conformal field theory can mapped to eigenfunctions of a 2-particle hyperbolic Calogero-Sutherland Hamiltonian. The latter describes two coupled Poeschl-Teller particles. Their interaction, whose strength depends smoothly on the dimension d, is known to be superintegrable. Our observation enables us to exploit the rich mathematical literature on Calogero-Sutherland models in deriving various results for conformal field theory. These include an explicit construction of conformal blocks in terms of Heckman-Opdam hypergeometric functions and a remarkable duality that relates the blocks of theories in different dimensions.

  19. Productivity assessment of Angola's oil blocks

    International Nuclear Information System (INIS)

    Barros, Carlos Pestana; Managi, Shunsuke

    2009-01-01

    This paper analyzes the change in productivity as a result of Angola oil policy from 2001 to 2007. Angola oil blocks are the main source of tax receipts and, therefore, strategically important for public finances. A Malmquist index with the input technological bias is applied to measure productivity change. Oil blocks on average became both more efficient and experienced technological progress. Our results indicate that the traditional growth accounting method, which assumes Hicks neutral technological change, is not appropriate for analyzing changes in productivity for Angola oil blocks. Policy implications are derived. (author)

  20. Superintegrability of d-dimensional conformal blocks

    Energy Technology Data Exchange (ETDEWEB)

    Isachenkov, Mikhail [Weizmann Institute of Science, Rehovot (Israel). Dept. of Particle Physics and Astronomy; Schomerus, Volker [DESY Theory Group, Hamburg (Germany)

    2016-02-15

    We observe that conformal blocks of scalar 4-point functions in a d-dimensional conformal field theory can mapped to eigenfunctions of a 2-particle hyperbolic Calogero-Sutherland Hamiltonian. The latter describes two coupled Poeschl-Teller particles. Their interaction, whose strength depends smoothly on the dimension d, is known to be superintegrable. Our observation enables us to exploit the rich mathematical literature on Calogero-Sutherland models in deriving various results for conformal field theory. These include an explicit construction of conformal blocks in terms of Heckman-Opdam hypergeometric functions and a remarkable duality that relates the blocks of theories in different dimensions.

  1. Round Gating for Low Energy Block Ciphers

    DEFF Research Database (Denmark)

    Banik, Subhadeep; Bogdanov, Andrey; Regazzoni, Francesco

    2016-01-01

    design techniques for implementing block ciphers in a low energy fashion. We concentrate on round based implementation and we discuss how gating, applied at round level can affect and improve the energy consumption of the most common lightweight block cipher currently used in the internet of things....... Additionally, we discuss how to needed gating wave can be generated. Experimental results show that our technique is able to reduce the energy consumption in most block ciphers by over 60% while incurring only a minimal overhead in hardware....

  2. PEO-related block copolymer surfactants

    DEFF Research Database (Denmark)

    Mortensen, K.

    2001-01-01

    Non-ionic block copolymer systems based on hydrophilic poly(ethylene oxide) and more hydrophobic co-polymer blocks are used intensively in a variety of industrial and personal applications. A brief description on the applications is presented. The physical properties of more simple model systems...... of such PEG-based block copolymers in aqueous suspensions are reviewed. Based on scattering experiments using either X-ray or neutrons, the phase behavior is characterized, showing that the thermo-reversible gelation is a result of micellar ordering into mesoscopic crystalline phases of cubic, hexagonal...

  3. Seismic proof test of shielding block walls

    International Nuclear Information System (INIS)

    Ohte, Yukio; Watanabe, Takahide; Watanabe, Hiroyuki; Maruyama, Kazuhide

    1989-01-01

    Most of the shielding block walls used for building nuclear facilities are built by dry process. When a nuclear facility is designed, seismic waves specific at each site are set as input seismic motions and they are adopted in the design. Therefore, it is necessary to assure safety of the shielding block walls for earthquake by performing anti-seismic experiments under the conditions at each site. In order to establish the normal form that can be applied to various seismic conditions in various areas, Shimizu Corp. made an actual-size test samples for the shielding block wall and confirmed the safety for earthquake and validity of normalization. (author)

  4. Functionalization of Block Copolymer Vesicle Surfaces

    Directory of Open Access Journals (Sweden)

    Wolfgang Meier

    2011-01-01

    Full Text Available In dilute aqueous solutions certain amphiphilic block copolymers self-assemble into vesicles that enclose a small pool of water with a membrane. Such polymersomes have promising applications ranging from targeted drug-delivery devices, to biosensors, and nanoreactors. Interactions between block copolymer membranes and their surroundings are important factors that determine their potential biomedical applications. Such interactions are influenced predominantly by the membrane surface. We review methods to functionalize block copolymer vesicle surfaces by chemical means with ligands such as antibodies, adhesion moieties, enzymes, carbohydrates and fluorophores. Furthermore, surface-functionalization can be achieved by self-assembly of polymers that carry ligands at their chain ends or in their hydrophilic blocks. While this review focuses on the strategies to functionalize vesicle surfaces, the applications realized by, and envisioned for, such functional polymersomes are also highlighted.

  5. Secure Block Ciphers - Cryptanalysis and Design

    DEFF Research Database (Denmark)

    Tiessen, Tyge

    be applied to the AES can be transferred to this block cipher, albeit with a higher attack complexity. The second publication introduces a new block cipher family which is targeted for new applications in fully homomorphic encryption and multi-party computation. We demonstrate the soundness of the design...... is encrypted using so-called symmetric ciphers. The security of our digital infrastructure thus rests at its very base on their security. The central topic of this thesis is the security of block ciphers – the most prominent form of symmetric ciphers. This thesis is separated in two parts. The first part...... is an introduction to block ciphers and their cryptanalysis, the second part contains publications written and published during the PhD studies. The first publication evaluates the security of a modification of the AES in which the choice of S-box is unknown to the attacker. We find that some of the attacks that can...

  6. Dynamic code block size for JPEG 2000

    Science.gov (United States)

    Tsai, Ping-Sing; LeCornec, Yann

    2008-02-01

    Since the standardization of the JPEG 2000, it has found its way into many different applications such as DICOM (digital imaging and communication in medicine), satellite photography, military surveillance, digital cinema initiative, professional video cameras, and so on. The unified framework of the JPEG 2000 architecture makes practical high quality real-time compression possible even in video mode, i.e. motion JPEG 2000. In this paper, we present a study of the compression impact using dynamic code block size instead of fixed code block size as specified in the JPEG 2000 standard. The simulation results show that there is no significant impact on compression if dynamic code block sizes are used. In this study, we also unveil the advantages of using dynamic code block sizes.

  7. EnviroAtlas - Phoenix, AZ - Block Groups

    Data.gov (United States)

    U.S. Environmental Protection Agency — This EnviroAtlas dataset is the base layer for the Phoenix, AZ EnviroAtlas area. The block groups are from the US Census Bureau and are included/excluded based on...

  8. EnviroAtlas - Fresno, CA - Block Groups

    Data.gov (United States)

    U.S. Environmental Protection Agency — This EnviroAtlas dataset is the base layer for the Fresno, CA EnviroAtlas area. The block groups are from the US Census Bureau and are included/excluded based on...

  9. Readiness for surgery after axillary block

    DEFF Research Database (Denmark)

    Koscielniak-Nielsen, Z J; Stens-Pedersen, H L; Lippert, F K

    1997-01-01

    required less time for block performance (mean 5.5 min) than multiple injections (mean 9.5 min), P requirement for supplemental nerve blocks was greater, after single injections (33 min and 57%) than after multiple injections (15.5 min and 7......We have assessed prospectively the time to readiness for surgery following axillary block (sum of block performance and latency times) in 80 patients. The brachial plexus was identified using a nerve stimulator, and anaesthetized with 45 mL of mepivacaine 1% with adrenaline 5 micrograms mL-1......%, respectively), P effectiveness was 100% in group 1 and 98% in group 2 (NS). The frequency of adverse effects (vessel puncture or paraesthesia) was similar...

  10. Scalable inference for stochastic block models

    KAUST Repository

    Peng, Chengbin; Zhang, Zhihua; Wong, Ka-Chun; Zhang, Xiangliang; Keyes, David E.

    2017-01-01

    Community detection in graphs is widely used in social and biological networks, and the stochastic block model is a powerful probabilistic tool for describing graphs with community structures. However, in the era of "big data," traditional inference

  11. Second derivative parallel block backward differentiation type ...

    African Journals Online (AJOL)

    Second derivative parallel block backward differentiation type formulas for Stiff ODEs. ... Log in or Register to get access to full text downloads. ... and the methods are inherently parallel and can be distributed over parallel processors. They are ...

  12. Compressed normalized block difference for object tracking

    Science.gov (United States)

    Gao, Yun; Zhang, Dengzhuo; Cai, Donglan; Zhou, Hao; Lan, Ge

    2018-04-01

    Feature extraction is very important for robust and real-time tracking. Compressive sensing provided a technical support for real-time feature extraction. However, all existing compressive tracking were based on compressed Haar-like feature, and how to compress many more excellent high-dimensional features is worth researching. In this paper, a novel compressed normalized block difference feature (CNBD) was proposed. For resisting noise effectively in a highdimensional normalized pixel difference feature (NPD), a normalized block difference feature extends two pixels in the original formula of NPD to two blocks. A CNBD feature can be obtained by compressing a normalized block difference feature based on compressive sensing theory, with the sparse random Gaussian matrix as the measurement matrix. The comparative experiments of 7 trackers on 20 challenging sequences showed that the tracker based on CNBD feature can perform better than other trackers, especially than FCT tracker based on compressed Haar-like feature, in terms of AUC, SR and Precision.

  13. EnviroAtlas - Cleveland, OH - Block Groups

    Data.gov (United States)

    U.S. Environmental Protection Agency — This EnviroAtlas dataset is the base layer for the Cleveland, OH EnviroAtlas community. The block groups are from the US Census Bureau and are included/excluded...

  14. Characterizing permanent magnet blocks with Helmholtz coils

    Science.gov (United States)

    Carnegie, D. W.; Timpf, J.

    1992-08-01

    Most of the insertion devices to be installed at the Advanced Photon Source will utilize permanent magnets in their magnetic structures. The quality of the spectral output is sensitive to the errors in the field of the device which are related to variations in the magnetic properties of the individual blocks. The Advanced Photon Source will have a measurement facility to map the field in the completed insertion devices and equipment to test and modify the magnetic strength of the individual magnet blocks. One component of the facility, the Helmholtz coil permanent magnet block measurement system, has been assembled and tested. This system measures the total magnetic moment vector of a block with a precision better than 0.01% and a directional resolution of about 0.05°. The design and performance of the system will be presented.

  15. Breast Cancer Gene Therapy: Development of Novel Non-Invasive Magnetic Resonance Assay to Optimize Efficacy

    National Research Council Canada - National Science Library

    Mason, Ralph P

    2007-01-01

    Gene therapy holds great promise for treatment of breast cancer. In particular clinical trials are underway to apply therapeutic genes related to pro-drug activation or to modulate the activity of oncogenes by blocking promoter sites...

  16. The diagnosis of blocked pulmonary abscess

    International Nuclear Information System (INIS)

    Vinner, M.G.; Khudyakov, L.M.; Mezentsev, I.A.

    1992-01-01

    Only spot bronchography, and if its results are negative, transthoracal puncture permit a correct diagnosis of blocked or partially blocked pulmonary abscess in 2/3 of cases. This result is of importance for the choice of the treatment strategy, in such patients. Use of thin or super-thin needles for puncture helped do without serious complications and obtain reliable diagnostic information in 90 % of cases

  17. Block copolymer membranes for aqueous solution applications

    KAUST Repository

    Nunes, Suzana Pereira

    2016-03-22

    Block copolymers are known for their intricate morphology. We review the state of the art of block copolymer membranes and discuss perspectives in this field. The main focus is on pore morphology tuning with a short introduction on non-porous membranes. The two main strategies for pore formation in block copolymer membranes are (i) film casting and selective block sacrifice and (ii) self-assembly and non-solvent induced phase separation (SNIPS). Different fundamental aspects involved in the manufacture of block copolymer membranes are considered, including factors affecting the equilibrium morphology in solid films, self-assembly of copolymer in solutions and macrophase separation by solvent-non-solvent exchange. Different mechanisms are proposed for different depths of the SNIPS membrane. Block copolymer membranes can be prepared with much narrower pore size distribution than homopolymer membranes. Open questions and indications of what we consider the next development steps are finally discussed. They include the synthesis and application of new copolymers and specific functionalization, adding characteristics to respond to stimuli and chemical environment, polymerization-induced phase separation, and the manufacture of organic-inorganic hybrids.

  18. Capacitor blocks for linear transformer driver stages.

    Science.gov (United States)

    Kovalchuk, B M; Kharlov, A V; Kumpyak, E V; Smorudov, G V; Zherlitsyn, A A

    2014-01-01

    In the Linear Transformer Driver (LTD) technology, the low inductance energy storage components and switches are directly incorporated into the individual cavities (named stages) to generate a fast output voltage pulse, which is added along a vacuum coaxial line like in an inductive voltage adder. LTD stages with air insulation were recently developed, where air is used both as insulation in a primary side of the stages and as working gas in the LTD spark gap switches. A custom designed unit, referred to as a capacitor block, was developed for use as a main structural element of the transformer stages. The capacitor block incorporates two capacitors GA 35426 (40 nF, 100 kV) and multichannel multigap gas switch. Several modifications of the capacitor blocks were developed and tested on the life time and self breakdown probability. Blocks were tested both as separate units and in an assembly of capacitive module, consisting of five capacitor blocks. This paper presents detailed design of capacitor blocks, description of operation regimes, numerical simulation of electric field in the switches, and test results.

  19. Direct block scheduling technology: Analysis of Avidity

    Directory of Open Access Journals (Sweden)

    Felipe Ribeiro Souza

    Full Text Available Abstract This study is focused on Direct Block Scheduling testing (Direct Multi-Period Scheduling methodology which schedules mine production considering the correct discount factor of each mining block, resulting in the final pit. Each block is analyzed individually in order to define the best target period. This methodology presents an improvement of the classical methodology derived from Lerchs-Grossmann's initial proposition improved by Whittle. This paper presents the differences between these methodologies, specially focused on the algorithms' avidity. Avidity is classically defined by the voracious search algorithms, whereupon some of the most famous greedy algorithms are Branch and Bound, Brutal Force and Randomized. Strategies based on heuristics can accentuate the voracity of the optimizer system. The applied algorithm use simulated annealing combined with Tabu Search. The most avid algorithm can select the most profitable blocks in early periods, leading to higher present value in the first periods of mine operation. The application of discount factors to blocks on the Lerchs-Grossmann's final pit has an accentuated effect with time, and this effect may make blocks scheduled for the end of the mine life unfeasible, representing a trend to a decrease in reported reserves.

  20. Block copolymer membranes for aqueous solution applications

    KAUST Repository

    Nunes, Suzana Pereira

    2016-01-01

    Block copolymers are known for their intricate morphology. We review the state of the art of block copolymer membranes and discuss perspectives in this field. The main focus is on pore morphology tuning with a short introduction on non-porous membranes. The two main strategies for pore formation in block copolymer membranes are (i) film casting and selective block sacrifice and (ii) self-assembly and non-solvent induced phase separation (SNIPS). Different fundamental aspects involved in the manufacture of block copolymer membranes are considered, including factors affecting the equilibrium morphology in solid films, self-assembly of copolymer in solutions and macrophase separation by solvent-non-solvent exchange. Different mechanisms are proposed for different depths of the SNIPS membrane. Block copolymer membranes can be prepared with much narrower pore size distribution than homopolymer membranes. Open questions and indications of what we consider the next development steps are finally discussed. They include the synthesis and application of new copolymers and specific functionalization, adding characteristics to respond to stimuli and chemical environment, polymerization-induced phase separation, and the manufacture of organic-inorganic hybrids.

  1. Efficient Eulerian gyrokinetic simulations with block-structured grids

    International Nuclear Information System (INIS)

    Jarema, Denis

    2017-01-01

    applied to different Eulerian gyrokinetic simulation codes, as the technique relies on a general approach. We implemented and tested our block-structured grids in GENE (http://genecode.org), a highly parallel and heavily used gyrokinetic code, for which it is crucial to keep the good parallel characteristic of the implementation and allow developers to easily port the code written for the original grid to the block-structured counterpart. The presented scenarios clearly demonstrate benefits of the block-structured grids: a high speedup, a tremendously reduced memory footprint and size of diagnostic output data, and the capability to significantly advance the frontier of feasible simulations.

  2. Efficient Eulerian gyrokinetic simulations with block-structured grids

    Energy Technology Data Exchange (ETDEWEB)

    Jarema, Denis

    2017-01-20

    applied to different Eulerian gyrokinetic simulation codes, as the technique relies on a general approach. We implemented and tested our block-structured grids in GENE (http://genecode.org), a highly parallel and heavily used gyrokinetic code, for which it is crucial to keep the good parallel characteristic of the implementation and allow developers to easily port the code written for the original grid to the block-structured counterpart. The presented scenarios clearly demonstrate benefits of the block-structured grids: a high speedup, a tremendously reduced memory footprint and size of diagnostic output data, and the capability to significantly advance the frontier of feasible simulations.

  3. Combined KHFAC + DC nerve block without onset or reduced nerve conductivity after block

    Science.gov (United States)

    Franke, Manfred; Vrabec, Tina; Wainright, Jesse; Bhadra, Niloy; Bhadra, Narendra; Kilgore, Kevin

    2014-10-01

    Objective. Kilohertz frequency alternating current (KHFAC) waveforms have been shown to provide peripheral nerve conductivity block in many acute and chronic animal models. KHFAC nerve block could be used to address multiple disorders caused by neural over-activity, including blocking pain and spasticity. However, one drawback of KHFAC block is a transient activation of nerve fibers during the initiation of the nerve block, called the onset response. The objective of this study is to evaluate the feasibility of using charge balanced direct current (CBDC) waveforms to temporarily block motor nerve conductivity distally to the KHFAC electrodes to mitigate the block onset-response. Approach. A total of eight animals were used in this study. A set of four animals were used to assess feasibility and reproducibility of a combined KHFAC + CBDC block. A following randomized study, conducted on a second set of four animals, compared the onset response resulting from KHFAC alone and combined KHFAC + CBDC waveforms. To quantify the onset, peak forces and the force-time integral were measured during KHFAC block initiation. Nerve conductivity was monitored throughout the study by comparing muscle twitch forces evoked by supra-maximal stimulation proximal and distal to the block electrodes. Each animal of the randomized study received at least 300 s (range: 318-1563 s) of cumulative dc to investigate the impact of combined KHFAC + CBDC on nerve viability. Main results. The peak onset force was reduced significantly from 20.73 N (range: 18.6-26.5 N) with KHFAC alone to 0.45 N (range: 0.2-0.7 N) with the combined CBDC and KHFAC block waveform (p conductivity was observed after application of the combined KHFAC + CBDC block relative to KHFAC waveforms. Significance. The distal application of CBDC can significantly reduce or even completely prevent the KHFAC onset response without a change in nerve conductivity.

  4. Morbillivirus v proteins exhibit multiple mechanisms to block type 1 and type 2 interferon signalling pathways.

    Directory of Open Access Journals (Sweden)

    Senthil K Chinnakannan

    Full Text Available Morbilliviruses form a closely related group of pathogenic viruses which encode three non-structural proteins V, W and C in their P gene. Previous studies with rinderpest virus (RPV and measles virus (MeV have demonstrated that these non-structural proteins play a crucial role in blocking type I (IFNα/β and type II (IFNγ interferon action, and various mechanisms have been proposed for these effects. We have directly compared four important morbilliviruses, rinderpest (RPV, measles virus (MeV, peste des petits ruminants virus (PPRV and canine distemper virus (CDV. These viruses and their V proteins could all block type I IFN action. However, the viruses and their V proteins had varying abilities to block type II IFN action. The ability to block type II IFN-induced gene transcription correlated with co-precipitation of STAT1 with the respective V protein, but there was no correlation between co-precipitation of either STAT1 or STAT2 and the abilities of the V proteins to block type I IFN-induced gene transcription or the creation of the antiviral state. Further study revealed that the V proteins of RPV, MeV, PPRV and CDV could all interfere with phosphorylation of the interferon-receptor-associated kinase Tyk2, and the V protein of highly virulent RPV could also block the phosphorylation of another such kinase, Jak1. Co-precipitation studies showed that morbillivirus V proteins all form a complex containing Tyk2 and Jak1. This study highlights the ability of morbillivirus V proteins to target multiple components of the IFN signalling pathways to control both type I and type II IFN action.

  5. Pectoral nerve block (Pecs block) with sedation for breast conserving surgery without general anesthesia.

    Science.gov (United States)

    Moon, Eun-Jin; Kim, Seung-Beom; Chung, Jun-Young; Song, Jeong-Yoon; Yi, Jae-Woo

    2017-09-01

    Most regional anesthesia in breast surgeries is performed as postoperative pain management under general anesthesia, and not as the primary anesthesia. Regional anesthesia has very few cardiovascular or pulmonary side-effects, as compared with general anesthesia. Pectoral nerve block is a relatively new technique, with fewer complications than other regional anesthesia. We performed Pecs I and Pec II block simultaneously as primary anesthesia under moderate sedation with dexmedetomidine for breast conserving surgery in a 49-year-old female patient with invasive ductal carcinoma. Block was uneventful and showed no complications. Thus, Pecs block with sedation could be an alternative to general anesthesia for breast surgeries.

  6. Use of induced chlorophyll deficient mutants to identify 'heterotic blocks' in pearl millet chromosomes

    International Nuclear Information System (INIS)

    Burton, G.W.

    1989-01-01

    Full text: Chlorophyll deficient mutant stocks induced in 'Tift 23' of pearl millet (Pennisetum americanum L. Leeke) were crossed with 'Tift 23' and 5 other normal inbreds to study the effect of these deleterious recessive genes on yield. The difference between near-isogenic S 1 (F 2 ) populations homozygous or heterozygous for the chlorophyll deficiency was not significant. However among 69 S 1 progenies from crosses with other inbreds the heterozygotes were higher yielding than the homozygotes in 53 cases, 15 of which were significant. A mutant like 'M5' identified a high yield 'heterotic block' in 'Inbred 104' and a very low yield 'heterotic block' in 'Inbred 186'. (author)

  7. Blocking CGRP in migraine patients - a review of pros and cons

    DEFF Research Database (Denmark)

    Deen, Marie; Correnti, Edvige; Kamm, Katharina

    2017-01-01

    Migraine is the most prevalent neurological disorder worldwide and it has immense socioeconomic impact. Currently, preventative treatment options for migraine include drugs developed for diseases other than migraine such as hypertension, depression and epilepsy. During the last decade, however......, blocking calcitonin gene-related peptide (CGRP) has emerged as a possible mechanism for prevention of migraine attacks. CGRP has been shown to be released during migraine attacks and it may play a causative role in induction of migraine attacks. Here, we review the pros and cons of blocking CGRP...

  8. QuaBingo: A Prediction System for Protein Quaternary Structure Attributes Using Block Composition

    Directory of Open Access Journals (Sweden)

    Chi-Hua Tung

    2016-01-01

    Full Text Available Background. Quaternary structures of proteins are closely relevant to gene regulation, signal transduction, and many other biological functions of proteins. In the current study, a new method based on protein-conserved motif composition in block format for feature extraction is proposed, which is termed block composition. Results. The protein quaternary assembly states prediction system which combines blocks with functional domain composition, called QuaBingo, is constructed by three layers of classifiers that can categorize quaternary structural attributes of monomer, homooligomer, and heterooligomer. The building of the first layer classifier uses support vector machines (SVM based on blocks and functional domains of proteins, and the second layer SVM was utilized to process the outputs of the first layer. Finally, the result is determined by the Random Forest of the third layer. We compared the effectiveness of the combination of block composition, functional domain composition, and pseudoamino acid composition of the model. In the 11 kinds of functional protein families, QuaBingo is 23% of Matthews Correlation Coefficient (MCC higher than the existing prediction system. The results also revealed the biological characterization of the top five block compositions. Conclusions. QuaBingo provides better predictive ability for predicting the quaternary structural attributes of proteins.

  9. Decoding Synteny Blocks and Large-Scale Duplications in Mammalian and Plant Genomes

    Science.gov (United States)

    Peng, Qian; Alekseyev, Max A.; Tesler, Glenn; Pevzner, Pavel A.

    The existing synteny block reconstruction algorithms use anchors (e.g., orthologous genes) shared over all genomes to construct the synteny blocks for multiple genomes. This approach, while efficient for a few genomes, cannot be scaled to address the need to construct synteny blocks in many mammalian genomes that are currently being sequenced. The problem is that the number of anchors shared among all genomes quickly decreases with the increase in the number of genomes. Another problem is that many genomes (plant genomes in particular) had extensive duplications, which makes decoding of genomic architecture and rearrangement analysis in plants difficult. The existing synteny block generation algorithms in plants do not address the issue of generating non-overlapping synteny blocks suitable for analyzing rearrangements and evolution history of duplications. We present a new algorithm based on the A-Bruijn graph framework that overcomes these difficulties and provides a unified approach to synteny block reconstruction for multiple genomes, and for genomes with large duplications.

  10. Ultrasound guided TAP block versus ultrasound guided caudal block for pain relief in children undergoing lower abdominal surgeries

    Directory of Open Access Journals (Sweden)

    Wafaa Mohamed Alsadek

    2015-04-01

    Conclusion: TAP block and caudal block under ultrasound guidance proved to be safe with no recorded complications either intra or postoperatively. Patient and parent satisfaction was markedly observed in case of TAP block.

  11. Photo-Induced Micellization of Block Copolymers

    Directory of Open Access Journals (Sweden)

    Satoshi Kuwayama

    2010-11-01

    Full Text Available We found novel photo-induced micellizations through photolysis, photoelectron transfer, and photo-Claisen rearrangement. The photolysis-induced micellization was attained using poly(4-tert-butoxystyrene-block-polystyrene diblock copolymer (PBSt-b-PSt. BSt-b-PSt showed no self-assembly in dichloromethane and existed as isolated copolymers. Dynamic light scattering demonstrated that the copolymer produced spherical micelles in this solvent due to irradiation with a high-pressure mercury lamp in the presence of photo-acid generators, such as bis(alkylphenyliodonium hexafluorophosphate, diphenyliodonium hexafluorophosphate, and triphenylsulfonium triflate. The 1H NMR analysis confirmed that PBSt-b-PSt was converted into poly(4-vinylphenol-block-PSt by the irradiation, resulting in self-assembly into micelles. The irradiation in the presence of the photo-acid generator also induced the micellization of poly(4-pyridinemethoxymethylstyrene-block-polystyrene diblock copolymer (PPySt-b-PSt. Micellization occurred by electron transfer from the pyridine to the photo-acid generator in their excited states and provided monodispersed spherical micelles with cores of PPySt blocks. Further, the photo-Claisen rearrangement caused the micellization of poly(4-allyloxystyrene-block-polystyrene diblock copolymer (PASt-b-PSt. Micellization was promoted in cyclohexane at room temperature without a catalyst. During micellization, the elimination of the allyl groups competitively occurred along with the photorearrangement of the 4-allyloxystyrene units into the 3-allyl-4-hydroxystyrene units.

  12. Application of multi-block methods in cement production

    DEFF Research Database (Denmark)

    Svinning, K.; Høskuldsson, Agnar

    2008-01-01

    distribution and the two last blocks the superficial microstructure analysed by differential thermo gravimetric analysis. The multi-block method is used to identify the role of each part. The score vectors of each block can be analysed separately or together with score vectors of other blocks. Stepwise......Compressive strength at 1 day of Portland cement as a function of the microstructure of cement was statistically modelled by application of multi-block regression method. The observation X-matrix was partitioned into four blocks, the first block representing the mineralogy, the second particle size...... regression is used to find minimum number of variables of each block. The multi-block method proved useful in determining the modelling strength of each data block and finding minimum number of variables within each data block....

  13. Radial expansion for spinning conformal blocks

    CERN Document Server

    Costa, Miguel S.; Penedones, João; Trevisani, Emilio

    2016-07-12

    This paper develops a method to compute any bosonic conformal block as a series expansion in the optimal radial coordinate introduced by Hogervorst and Rychkov. The method reduces to the known result when the external operators are all the same scalar operator, but it allows to compute conformal blocks for external operators with spin. Moreover, we explain how to write closed form recursion relations for the coefficients of the expansions. We study three examples of four point functions in detail: one vector and three scalars; two vectors and two scalars; two spin 2 tensors and two scalars. Finally, for the case of two external vectors, we also provide a more efficient way to generate the series expansion using the analytic structure of the blocks as a function of the scaling dimension of the exchanged operator.

  14. Rapid ordering of block copolymer thin films

    International Nuclear Information System (INIS)

    Majewski, Pawel W; Yager, Kevin G

    2016-01-01

    Block-copolymers self-assemble into diverse morphologies, where nanoscale order can be finely tuned via block architecture and processing conditions. However, the ultimate usage of these materials in real-world applications may be hampered by the extremely long thermal annealing times—hours or days—required to achieve good order. Here, we provide an overview of the fundamentals of block-copolymer self-assembly kinetics, and review the techniques that have been demonstrated to influence, and enhance, these ordering kinetics. We discuss the inherent tradeoffs between oven annealing, solvent annealing, microwave annealing, zone annealing, and other directed self-assembly methods; including an assessment of spatial and temporal characteristics. We also review both real-space and reciprocal-space analysis techniques for quantifying order in these systems. (topical review)

  15. Single molecule magnets from magnetic building blocks

    Science.gov (United States)

    Kroener, W.; Paretzki, A.; Cervetti, C.; Hohloch, S.; Rauschenbach, S.; Kern, K.; Dressel, M.; Bogani, L.; M&üLler, P.

    2013-03-01

    We provide a basic set of magnetic building blocks that can be rationally assembled, similar to magnetic LEGO bricks, in order to create a huge variety of magnetic behavior. Using rare-earth centers and multipyridine ligands, fine-tuning of intra and intermolecular exchange interaction is demonstrated. We have investigated a series of molecules with monomeric, dimeric and trimeric lanthanide centers using SQUID susceptometry and Hall bar magnetometry. A home-made micro-Hall-probe magnetometer was used to measure magnetic hysteresis loops at mK temperatures and fields up to 17 T. All compounds show hysteresis below blocking temperatures of 3 to 4 K. The correlation of the assembly of the building blocks with the magnetic properties will be discussed.

  16. GEOMECHANICAL OBSERVATIONS DURING THE LARGE BLOCK TEST

    International Nuclear Information System (INIS)

    STEPHEN C. BLAIR AND STEPHANIE A. WOOD

    1998-01-01

    This paper presents an overview of the geomechanical studies conducted at the Large Block Test at Fran Ridge, near Yucca Mountain, Nevada. The 3-dimensional geomechanical response of the rock to heating is being monitored using instrumentation mounted in boreholes and on the surface of the block. Results show that thermal expansion of the block began a few hours after the start of heating, and is closely correlated with the thermal history. Horizontal expansion increases as a linear function of height. Comparison of observed deformations with continuum simulations shows that below the heater plane deformation is smaller than predicted, while above the heater plane, observed deformation is larger than predicted, and is consistent with opening of vertical fractures. Fracture monitors indicate that movement on a large horizontal fracture is associated with hydrothermal behavior

  17. Arthroscopic medial meniscus trimming or repair under nerve blocks: Which nerves should be blocked?

    Science.gov (United States)

    Taha, AM; Abd-Elmaksoud, AM

    2016-01-01

    Background: This study aimed to determine the role of the sciatic and obturator nerve blocks (in addition to femoral block) in providing painless arthroscopic medial meniscus trimming/repair. Materials and Methods: One hundred and twenty patients with medial meniscus tear, who had been scheduled to knee arthroscopy, were planned to be included in this controlled prospective double-blind study. The patients were randomly allocated into three equal groups; FSO, FS, and FO. The femoral, sciatic, and obturator nerves were blocked in FSO groups. The femoral and sciatic nerves were blocked in FS group, while the femoral and obturator nerves were blocked in FO group. Intraoperative pain and its causative surgical maneuver were recorded. Results: All the patients (n = 7, 100%) in FO group had intraoperative pain. The research was terminated in this group but completed in FS and FSO groups (40 patients each). During valgus positioning of the knee for surgical management of the medial meniscus tear, the patients in FS group experienced pain more frequently than those in FSO group (P = 0.005). Conclusion: Adding a sciatic nerve block to the femoral nerve block is important for painless knee arthroscopy. Further adding of an obturator nerve block may be needed when a valgus knee position is required to manage the medial meniscus tear. PMID:27375382

  18. Blending of styrene-block-butadiene-block-styrene copolymer with sulfonated vinyl aromatic polymers

    NARCIS (Netherlands)

    Ruggeri, Giacomo; Passaglia, Elisa; Giorgi, Ivan; Picchioni, Francesco; Aglietto, Mauro

    2001-01-01

    Different polymers containing sulfonic groups attached to the phenyl rings were prepared by sulfonation of polystyrene (PS) and styrene-block-(ethylene-co-1-butene)-block-styrene (SEBS). The sulfonation degree (SD) was varied between 1 and 20 mol% of the styrene units. Polyphase materials containing

  19. Ipsilateral Brachial Plexus Block and Hemidiaphragmatic Paresis as Adverse Effect of a High Thoracic Paravertebral Block

    NARCIS (Netherlands)

    Renes, Steven H.; van Geffen, Geert J.; Snoeren, Miranda M.; Gielen, Matthieu J.; Groen, Gerbrand J.

    Background: Thoracic paravertebral block is regularly used for unilateral chest and abdominal surgery and is associated with a low complication rate. Case Reports: We describe 2 patients with an ipsilateral brachial plexus block with Horner syndrome after a high continuous thoracic paravertebral

  20. Synthesis of amylose-block-polystyrene rod-coil block copolymers

    NARCIS (Netherlands)

    Loos, Katja; Stadler, Reimund

    1997-01-01

    In the present communication we demonstrate the synthesis of a hybrid block copolymer based on the combination of a biopolymer (amylose) with a synthetic block (polystyrene). To obtain such materials, amino-functionalized polymers were modified with maltoheptaose moieties that serve as initiators

  1. Fabrication and handling of bentonite blocks

    International Nuclear Information System (INIS)

    1978-06-01

    In accordance with the project for the final storage of spent nuclear fuel, the waste will be encapsulated into copper canisters, which will be deposited in a final repository located in rock 500 m below ground level. The canisters will be placed in vertical holes in the bottoms of the tunnels, where the copper cylinders will be surrounded by blocks of highly compacted bentonite. When the blocks are saturated with water and expansion is essentially retained as in the actual case, a very high swelling pressure will arise. The bentonite will be extremely impermeable and thus it will form a barrier against transport of corrosive matters to the canister. The blocks are fabricated by means of cold isostatic pressing of bentonite powder. The base material in the form of powder is enclosed in flexible forms, which are introduced into pressure vessels where the forms are surrounded by oil or water. Thus the powder is compacted into rigid bodies with a bulk density of about 2.2 t/m 3 for ''air dry'' bentonite, which might be compared with a specific density of about 2.7 t/m 3 . The placing of a canister is preceded by piling up bentonite blocks to a level just below the canister lid position, after which the slot around the blocks is filled with bentonite powder. The rest of the blocks are mounted after filling bentonite powder into the inner slot around the canister as well. Finally the storage tunnels will be sealed by filling them with a mixture o02067NRM 0000181 45

  2. Peripheral nerve blocks in pediatric anesthesia

    Directory of Open Access Journals (Sweden)

    Novaković Dejan

    2009-01-01

    Full Text Available Introduction Most children undergoing surgery can benefit from regional anesthetic techniques, either as the sole anesthetic regimen or, as usual in pediatric practice, in combination with general anesthesia. The use of peripheral nerve blocks (PNBs in pediatric anesthesia is an effective way to decrease the side-effects and complications associated with central blocks. In spite of their many advantages, including easy performance end efficacy, peripheral nerve blocks are still underused. Objective This article discusses a general approach to PNBs in children and provides data concerning the practice of this regional technique in different age groups. Methods Data from 1,650 procedures were prospectively collected during the period from March 1, 2007 to February 29, 2008. The type of PNB, if any, as well as the patient age were noted. Our patients were divided into four groups: 0-3 years, 4-7 years, 8-12 years and 13-18 years. Results During the investigated period, PNBs as a sole technique or in anesthetized children were performed in 7.45% of cases. Ilioingunal/iliohypogastric nerve block and penile block were the most common (70% of all PNBs distributed mainly among the children between 4-7 years of age (p<0.05. In older children, extremity PNBs predominate in regard to other types of blocks. PNBs are most frequently performed under general anesthesia (85%, so the perineural approach requires a safe technique to avoid nerve damage. Conclusion The observed differences in PNB usage seem to be related to patient age and correlate with common pathology and also with technical availability of PNB performance.

  3. Ophthalmic regional blocks: management, challenges, and solutions

    Directory of Open Access Journals (Sweden)

    Palte HD

    2015-08-01

    Full Text Available Howard D Palte Department of Anesthesiology, Perioperative Medicine and Pain Management, Miller School of Medicine, University of Miami, Miami, FL, USA Abstract: In the past decade ophthalmic anesthesia has witnessed a major transformation. The sun has set on the landscape of ophthalmic procedures performed under general anesthesia at in-hospital settings. In its place a new dawn has ushered in the panorama of eye surgeries conducted under regional and topical anesthesia at specialty eye care centers. The impact of the burgeoning geriatric population is that an increasing number of elderly patients will present for eye surgery. In order to accommodate increased patient volumes and simultaneously satisfy administrative initiatives directed at economic frugality, administrators will seek assistance from anesthesia providers in adopting measures that enhance operating room efficiency. The performance of eye blocks in a holding suite meets many of these objectives. Unfortunately, most practicing anesthesiologists resist performing ophthalmic regional blocks because they lack formal training. In future, anesthesiologists will need to block eyes and manage common medical conditions because economic pressures will eliminate routine preoperative testing. This review addresses a variety of topical issues in ophthalmic anesthesia with special emphasis on cannula and needle-based blocks and the new-generation antithrombotic agents. In a constantly evolving arena, the sub-Tenon’s block has gained popularity while the deep angulated intraconal (retrobulbar block has been largely superseded by the shallower extraconal (peribulbar approach. Improvements in surgical technique have also impacted anesthetic practice. For example, phacoemulsification techniques facilitate the conduct of cataract surgery under topical anesthesia, and suture-free vitrectomy ports may cause venous air embolism during air/fluid exchange. Hyaluronidase is a useful adjuvant because it

  4. Wilson loop invariants from WN conformal blocks

    Directory of Open Access Journals (Sweden)

    Oleg Alekseev

    2015-12-01

    Full Text Available Knot and link polynomials are topological invariants calculated from the expectation value of loop operators in topological field theories. In 3D Chern–Simons theory, these invariants can be found from crossing and braiding matrices of four-point conformal blocks of the boundary 2D CFT. We calculate crossing and braiding matrices for WN conformal blocks with one component in the fundamental representation and another component in a rectangular representation of SU(N, which can be used to obtain HOMFLY knot and link invariants for these cases. We also discuss how our approach can be generalized to invariants in higher-representations of WN algebra.

  5. Identification of critical technology building blocks

    DEFF Research Database (Denmark)

    Ravn, Poul Martin; Mortensen, Niels Henrik; Hvam, Lars

    2017-01-01

    on competition, the challenge is to know how to identify and prioritize the development tasks. If possible, an effective strategy can be defined. This article suggests a framework for identification and analysis of a product portfolio, with special emphasis on identifying critical technology building blocks...... development steps. The framework is based on methods and theories in literature. The analysis of the portfolio is carried out through the framework in three steps: by creating an overview of the portfolio encompassing product and technology, assessing the elements in the overview with assessment metrics......, and using property chains to identify critical technology building blocks....

  6. Nanoscale freestanding gratings for ultraviolet blocking filters

    Energy Technology Data Exchange (ETDEWEB)

    van Beek, J.T.; Fleming, R.C.; Hindle, P.S.; Prentiss, J.D.; Schattenburg, M.L. [Massachusetts Institute of Technology, Cambridge, Massachusetts 02139 (United States); Ritzau, S. [Los Alamos National Laboratory, Los Alamos, New Mexico 87545 (United States)

    1998-11-01

    Ultraviolet (UV) blocking filters are needed for atomic flux imaging in environments where high levels of ultraviolet radiation are present. Freestanding gratings are a promising candidate for UV filtering. They have a high aspect ratio ({approximately}13), narrow ({approximately}40 nm) slots, and effectively block UV radiation. The grating fabrication process makes use of several etching, electroplating, and lithographic steps and includes an optional step to plug pinholes induced by particles during processing. Gratings were successfully manufactured and tested. Measured UV transmissions of {approximately}10{sup {minus}5} and particle transmissions of {approximately}10{percent} are in agreement with theoretical predictions. {copyright} {ital 1998 American Vacuum Society.}

  7. Infinite-degree-corrected stochastic block model

    DEFF Research Database (Denmark)

    Herlau, Tue; Schmidt, Mikkel Nørgaard; Mørup, Morten

    2014-01-01

    In stochastic block models, which are among the most prominent statistical models for cluster analysis of complex networks, clusters are defined as groups of nodes with statistically similar link probabilities within and between groups. A recent extension by Karrer and Newman [Karrer and Newman...... corrected stochastic block model as a nonparametric Bayesian model, incorporating a parameter to control the amount of degree correction that can then be inferred from data. Additionally, our formulation yields principled ways of inferring the number of groups as well as predicting missing links...

  8. Phrenic nerve block caused by interscalene brachial plexus block: breathing effects of different sites of injection.

    Science.gov (United States)

    Bergmann, Lars; Martini, Stefan; Kesselmeier, Miriam; Armbruster, Wolf; Notheisen, Thomas; Adamzik, Michael; Eichholz, Rϋdiger

    2016-07-29

    Interscalene brachial plexus (ISB) block is often associated with phrenic nerve block and diaphragmatic paresis. The goal of our study was to test if the anterior or the posterior ultrasound guided approach of the ISB is associated with a lower incidence of phrenic nerve blocks and impaired lung function. This was a prospective, randomized and single-blinded study of 84 patients scheduled for elective shoulder surgery who fullfilled the inclusion and exclusion critereria. Patients were randomized in two groups to receive either the anterior (n = 42) or the posterior (n = 42) approach for ISB. Clinical data were recorded. In both groups patients received ISB with a total injection volume of 15 ml of ropivacaine 1 %. Spirometry was conducted at baseline (T0) and 30 min (T30) after accomplishing the block. Changes in spirometrical variables between T0 and T30 were investigated by Wilcoxon signed-rank test for each puncture approach. The temporal difference between the posterior and the anterior puncture approach groups were again analyzed by the Wilcoxon-Mann-Whitney test. The spirometric results showed a significant decrease in vital capacity, forced expiratory volume per second, and maximum nasal inspiratory breathing after the Interscalene brachial plexus block; indicating a phrenic nerve block (p Wilcoxon signed-rank). A significant difference in the development of the spirometric parameters between the anterior and the posterior group could not be identified (Wilcoxon-Mann-Whitney test). Despite the changes in spirometry, no cases of dyspnea were reported. A different site of injection (anterior or posterior) did not show an effect in reducing the cervical block spread of the local anesthetic and the incidence of phrenic nerve blocks during during ultrasound guided Interscalene brachial plexus block. Clinical breathing effects of phrenic nerve blocks are, however, usually well compensated, and subjective dyspnea did not occur in our patients. German

  9. 30 CFR 250.611 - Traveling-block safety device.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 2 2010-07-01 2010-07-01 false Traveling-block safety device. 250.611 Section... Traveling-block safety device. After May 31, 1989, all units being used for well-workover operations which have both a traveling block and a crown block shall be equipped with a safety device which is designed...

  10. 30 CFR 250.511 - Traveling-block safety device.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 2 2010-07-01 2010-07-01 false Traveling-block safety device. 250.511 Section... Traveling-block safety device. All units being used for well-completion operations that have both a traveling block and a crown block must be equipped with a safety device that is designed to prevent the...

  11. 21 CFR 520.1448a - Monensin blocks.

    Science.gov (United States)

    2010-04-01

    ...) Limitations. Block to be fed free choice to pasture cattle (slaughter, stocker, feeder, and dairy and beef.... Blocks to be fed free choice to pasture cattle (slaughter, stocker, feeder, and dairy and beef.... Blocks to be fed free choice to pasture cattle (slaughter, stocker, and feeder). Provide at least 1 block...

  12. 21 CFR 882.1925 - Ultrasonic scanner calibration test block.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Ultrasonic scanner calibration test block. 882... Ultrasonic scanner calibration test block. (a) Identification. An ultrasonic scanner calibration test block is a block of material with known properties used to calibrate ultrasonic scanning devices (e.g., the...

  13. The iSelect 9 K SNP analysis revealed polyploidization induced revolutionary changes and intense human selection causing strong haplotype blocks in wheat.

    Science.gov (United States)

    Hao, Chenyang; Wang, Yuquan; Chao, Shiaoman; Li, Tian; Liu, Hongxia; Wang, Lanfen; Zhang, Xueyong

    2017-01-30

    A Chinese wheat mini core collection was genotyped using the wheat 9 K iSelect SNP array. Total 2420 and 2396 polymorphic SNPs were detected on the A and the B genome chromosomes, which formed 878 haplotype blocks. There were more blocks in the B genome, but the average block size was significantly (P polyploidization of wheat (both tetraploidization and hexaploidization) induced revolutionary changes in both the A and the B genomes, with a greater increase of gene diversity compared to their diploid ancestors. Modern breeding has dramatically increased diversity in the gene coding regions, though obvious blocks were formed on most of the chromosomes in both tetraploid and hexaploid wheats. Tag-SNP markers identified in this study can be used for marker assisted selection using haplotype blocks as a wheat breeding strategy. This strategy can also be employed to facilitate genome selection in other self-pollinating crop species.

  14. Compaction of bentonite blocks. Development of techniques for production of blocks with different shapes and sizes

    International Nuclear Information System (INIS)

    Johannesson, Lars-Erik; Boergesson, Lennart

    1998-09-01

    In this report useful techniques for producing both smaller blocks manageable by man (10-15 kg) and larger blocks which need special equipment for handling (weight up to 600 kg) are described. Tests for producing blocks with a weight of approximately 10 kg were carried out at Hoeganaes Bjuf AB in Bjuv. This industry is normally producing refractory bricks and other refractory products. The plant has facilities for handling large volumes of clay. It also has machines suitable for producing uniaxially compacted blocks. Tests performed at the plant show that it is possible to compact blocks with good quality. The best quality was reached with a coarsely ground bentonite at a water ratio of 17 %. The compaction rate was high and performed with lubricated form and stepwise loading. Tests, in order to find a technique for producing larger blocks with a diameter of the same size as a deposition hole (about 1.65 m), were also made. The technique was developed in a smaller scale (250 mm). Ring-shaped blocks with the same outer diameter and with an inner diameter of about 156 mm were also compacted. The compaction was made with vacuum in the form. The outer surface of the form was conical and most of the tests were performed with a lubricated form. Tests were performed with different water ratios of the bentonite. All the blocks had a good quality. In consequence of the good test results a form with a 1000 mm diameter was constructed and a number of compaction tests were performed. The same technique was used as for the smaller blocks. The compaction pressure in most tests was 100 MPa (maximum compaction load 80.000 kN). The tests were performed at HYDROWELD in Ystad in a press with a maximum capacity of 300.000 kN. All tests were performed with MX-80. Most of the blocks had a good quality. A small damage close to the upper surface of all blocks was observed but is considered to be of no importance for the possibility to handle the blocks and is not affecting the properties

  15. Compaction of bentonite blocks. Development of techniques for production of blocks with different shapes and sizes

    Energy Technology Data Exchange (ETDEWEB)

    Johannesson, Lars-Erik; Boergesson, Lennart [Clay Technology AB, Lund (Sweden)

    1998-09-01

    In this report useful techniques for producing both smaller blocks manageable by man (10-15 kg) and larger blocks which need special equipment for handling (weight up to 600 kg) are described. Tests for producing blocks with a weight of approximately 10 kg were carried out at Hoeganaes Bjuf AB in Bjuv. This industry is normally producing refractory bricks and other refractory products. The plant has facilities for handling large volumes of clay. It also has machines suitable for producing uniaxially compacted blocks. Tests performed at the plant show that it is possible to compact blocks with good quality. The best quality was reached with a coarsely ground bentonite at a water ratio of 17 %. The compaction rate was high and performed with lubricated form and stepwise loading. Tests, in order to find a technique for producing larger blocks with a diameter of the same size as a deposition hole (about 1.65 m), were also made. The technique was developed in a smaller scale (250 mm). Ring-shaped blocks with the same outer diameter and with an inner diameter of about 156 mm were also compacted. The compaction was made with vacuum in the form. The outer surface of the form was conical and most of the tests were performed with a lubricated form. Tests were performed with different water ratios of the bentonite. All the blocks had a good quality. In consequence of the good test results a form with a 1000 mm diameter was constructed and a number of compaction tests were performed. The same technique was used as for the smaller blocks. The compaction pressure in most tests was 100 MPa (maximum compaction load 80.000 kN). The tests were performed at HYDROWELD in Ystad in a press with a maximum capacity of 300.000 kN. All tests were performed with MX-80. Most of the blocks had a good quality. A small damage close to the upper surface of all blocks was observed but is considered to be of no importance for the possibility to handle the blocks and is not affecting the properties

  16. Exploring Energy Efficiency of Lightweight Block Ciphers

    DEFF Research Database (Denmark)

    Banik, Subhadeep; Bogdanov, Andrey; Regazzoni, Francesco

    2016-01-01

    is the encryption of one plaintext. By studying the energy consumption model of a CMOS gate, we arrive at the conclusion that the energy consumed per cycle during the encryption operation of an r-round unrolled architecture of any block cipher is a quadratic function in r. We then apply our model to 9 well known...

  17. Block Grants: The View from the Dome.

    Science.gov (United States)

    Shreve, David L.

    1996-01-01

    Reviews characteristics and operations of state legislatures in the context of the current reforms proposed by the federal government and the devolution of authority to the states via block grants. Examines proposed changes related to welfare, Medicaid, workforce training, and taxation, highlighting the impact of these reforms on state…

  18. Block Tridiagonal Matrices in Electronic Structure Calculations

    DEFF Research Database (Denmark)

    Petersen, Dan Erik

    in the Landauer–Büttiker ballistic transport regime. These calculations concentrate on determining the so– called Green’s function matrix, or portions thereof, which is the inverse of a block tridiagonal general complex matrix. To this end, a sequential algorithm based on Gaussian elimination named Sweeps...

  19. Building blocks for modular data acquisition systems

    Energy Technology Data Exchange (ETDEWEB)

    Hoffmann, B

    1996-12-31

    The principles of building blocks for modular data acquisition systems by means of the VIC bus are discussed. Real time operating systems based on the VME environment for program development drastically reducing the time needed to develop a working system. 4 figs.

  20. Orientation: Automotive Mechanics Instructional Program. Block 1.

    Science.gov (United States)

    O'Brien, Ralph D.

    The first six instructional blocks in automotive mechanics, the lessons and supportive information in the document provide a guide for teachers in planning an instructional program in the basic theory and practice of a beginning course at the secondary and post-secondary level. The material, as organized, is a suggested sequence of instruction…

  1. Iron Blocks of CMS Magnet Barrel Yoke.

    CERN Multimedia

    2000-01-01

    On the occasion of presenting the CMS Award 2000 to Deggendorfer Werft und Eisenbau GmbH the delivered blocks were inspected at CERN Point 5. From left to right: H. Gerwig (CERN, CMS Magnet Barrel Yoke Coordinator), G. Waurick (CERN), F. Leher (DWE, Project Engineer) and W. Schuster (DWE, Project Manager).

  2. Seismic analysis of fast breeder reactor block

    International Nuclear Information System (INIS)

    Gantenbein, F.

    1990-01-01

    Seismic analysis of LMFBR reactor block is complex due mainly to the fluid structure interaction and the 3D geometry of the structure. Analytical methods which have been developed for this analysis will be briefly described in the paper and applications to a geometry similar to SPX1 will be shown

  3. Laughter-induced left bundle branch block.

    Science.gov (United States)

    Chow, Grant V; Desai, Dipan; Spragg, David D; Zakaria, Sammy

    2012-10-01

    We present the case of a patient with ischemic heart disease and intermittent left bundle branch block, reproducibly induced by laughter. Following treatment of ischemia with successful deployment of a drug-eluting stent, no further episodes of inducible LBBB were seen. Transient ischemia, exacerbated by elevated intrathoracic pressure during laughter, may have contributed to onset of this phenomenon. © 2012 Wiley Periodicals, Inc.

  4. Freeze block testing of buried waste lines

    International Nuclear Information System (INIS)

    Robbins, E.D.; Willi, J.C.

    1976-01-01

    An investigation was conducted to demonstrate application of freeze blocking in waste transfer lines such that a hydrostatic pressure test can be applied. A shop test was conducted on a 20-foot length, 3-inch schedule 40, carbon steel pipe using a coolant of dry ice and Freon. The positive results from these tests prompted a similar employment of the freeze block method in hydrostatic pressure testing the feed inlet leading to 241-S-101 Waste Tank. This pipeline is a 3-inch schedule 10, stainless steel pipe approximately 800 feet long. The freeze block was formed near the lower end of the pipe as it entered the 101-S Waste Tank and a pressure hold test was applied to this pipeline. This test proved the integrity of the pipeline in question, and demonstrated the validity of freeze blocking an open-ended pipeline which could not be hydrotested in other conventional ways. The field demonstration facility, costing $30,200 was completed late in 1975

  5. Neuraxial block and postoperative epidural analgesia

    DEFF Research Database (Denmark)

    Leslie, K; McIlroy, D; Kasza, J

    2016-01-01

    BACKGROUND: We assessed associations between intraoperative neuraxial block and postoperative epidural analgesia, and a composite primary outcome of death or non-fatal myocardial infarction, at 30 days post-randomization in POISE-2 Trial subjects. METHODS: 10 010 high-risk noncardiac surgical pat...

  6. Role of dexamethasone in brachial plexus block

    International Nuclear Information System (INIS)

    Dawood, M.

    2015-01-01

    To evaluate the effect of dexamethasone added to (lignocaine) on the onset and duration of axillary brachial plexus block. Study Design: Randomized controlled trial. Place and Duration of Study: Combined Military Hospital Rawalpindi, from September 2009 to March 2010. Patients and Methods: A total of 100 patients, who were scheduled for elective hand and forearm surgery under axillary brachial plexus block, were randomly allocated to group A in which patients received 40 ml 1.5% lidocaine with 2 ml of isotonic saline (0.9%) and group B in which patients received 40 ml 1.5% lidocaine with 2 ml of dexamethasone (8 mg). Nerve stimulator with insulated needle for multiple stimulations technique was used to locate the brachial plexus nerves. After the injection onset of action and duration of sensory blockade of brachial plexus were recorded at 5 minutes and 15 minutes interval. Results: Group A showed the onset of action of 21.64 ± 2.30 min and in group B it was 15.42 ± 1.44 min (p< 0.001). Duration of nerve block was 115.08 ± 10.92 min in group A and 265.42 ± 16.56 min in group B (p < 0.001). Conclusion: The addition of dexamethasone to 1.5% lignocaine solution in axillary brachial plexus block prolongs the duration of sensory blockade significantly. (author)

  7. Box and block test in Beninese adults.

    Science.gov (United States)

    Natta, Ditouah Didier Niama; Alagnidé, Etienne; Kpadonou, Toussaint Godonou; Detrembleur, Christine; Lejeune, Thierry M; Stoquart, Gaëtan G

    2015-11-01

    To determine the Box and Block Test norm in a sub-Saharan population and to compare these data with published norms for North American adults. A total of 692 healthy Beninese people, age range 20-85 years, were recruited. These subjects were asked to perform the Box and Block Test with both hands. Box and Block Test scores (mean and standard deviation (SD)) for women and men were, respectively, 81.3 (15.4) and 79 (16.6) for the dominant hand and 73.2 (13.7) and 72 (14.8) for the non-dominant hand. Mean Box and Block Test scores ranged from 89.1 (12.7) for people under the age of 25 years to 55.23 (10.5) for people over the age of 74 years. Manual dexterity was better for women than men, for dominant hand than non-dominant hand, and for younger subjects. In comparison with published results for US subjects, Beninese subjects had better dexterity below the age of 50 years in both sexes for the right hand and worse dexterity over 64 years of age in both sexes for the right hand. Developing and validating outcome scales in Africa will help to improve functional assessment of African populations in clinical practice and research.

  8. Colour Blocking: Disregarding Traditional Artistic Colour Harmonies ...

    African Journals Online (AJOL)

    A development in the world of design – costume, fashion, graphics, architecture and general decor whereby traditional colour harmonies are reengineered to suite the taste of the time engages the attention of the paper. The trending phenomenon popularly referred to as 'colour blocking' involves the use of bright ...

  9. SODART optical block of the SRG satellite

    DEFF Research Database (Denmark)

    Christensen, Finn Erland; Frederiksen, P.; Polny, Josef

    1998-01-01

    This paper describes the design and the successful integration of the optical block of the SODART telescopes to be flown on the Spectrum Roentgen Gamma satellite. The integration involves both the integration of the two high throughput x-ray telescopes as well as the objective crystal spectrometer...

  10. Observations on the SIMON Block Cipher Family

    DEFF Research Database (Denmark)

    Kölbl, Stefan; Leander, Gregor; Tiessen, Tyge

    2015-01-01

    In this paper we analyse the general class of functions underlying the Simon block cipher. In particular, we derive efficiently computable and easily implementable expressions for the exact differential and linear behaviour of Simon-like round functions. Following up on this, we use those...

  11. Building blocks of Collagen based biomaterial devices

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. Building blocks of Collagen based biomaterial devices. Collagen as a protein. Collagen in tissues and organs. Stabilizing and cross linking agents. Immunogenicity. Hosts (drugs). Controlled release mechanisms of hosts. Biodegradability, workability into devices ...

  12. Seed conformal blocks in 4D CFT

    Energy Technology Data Exchange (ETDEWEB)

    Echeverri, Alejandro Castedo; Elkhidir, Emtinan; Karateev, Denis [SISSA and INFN,Via Bonomea 265, I-34136 Trieste (Italy); Serone, Marco [SISSA and INFN,Via Bonomea 265, I-34136 Trieste (Italy); ICTP,Strada Costiera 11, I-34151 Trieste (Italy)

    2016-02-29

    We compute in closed analytical form the minimal set of “seed' conformal blocks associated to the exchange of generic mixed symmetry spinor/tensor operators in an arbitrary representation (ℓ,ℓ̄) of the Lorentz group in four dimensional conformal field theories. These blocks arise from 4-point functions involving two scalars, one (0,|ℓ−ℓ̄|) and one (|ℓ−ℓ̄|,0) spinors or tensors. We directly solve the set of Casimir equations, that can elegantly be written in a compact form for any (ℓ,ℓ̄), by using an educated ansatz and reducing the problem to an algebraic linear system. Various details on the form of the ansatz have been deduced by using the so called shadow formalism. The complexity of the conformal blocks depends on the value of p=|ℓ−ℓ̄| and grows with p, in analogy to what happens to scalar conformal blocks in d even space-time dimensions as d increases. These results open the way to bootstrap 4-point functions involving arbitrary spinor/tensor operators in four dimensional conformal field theories.

  13. Robust block bootstrap panel predictability tests

    NARCIS (Netherlands)

    Westerlund, J.; Smeekes, S.

    2013-01-01

    Most panel data studies of the predictability of returns presume that the cross-sectional units are independent, an assumption that is not realistic. As a response to this, the current paper develops block bootstrap-based panel predictability tests that are valid under very general conditions. Some

  14. Reversible conduction block in peripheral nerve using electrical waveforms.

    Science.gov (United States)

    Bhadra, Niloy; Vrabec, Tina L; Bhadra, Narendra; Kilgore, Kevin L

    2018-01-01

    Electrical nerve block uses electrical waveforms to block action potential propagation. Two key features that distinguish electrical nerve block from other nonelectrical means of nerve block: block occurs instantly, typically within 1 s; and block is fully and rapidly reversible (within seconds). Approaches for achieving electrical nerve block are reviewed, including kilohertz frequency alternating current and charge-balanced polarizing current. We conclude with a discussion of the future directions of electrical nerve block. Electrical nerve block is an emerging technique that has many significant advantages over other methods of nerve block. This field is still in its infancy, but a significant expansion in the clinical application of this technique is expected in the coming years.

  15. Blocking Losses With a Photon Counter

    Science.gov (United States)

    Moision, Burce E.; Piazzolla, Sabino

    2012-01-01

    It was not known how to assess accurately losses in a communications link due to photodetector blocking, a phenomenon wherein a detector is rendered inactive for a short time after the detection of a photon. When used to detect a communications signal, blocking leads to losses relative to an ideal detector, which may be measured as a reduction in the communications rate for a given received signal power, or an increase in the signal power required to support the same communications rate. This work involved characterizing blocking losses for single detectors and arrays of detectors. Blocking may be mitigated by spreading the signal intensity over an array of detectors, reducing the count rate on any one detector. A simple approximation was made to the blocking loss as a function of the probability that a detector is unblocked at a given time, essentially treating the blocking probability as a scaling of the detection efficiency. An exact statistical characterization was derived for a single detector, and an approximation for multiple detectors. This allowed derivation of several accurate approximations to the loss. Methods were also derived to account for a rise time in recovery, and non-uniform illumination due to diffraction and atmospheric distortion of the phase front. It was assumed that the communications signal is intensity modulated and received by an array of photon-counting photodetectors. For the purpose of this analysis, it was assumed that the detectors are ideal, in that they produce a signal that allows one to reproduce the arrival times of electrons, produced either as photoelectrons or from dark noise, exactly. For single detectors, the performance of the maximum-likelihood (ML) receiver in blocking is illustrated, as well as a maximum-count (MC) receiver, that, when receiving a pulse-position-modulated (PPM) signal, selects the symbol corresponding to the slot with the largest electron count. Whereas the MC receiver saturates at high count rates

  16. Blocking CHK1 Expression Induces Apoptosis and Abrogates the G2 Checkpoint Mechanism

    Directory of Open Access Journals (Sweden)

    Yan Luo

    2001-01-01

    Full Text Available Checkpoint kinase 1 (Chki is a checkpoint gene that is activated after DNA damage. It phosphorylates and inactivates the Cdc2 activating phosphatase Cdc25C. This in turn inactivates Cdc2, which leads to G2/M arrest. We report that blocking Chki expression by antisense or ribozymes in mammalian cells induces apoptosis and interferes with the G2/M arrest induced by adriamycin. The Chki inhibitor UCN-01 also blocks the G2 arrest after DNA damage and renders cells more susceptible to adriamycin. These results indicate that Chki is an essential gene for the checkpoint mechanism during normal cell proliferation as well as in the DNA damage response.

  17. Gene expression

    International Nuclear Information System (INIS)

    Hildebrand, C.E.; Crawford, B.D.; Walters, R.A.; Enger, M.D.

    1983-01-01

    We prepared probes for isolating functional pieces of the metallothionein locus. The probes enabled a variety of experiments, eventually revealing two mechanisms for metallothionein gene expression, the order of the DNA coding units at the locus, and the location of the gene site in its chromosome. Once the switch regulating metallothionein synthesis was located, it could be joined by recombinant DNA methods to other, unrelated genes, then reintroduced into cells by gene-transfer techniques. The expression of these recombinant genes could then be induced by exposing the cells to Zn 2+ or Cd 2+ . We would thus take advantage of the clearly defined switching properties of the metallothionein gene to manipulate the expression of other, perhaps normally constitutive, genes. Already, despite an incomplete understanding of how the regulatory switch of the metallothionein locus operates, such experiments have been performed successfully

  18. Strength and deformability of hollow concrete blocks: correlation of block and cylindrical sample test results

    OpenAIRE

    Barbosa, C. S.; Hanai, J.B.

    2009-01-01

    This paper deals with correlations among mechanical properties of hollow blocks and those of concrete used to make them. Concrete hollow blocks and test samples were moulded with plastic consistency concrete, to assure the same material in all cases, in three diferente levels of strength (nominally 10 N/mm², 20 N/mm² and 30 N/mm²). The mechanical properties and structural behaviour in axial compression and tension tests were determined by standard tests in blocks and cylinders. Stress and str...

  19. The nucleocapsid protein of measles virus blocks host interferon response

    International Nuclear Information System (INIS)

    Takayama, Ikuyo; Sato, Hiroki; Watanabe, Akira; Omi-Furutani, Mio; Sugai, Akihiro; Kanki, Keita; Yoneda, Misako; Kai, Chieko

    2012-01-01

    Measles virus (MV) belongs to the genus Morbillivirus of the family Paramyxoviridae. A number of paramyxoviruses inhibit host interferon (IFN) signaling pathways in host immune systems by various mechanisms. Inhibition mechanisms have been described for many paramyxoviruses. Although there are inconsistencies among previous reports concerning MV, it appears that P/V/C proteins interfere with the pathways. In this study, we confirmed the effects of MV P gene products of a wild MV strain on IFN pathways and examined that of other viral proteins on it. Interestingly, we found that N protein acts as an IFN-α/β and γ-antagonist as strong as P gene products. We further investigated the mechanisms of MV-N inhibition, and revealed that MV-N blocks the nuclear import of activated STAT without preventing STAT and Jak activation or STAT degradation, and that the nuclear translocation of MV-N is important for the inhibition. The inhibitory effect of the N protein was observed as a common feature of other morbilliviruses. The results presented in this report suggest that N protein of MV as well as P/V/C proteins is involved in the inhibition of host IFN signaling pathways.

  20. The nucleocapsid protein of measles virus blocks host interferon response

    Energy Technology Data Exchange (ETDEWEB)

    Takayama, Ikuyo; Sato, Hiroki; Watanabe, Akira; Omi-Furutani, Mio; Sugai, Akihiro; Kanki, Keita; Yoneda, Misako; Kai, Chieko, E-mail: ckai@ims.u-tokyo.ac.jp

    2012-03-01

    Measles virus (MV) belongs to the genus Morbillivirus of the family Paramyxoviridae. A number of paramyxoviruses inhibit host interferon (IFN) signaling pathways in host immune systems by various mechanisms. Inhibition mechanisms have been described for many paramyxoviruses. Although there are inconsistencies among previous reports concerning MV, it appears that P/V/C proteins interfere with the pathways. In this study, we confirmed the effects of MV P gene products of a wild MV strain on IFN pathways and examined that of other viral proteins on it. Interestingly, we found that N protein acts as an IFN-{alpha}/{beta} and {gamma}-antagonist as strong as P gene products. We further investigated the mechanisms of MV-N inhibition, and revealed that MV-N blocks the nuclear import of activated STAT without preventing STAT and Jak activation or STAT degradation, and that the nuclear translocation of MV-N is important for the inhibition. The inhibitory effect of the N protein was observed as a common feature of other morbilliviruses. The results presented in this report suggest that N protein of MV as well as P/V/C proteins is involved in the inhibition of host IFN signaling pathways.

  1. About Block Dynamic Model of Earthquake Source.

    Science.gov (United States)

    Gusev, G. A.; Gufeld, I. L.

    One may state the absence of a progress in the earthquake prediction papers. The short-term prediction (diurnal period, localisation being also predicted) has practical meaning. Failure is due to the absence of the adequate notions about geological medium, particularly, its block structure and especially in the faults. Geological and geophysical monitoring gives the basis for the notion about geological medium as open block dissipative system with limit energy saturation. The variations of the volume stressed state close to critical states are associated with the interaction of the inhomogeneous ascending stream of light gases (helium and hydrogen) with solid phase, which is more expressed in the faults. In the background state small blocks of the fault medium produce the sliding of great blocks in the faults. But for the considerable variations of ascending gas streams the formation of bound chains of small blocks is possible, so that bound state of great blocks may result (earthquake source). Recently using these notions we proposed a dynamical earthquake source model, based on the generalized chain of non-linear bound oscillators of Fermi-Pasta-Ulam type (FPU). The generalization concerns its in homogeneity and different external actions, imitating physical processes in the real source. Earlier weak inhomogeneous approximation without dissipation was considered. Last has permitted to study the FPU return (return to initial state). Probabilistic properties in quasi periodic movement were found. The chain decay problem due to non-linearity and external perturbations was posed. The thresholds and dependence of life- time of the chain are studied. The great fluctuations of life-times are discovered. In the present paper the rigorous consideration of the inhomogeneous chain including the dissipation is considered. For the strong dissipation case, when the oscillation movements are suppressed, specific effects are discovered. For noise action and constantly arising

  2. Solving block linear systems with low-rank off-diagonal blocks is easily parallelizable

    Energy Technology Data Exchange (ETDEWEB)

    Menkov, V. [Indiana Univ., Bloomington, IN (United States)

    1996-12-31

    An easily and efficiently parallelizable direct method is given for solving a block linear system Bx = y, where B = D + Q is the sum of a non-singular block diagonal matrix D and a matrix Q with low-rank blocks. This implicitly defines a new preconditioning method with an operation count close to the cost of calculating a matrix-vector product Qw for some w, plus at most twice the cost of calculating Qw for some w. When implemented on a parallel machine the processor utilization can be as good as that of those operations. Order estimates are given for the general case, and an implementation is compared to block SSOR preconditioning.

  3. Atrial Fibrillation, Atrioventricular Blocks and Bundle Branch Blocks in Hemodialysis Patients

    OpenAIRE

    Mandic, Ante; Tomic, Monika; Petrov, Bozo; Romic, Zeljko

    2012-01-01

    Atrial fibrillation is one of the most frequent arrhythmias diagnosed in clinical practice and it is also relatively common in dialysis patients. Atrioventricular and intraventricular conduction disturbances are less investigated in hemodialysis patients and data about their prevalence are insufficient. The objective of this study was to determine the prevalence of atrial fibrillation, atrioventricular blocks and bundle branch blocks in hemodialysis patients and to analyze different clinical ...

  4. Brief Announcement: ZeroBlock: Timestamp-Free Prevention of Block-Withholding Attack in Bitcoin

    OpenAIRE

    Solat , Siamak; Potop-Butucaru , Maria

    2017-01-01

    International audience; Bitcoin was recently introduced as a peer-to-peer electronic currency in order to facilitate transactions outside the traditional financial system. The core of Bitcoin, the Blockchain, is the history of the transactions in the system maintained by all miners as a distributed shared register. New blocks in the Blockchain contain the last transactions in the system and are added by miners after a block mining process that consists in solving a resource consuming proof-of...

  5. Evaluation on Behavior of Single Block Subject to Harmonic Excitation

    International Nuclear Information System (INIS)

    Choi, Woo-Seok; Kim, Dong-Ok; Park, Keun-Bae; Lee, Won-Jae

    2007-01-01

    NHDD(Nuclear Hydrogen Development and Demonstration) project team in KAERI(Korea Atomic Energy Research Institute) has been developing a methodology on the seismic evaluation of VHTR(Very High Temperature Reactor). Roughly, there are a block type and a pebble type reactor in VHTR. In the block type reactor, several blocks are stacked and the stacked blocks are arrayed in certain pattern. To evaluate a behavior style and an integrity of the stacked structure subject to a seismic load, a modeling technique to represent the contact surface characteristics between a block and a block support structure and between blocks is necessary. The way to evaluate a load path is also needed. However, it is difficult to deal with a realistic seismic load and to figure out the characteristic of block behavior since it has very complicated time history. In this study, the evaluation of single block subject to a harmonic excitation is conducted for a preliminary evaluation

  6. Comparison of the Cellient(™) automated cell block system and agar cell block method.

    Science.gov (United States)

    Kruger, A M; Stevens, M W; Kerley, K J; Carter, C D

    2014-12-01

    To compare the Cellient(TM) automated cell block system with the agar cell block method in terms of quantity and quality of diagnostic material and morphological, histochemical and immunocytochemical features. Cell blocks were prepared from 100 effusion samples using the agar method and Cellient system, and routinely sectioned and stained for haematoxylin and eosin and periodic acid-Schiff with diastase (PASD). A preliminary immunocytochemical study was performed on selected cases (27/100 cases). Sections were evaluated using a three-point grading system to compare a set of morphological parameters. Statistical analysis was performed using Fisher's exact test. Parameters assessing cellularity, presence of single cells and definition of nuclear membrane, nucleoli, chromatin and cytoplasm showed a statistically significant improvement on Cellient cell blocks compared with agar cell blocks (P cell groups, PASD staining or the intensity or clarity of immunocytochemical staining. A discrepant immunocytochemistry (ICC) result was seen in 21% (13/63) of immunostains. The Cellient technique is comparable with the agar method, with statistically significant results achieved for important morphological features. It demonstrates potential as an alternative cell block preparation method which is relevant for the rapid processing of fine needle aspiration samples, malignant effusions and low-cellularity specimens, where optimal cell morphology and architecture are essential. Further investigation is required to optimize immunocytochemical staining using the Cellient method. © 2014 John Wiley & Sons Ltd.

  7. [Postoperative analgesia in knee arthroplasty using an anterior sciatic nerve block and a femoral nerve block].

    Science.gov (United States)

    del Fresno Cañiaveras, J; Campos, A; Galiana, M; Navarro-Martínez, J A; Company, R

    2008-11-01

    To evaluate the efficacy of a nerve block as an alternative technique for analgesia after knee arthroplasty and to indicate the usefulness and advantages of the anterior approach to the sciatic nerve block. Between April 2004 and March 2006, we studied a series of consecutive patients undergoing knee arthroplasty in which a subarachnoid block was used as the anesthetic technique and postoperative analgesia was provided by means of a combined peripheral femoral nerve block and an anterior sciatic nerve block. We evaluated the mean length of time free from pain, quality of analgesia, and length of stay in hospital. Seventy-eight patients were included in the study. The mean (SD) length of time free from pain for the group was 42.1 (3.9) hours. Patients reported mild pain after 34.8 (4.1) hours and moderate to severe pain after 42.4 (3.5) hours. By the third day, 62.8% of patients were able to bend the knee to 90 degrees. There were no complications resulting from the technique and the level of patient satisfaction was high. A combined femoral-sciatic nerve block is effective in knee arthroplasty. It controls postoperative pain and allows for early rehabilitation. The anterior approach to the sciatic nerve is relatively simple to perform without removing the pressure bandaging from the thigh after surgery. This approach also makes it unnecessary to move the patient.

  8. Strength and deformability of hollow concrete blocks: correlation of block and cylindrical sample test results

    Directory of Open Access Journals (Sweden)

    C. S. Barbosa

    Full Text Available This paper deals with correlations among mechanical properties of hollow blocks and those of concrete used to make them. Concrete hollow blocks and test samples were moulded with plastic consistency concrete, to assure the same material in all cases, in three diferente levels of strength (nominally 10 N/mm², 20 N/mm² and 30 N/mm². The mechanical properties and structural behaviour in axial compression and tension tests were determined by standard tests in blocks and cylinders. Stress and strain analyses were made based on concrete’s modulus of elasticity obtained in the sample tests as well as on measured strain in the blocks’ face-shells and webs. A peculiar stress-strain analysis, based on the superposition of effects, provided an estimation of the block load capacity based on its deformations. In addition, a tentative method to preview the block deformability from the concrete mechanical properties is described and tested. This analysis is a part of a broader research that aims to support a detailed structural analysis of blocks, prisms and masonry constructions.

  9. Mud concrete paving block for pedestrian pavements

    Directory of Open Access Journals (Sweden)

    Chameera Udawattha

    2017-12-01

    This is an attempt to search for alternative eco-friendly earth paving material for public walkways with both the strength and durable properties of concrete while ensuring pedestrian comfort. Approaches were made to change the fine particle percentage while keeping the sand and gravel constant, once the optimum most practical mixture was known, the standard tests were done. The results obtained revealed that the proposed self-compacting block can be produced by using soil with less than 5% fine particles, 55% of 65% sand particles and 18% of 22% cement by weight together with the moisture content between 14% and 15%The tested mud concrete paving blocks were already used in practical application in Sri Lankan urban context.

  10. Osmosis and thermodynamics explained by solute blocking.

    Science.gov (United States)

    Nelson, Peter Hugo

    2017-01-01

    A solute-blocking model is presented that provides a kinetic explanation of osmosis and ideal solution thermodynamics. It validates a diffusive model of osmosis that is distinct from the traditional convective flow model of osmosis. Osmotic equilibrium occurs when the fraction of water molecules in solution matches the fraction of pure water molecules that have enough energy to overcome the pressure difference. Solute-blocking also provides a kinetic explanation for why Raoult's law and the other colligative properties depend on the mole fraction (but not the size) of the solute particles, resulting in a novel kinetic explanation for the entropy of mixing and chemical potential of ideal solutions. Some of its novel predictions have been confirmed; others can be tested experimentally or by simulation.

  11. Essential Building Blocks of Human Nature

    CERN Document Server

    Frey, Ulrich J; Willführ, Kai P

    2011-01-01

    To understand why we humans are as we are, it is necessary to look at the essential building blocks that comprise our nature. The foundations of this structure are our evolutionary origins as primates and our social roots. Upon these rest features such as our emotions, language and aesthetic preferences, with our self-perceptions, self-deceptions and thirst for knowledge right at the top. The unifying force holding these blocks together is evolutionary theory. Evolution provides a deeper understanding of human nature and, in particular, of the common roots of these different perspectives. To build a reliable and coherent model of man, leading authors from fields as diverse as primatology, anthropology, neurobiology and philosophy have joined forces to present essays  each describing their own expert perspective. Together they provide a convincing and complete picture of our own human nature.

  12. Hybrid, Nanoscale Phospholipid/Block Copolymer Vesicles

    Directory of Open Access Journals (Sweden)

    Bo Liedberg

    2013-09-01

    Full Text Available Hybrid phospholipid/block copolymer vesicles, in which the polymeric membrane is blended with phospholipids, display interesting self-assembly behavior, incorporating the robustness and chemical versatility of polymersomes with the softness and biocompatibility of liposomes. Such structures can be conveniently characterized by preparing giant unilamellar vesicles (GUVs via electroformation. Here, we are interested in exploring the self-assembly and properties of the analogous nanoscale hybrid vesicles (ca. 100 nm in diameter of the same composition prepared by film-hydration and extrusion. We show that the self-assembly and content-release behavior of nanoscale polybutadiene-b-poly(ethylene oxide (PB-PEO/1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine (POPC hybrid phospholipid/block copolymer vesicles can be tuned by the mixing ratio of the amphiphiles. In brief, these hybrids may provide alternative tools for drug delivery purposes and molecular imaging/sensing applications and clearly open up new avenues for further investigation.

  13. Nerve injury caused by mandibular block analgesia

    DEFF Research Database (Denmark)

    Hillerup, S; Jensen, Rigmor H

    2006-01-01

    Fifty-four injection injuries in 52 patients were caused by mandibular block analgesia affecting the lingual nerve (n=42) and/or the inferior alveolar nerve (n=12). All patients were examined with a standardized test of neurosensory functions. The perception of the following stimuli was assessed......: feather light touch, pinprick, sharp/dull discrimination, warm, cold, point location, brush stroke direction, 2-point discrimination and pain perception. Gustation was tested for recognition of sweet, salt, sour and bitter. Mandibular block analgesia causes lingual nerve injury more frequently than...... inferior alveolar nerve injury. All grades of loss of neurosensory and gustatory functions were found, and a range of persisting neurogenic malfunctions was reported. Subjective complaints and neurosensory function tests indicate that lingual nerve lesions are more incapacitating than inferior alveolar...

  14. Osmosis and thermodynamics explained by solute blocking

    Science.gov (United States)

    Nelson, Peter Hugo

    2016-01-01

    A solute-blocking model is presented that provides a kinetic explanation of osmosis and ideal solution thermodynamics. It validates a diffusive model of osmosis that is distinct from the traditional convective flow model of osmosis. Osmotic equilibrium occurs when the fraction of water molecules in solution matches the fraction of pure water molecules that have enough energy to overcome the pressure difference. Solute-blocking also provides a kinetic explanation for why Raoult’s law and the other colligative properties depend on the mole fraction (but not the size) of the solute particles, resulting in a novel kinetic explanation for the entropy of mixing and chemical potential of ideal solutions. Some of its novel predictions have been confirmed, others can be tested experimentally or by simulation. PMID:27225298

  15. HEAO Block 2 study executive summary

    International Nuclear Information System (INIS)

    1976-03-01

    An executive summary is presented of a preliminary study done on several potential High Energy Astronomy Observatory (HEAO) missions which are follow-on missions to the currently defined HEAO program. The purpose was to examine several typical missions and determine the relative complexities associated with them. The four payloads investigated were a 1.2 m Diameter x-ray Telescope observatory, a Large Area Moderate Angular Resolution (LAMAR) observatory, a cosmic ray observatory, and (4) a gamma ray observatory. Each of the four observatories was considered a national facility. Low cost approaches were stressed throughout, with considerable use of HEAO Block I experience and designs effected to provide a high degree of confidence that such approaches were achievable. The use of the Multi-Mission Spacecraft (MMS) and the HEAO Block I spacecraft was considered as a result of this low cost emphasis. Also, NASA standard components were considered, where applicable

  16. Remediation of spent block in Uvanas deposit

    International Nuclear Information System (INIS)

    Nurgaziev, M.A.; Iskakov, M.M.

    2012-01-01

    In 2007 by 'Kazatomprom' and 'Mining company' board decision, the branch of 'Mining company', 'Steppe ore management body' is reorganized in structure subdivision, the basic activity of which is organization and carrying out remediation works on spent blocks of PSV uranium deposit. In 2002 works are completed on OVOS for operating deposits Uvanas, Kanjugan, Northern Karamurun and Eastern Minkuduk. The results of present work were reported in IAEA conference. The working project 'Remediation of spent blocks of PSV uranium deposit PV-17 polygon of Steppe ore management body' approved in 2005 was developed for carrying out the remediation works. Works funding were carried out from liquidation fund of the current deposit established in accordance with the Republic of Kazakhstan law 'About interior and interior use'. Deposits remediation is the part of deposit operation life cycle which obliges to operate deposits with minimum expenditures for remediation.

  17. SANS study of coated block copolymer micelles

    Czech Academy of Sciences Publication Activity Database

    Pleštil, Josef; Kříž, Jaroslav; Koňák, Čestmír; Pospíšil, Herman; Kadlec, Petr; Sedláková, Zdeňka; Grillo, I.; Cubitt, R.

    2005-01-01

    Roč. 206, č. 12 (2005), s. 1206-1215 ISSN 1022-1352 R&D Projects: GA ČR GA203/03/0600; GA AV ČR IAA1050201; GA AV ČR KSK4050111 Institutional research plan: CEZ:AV0Z40500505 Keywords : block copolymer micelles * core-shell polymers * nanoparticles Subject RIV: CD - Macromolecular Chemistry Impact factor: 2.111, year: 2005

  18. Salt Block II: description and results

    International Nuclear Information System (INIS)

    Hohlfelder, J.J.

    1980-06-01

    A description of and results from the Salt Block II experiment, which involved the heating of and measurement of water transport within a large sample of rock salt, are presented. These results include the measurement of water released into a heated borehole in the sample as well as measured temperatures within the salt. Measured temperatures are compared with the results of a mathematical model of the experiment

  19. Hyperkalemia-induced complete heart block

    Directory of Open Access Journals (Sweden)

    Alireza Baratloo

    2015-05-01

    Full Text Available Background: Potassium, as an extracellular ion, plays an important role in the electrophysiologic function of the myocardium and any change in extracellular concentration of this ion might have a marked impression upon myocyte electrophysiologic gain. High serum potassium levels are thought to impair pulse conduction in Purkinje fibers and ventricles more than that in the Atrioventricular (AV node. Therefore, although complete AV block can occur, it is a rare initial presentation. Case Report: We describe a 62-year-old man with a history of diabetes mellitus, ischemic heart disease and previous Coronary Artery Bypass Graft (CABG, who came to our emergency department due to generalized weakness starting 2 days before admission. The patient also had decreased force in lower limbs, exacerbating from the morning, and was finally diagnosed as a hyperkalemia-induced Complete Heart Block (CHB. It should also be noted that the patient responded dramatically to the administration of 10 mL of 10% calcium gluconate along with external pacing until potassium level correction became effective. Conclusion: In spite of the fact that Hyperkalemia can be associated with frequent Electrocardiogram (ECG abnormality, advanced heart blocks (second- and third-degree AV blocks are usually found only in patients with pre-existing heart failure, conduction abnormalities, or other cardiac diseases. Institution of effective treatment rapidly and forgiveness of traditional non-effective, time consumptive and sometimes risking full-adjustment modalities, such as sodium bicarbonate infusion or exchange resins that prevent their use in the emergent phase, can help minimize patient morbidity and mortality.

  20. The Changeable Block Distance System Analysis

    Science.gov (United States)

    Lewiński, Andrzej; Toruń, Andrzej

    The paper treats about efficiency analysis in Changeable Block Distance (CBD) System connected with wireless positioning and control of train. The analysis is based on modeling of typical ERTMS line and comparison with actual and future traffic. The calculations are related to assumed parameters of railway traffic corresponding to real time - table of distance Psary - Góra Włodowska from CMK line equipped in classic, ETCS Level 1 and ETCS with CBD systems.

  1. Amphiphilic block copolymers for biomedical applications

    Science.gov (United States)

    Zupancich, John Andrew

    Amphiphilic block copolymer self-assembly provides a versatile means to prepare nanoscale objects in solution. Control over aggregate shape is granted through manipulation of amphiphile composition and the synthesis of well-defined polymers offers the potential to produce micelles with geometries optimized for specific applications. Currently, polymer micelles are being investigated as vehicles for the delivery of therapeutics and attempts to increase efficacy has motivated efforts to incorporate bioactive ligands and stimuli-responsive character into these structures. This thesis reports the synthesis and self-assembly of biocompatible, degradable polymeric amphiphiles. Spherical, cylindrical, and bilayered vesicle structures were generated spontaneously by the direct dispersion of poly(ethylene oxide)-b-poly(gamma-methyl-ε-caprolactone) block copolymers in water and solutions were characterized with cryogenic transmission electron microscopy (cryo-TEM). The dependence of micelle structure on diblock copolymer composition was examined through the systematic variation of the hydrophobic block molecular weight. A continuous evolution of morphology was observed with coexistence of aggregate structures occurring in windows of composition intermediate to that of pure spheres, cylinders and vesicles. A number of heterobifunctional poly(ethylene oxide) polymers were synthesized for the preparation of ligand-functionalized amphiphilic diblock copolymers. The effect of ligand conjugation on block copolymer self-assembly and micelle morphology was also examined. An RGD-containing peptide sequence was efficiently conjugated to a set of well characterized poly(ethylene oxide)-b-poly(butadiene) copolymers. The reported aggregate morphologies of peptide-functionalized polymeric amphiphiles deviated from canonical structures and the micelle clustering, cylinder fragmentation, network formation, and multilayer vesicle generation documented with cryo-TEM was attributed to

  2. Temporary Blindness after Inferior Alveolar Nerve Block.

    Science.gov (United States)

    Barodiya, Animesh; Thukral, Rishi; Agrawal, Shaila Mahendra; Rai, Anshul; Singh, Siddharth

    2017-03-01

    Inferior Alveolar Nerve Block (IANB) anaesthesia is one of the common procedures in dental clinic. This procedure is safe, but complications may still occur. Ocular complications such as diplopia, loss of vision, or ophthalmoplegia are extremely rare. This case report explains an event where due to individual anatomic variation of the sympathetic vasoconstrictor nerve and maxillary and middle meningeal arteries, intravascular administration of anaesthetic agent caused unusual ocular signs and symptoms such as temporary blindness.

  3. Multichannel conformal blocks for scattering amplitudes

    Science.gov (United States)

    Belitsky, A. V.

    2018-05-01

    By performing resummation of small fermion-antifermion pairs within the pentagon form factor program to scattering amplitudes in planar N = 4 superYang-Mills theory, we construct multichannel conformal blocks within the flux-tube picture for N-sided NMHV polygons. This procedure is equivalent to summation of descendants of conformal primaries in the OPE framework. The resulting conformal partial waves are determined by multivariable hypergeometric series of Lauricella-Saran type.

  4. 3D Reasoning from Blocks to Stability.

    Science.gov (United States)

    Zhaoyin Jia; Gallagher, Andrew C; Saxena, Ashutosh; Chen, Tsuhan

    2015-05-01

    Objects occupy physical space and obey physical laws. To truly understand a scene, we must reason about the space that objects in it occupy, and how each objects is supported stably by each other. In other words, we seek to understand which objects would, if moved, cause other objects to fall. This 3D volumetric reasoning is important for many scene understanding tasks, ranging from segmentation of objects to perception of a rich 3D, physically well-founded, interpretations of the scene. In this paper, we propose a new algorithm to parse a single RGB-D image with 3D block units while jointly reasoning about the segments, volumes, supporting relationships, and object stability. Our algorithm is based on the intuition that a good 3D representation of the scene is one that fits the depth data well, and is a stable, self-supporting arrangement of objects (i.e., one that does not topple). We design an energy function for representing the quality of the block representation based on these properties. Our algorithm fits 3D blocks to the depth values corresponding to image segments, and iteratively optimizes the energy function. Our proposed algorithm is the first to consider stability of objects in complex arrangements for reasoning about the underlying structure of the scene. Experimental results show that our stability-reasoning framework improves RGB-D segmentation and scene volumetric representation.

  5. Responsive linear-dendritic block copolymers.

    Science.gov (United States)

    Blasco, Eva; Piñol, Milagros; Oriol, Luis

    2014-06-01

    The combination of dendritic and linear polymeric structures in the same macromolecule opens up new possibilities for the design of block copolymers and for applications of functional polymers that have self-assembly properties. There are three main strategies for the synthesis of linear-dendritic block copolymers (LDBCs) and, in particular, the emergence of click chemistry has made the coupling of preformed blocks one of the most efficient ways of obtaining libraries of LDBCs. In these materials, the periphery of the dendron can be precisely functionalised to obtain functional LDBCs with self-assembly properties of interest in different technological areas. The incorporation of stimuli-responsive moieties gives rise to smart materials that are generally processed as self-assemblies of amphiphilic LDBCs with a morphology that can be controlled by an external stimulus. Particular emphasis is placed on light-responsive LDBCs. Furthermore, a brief review of the biomedical or materials science applications of LDBCs is presented. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Modelling of multi-block data

    DEFF Research Database (Denmark)

    Høskuldsson, Agnar; Svinning, K.

    2006-01-01

    Here is presented a unified approach to modelling multi-block regression data. The starting point is a partition of the data X into L data blocks, X = (X-1, X-2,...X-L), and the data Y into M data-blocks, Y = (Y-1, Y-2,...,Y-M). The methods of linear regression, X -> Y, are extended to the case...... of a linear relationship between each X-i and Y-j. X-i -> Y-j. A modelling strategy is used to decide if the residual X-i should take part in the modelling of one or more Y(j)s. At each step the procedure of finding score vectors is based on well-defined optimisation procedures. The principle of optimisation...... is based on that the score vectors should give the sizes of the resulting Y(j)s loading vectors as large as possible. The partition of X and Y are independent of each other. The choice of Y-j can be X-j, Y-i = X-i, thus including the possibility of modelling X -> X-i,i=1,...,L. It is shown how...

  7. Block Storage Service: Status and Performance

    CERN Document Server

    Van der Ster, Daniel

    2014-01-01

    This memo summarizes the current status of the Ceph block storage service as it is used for OpenStack Cinder Volumes and Glance Images as of May 2014. We present the block storage activity on the current cluster, measuring IOPS and latencies, and present a cost/benefit analysis of using SSDs to optimize the cost and performance efficiency of the service. During tests in collaboration with IT-CF, we have concluded that by adding SSDs as the synchronous write journals (used to guarantee data durability), we are able increase the IOPS capacity by 4-5 times, at a cost of decreasing the available volume by 20%. Further, the testing has shown that the Ceph implementation is able to operate at the limit of the hardware performance; software-induced performance limitations were not yet observed in either the spinning disk or SSD configurations. In addition, we believe that increasing small write performance with SSDs is applicable only to the block storage use-case; high-bandwidth use-cases such as physics data stora...

  8. Rapid self-assembly of block copolymers to photonic crystals

    Science.gov (United States)

    Xia, Yan; Sveinbjornsson, Benjamin R; Grubbs, Robert H; Weitekamp, Raymond; Miyake, Garret M; Atwater, Harry A; Piunova, Victoria; Daeffler, Christopher Scot; Hong, Sung Woo; Gu, Weiyin; Russell, Thomas P.

    2016-07-05

    The invention provides a class of copolymers having useful properties, including brush block copolymers, wedge-type block copolymers and hybrid wedge and polymer block copolymers. In an embodiment, for example, block copolymers of the invention incorporate chemically different blocks comprising polymer size chain groups and/or wedge groups that significantly inhibit chain entanglement, thereby enhancing molecular self-assembly processes for generating a range of supramolecular structures, such as periodic nanostructures and microstructures. The present invention also provides useful methods of making and using copolymers, including block copolymers.

  9. [Construction of haplotype and haplotype block based on tag single nucleotide polymorphisms and their applications in association studies].

    Science.gov (United States)

    Gu, Ming-liang; Chu, Jia-you

    2007-12-01

    Human genome has structures of haplotype and haplotype block which provide valuable information on human evolutionary history and may lead to the development of more efficient strategies to identify genetic variants that increase susceptibility to complex diseases. Haplotype block can be divided into discrete blocks of limited haplotype diversity. In each block, a small fraction of ptag SNPsq can be used to distinguish a large fraction of the haplotypes. These tag SNPs can be potentially useful for construction of haplotype and haplotype block, and association studies in complex diseases. There are two general classes of methods to construct haplotype and haplotype blocks based on genotypes on large pedigrees and statistical algorithms respectively. The author evaluate several construction methods to assess the power of different association tests with a variety of disease models and block-partitioning criteria. The advantages, limitations and applications of each method and the application in the association studies are discussed equitably. With the completion of the HapMap and development of statistical algorithms for addressing haplotype reconstruction, ideas of construction of haplotype based on combination of mathematics, physics, and computer science etc will have profound impacts on population genetics, location and cloning for susceptible genes in complex diseases, and related domain with life science etc.

  10. Spring-block Model for Barkhausen Noise

    International Nuclear Information System (INIS)

    Kovacs, K.; Brechet, Y.; Neda, Z.

    2005-01-01

    A simple mechanical spring-block model is used for studying Barkhausen noise (BN). The model incorporates the generally accepted physics of domain wall movement and pinning. Computer simulations on this model reproduces the main features of the hysteresis loop and Barkhausen jumps. The statistics of the obtained Barkhausen jumps follows several scaling laws, in qualitative agreement with experimental results. The model consists of a one-dimensional frictional spring-block system. The blocks model the Bloch-walls that separate inversely oriented magnetic domains, and springs correspond to the magnetized regions. Three types of realistic forces are modelled with this system: 1. the force resulting from the magnetic energy of the neighboring domains in external magnetic field (modelled by forces having alternating orientations and acting directly on the blocks); 2. the force resulting from the magnetic self-energy of each domain (modelled by the elastic forces of the springs); 3. the pinning forces acting on the domain walls (modelled by position dependent static friction acting on blocks). The dynamics of the system is governed by searching for equilibrium: one particular domain wall can jump to the next pinning center if the resultant of forces 1. and 2. is greater then the pinning force. The external magnetic field is successively increased (or decreased) and the system is relaxed to mechanical equilibrium. During the simulations we are monitoring the variation of the magnetization focusing on the shape of the hysteresis loop, power spectrum, jump size (avalanche size) distribution, signal duration distribution, signal area distribution. The simulated shape of the hysteresis loops fulfills all the requirements for real magnetization phenomena. The power spectrum indicates different behavior in the low (1/f noise) and high (white noise) frequency region. All the relevant distribution functions show scaling behavior over several decades of magnitude with a naturally

  11. Suprascapular block associated with supraclavicular block: An alternative to isolated interscalene block for analgesia in shoulder instability surgery?

    Science.gov (United States)

    Trabelsi, W; Ben Gabsia, A; Lebbi, A; Sammoud, W; Labbène, I; Ferjani, M

    2017-02-01

    Interscalene brachial plexus block (ISB) is the gold standard for postoperative pain management in shoulder surgery. However, this technique has side effects and potentially serious complications. The aim of this study was to compare the combinations of ultrasound-guided suprascapular (SSB) associated with supraclavicular nerve block (SCB) and ultrasound-guided ISB for postoperative analgesia after shoulder instability surgery. Sixty ASA physical status I-II patients scheduled to undergo shoulder instability surgery were included. Two groups: (i) the SSB+SCB group (n=30) in which the patients received a combination of US-guided SSB (15mL of bupivacaine 0.25%) and US-guided SCB (15mL of bupivacaine 0.25%) and (ii) the ISB group (n=30) in which the patients received US-guided ISB with 30mL of bupivacaine 0.25%. General anesthesia was administered to all patients. During the first 24h, the variables assessed were time to administer the anesthesia, duration of the analgesia, onset and duration of motor and sensory blockade, opioid consumption, cardiovascular stability, complications, and patient satisfaction. Anesthesia induction took more time for the SSB+SCB group than for the ISB group. However, the onset time of motor and sensory blockade was similar in the two groups. Statistical analysis of the visual analog postoperative pain scoring at H0, H6, H12, and H24 showed nonsignificant differences between the groups. Analgesia, the first request for morphine, and total morphine consumption during the first 24h was similar in both groups. No complication was recorded in the SSB+SCB group. However, phrenic nerve block occurred in all patients in the ISB group. US-guided SCB combined with US-guided SSB was as effective as ISB for postoperative analgesia after shoulder instability surgery without decreasing potential side effects. NCT identifier: NCT02397330. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  12. Trichoderma genes

    Science.gov (United States)

    Foreman, Pamela [Los Altos, CA; Goedegebuur, Frits [Vlaardingen, NL; Van Solingen, Pieter [Naaldwijk, NL; Ward, Michael [San Francisco, CA

    2012-06-19

    Described herein are novel gene sequences isolated from Trichoderma reesei. Two genes encoding proteins comprising a cellulose binding domain, one encoding an arabionfuranosidase and one encoding an acetylxylanesterase are described. The sequences, CIP1 and CIP2, contain a cellulose binding domain. These proteins are especially useful in the textile and detergent industry and in pulp and paper industry.

  13. Recurrence relations for toric N = 1 superconformal blocks

    Science.gov (United States)

    Hadasz, Leszek; Jaskólski, Zbigniew; Suchanek, Paulina

    2012-09-01

    General 1-point toric blocks in all sectors of N = 1 superconformal field theories are analyzed. The recurrence relations for blocks coefficients are derived by calculating their residues and large Δ asymptotics.

  14. [Reversible first-degree atrioventricular block due to hyperthyroidism].

    Science.gov (United States)

    Çelebi, Aksüyek Savaş; Amasyalı, Basri

    2017-04-01

    Hyperthyroidism often causes tachyarrhythmia. Reversible atrioventricular block caused by hyperthyroidism is rare occurrence. Presently described is a case of atrioventricular block due to hyperthyroidism and recovery after antithyroid treatment.

  15. From global to heavy-light: 5-point conformal blocks

    International Nuclear Information System (INIS)

    Alkalaev, Konstantin; Belavin, Vladimir

    2016-01-01

    We consider Virasoro conformal blocks in the large central charge limit. There are different regimes depending on the behavior of the conformal dimensions. The most simple regime is reduced to the global sl(2,ℂ) conformal blocks while the most complicated one is known as the classical conformal blocks. Recently, Fitzpatrick, Kaplan, and Walters showed that the two regimes are related through the intermediate stage of the so-called heavy-light semiclassical limit. We study this idea in the particular case of the 5-point conformal block. To find the 5-point global block we use the projector technique and the Casimir operator approach. Furthermore, we discuss the relation between the global and the heavy-light limits and construct the heavy-light block from the global block. In this way we reproduce our previous results for the 5-point perturbative classical block obtained by means of the monodromy method.

  16. Lifting of a sector block for YE-2 at Kawasaki.

    CERN Multimedia

    R. Loveless/U. of Wisconsin

    2000-01-01

    YE-2 is build from machined sector blocks. Trial assembly is carried out horizontally. This picture represents the lifting of a machined sector block destined to the trial assembly of a half disk YE-2 at Kawasaki (KHI) Kobe, Japan.

  17. Designing block copolymer architectures for targeted membrane performance

    KAUST Repository

    Dorin, Rachel Mika; Phillip, William A.; Sai, Hiroaki; Werner, Jö rg; Elimelech, Menachem; Wiesner, Ulrich

    2014-01-01

    Using a combination of block copolymer self-assembly and non-solvent induced phase separation, isoporous ultrafiltration membranes were fabricated from four poly(isoprene-b-styrene-b-4-vinylpyridine) triblock terpolymers with similar block volume

  18. Two injection digital block versus single subcutaneous palmar injection block for finger lacerations.

    Science.gov (United States)

    Okur, O M; Şener, A; Kavakli, H Ş; Çelik, G K; Doğan, N Ö; Içme, F; Günaydin, G P

    2017-12-01

    We aimed to compare two digital nerve block techniques in patients due to traumatic digital lacerations. This was a randomized-controlled study designed prospectively in the emergency department of a university-based training and research hospital. Randomization was achieved by sealed envelopes. Half of the patients were randomised to traditional (two-injection) digital nerve block technique while single-injection digital nerve block technique was applied to the other half. Score of pain due to anesthetic infiltration and suturing, onset time of total anesthesia, need for an additional rescue injection were the parameters evaluated with both groups. Epinephrin added lidocaine hydrochloride preparation was used for the anesthetic application. Visual analog scale was used for the evaluation of pain scores. Outcomes were compared by using Mann-Whitney U test and Student t-test. Fifty emergency department patients ≥18 years requiring digital nerve block were enrolled in the study. Mean age of the patients was 33 (min-max: 19-86) and 39 (78 %) were male. No statistically significant difference was found between the two groups in terms of our main parameters; anesthesia pain score, suturing pain score, onset time of total anesthesia and rescue injection need. Single injection volar digital nerve block technique is a suitable alternative for digital anesthesias in emergency departments.

  19. Garlic (Allium sativum) stimulates lipopolysaccharide-induced tumor necrosis factor-alpha production from J774A.1 murine macrophages.

    Science.gov (United States)

    Sung, Jessica; Harfouche, Youssef; De La Cruz, Melissa; Zamora, Martha P; Liu, Yan; Rego, James A; Buckley, Nancy E

    2015-02-01

    Garlic (Allium sativum) is known to have many beneficial attributes such as antimicrobial, antiatherosclerotic, antitumorigenetic, and immunomodulatory properties. In the present study, we investigated the effects of an aqueous garlic extract on macrophage cytokine production by challenging the macrophage J774A.1 cell line with the garlic extract in the absence or presence of lipopolysaccharide (LPS) under different conditions. The effect of allicin, the major component of crushed garlic, was also investigated. Using enzyme-linked immunosorbent assay and reverse transcriptase-quantitative polymerase chain reaction, it was found that garlic and synthetic allicin greatly stimulated tumor necrosis factor-alpha (TNF-α) production in macrophages treated with LPS. The TNF-α secretion levels peaked earlier and were sustained for a longer time in cells treated with garlic and LPS compared with cells treated with LPS alone. Garlic acted in a time-dependent manner. We suggest that garlic, at least partially via its allicin component, acts downstream from LPS to stimulate macrophage TNF-α secretion. © 2014 The Authors. Phytotherapy Research published by John Wiley & Sons, Ltd.

  20. Mitochondrial reactive oxygen species mediate the lipopolysaccharide-induced pro-inflammatory response in human gingival fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Li, Xue; Wang, Xiaoxuan [Department of Periodontology, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081 (China); Zheng, Ming, E-mail: zhengm@bjmu.edu.cn [Department of Physiology and Pathophysiology, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing 100191 (China); Luan, Qing Xian, E-mail: kqluanqx@126.com [Department of Periodontology, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081 (China)

    2016-09-10

    Although periodontal diseases are initiated by bacteria that colonize the tooth surface and gingival sulcus, the host response is believed to play an essential role in the breakdown of connective tissue and bone. Mitochondrial reactive oxygen species (mtROS) have been proposed to regulate the activation of the inflammatory response by the innate immune system. However, the role of mtROS in modulating the response of human gingival fibroblasts (HGFs) to immune stimulation by lipopolysaccharides (LPS) has yet to be fully elucidated. Here, we showed that LPS from Porphyromonas gingivalis stimulated HGFs to increase mtROS production, which could be inhibited by treatment with a mitochondrial-targeted exogenous antioxidant (mito-TEMPO) or transfection with manganese superoxide dismutase (MnSOD). A time-course study revealed that an increase in the concentration of mtROS preceded the expression of inflammatory cytokines in HGFs. Mito-TEMPO treatment or MnSOD transfection also significantly prevented the LPS-induced increase of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α. Furthermore, suppressing LPS-induced mtROS generation inhibited the activation of p38, c-Jun N-terminal kinase, and inhibitor of nuclear factor-κB kinase, as well as the nuclear localization of nuclear factor-κB. These results demonstrate that mtROS generation is a key signaling event in the LPS-induced pro-inflammatory response of HGFs. - Highlights: • Inflammation is thought to promote pathogenic changes in periodontitis. • We investigated mtROS as a regulator of inflammation in gingival fibroblasts. • Targeted antioxidants were used to inhibit mtROS production after LPS challenge. • Inhibiting mtROS generation suppressed the secretion of pro-inflammatory cytokines. • JNK, p38, IKK, and NF-κB were shown to act as transducers of mtROS signaling.