Sample records for beta3 aggravates experimental

  1. Macrophage migration inhibitory factor promotes cell death and aggravates neurologic deficits after experimental stroke. (United States)

    Inácio, Ana R; Ruscher, Karsten; Leng, Lin; Bucala, Richard; Deierborg, Tomas


    Multiple mechanisms contribute to tissue demise and functional recovery after stroke. We studied the involvement of macrophage migration inhibitory factor (MIF) in cell death and development of neurologic deficits after experimental stroke. Macrophage migration inhibitory factor is upregulated in the brain after cerebral ischemia, and disruption of the Mif gene in mice leads to a smaller infarct volume and better sensory-motor function after transient middle cerebral artery occlusion (tMCAo). In mice subjected to tMCAo, we found that MIF accumulates in neurons of the peri-infarct region, particularly in cortical parvalbumin-positive interneurons. Likewise, in cultured cortical neurons exposed to oxygen and glucose deprivation, MIF levels increase, and inhibition of MIF by (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester (ISO-1) protects against cell death. Deletion of MIF in Mif(-/-) mice does not affect interleukin-1β protein levels in the brain and serum after tMCAo. Furthermore, disruption of the Mif gene in mice does not affect CD68, but it is associated with higher galectin-3 immunoreactivity in the brain after tMCAo, suggesting that MIF affects the molecular/cellular composition of the macrophages/microglia response after experimental stroke. We conclude that MIF promotes neuronal death and aggravates neurologic deficits after experimental stroke, which implicates MIF in the pathogenesis of neuronal injury after stroke.

  2. Administration of Mycobacterium leprae rHsp65 aggravates experimental autoimmune uveitis in mice.

    Directory of Open Access Journals (Sweden)

    Eliana B Marengo

    Full Text Available The 60 kDa heat shock protein family, Hsp60, constitutes an abundant and highly conserved class of molecules that are highly expressed in chronic-inflammatory and autoimmune processes. Experimental autoimmune uveitis [EAU] is a T cell mediated intraocular inflammatory disease that resembles human uveitis. Mycobacterial and homologous Hsp60 peptides induces uveitis in rats, however their participation in aggravating the disease is poorly known. We here evaluate the effects of the Mycobacterium leprae Hsp65 in the development/progression of EAU and the autoimmune response against the eye through the induction of the endogenous disequilibrium by enhancing the entropy of the immunobiological system with the addition of homologous Hsp. B10.RIII mice were immunized subcutaneously with interphotoreceptor retinoid-binding protein [IRBP], followed by intraperitoneally inoculation of M. leprae recombinant Hsp65 [rHsp65]. We evaluated the proliferative response, cytokine production and the percentage of CD4(+IL-17(+, CD4(+IFN-gamma(+ and CD4(+Foxp3(+ cells ex vivo, by flow cytometry. Disease severity was determined by eye histological examination and serum levels of anti-IRBP and anti-Hsp60/65 measured by ELISA. EAU scores increased in the Hsp65 group and were associated with an expansion of CD4(+IFN-gamma(+ and CD4(+IL-17(+ T cells, corroborating with higher levels of IFN-gamma. Our data indicate that rHsp65 is one of the managers with a significant impact over the immune response during autoimmunity, skewing it to a pathogenic state, promoting both Th1 and Th17 commitment. It seems comprehensible that the specificity and primary function of Hsp60 molecules can be considered as a potential pathogenic factor acting as a whistleblower announcing chronic-inflammatory diseases progression.

  3. FR167653, a p38 mitogen-activated protein kinase inhibitor, aggravates experimental colitis in mice

    Institute of Scientific and Technical Information of China (English)

    Takashi Nishimura; Akira Andoh; Atsushi Nishida; Makoto Shioya; Yuhsuke Koizumi; Tomoyuki Tsujikawa; Yoshihide Fujiyama


    AIM: To investigate the effects of FR167653 on the development of dextran sulfate sodium (DSS)-induced colitis in mice.METHODS: BALB/c mice were fed rodent chow containing 3.5% (wt/wt) DSS. The recipient mice underwent intra-peritoneal injection of vehicles or FR167653 (30 mg/kg per day). The mice were sacrificed on day 14, and the degree of colitis was assessed. Immunohistochemical analyses for CD4+ T cell and F4/80+ macrophage infiltration were also performed. Mucosal o/tokine expression was analyzed by RT-PCR.RESULTS: The body weight loss was more apparent in the FR167653-treated DSS mice than in the vehicle-treated DSS mice. The colon length was shorter in the FR167653-treated DSS mice than in the vehicle-treated DSS mice. Disease activity index and histological colitis score were significantly higher in FR167653- than in vehicle-treated DSS animals. Microscopically, mucosal edema, cellular infiltration (CD4 T cells and F4/80 macrophages), and the disruption of the epithelium were much more severe in FR167653-treated mice than in controls. Mucosal mRNA expression for interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were found to be markedly reduced in FR167653-treated DSS mice.CONCLUSION: Treatment with FR167653 aggravated DSS colitis in mice. This effect was accompanied by a reduction of mucosal IL-1β and TNF-α expression, suggesting a role of p38 mitogen-activated protein kinase (MAPK)-mediated proinflammatory cytokine induction in host defense mechanisms.

  4. Response to Comment on "Tissue Factor-Dependent Chemokine Production Aggravates Experimental Colitis"

    NARCIS (Netherlands)

    Queiroz, K.C.; Spek, C.A.


    In our recent work we utilized genetically modified mice to investigate the role of tissue factor (TF) in experimental colitis. We present evidence suggesting TF plays a detrimental role in this disease via signal transduction dependent KC production in colon epithelial cells, which provokes granulo

  5. Increase in hippocampal water diffusion and volume during experimental pneumococcal meningitis is aggravated by bacteremia

    DEFF Research Database (Denmark)

    Holler, Jon G; Brandt, Christian T; Leib, Stephen L;


    pneumococci. The study comprised of four experimental groups. I. Uninfected controls (n = 8); II. Meningitis (n = 11); III. Meningitis with early onset bacteremia by additional i.v. injection of live pneumococci (n = 10); IV. Meningitis with attenuated bacteremia by treatment with serotype-specific anti...

  6. Macrophage migration inhibitory factor promotes cell death and aggravates neurologic deficits after experimental stroke


    Inácio, Ana R; Ruscher, Karsten; Leng, Lin; Bucala, Richard; Deierborg, Tomas


    Multiple mechanisms contribute to tissue demise and functional recovery after stroke. We studied the involvement of macrophage migration inhibitory factor (MIF) in cell death and development of neurologic deficits after experimental stroke. Macrophage migration inhibitory factor is upregulated in the brain after cerebral ischemia, and disruption of the Mif gene in mice leads to a smaller infarct volume and better sensory-motor function after transient middle cerebral artery occlusion (tMCAo)....

  7. Deficiency of Nuclear Receptor Nur77 Aggravates Mouse Experimental Colitis by Increased NFκB Activity in Macrophages.

    Directory of Open Access Journals (Sweden)

    Anouk A J Hamers

    Full Text Available Nuclear receptor Nur77, also referred to as NR4A1 or TR3, plays an important role in innate and adaptive immunity. Nur77 is crucial in regulating the T helper 1/regulatory T-cell balance, is expressed in macrophages and drives M2 macrophage polarization. In this study we aimed to define the function of Nur77 in inflammatory bowel disease. In wild-type and Nur77-/- mice, colitis development was studied in dextran sodium sulphate (DSS- and 2,4,6-trinitrobenzene sulfonic acid (TNBS-induced models. To understand the underlying mechanism, Nur77 was overexpressed in macrophages and gut epithelial cells. Nur77 protein is expressed in colon tissues from Crohn's disease and Ulcerative colitis patients and colons from colitic mice in inflammatory cells and epithelium. In both mouse colitis models inflammation was increased in Nur77-/- mice. A higher neutrophil influx and enhanced IL-6, MCP-1 and KC production was observed in Nur77-deficient colons after DSS-treatment. TNBS-induced influx of T-cells and inflammatory monocytes into the colon was higher in Nur77-/- mice, along with increased expression of MCP-1, TNFα and IL-6, and decreased Foxp3 RNA expression, compared to wild-type mice. Overexpression of Nur77 in lipopolysaccharide activated RAW macrophages resulted in up-regulated IL-10 and downregulated TNFα, MIF-1 and MCP-1 mRNA expression through NFκB repression. Nur77 also strongly decreased expression of MCP-1, CXCL1, IL-8, MIP-1α and TNFα in gut epithelial Caco-2 cells. Nur77 overexpression suppresses the inflammatory status of both macrophages and gut epithelial cells and together with the in vivo mouse data this supports that Nur77 has a protective function in experimental colitis. These findings may have implications for development of novel targeted treatment strategies regarding inflammatory bowel disease and other inflammatory diseases.

  8. The in-vivo use of superparamagnetic iron oxide nanoparticles to detect inflammation elicits a cytokine response but does not aggravate experimental arthritis.

    Directory of Open Access Journals (Sweden)

    Eline A Vermeij

    Full Text Available Superparamagnetic Iron Oxide Nanoparticles (SPION are used in diagnostic imaging of a variety of different diseases. For such in-vivo application, an additional coating with a polymer, for example polyvinyl alcohol (PVA, is needed to stabilize the SPION and prevent aggregation. As the particles are foreign to the body, reaction against the SPION could occur. In this study we investigated the effects that SPION may have on experimental arthritis after intra-articular (i.a. or intravenous (i.v. injection.PVA-coated SPION were injected either i.a. (6 or 24 μg iron or i.v. (100 μg or 1 mg iron into naïve Toll-like receptor-4 deficient (TLR4-/- or wild-type C57Bl/6 mice, or C57Bl/6 mice with antigen-induced arthritis. As control, some mice were injected with PVA or PBS. MR imaging was performed at 1 and 7 days after injection. Mice were sacrificed 2 hours and 1, 2, 7, 10 and 14 days after injection of the SPION, and RNA from synovium and liver was isolated for pro-inflammatory gene expression analysis. Serum cytokine measurements and whole knee joint histology were also performed.Injection of a high dose of SPION or PVA into naïve knee joints resulted in an immediate upregulation of pro-inflammatory gene expression in the synovium. A similar gene expression profile was observed after SPION or PVA injection into knee joints of TLR4-/- mice, indicating that this effect is not due to LPS contamination. Histological analysis of the knee joints also revealed synovial inflammation after SPION injection. Two hours after i.v. injection of SPION or PVA into naïve mice, an upregulation of pro-inflammatory gene expression was detected in the liver. Administration of SPION or PVA into arthritic mice via i.a. injection did not result in an upregulation in gene expression and also no additional effects were observed on histology. MR imaging and histology showed long-term retention of SPION in the inflamed joint. However, 14 days after the injections no long

  9. [Beta 3 adrenergic receptor polymorphism and obesity]. (United States)

    Yoshida, T; Umekawa, T


    The beta 3-adrenoceptor plays a significant role in the control of lipolysis and thermogenesis in the brown adipose tissue of rodents and humans. In human beta 3-adrenoceptor, a Trp to Arg replacement has recently been discovered. This change which occurs at position 64, in the first coding exon, has been correlated with increased weight gain, difficulty in losing weight, insulin resistance syndrome, and worsened diabetic situation. Higher percentages of this mutation are observed in Pima Indians (over 30%) and Japanese (20%). The possible functional mechanism of Trp54Arg is reported using human HEK293 cell line stably expressing the wild type and the [Arg64] beta 3-adrenoceptor type. Beta 3-adrenoceptor agonists available for humans are been also developing. In this paper we describe these points up-to-date.

  10. Genetics Home Reference: potassium-aggravated myotonia (United States)

    ... structure and function of sodium channels. The altered channels cannot properly regulate ion flow, increasing the movement of sodium ions into ... area? Other Names for This Condition PAM sodium channel ... and Rare Diseases Information Center (1 link) Potassium aggravated myotonia Additional ...

  11. Role of human GABA(A) receptor beta3 subunit in insecticide toxicity. (United States)

    Ratra, G S; Kamita, S G; Casida, J E


    The gamma-aminobutyric acid type A (GABA(A)) receptor is the target for the major insecticides alpha-endosulfan, lindane, and fipronil and for many analogs. Their action as chloride channel blockers is directly measured by binding studies with [(3)H]ethynylbicycloorthobenzoate ([(3)H]EBOB). This study tests the hypothesis that GABA(A) receptor subunit composition determines the sensitivity and selectivity of insecticide toxicity. Human receptor subtypes were expressed individually (alpha1, alpha6, beta1, beta3, and gamma2) and in combination in insect Sf9 cells. Binding parameters were similar for [(3)H]EBOB in the beta3 homooligomer, alpha1beta3gamma2 heterooligomer, and native brain membranes, but toxicological profiles were very different. Surprisingly, alpha-endosulfan, lindane, and fipronil were all remarkably potent on the recombinant beta3 homooligomeric receptor (IC50 values of 0.5-2.4 nM), whereas they were similar in potency on the alpha1beta3gamma2 subtype (IC50 values of 16-33 nM) and highly selective on the native receptor (IC50 values of 7.3, 306, and 2470 nM, respectively). The selectivity order for 29 insecticides and convulsants as IC50 ratios for native/beta3 or alpha1beta3gamma2/beta3 was as follows: fipronil > lindane > 19 other insecticides including alpha-endosulfan and picrotoxinin > 4 trioxabicyclooctanes and dithianes (almost nonselective) > tetramethylenedisulfotetramine, 4-chlorophenylsilatrane, or alpha-thujone. Specificity between mammals and insects at the target site (fipronil > lindane > alpha-endosulfan) paralleled that for toxicity. Potency at the native receptor is more predictive for inhibition of GABA-stimulated chloride uptake than that at the beta3 or alpha1beta3gamma2 receptors. Therefore, the beta3 subunit contains the insecticide target and other subunits differentially modulate the binding to confer compound-dependent specificity and selective toxicity.

  12. Pregnancy aggravates proteinuria in subclinical glomerulonephritis in the rat

    NARCIS (Netherlands)

    Faas, MM; Bakker, WW; Poelman, RT; Schuiling, GA


    Because subclinical renal disease may be aggravated during pregnancy-as reflected in the occurrence of proteinuria, for example-we investigated whether a subclinical glomerulonephritis (SG) in the non-pregnant rat (passive Heymann nephritis), a condition without proteinuria, is aggravated when the a

  13. The TF1-ATPase and ATPase activities of assembled alpha 3 beta 3 gamma, alpha 3 beta 3 gamma delta, and alpha 3 beta 3 gamma epsilon complexes are stimulated by low and inhibited by high concentrations of rhodamine 6G whereas the dye only inhibits the alpha 3 beta 3, and alpha 3 beta 3 delta complexes. (United States)

    Paik, S R; Yokoyama, K; Yoshida, M; Ohta, T; Kagawa, Y; Allison, W S


    The ATPase activity of the F1-ATPase from the thermophilic bacterium PS3 is stimulated at concentrations of rhodamine 6G up to about 10 microM where 70% stimulation is observed at 36 degrees C. Half maximal stimulation is observed at about 3 microM dye. At rhodamine 6G concentrations greater than 10 microM, ATPase activity declines with 50% inhibition observed at about 75 microM dye. The ATPase activities of the alpha 3 beta 3 gamma and alpha 3 beta 3 gamma delta complexes assembled from isolated subunits of TF1 expressed in E. coli deleted of the unc operon respond to increasing concentrations of rhodamine 6G nearly identically to the response of TF1. In contrast, the ATPase activities of the alpha 3 beta 3 and alpha 3 beta 3 delta complexes are only inhibited by rhodamine 6G with 50% inhibition observed, respectively, at 35 and 75 microM dye at 36 degrees C. The ATPase activity of TF1 is stimulated up to 4-fold by the neutral detergent, LDAO. In the presence of stimulating concentrations of LDAO, the ATPase activity of TF1 is no longer stimulated by rhodamine 6G, but rather, it is inhibited with 50% inhibition observed at about 30 microM dye at 30 degrees C. One interpretation of these results is that binding of rhodamine 6G to a high-affinity site on TF1 stimulates ATPase activity and unmasks a low-affinity, inhibitory site for the dye which is also exposed by LDAO.

  14. [Keeping dogs indoor aggravates infantile atopic dermatitis]. (United States)

    Endo, K; Hizawa, T; Fukuzumi, T; Kataoka, Y


    We had a two-month-old girl with severe dermatitis since birth. Her serum RAST to HD, Df and Dp were 1.06, 0.03 and 0.01 Ua/ml respectively. A Yorkshire terrier were kept at her mother's parents' home where the patient had lived for a month since birth. Her eczema, which became markedly aggravated whenever she visited there, improved after the elimination of the dog. We investigated the relationship between keeping dogs and infantile atopic dermatitis. We studied 368 patients under the age of two years (211 boys and 157 girls). Skin symptoms were graded globally mild, moderate or severe. Total serum IgE and specific antibody titer to dog dander were measured. We asked them whether they kept dogs and specifically, where they kept dogs, outdoor, indoor, in their own house, or in their grandparents' house. 197 patients had no contact with dogs, 90 patients kept dogs outdoor and 81 patients did indoor. The positive rate of RAST (> or = 0.7 Ua/ml) to dog dander was 6.1%, 17.8% and 46.9% respectively in these three groups. There were strong statistical differences between three groups. On the other hand, among the 81 patients who kept indoor, the RAST positive rates were almost same regarding where the dogs were kept, in their own house or their grandparents' house. Interestingly this difference happens only with patients under the age of 3 months. Patients older than 4 months showed no significant differences in the positive RAST rates, whether they kept dogs indoor or outdoor. This suggests the sensitization occurs before the age of 3 months. Speaking of symptoms, patients who kept dogs indoor showed significantly more severe symptoms than patients who had no contact with dogs and patients who kept dogs outdoor. There was no significant difference between the symptoms of patients who had no contact with dogs and those of patients who kept dogs outdoor. This implies the patient's symptom will improve only by moving the dog out of the house.

  15. [Beta-3 adrenergic receptor--structure and role in obesity and metabolic disorders]. (United States)

    Wiejak, J; Wyroba, E


    Structure and essential motifs of beta 3-adrenergic receptor (known previously as atypical beta-AR), which plays a central role in regulation of lipid metabolism have been described. Obesity results from an imbalance between caloric intake and energy expenditure. The consequence of catecholamine activation of beta 3-AR is increased mobilization of fatty acids from triglyceride stores (lipolysis) in brown and white adipose tissue as well as increased fatty acid beta-oxidation and heat-production via UCP-1 (thermogenesis) in brown adipose tissue. A pharmacokinetic effects of beta 3-agonists and putative involvement of Trp/Arg mutation in beta 3-AR gene in obesity and another metabolic disorders have been discussed.

  16. Homology modeling of human alpha 1 beta 2 gamma 2 and house fly beta 3 GABA receptor channels and Surflex-docking of fipronil. (United States)

    Cheng, Jin; Ju, Xiu-Lian; Chen, Xiang-Yang; Liu, Gen-Yan


    To further explore the mechanism of selective binding of the representative gamma-aminobutyric acid receptors (GABARs) noncompetitive antagonist (NCA) fipronil to insect over mammalian GABARs, three-dimensional models of human alpha 1 beta 2 gamma 2 and house fly beta 3 GABAR were generated by homology modeling, using the cryo-electron microscopy structure of the nicotinic acetylcholine receptor (nAChR) of Torpedo marmorata as a template. Fipronil was docked into the putative binding site of the human alpha 1 beta 2 gamma 2 and house fly beta 3 receptors by Surflex-docking, and the calculated docking energies are in agreement with experimental results. The GABA receptor antagonist fipronil exhibited higher potency with house fly beta 3 GABAR than with human alpha 1 beta 2 gamma 2 GABAR. Furthermore, analyses of Surflex-docking suggest that the H-bond interaction of fipronil with Ala2 and Thr6 in the second transmembrane segment (TM2) of these GABARs plays a relatively important role in ligand selective binding. The different subunit assemblies of human alpha 1 beta 2 gamma 2 and house fly beta 3 GABARs may result in differential selectivity for fipronil.

  17. [Aggravation after Diagnosis of Sudden Sensorineural Hearing Loss]. (United States)

    Fukumoto, Ichiro; Nemoto, Toshimitsu; Tsukuda, Tomoko; Koshizuka, Keiichi


    Among 95 patients with sudden sensorineural hearing loss who received inpatient treatment at our hospital within the 27-month period between October 2009 and December 2011, those in whom hearing loss was aggravated after diagnosis were compared with a control group. Hearing loss aggravation was defined as a decrease by 10 dB or more in the mean hearing threshold at 5 frequencies from 250 to 4,000 Hz or decrease of 15 dB or more in the hearing threshold at 2 consecutive frequencies. Hearing loss was aggravated after diagnosis in 22 (23.2%) of the 95 patients, showing a similar tendency to that previously reported. Although the grades of hearing loss in these patients were higher than those in 73 control group patients, according to the sudden hearing loss severity classification, their outcomes were favorable. The hearing loss aggravation group consisted of those with steroid-dependent hearing loss (6) and those who had undergone perilymphatic fistula repair (4), in addition to a large number of patients with idiopathic hearing loss, including suspicious perilymphatic fistula (10). When hearing loss becomes aggravated after the diagnosis of sudden sensorineural hearing loss, it may be important to determine the most appropriate approach in each case, such as a careful and gradual decrease in the adenocortical steroid dose and the consideration of perilymphatic fistula repair.

  18. Aggravation of symptomatic occipital epilepsy of childhood by carbamazepine

    Directory of Open Access Journals (Sweden)

    Škrijelj Fadil E.


    Full Text Available Introduction. Carbamazepine can lead to aggravation of epileptic seizures in generalized epilepsies (primary or secondary with clinical manifestations of absence (typical or atypical and/or myoclonic seizures. However, some focal epilepsies can be also aggravated by the introduction of carbamazepine. Case report. We presented a 10-year-old boy born after a complicated and prolonged delivery completed by vacuum extraction, of early psychomotor development within normal limits. At the age of 8 years he had the first epileptic seizure of simple occipital type with generalization and urination. Brain magnetic resonance imaging (MRI showed focal cortical reductions in the left parietal and occipital regions. Interictal EEG recorded slowed basic activities above the posterior regions of the left hemisphere, with intermittent occurrence of occipital sharp waves and bioccipital sharp and slow-wave complexes. Initially, treatment with valproate was administered; however, the addition of carbamazepine into therapy induced aggravation of seizures and EEG findings, changed behavior and poor performance at school. By withdrawal of carbamazepine the condition improved both clinically and in EEG findings. Conclusion. Childhood occipital epilepsy lesions show deterioration due to carbamazepine, which if administered induces aggravation of seizures, behavior changes, cognition with occurrence of long-term bilateral discharges, and posterior sharp and slow wave high amplitude complexes recorded by EEG.

  19. 38 CFR 3.306 - Aggravation of preservice disability. (United States)


    ... disability. 3.306 Section 3.306 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS... Connection § 3.306 Aggravation of preservice disability. (a) General. A preexisting injury or disease will be... disability during such service, unless there is a specific finding that the increase in disability is due...

  20. Inducing and Aggravating Factors of Gastroesophageal Reflux Symptoms

    Directory of Open Access Journals (Sweden)

    Radhiyatam Mardhiyah


    Full Text Available Gastroesophageal reflux disease (subsequently abbreviated as GERD is a disease commonly found in the community. Several factors have been recognized as inducing and aggravating factors of GERD symptoms such as older age, female gender, obesity, smoking habit, alcohol consumption, certain diet and poor eating habit like eating fatty, spicy, and acid food.

  1. The pharmacology of spontaneously open alpha 1 beta 3 epsilon GABA A receptor-ionophores. (United States)

    Maksay, Gábor; Thompson, Sally A; Wafford, Keith A


    Human alpha(1)beta(3) epsilon GABA(A) receptors were expressed in Xenopus oocytes and examined using the conventional two-electrode voltage-clamp technique and compared to alpha(1)beta(3)gamma(2) receptors. The effects of several GABA(A) agonists were studied, and the allosteric modulation of the channel by a number of GABAergic modulators investigated. The presence of the epsilon subunit increased the potency and efficacy of direct activation by partial GABA(A) agonists (piperidine-4-sulphonic acid and thio-4-PIOL), pentobarbital and neuro-steroids. Direct activation by 3-hydroxylated neurosteroids was restricted to 3alpha epimers, while chirality at C5 was indifferent. The 3beta-sulfate esters of pregnenolone and dehydroepiandrosterone inhibited the spontaneous currents with efficacies higher, while bicuculline methiodide and SR 95531 did so lower than picrotoxin and TBPS. Furosemide, fipronil, triphenylcyanoborate and Zn(2+) blocked the spontaneous currents of alpha(1)beta(3) epsilon receptors with different efficacies. Flunitrazepam and 4'-chlorodiazepam inhibited the spontaneous currents with micromolar potencies. In conclusion, spontaneously active alpha(1)beta(3) epsilon GABA(A) receptors can be potentiated and blocked by GABAergic agents within a broad range of efficacy.

  2. Fipronil-based photoaffinity probe for Drosophila and human beta 3 GABA receptors. (United States)

    Sirisoma, N S; Ratra, G S; Tomizawa, M; Casida, J E


    Modification of the major insecticide fipronil (1) by replacing three pyrazole substituents (hydrogen for both cyano and amino and trifluoromethyldiazirinyl for trifluoromethylsulfinyl) gives a candidate photoaffinity probe (3) of high potency (IC(50) 2-28 nM) in blocking the chloride channel of Drosophila and human beta 3 GABA receptors.

  3. Rat beta(3)-adrenoceptor protein expression : antibody validation and distribution in rat gastrointestinal and urogenital tissues

    NARCIS (Netherlands)

    Cernecka, Hana; Pradidarcheep, Wisuit; Lamers, Wouter H.; Schmidt, Martina; Michel, Martin C.


    beta(3)-Adrenoceptors play important roles in the regulation of urogenital and probably gastrointestinal function. However, despite recent progress, their detection at the protein level has remained difficult due to a lack of sufficiently validated selective antibodies. Therefore, we have explored t

  4. Selective activation of beta3-adrenoceptors by octopamine: comparative studies in mammalian fat cells. (United States)

    Carpéné, C; Galitzky, J; Fontana, E; Atgié, C; Lafontan, M; Berlan, M


    Numerous synthetic agonists selectively stimulate beta3-adrenoceptors (ARs). The endogenous catecholamines, noradrenaline and adrenaline, however, stimulate all the beta-AR subtypes, and no selective physiological agonist for beta3-ARs has been described so far. The aim of this study was to investigate whether any naturally occurring amine can stimulate selectively beta3-ARs. Since activation of lipolysis is a well-known beta-adrenergic function, the efficacy and potency of various biogenic amines were compared with those of noradrenaline, isoprenaline, and beta3-AR agonists 4-(-{[2-hydroxy-(3-chlorophenyl)ethyl]-amino} propyl)phenoxyacetate (BRL 37,344) and (R,R)-5-(2-{[2-(3-chlorophenyl )-2-hydroxyethyl]-amino} propyl)-1,3-benzo-dioxole-2,2-dicarboxylate (CL 316,243) by testing their lipolytic action in white fat cells. Five mammalian species were studied: rat, hamster and dog, in which selective beta-AR agonists act as full lipolytic agents, and guinea-pigs and humans, in which beta3-AR agonists are less potent activators of lipolysis. Several biogenic amines were inefficient (e.g. dopamine, tyramine and beta-phenylethylamine) while others (synephrine, phenylethanolamine, epinine) were partially active in stimulating lipolysis in all species studied. Their actions were inhibited by all the beta-AR antagonists tested, including those selective for beta1- or beta2-ARs. Octopamine was the only amine fully stimulating lipolysis in rat, hamster and dog fat cells, while inefficient in guinea-pig or human fat cells, like the beta3-AR agonists. In rat white fat cells, beta-AR antagonists inhibited the lipolytic effect of octopamine with a relative order of potency very similar to that observed against CL 316,243. Competitive antagonism of octopamine effect resulted in the following apparent pA2 [-log(IC50), where IC50 is the antagonist concentration eliciting half-maximal inhibition] values: 7.77 (bupranolol), 6.48 [3-(2-ethyl-phenoxy)-1[(1 S)-1,2,3,4-tetrahydronaphth-1

  5. Differential regulation of chemoattractant-stimulated beta 2, beta 3, and beta 7 integrin activity. (United States)

    Sadhu, C; Masinovsky, B; Staunton, D E


    Leukocyte adhesion to endothelium and extravasation are dynamic processes that require activation of integrins. Chemoattractants such as IL-8 and FMLP are potent activators of leukocyte integrins. To compare the chemoattractant-stimulated activation of three integrins, alpha 4 beta 7, alpha L beta 2, and alpha V beta 3, in the same cellular context, we expressed an IL-8 receptor (IL-8RA) and FMLP receptor (FPR) in the lymphoid cell line JY. Chemoattractants induced a rapid increase in alpha L beta 2- and alpha V beta 3-dependent JY adhesion within 5 min, and it was sustained for 30 min. In contrast, stimulation of alpha 4 beta 7-dependent adhesion was transient, returning to basal levels by 30 min. The activation profiles of the integrins were similar regardless of whether IL-8 or FMLP was used for induction. We also demonstrate that alpha 4 beta 7-dependent adhesion was uniquely responsive to the F actin-disrupting agent cytochalasin D and the protein kinase C (PKC) inhibitor chelerythrin. While alpha V beta 3- and alpha L beta 2-mediated cell adhesion was significantly reduced by cytochalasin D, alpha 4 beta 7-mediated adhesion was enhanced. Chelerythrin inhibited both the IL-8 and PMA activation of alpha L beta 2 and alpha V beta 3. In contrast, inducible alpha 4 beta 7 activity was unaffected, and basal activity was increased. These findings demonstrate that the mechanism of alpha 4 beta 7 regulation by chemoattractants is different from that of alpha L beta 2 and alpha V beta 3 and that it appears to involve distinct cytoskeletal and PKC dependencies. In addition, PKC activity may be a positive or negative regulator of integrin-dependent adhesion.

  6. Aggravating andmitigating factors associated with cyclist injury severity in Denmark

    DEFF Research Database (Denmark)

    Kaplan, Sigal; Vavatsoulas,, Konstantinos; Prato, Carlo Giacomo


    Denmark is one of the leading cycling nations, where cycling trips constitute a large share of the total trips, and cycling safety assumes a top priority position in the agenda of policy makers. The current study sheds light on the aggravating and mitigating factors associated with cyclist injury...... severity on Danish roads by examining a comprehensive set of accidents involving a cyclist and a collision partner between 2007 and 2011. Method: This study estimates a generalized ordered logit model of the severity of cyclist injuries because of its ability to accommodate the ordered-response nature...... of severity while relaxing the proportional odds assumption. Results: Model estimates show that cyclist fragility (children under 10 years old and elderly cyclists over 60 years of age) and cyclist intoxication are aggravating individual factors,while helmet use is a mitigating factor. Speed limits above 70...

  7. DMPD: Immunoreceptor-like signaling by beta 2 and beta 3 integrins. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17913496 Immunoreceptor-like signaling by beta 2 and beta 3 integrins. Jakus Z, Fod...or S, Abram CL, Lowell CA, Mocsai A. Trends Cell Biol. 2007 Oct;17(10):493-501. (.png) (.svg) (.html) (.csml) Show Immunore...ceptor-like signaling by beta 2 and beta 3 integrins. PubmedID 17913496 Title Immunoreceptor-

  8. Heterocyclic acetamide and benzamide derivatives as potent and selective beta3-adrenergic receptor agonists with improved rodent pharmacokinetic profiles. (United States)

    Goble, Stephen D; Wang, Liping; Howell, K Lulu; Bansal, Alka; Berger, Richard; Brockunier, Linda; DiSalvo, Jerry; Feighner, Scott; Harper, Bart; He, Jiafang; Hurley, Amanda; Hreniuk, Donna; Parmee, Emma; Robbins, Michael; Salituro, Gino; Sanfiz, Anthony; Streckfuss, Eric; Watkins, Eloisa; Weber, Ann E; Struthers, Mary; Edmondson, Scott D


    A series of amide derived beta(3)-adrenergic receptor (AR) agonists is described. The discovery and optimization of several series of compounds derived from 1, is used to lay the SAR foundation for second generation beta(3)-AR agonists for the treatment of overactive bladder.

  9. Aggravated neuromuscular symptoms of mercury exposure from dental amalgam fillings. (United States)

    Akbal, Ayla; Yılmaz, Hınç; Tutkun, Engin; Köş, Durdu Mehmet


    Dental amalgam fillings are widely used all over the world. However, their mercury content can lead to various side effects and clinical problems. Acute or chronic mercury exposure can cause several side effects on the central nerve system, renal and hepatic functions, immune system, fetal development and it can play a role on exacerbation of neuromuscular diseases. In this case, we will present a patient with vacuolar myopathy whose symptoms were started and aggravated with her dental amalgam fillings.

  10. Beta(3)-adrenergic signaling acutely down regulates adipose triglyceride lipase in brown adipocytes. (United States)

    Deiuliis, Jeffrey A; Liu, Li-Fen; Belury, Martha A; Rim, Jong S; Shin, Sangsu; Lee, Kichoon


    Mice exposed to cold rely upon brown adipose tissue (BAT)-mediated nonshivering thermogenesis to generate body heat using dietary glucose and lipids from the liver and white adipose tissue. In this report, we investigate how cold exposure affects the PI3 K/Akt signaling cascade and the expression of genes involved in lipid metabolism and trafficking in BAT. Cold exposure at an early time point led to the activation of the PI3 K/Akt, insulin-like signaling cascade followed by a transient decrease in adipose triglyceride lipase (ATGL) gene and protein expression in BAT. To further investigate how cold exposure-induced signaling altered ATGL expression, cultured primary brown adipocytes were treated with the beta(3)-adrenergic receptor (beta(3)AR) agonist CL 316,243 (CL) resulting in activation of PI3 K/Akt, ERK 1/2, and p38 signaling pathways and significantly decreased ATGL protein levels. ATGL protein levels decreased significantly 30 min post CL treatment suggesting protein degradation. Inhibition of PKA signaling by H89 rescued ATGL levels. The effects of PKA signaling on ATGL were shown to be independent of relevant pathways downstream of PKA such as PI3 K/Akt, ERK 1/2, and p38. However, CL treatment in 3T3-L1 adipocytes did not decrease ATGL protein and mRNA expression, suggesting a distinct response in WAT to beta3-adrenergic agonism. Transitory effects, possibly attributed to acute Akt activation during the early recruitment phase, were noted as well as stable changes in gene expression which may be attributed to beta3-adrenergic signaling in BAT.

  11. Structure of the integrin beta3 transmembrane segment in phospholipid bicelles and detergent micelles. (United States)

    Lau, Tong-Lay; Partridge, Anthony W; Ginsberg, Mark H; Ulmer, Tobias S


    Integrin adhesion receptors transduce bidirectional signals across the plasma membrane, with the integrin transmembrane domains acting as conduits in this process. Here, we report the first high-resolution structure of an integrin transmembrane domain. To assess the influence of the membrane model system, structure determinations of the beta3 integrin transmembrane segment and flanking sequences were carried out in both phospholipid bicelles and detergent micelles. In bicelles, a 30-residue linear alpha-helix, encompassing residues I693-H772, is adopted, of which I693-I721 appear embedded in the hydrophobic bicelle core. This relatively long transmembrane helix implies a pronounced helix tilt within a typical lipid bilayer, which facilitates the snorkeling of K716's charged side chain out of the lipid core while simultaneously immersing hydrophobic L717-I721 in the membrane. A shortening of bicelle lipid hydrocarbon tails does not lead to the transfer of L717-I721 into the aqueous phase, suggesting that the reported embedding represents the preferred beta3 state. The nature of the lipid headgroup affected only the intracellular part of the transmembrane helix, indicating that an asymmetric lipid distribution is not required for studying the beta3 transmembrane segment. In the micelle, residues L717-I721 are also embedded but deviate from linear alpha-helical conformation in contrast to I693-K716, which closely resemble the bicelle structure.

  12. High isoproterenol doses are required to activate beta3-adrenoceptor-mediated functions in dogs. (United States)

    Pelat, Michel; Verwaerde, Patrick; Galitzky, Jean; Lafontan, Max; Berlan, Michel; Senard, Jean-Michel; Montastruc, Jean-Louis


    The "in vivo" conditions for beta3-adrenoceptors (beta-AR) activation by isoproterenol were investigated in dog. Experiments were carried out in anesthetized dogs using isoproterenol as a nonselective beta-AR agonist. Intravenous infusion of isoproterenol (0.4 nmol/kg/min) induced arterial hypotension and tachycardia with a slight decrease in cutaneous blood flow. At this dose, isoproterenol increased glucose, glycerol, and nonesterified fatty acid plasma levels. The changes in cardiovascular and endocrine-metabolic parameters, induced by the low dose of isoproterenol, were suppressed by pretreatment with nadolol (1 mg/kg, i.v.). After nadolol administration, however, a 10-fold higher dose (4 nmol/kg/min) of isoproterenol was able to induce a decrease in arterial blood pressure with a slight tachycardia and an increase in cutaneous blood flow. This high dose of isoproterenol increased nonesterified fatty acid and glycerol plasma levels but failed to change glucose plasma levels. All these effects were abolished by a pretreatment with nadolol (1 mg/kg, i.v.) plus SR59230A [a selective beta3-adrenoceptor antagonist; (3-(2-ethylphenoxy)-1(1S)-1,2,3,4-tetrahydronaphth-1-ylaminol-(2S)2-propanol oxalate); 1 mg/kg, i.v.]. Moreover, as observed with the high dose of isoproterenol under nadolol pretreatment, an infusion of SR58611A [a selective beta3-adrenoceptor agonist; ((N2S)-7-carbethoxymethoxy-1,2,3,4-tetrahydronaphth-2-yl-(2R)-2-hydroxy-2-chlorophenyl) ethanamine hydrochloride] induces a decrease in mean arterial blood pressure associated with an increase in heart rate, cutaneous blood flow, and nonesterified fatty acid and glycerol plasma levels. These results demonstrate that the in vivo activation of beta3-adrenoceptors requires higher doses of catecholamine than those necessary for beta1- and/or beta2-adrenoceptor stimulation. These results also argue for the lack of a beta3-AR involvement in the control of heart rate and glycogenolysis in dogs.

  13. Aldosterone aggravates glucose intolerance induced by high fructose. (United States)

    Sherajee, Shamshad J; Rafiq, Kazi; Nakano, Daisuke; Mori, Hirohito; Kobara, Hideki; Hitomi, Hirofumi; Fujisawa, Yoshihide; Kobori, Hiroyuki; Masaki, Tsutomu; Nishiyama, Akira


    We previously reported that aldosterone impaired vascular insulin signaling in vivo and in vitro. Fructose-enriched diet induces metabolic syndrome including hypertension, insulin resistance, hyperlipidemia and diabetes in animal. In the current study, we hypothesized that aldosterone aggravated fructose feeding-induced glucose intolerance in vivo. Rats were divided into five groups for six-week treatment; uninephrectomy (Unx, n=8), Unx+aldosterone (aldo, 0.75 µg/h, s.c., n=8), Unx+fructose (fruc, 10% in drinking water, n=8), Unx+aldo+fruc, (aldo+fruc, n=8), and Unx+aldo+fruc+spironolactone, a mineralocorticoid receptor antagonist (aldo+fruc+spiro, 20mg/kg/day, p.o., n=8). Aldo+fruc rats manifested the hypertension, and induced glucose intolerance compared to fruc intake rats assessed by oral glucose tolerance test, homeostasis model assessment of insulin resistance and hyperinsulinemic-euglycemic clamp study. Spironolactone, significantly improved the aldosterone-accelerated glucose intolerance. Along with improvement in insulin resistance, spironolactone suppressed upregulated mineralocorticoid receptor (MR) target gene, serum and glucocorticoid-regulated kinases-1 mRNA expression in skeletal muscle in aldo+fruc rats. In conclusion, these data suggested that aldosterone aggravates fructose feeding-induced glucose intolerance through MR activation.

  14. Aggravation of viral hepatitis by platelet-derived serotonin. (United States)

    Lang, Philipp A; Contaldo, Claudio; Georgiev, Panco; El-Badry, Ashraf Mohammad; Recher, Mike; Kurrer, Michael; Cervantes-Barragan, Luisa; Ludewig, Burkhard; Calzascia, Thomas; Bolinger, Beatrice; Merkler, Doron; Odermatt, Bernhard; Bader, Michael; Graf, Rolf; Clavien, Pierre-Alain; Hegazy, Ahmed N; Löhning, Max; Harris, Nicola L; Ohashi, Pamela S; Hengartner, Hans; Zinkernagel, Rolf M; Lang, Karl S


    More than 500 million people worldwide are persistently infected with hepatitis B virus or hepatitis C virus. Although both viruses are poorly cytopathic, persistence of either virus carries a risk of chronic liver inflammation, potentially resulting in liver steatosis, liver cirrhosis, end-stage liver failure or hepatocellular carcinoma. Virus-specific T cells are a major determinant of the outcome of hepatitis, as they contribute to the early control of chronic hepatitis viruses, but they also mediate immunopathology during persistent virus infection. We have analyzed the role of platelet-derived vasoactive serotonin during virus-induced CD8(+) T cell-dependent immunopathological hepatitis in mice infected with the noncytopathic lymphocytic choriomeningitis virus. After virus infection, platelets were recruited to the liver, and their activation correlated with severely reduced sinusoidal microcirculation, delayed virus elimination and increased immunopathological liver cell damage. Lack of platelet-derived serotonin in serotonin-deficient mice normalized hepatic microcirculatory dysfunction, accelerated virus clearance in the liver and reduced CD8(+) T cell-dependent liver cell damage. In keeping with these observations, serotonin treatment of infected mice delayed entry of activated CD8(+) T cells into the liver, delayed virus control and aggravated immunopathological hepatitis. Thus, vasoactive serotonin supports virus persistence in the liver and aggravates virus-induced immunopathology.

  15. Beyond bullying: Aggravating elements of peer victimization episodes. (United States)

    Turner, Heather A; Finkelhor, David; Shattuck, Anne; Hamby, Sherry; Mitchell, Kimberly


    This study sought to identify features of peer victimization that aggravate negative outcomes in children. The features that were assessed include "power imbalance," a commonly used criterion in defining bullying, and 5 other characteristics: injury, weapon involvement, Internet involvement, sexual content, and bias content. Three outcomes were assessed: level of fear, missing school, and trauma symptoms. A nationally representative sample of 3,164 children and youth ages 6-17 (51.8% male; 68.4% white, 12.5% black, 13.5% Hispanic, 5.7% other race) was obtained through Random Digit Dial and supplemented with an address-based sample to capture cell-phone-only households. One child was randomly selected from each household. Interviews were conducted with parents of children age 6-9 and with the youths themselves if they were age 10-17. Peer victimization was assessed with the Juvenile Victimization Questionnaire (JVQ). Almost half (48.4%) of the entire sample of school-age children experienced at least 1 form of peer victimization in the past year. Injury and power imbalance independently increased the impact on children for all 3 outcomes. Additionally, weapon involvement and sexual content were associated with trauma symptoms, with sexual content having the strongest effect (B = .23, p bullying with its exclusionary power imbalance definition as the central focus for prevention and intervention. We recommend a broader focus on peer victimization along with more research to identify the aggravating features that signal the greatest need for intervention.

  16. Andes virus recognition of human and Syrian hamster beta3 integrins is determined by an L33P substitution in the PSI domain. (United States)

    Matthys, Valery S; Gorbunova, Elena E; Gavrilovskaya, Irina N; Mackow, Erich R


    Andes virus (ANDV) causes a fatal hantavirus pulmonary syndrome (HPS) in humans and Syrian hamsters. Human alpha(v)beta(3) integrins are receptors for several pathogenic hantaviruses, and the function of alpha(v)beta(3) integrins on endothelial cells suggests a role for alpha(v)beta(3) in hantavirus directed vascular permeability. We determined here that ANDV infection of human endothelial cells or Syrian hamster-derived BHK-21 cells was selectively inhibited by the high-affinity alpha(v)beta(3) integrin ligand vitronectin and by antibodies to alpha(v)beta(3) integrins. Further, antibodies to the beta(3) integrin PSI domain, as well as PSI domain polypeptides derived from human and Syrian hamster beta(3) subunits, but not murine or bovine beta(3), inhibited ANDV infection of both BHK-21 and human endothelial cells. These findings suggest that ANDV interacts with beta(3) subunits through PSI domain residues conserved in both Syrian hamster and human beta(3) integrins. Sequencing the Syrian hamster beta(3) integrin PSI domain revealed eight differences between Syrian hamster and human beta(3) integrins. Analysis of residues within the PSI domains of human, Syrian hamster, murine, and bovine beta(3) integrins identified unique proline substitutions at residues 32 and 33 of murine and bovine PSI domains that could determine ANDV recognition. Mutagenizing the human beta(3) PSI domain to contain the L33P substitution present in bovine beta(3) integrin abolished the ability of the PSI domain to inhibit ANDV infectivity. Conversely, mutagenizing either the bovine PSI domain, P33L, or the murine PSI domain, S32P, to the residue present human beta(3) permitted PSI mutants to inhibit ANDV infection. Similarly, CHO cells transfected with the full-length bovine beta(3) integrin containing the P33L mutation permitted infection by ANDV. These findings indicate that human and Syrian hamster alpha(v)beta(3) integrins are key receptors for ANDV and that specific residues within the

  17. Short-term air pollution exposure aggravates Parkinson’s disease in a population-based cohort (United States)

    Lee, Hyewon; Myung, Woojae; Kim, Doh Kwan; Kim, Satbyul Estella; Kim, Clara Tammy; Kim, Ho


    Increasing experimental evidence has suggested air pollution as new risk factor for neurological disease. Although long-term exposure is reportedly related to neurological disease, information on association with short-term exposure is scarce. We examined the association of short-term exposure to particles Health Insurance Service–National Sample Cohort, Korea during 2002–2013. PD aggravation cases were defined as emergency hospital admissions for primarily diagnosed PD and analyzed with a case-crossover analysis, designed for rare acute outcomes. Pollutants concentrations on case and control days were compared and effect modifications were explored. A unit increase in 8-day moving average of concentrations was significantly associated with PD aggravation. The association was consistent for PM2.5 (odds ratio [95% confidence interval]: 1.61 [1.14–2.29] per 10 μg/m3), NO2 (2.35 [1.39–3.97] per 10 ppb), SO2 (1.54 [1.11–2.14] per 1 ppb), and CO (1.46 [1.05–2.04] per 0.1 ppm). The associations were stronger in women, patients aged 65–74 years, and cold season, but not significant. In conclusion, short-term air pollution exposure increased risk of PD aggravation, and may cause neurological disease progression in humans. PMID:28300224

  18. Structural policy in the context of international competition aggravation

    Directory of Open Access Journals (Sweden)

    Volodymyr Bodrov


    Full Text Available This article researches the essence and peculiarities of the structural policy, performs classification of its models and determines possibilities of their use in the context of increasing international competition. It discovers the main components of the economic structure and trends of the state policy regarding their modernization. Measures on improvement of state regulation instruments are offered, factors of influence upon improvement of the Ukrainian economy structure are analyzed and priority goals are systematized which require urgent implementation in the terms of competitive struggle aggravation at the global markets. The article also researches the matter of importance of performing a complex of state functional and selective measures in the form of matrix policy for the purpose of protecting national interests of the country in the context of global challenges

  19. Aggravated Cardiac Remodeling post Aortocaval Fistula in Unilateral Nephrectomized Rats.

    Directory of Open Access Journals (Sweden)

    Jie Wu

    Full Text Available Aortocaval fistula (AV in rat is a unique model of volume-overload congestive heart failure and cardiac hypertrophy. Living donor kidney transplantation is regarded as beneficial to allograft recipients and not particularly detrimental to the donors. Impact of AV on animals with mild renal dysfunction is not fully understood. In this study, we explored the effects of AV in unilateral nephrectomized (UNX rats.Adult male Sprague-Dawley (SD rats were divided into Sham (n = 10, UNX (right kidney remove, n = 10, AV (AV established between the levels of renal arteries and iliac bifurcation, n = 18 and UNX+AV (AV at one week after UNX, n = 22, respectively. Renal outcome was measured by glomerular filtration rate, effective renal plasma flow, fractional excretion of sodium, albuminuria, plasma creatinine, and cystatin C. Focal glomerulosclerosis (FGS incidence was evaluated by renal histology. Cardiac function was measured by echocardiography and hemodynamic measurements.UNX alone induced compensatory left kidney enlargement, increased plasma creatinine and cystatin C levels, and slightly reduced glomerular filtration rate and increased FGS. AV induced significant cardiac enlargement and hypertrophy and reduced cardiac function and increased FGS, these changes were aggravated in UNX+AV rats.Although UNX only induces minor renal dysfunction, additional chronic volume overload placement during the adaptation phase of the remaining kidney is associated with aggravated cardiac dysfunction and remodeling in UNX rats, suggesting special medical care is required for UNX or congenital monokidney subjects in case of chronic volume overload as in the case of pregnancy and hyperthyroidism to prevent further adverse cardiorenal events in these individuals.

  20. Two-Dimensional Infrared (2DIR) Spectroscopy of the Peptide Beta3s Folding (United States)

    Lai, Zaizhi; Preketes, Nicholas K; Jiang, Jun; Mukamel, Shaul; Wang, Jin


    Probing underlying free energy landscape, pathways, and mechanism is the key for understanding protein folding in theory and experiment. Recently time-resolved two-dimensional infrared (2DIR) with femtosecond laser pulses, has emerged as a promising tool for investigating the protein folding dynamics on faster timescales than possible by NMR. We have employed molecular dynamics simulations to compute 2DIR spectra of the folding process of a peptide, Beta3s. Simulated non-chiral and chiral 2DIR signals illustrate the variation of the spectra as the peptide conformation evolves along the free energy landscape. Chiral spectra show stronger changes than the non-chiral signals because cross peaks caused by the formation of the β-sheet are clearly resolved. Chirality-induced 2DIR may be used to detect the folding of β-sheet proteins with high spectral and temporal resolution. PMID:23956818

  1. Integrin-beta3 clusters recruit clathrin-mediated endocytic machinery in the absence of traction force (United States)

    Yu, Cheng-han; Rafiq, Nisha Bte Mohd; Cao, Fakun; Zhou, Yuhuan; Krishnasamy, Anitha; Biswas, Kabir Hassan; Ravasio, Andrea; Chen, Zhongwen; Wang, Yu-Hsiu; Kawauchi, Keiko; Jones, Gareth E.; Sheetz, Michael P.


    The turnover of integrin receptors is critical for cell migration and adhesion dynamics. Here we find that force development at integrins regulates adaptor protein recruitment and endocytosis. Using mobile RGD (Arg-Gly-Asp) ligands on supported lipid membranes (RGD membranes) and rigid RGD ligands on glass (RGD-glass), we find that matrix force-dependent integrin signals block endocytosis. Dab2, an adaptor protein of clathrin-mediated endocytosis, is not recruited to activated integrin-beta3 clusters on RGD-glass; however, it is recruited to integrin-mediated adhesions on RGD membranes. Further, when force generation is inhibited on RGD-glass, Dab2 binds to integrin-beta3 clusters. Dab2 binding to integrin-beta3 excludes other adhesion-related adaptor proteins, such as talin. The clathrin-mediated endocytic machinery combines with Dab2 to facilitate the endocytosis of RGD-integrin-beta3 clusters. From these observations, we propose that loss of traction force on ligand-bound integrin-beta3 causes recruitment of Dab2/clathrin, resulting in endocytosis of integrins. PMID:26507506

  2. Vitamin D depletion aggravates hypertension and target-organ damage

    DEFF Research Database (Denmark)

    Andersen, Louise Bjørkholt; Przybyl, Lukasz; Haase, Nadine;


    BACKGROUND: We tested the controversial hypothesis that vitamin D depletion aggravates hypertension and target-organ damage by influencing renin. METHODS AND RESULTS: Four-week-old double-transgenic rats (dTGR) with excess angiotensin (Ang) II production due to overexpression of the human renin (h......REN) and angiotensinogen (hAGT) genes received vitamin D-depleted (n=18) or standard chow (n=15) for 3 weeks. The depleted group had very low serum 25-hydroxyvitamin D levels (mean±SEM; 3.8±0.29 versus 40.6±1.19 nmol/L) and had higher mean systolic BP at week 5 (158±3.5 versus 134.6±3.7 mm Hg, P....6±3.3 versus 162.3±3.8 mm Hg, PVitamin D depletion led to increased relative heart weights and increased serum creatinine concentrations. Furthermore, the mRNAs of natriuretic peptides, neutrophil gelatinase-associated lipocalin, hREN, and r...

  3. Pain in Breast Cancer Treatment: Aggravating Factors and Coping Mechanisms

    Directory of Open Access Journals (Sweden)

    Maria de Fatima Guerreiro Godoy


    Full Text Available The objective of this study was to evaluate pain in women with breast cancer-related lymphedema and the characteristics of aggravating factors and coping mechanisms. The study was conducted in the Clinica Godoy, São Jose do Rio Preto, with a group of 46 women who had undergone surgery for the treatment of breast cancer. The following variables were evaluated: type and length of surgery; number of radiotherapy and chemotherapy sessions; continued feeling of the removed breast (phantom limb, infection, intensity of pain, and factors that improve and worsen the pain. The percentage of events was used for statistical analysis. About half the participants (52.1% performed modified radical surgery, with 91.3% removing only one breast; 82.6% of the participants did not perform breast reconstruction surgery. Insignificant pain was reported by 32.60% of the women and 67.3% said they suffered pain; it was mild in 28.8% of the cases (scale 1–5, moderate in 34.8% (scale 6–9, and severe in 4.3%. The main mechanisms used to cope with pain were painkillers in 41.30% of participants, rest in 21.73%, religious ceremonies in 17.39%, and chatting with friends in 8.69%. In conclusion, many mastectomized patients with lymphedema complain of pain, but pain is often underrecognized and undertreated.

  4. Seawater Immersion Aggravates Burn Injury Causing Severe Blood Coagulation Dysfunction

    Directory of Open Access Journals (Sweden)

    Hong Yan


    Full Text Available This study aimed to investigate the endothelial function in a canine model of burn injury combined with seawater immersion. The model of burn injury was established. The dogs were randomly divided into four groups including dogs with burn injury (B group, or burn injury combined with seawater immersion (BI group, or only immersion in seawater (I group, or control animals with no injury or immersion (C group. The circulating endothelial cell (CEC count and coagulation-fibrinolysis parameters were measured. The CEC count in B group increased at 4 h, 7 h, and 10 h after injury and then reduced, whereas it continuously increased to a greater extent in BI group (P<0.05. The von Willebrand factor (vWF activity, plasminogen activator inhibitor (PAI-1, and the ratio of thromboxane B2 (TXB2 to 6-keto-prostaglandin F1α (6-K-PGF1α in BI group had a marked increase after injury, and the tissue-type plasminogen activator (tPA in the BI group decreased. Microscope observations revealed thrombus formation in lungs of the animals in BI group, but not in C, I, or B groups. Burn injury causes endothelial dysfunction, and seawater immersion lastingly aggravates this injury, leading to a higher risk of developing thrombosis.

  5. Tolbutamide attenuates diazoxide-induced aggravation of hypoxic cell injury. (United States)

    Pissarek, M; Reichelt, C; Krauss, G J; Illes, P


    ATP-dependent potassium (KATP) channels of neurons are closed in the presence of physiological levels of intracellular ATP and open when ATP is depleted during hypoxia or metabolic damage. The present study investigates hypoxic alterations of purine and pyrimidine nucleotide levels supposed to intracellularly modulate KATP channels. In addition, the effects of the KATP channel activator diazoxide and its antagonist tolbutamide were investigated on ATP, GTP, CTP and UTP levels in slices of the parietal cortex. Hypoxia was evoked by saturation of the medium with 95% N2-5% CO2 instead of 95% O2-5% CO2 for 5 min. Nucleotide contents were measured by anion-exchange HPLC in neutralized perchloric acid extracts obtained from slices frozen immediately at the end of incubation. Hypoxia per se decreased purine and pyrimidine nucleoside triphosphate contents. Thus, ATP and GTP contents were reduced to 69.9 and 77.6% of the respective normoxic levels. UTP and CTP contents were even more decreased (to 60.9 and 41.6%),, probably because the salvage pathway of these pyrimidine nucleotides is less effective than that of the purine nucleotides ATP and GTP. While tolbutamide (30 microM) had no effect on the hypoxia-induced decrease of nucleotides, diazoxide at 300, but not 30 microM aggravated the decline of ATP, UTP and CTP to 51.8, 37.5 and 28.5% of the contents observed at normoxia; GTP levels also showed a tendency to decrease after diazoxide application. Tolbutamide (300 microM) antagonized the effects of diazoxide (300 but not 30 microM aggravated the decline of ATP, UTP and CTP to 51.8, 37.5 and 28.5% of the contents observed at normoxia; GTP levels also showed a tendency to decrease after diazoxide application. Tolbutamide (300 microM) antagonized the effects of diazoxide (300 MicroM). Nucleoside diphosphate (ADP, GDP and UDP) levels were uniformly increased by hypoxia. There was no hypoxia-induced increase of ADP contents in the presence of tolbutamide (300 microM). The ATP

  6. Dietary hypercholesterolemia aggravates contrast media-induced nephropathy

    Institute of Scientific and Technical Information of China (English)

    杨定位; 贾汝汉; 杨定平; 丁国华; 黄从新


    Background Contrast media administration can result in severe nephrotoxicity under pathological conditions such as diabetic nephropathy, congestive heart failure, dehydration, et al. The purpose of this study was to evaluate the effects of dietary hypercholesterolemia on contrast media-induced changes in renal function, blood flow, and histopathology.Methods Rats were fed either on a normal rodent diet (group N) or a high-cholesterol supplemented diet (group H; 4% cholesterol and 1% cholic acid) for 8 weeks. Half of the animals (n =6) from each diet group were then given a tail vein injection of 60% diatrizoate (6 ml/kg; group NC and group HC)and the other half were administered saline. Total serum cholesterol, triglyceride, serum creatinine,creatinine clearance rate, fractional excretion of sodium and potassium, and cortical nitric oxide production were determined one day following contrast media administration. Renal blood flow was determined by color Doppler flow imaging and pulsed-mode Doppler. Renal histopathology was observed by light microscopy.Results Total serum cholesterol and resistance indices of renal blood vessels increased significantly,while creatinine clearance rate and production of nitric oxide in the renal cortex decreased markedly in group HC and group H when compared to group N and group NC. The creatinine clearance rate decreased significantly in group HC compared to group H. Serum creatinine levels and fractional excretion of sodium and potassium in group HC were significantly higher than those in the other three groups. Severe tubular degeneration and necrosis, protein cast accumulation, and medullary congestion were found in group HC.Conclusion Hypercholesterolemia is a risk factor for contrast media-induced nephropathy.Hypercholesterolemia aggravates contrast media-induced nephrotoxicity through the reduced production of nitric oxide.

  7. Imprecise methods may both obscure and aggravate a relation between fat and breast cancer

    DEFF Research Database (Denmark)

    Heitmann, B L; Frederiksen, Peder


    Bias in diet reporting may be both random and non-random, and may be found with simpler as well as more advanced dietary instruments. A random bias will contribute to obscure relations between diet and disease. A systematic bias may obscure or aggravate such associations. Underreporting of non......-protein energy has been found to be substantial, particularly among those who are obese or have high dietary intakes. Such a non-random bias on the group level would tend to aggravate associations between dietary non-protein and disease. Whether the net result of the random and non-random bias aggravates...

  8. Aggravation of excessive daytime sleepiness concurrent with aggravation of an injured ascending reticular activating system in a patient with mild traumatic brain injury (United States)

    Jang, Sung Ho; Kwon, Hyeok Gyu


    Abstract Background: We report on a patient who developed aggravation of excessive daytime sleepiness (EDS) concurrent with aggravation of an injured ascending reticular activating system (ARAS) following mild traumatic brain injury (TBI), demonstrated by follow-up diffusion tensor tractographies (DTTs). Methods: A 42-year-old male patient experienced head trauma resulting from flexion-hyperextension injury after collision with another vehicle from behind while stopped at an intersection. The patient lost consciousness for approximately 10 seconds and experienced no post-traumatic amnesia following the accident. The patient's Glasgow Coma Scale score was 15. No specific lesion was observed on the conventional brain MRI performed at 10 weeks after onset. The patient complained of EDS after the head trauma and aggravation of EDS with passage of time. The Epworth Sleepiness Scale indicated abnormality with a score of 12 at 10 weeks after onset (cut-off: 10 points full mark: 24 score) and it was aggravated with a score of 18 at 16 months. Results: On 10-week DTT, decreased neural connectivity of the intralaminar thalamic nucleus to the prefrontal cortex and basal forebrain was observed in both hemispheres. However, no significant abnormality was observed in the dorsal and ventral lower ARAS. On 16-month DTT, the upper portion of the left dorsal lower ARAS showed partial tearing and the ventral lower ARAS showed thinning (both sides) and partial tearing (right side). Conclusions: Aggravation of EDS concurrent with aggravation of an injured ARAS was demonstrated in a patient with mild TBI using DTT. PMID:28121943

  9. Metallothionein deficiency aggravates depleted uranium-induced nephrotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Hao, Yuhui; Huang, Jiawei; Gu, Ying; Liu, Cong; Li, Hong; Liu, Jing; Ren, Jiong; Yang, Zhangyou [State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, No. 30 Gaotanyan Street, Shapingba District, Chongqing 400038 (China); Peng, Shuangqing [Evaluation and Research Center for Toxicology, Institute of Disease Control and Prevention, Academy of Military Medical Science, 20 Dongdajie Street, Fengtai District, Beijing 100071 (China); Wang, Weidong, E-mail: [Department of Radiation Oncology, Shanghai Jiao Tong University Affiliated Sixth People' s Hospital, Shanghai 200233 (China); Li, Rong, E-mail: [State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, No. 30 Gaotanyan Street, Shapingba District, Chongqing 400038 (China)


    Depleted uranium (DU) has been widely used in both civilian and military activities, and the kidney is the main target organ of DU during acute high-dose exposures. In this study, the nephrotoxicity caused by DU in metallothionein-1/2-null mice (MT −/−) and corresponding wild-type (MT +/+) mice was investigated to determine any associations with MT. Each MT −/− or MT +/+ mouse was pretreated with a single dose of DU (10 mg/kg, intraperitoneal injection) or an equivalent volume of saline. After 4 days of DU administration, kidney changes were assessed. After DU exposure, serum creatinine and serum urea nitrogen in MT −/− mice significantly increased than in MT +/+ mice, with more severe kidney pathological damage. Moreover, catalase and superoxide dismutase (SOD) decreased, and generation of reactive oxygen species and malondialdehyde increased in MT −/− mice. The apoptosis rate in MT −/− mice significantly increased, with a significant increase in both Bax and caspase 3 and a decrease in Bcl-2. Furthermore, sodium-glucose cotransporter (SGLT) and sodium-phosphate cotransporter (NaPi-II) were significantly reduced after DU exposure, and the change of SGLT was more evident in MT −/− mice. Finally, exogenous MT was used to evaluate the correlation between kidney changes induced by DU and MT doses in MT −/− mice. The results showed that, the pathological damage and cell apoptosis decreased, and SOD and SGLT levels increased with increasing dose of MT. In conclusion, MT deficiency aggravated DU-induced nephrotoxicity, and the molecular mechanisms appeared to be related to the increased oxidative stress and apoptosis, and decreased SGLT expression. - Highlights: • MT −/− and MT +/+ mice were used to evaluate nephrotoxicity of DU. • Renal damage was more evident in the MT −/− mice after exposure to DU. • Exogenous MT also protects against DU-induced nephrotoxicity. • MT deficiency induced more ROS and apoptosis after exposure to

  10. Feed exposure to FB1 can aggravate pneumonic damages in pigs provoked by P. multocida. (United States)

    Kovács, Melinda; Pósa, Roland; Tuboly, Tamás; Donkó, Tamás; Repa, Imre; Tossenberger, János; Szabó-Fodor, Judit; Stoev, Stoycho; Magyar, Tibor


    The possible interaction between Pasteurella multocida and the mycotoxin fumonisin B1 (FB1), recognised as one of the most often food/feed contaminant, was studied with the aim to evaluate whether and how FB1 can influence and/or complicate the development and severity of various pathological damages provoked by Pasteurella multocida in some internal organs of pigs. Heavier lung pathology was seen in pigs experimentally infected with Pasteurella multocida, when the same were exposed to 20ppm dietary levels of fumonisin B1 (FB1) as was assessed by gross pathology, pathomorphological examinations, clinical biochemistry and some immunological investigations. The most typical damages in FB1 treated pigs were the strong oedema in the lung and the slight oedema in the other internal organs and mild degenerative changes in the kidneys, whereas the typical pathomorphological findings in pigs infected with Pasteurella multocida was broncho-interstitial pneumonia. FB1 was found to aggravate pneumonic changes provoked by P. multocida in the cranial lobes of the lung and to complicate pneumonic damages with interstitial oedema in the lung. No macroscopic damages were observed in the pigs infected only with Pasteurella multocida. It can be concluded that the feed intake of FB1 in pigs may complicate or exacerbate the course of P. multocida serotype A infection.

  11. Ocean acidification may aggravate social-ecological trade-offs in coastal fisheries.

    Directory of Open Access Journals (Sweden)

    Rudi Voss

    Full Text Available Ocean Acidification (OA will influence marine ecosystems by changing species abundance and composition. Major effects are described for calcifying organisms, which are significantly impacted by decreasing pH values. Direct effects on commercially important fish are less well studied. The early life stages of fish populations often lack internal regulatory mechanisms to withstand the effects of abnormal pH. Negative effects can be expected on growth, survival, and recruitment success. Here we study Norwegian coastal cod, one of the few stocks where such a negative effect was experimentally quantified, and develop a framework for coupling experimental data on OA effects to ecological-economic fisheries models. In this paper, we scale the observed physiological responses to the population level by using the experimentally determined mortality rates as part of the stock-recruitment relationship. We then use an ecological-economic optimization model, to explore the potential effect of rising CO2 concentration on ecological (stock size, economic (profits, consumer-related (harvest and social (employment indicators, with scenarios ranging from present day conditions up to extreme acidification. Under the assumptions of our model, yields and profits could largely be maintained under moderate OA by adapting future fishing mortality (and related effort to changes owing to altered pH. This adaptation comes at the costs of reduced stock size and employment, however. Explicitly visualizing these ecological, economic and social tradeoffs will help in defining realistic future objectives. Our results can be generalized to any stressor (or stressor combination, which is decreasing recruitment success. The main findings of an aggravation of trade-offs will remain valid. This seems to be of special relevance for coastal stocks with limited options for migration to avoid unfavorable future conditions and subsequently for coastal fisheries, which are often small

  12. Ocean acidification may aggravate social-ecological trade-offs in coastal fisheries. (United States)

    Voss, Rudi; Quaas, Martin F; Schmidt, Jörn O; Kapaun, Ute


    Ocean Acidification (OA) will influence marine ecosystems by changing species abundance and composition. Major effects are described for calcifying organisms, which are significantly impacted by decreasing pH values. Direct effects on commercially important fish are less well studied. The early life stages of fish populations often lack internal regulatory mechanisms to withstand the effects of abnormal pH. Negative effects can be expected on growth, survival, and recruitment success. Here we study Norwegian coastal cod, one of the few stocks where such a negative effect was experimentally quantified, and develop a framework for coupling experimental data on OA effects to ecological-economic fisheries models. In this paper, we scale the observed physiological responses to the population level by using the experimentally determined mortality rates as part of the stock-recruitment relationship. We then use an ecological-economic optimization model, to explore the potential effect of rising CO2 concentration on ecological (stock size), economic (profits), consumer-related (harvest) and social (employment) indicators, with scenarios ranging from present day conditions up to extreme acidification. Under the assumptions of our model, yields and profits could largely be maintained under moderate OA by adapting future fishing mortality (and related effort) to changes owing to altered pH. This adaptation comes at the costs of reduced stock size and employment, however. Explicitly visualizing these ecological, economic and social tradeoffs will help in defining realistic future objectives. Our results can be generalized to any stressor (or stressor combination), which is decreasing recruitment success. The main findings of an aggravation of trade-offs will remain valid. This seems to be of special relevance for coastal stocks with limited options for migration to avoid unfavorable future conditions and subsequently for coastal fisheries, which are often small scale local

  13. RPTP-alpha acts as a transducer of mechanical force on alphav/beta3-integrin-cytoskeleton linkages

    DEFF Research Database (Denmark)

    von Wichert, Gotz; Jiang, Guoying; Kostic, Ana


    of alphav/beta3-integrin-cytoskeleton connections during the initial phase of ECM contact. These observations indicate that Src family kinases have distinct functions during adhesion site assembly, and that RPTPalpha is an early component in force-dependent signal transduction pathways leading......Cell motility on ECM critically depends on the cellular response to force from the matrix. We find that force-dependent reinforcement of alphav/beta3-integrin-mediated cell-matrix connections requires the receptor-like tyrosine phosphatase alpha (RPTPalpha). RPTPalpha colocalizes with alphav......-integrins at the leading edge during early spreading, and coimmunoprecipitates with alphav-integrins during spreading on fibronectin and vitronectin. RPTPalpha-dependent activation of Src family kinases, in particular activation of Fyn, is required for the force-dependent formation of focal complexes and strengthening...

  14. Involvement of PLC-beta3 in the effect of morphine on memory retrieval in passive avoidance task. (United States)

    Bianchi, E; Lehmann, D; Vivoli, E; Norcini, M; Ghelardini, C


    Phospholipase C (PLC) is one signalling effector enzyme whose activity is directly modulated by opioids. Several physiological studies have implicated PLC-linked pathways in in-vivo pain regulation and opioid tolerance. Co-administration of PLC-beta(2/3) activity blocker M119 with morphine resulted in a dramatic increase in morphine-induced amnesic effect in mice, proving a role for beta subunit of PLC enzyme in these processes. Administration of morphine to mice at amnesic dose increased PLC-beta(3) activity, with respect to basal value, in the membrane-soluble material from anterior cortex and hippocampal formation in brain areas. PLC-beta(3) appears to be simultaneously implicated in both analgesic and amnesic effects induced by administration of morphine to mice suggesting a commonality in the molecular mechanisms of morphine-induced analgesia and memory impairment.

  15. Sleep-related hypoxemia aggravates systematic inflammation in emphysematous rats

    Institute of Scientific and Technical Information of China (English)

    FENG Jing; Ambrose An-Po Chiang; WU Qi; CHEN Bao-yuan; CUI Lin-yang; LIANG Dong-chun; ZHANG Ze-li; YAO Wo


    mean linear intercept (MLI) and mean alveolar number (MAN) values than SRHCtrl group. MLI values in SRHStand group were the highest (ail P <0.05). O2Sat in SRHStand rats when SRH exposure was (83.45±1.76)%. Histological scores of lung, liver, pancreas and right carotid artery were higher in emphysematous groups than SRHCtrl group, and SRHStand group were the highest (all P <0.05) (SOD and CAT values were lower and MDA values were higher in groups with emphysema than without and in SRHStand group than in ECtrl group (all P <0.05)). MDA values were the highest in SRHStand group (all P <0.05). Total cellular score in BALF and White blood cell (WBC) in whole blood were the highest in SRHStand group (all P <0.05). Lymphocyte ratios were the highest in SRHStand group both in BALF and blood (all P <0.05). Red blood cell (RBC) and hemoglobin in emphysematous groups were higher than that in SRHCtrl group, and SRHStand group were higher than ECtrl group (all P <0.05).Conclusions With a proper novo model of SRHIE with Wistar rats, we have demonstrated SRH may aggravate the degree of emphysematous changes, polycythemia,oxidative stress and systematic inflammation. SRH and emphysema may have a synergistic action in causing systematic damages, and lymphocyte may be playing a central role in this process. Longer duration and more severe extent of SRHIE exposure also seem to result in more serious systematic damages. The mechanisms of all these concerned processes remain to be studied.

  16. Peripheral cardiovascular actions of SR 58611 A, a beta 3-adrenoceptor agonist, in the dog: lack of central effect. (United States)

    Montastruc, J L; Verwaerde, P; Pelat, M; Galitzky, J; Langin, D; Lafontan, M; Berlan, M


    In order to investigate the putative role of beta3-adrenoceptors in central and peripheral cardiovascular regulations, the effects of intracisternal (i.c.) and intravenous (i.v.) injections of SR 58611 A (10, 50, 100 and 200 nmol kg-1), a selective beta3-adrenoceptor agonist, were investigated in chloralose anaesthetized dogs. In normal dogs, i.v. SR 58611 A (100 and 200 nmol kg-1) induced a dose-dependent increase in heart rate with no change in blood pressure. After i.c. injection, SR 58611 A failed to modify blood pressure and heart rate (except at the highest dose 200 nmol kg-1 which induced a positive chronotropic effect). The positive chronotropic effect of SR 58611 A (200 nmol kg-1) appeared earlier and was significantly more pronounced after i.v. than i.c. administration. The positive chronotropic effect of i.v. SR 58611 A (200 nmol kg-1) was reduced by pretreatment with beta-adrenoceptor antagonists [propranolol, nadolol, bupranolol or the beta3-adrenoceptor selective antagonist, SR 59230 A (2 mg kg-1 i.v.)] and suppressed after sinoaortic denervation (i.e. after removal of vagal tone to the heart). These experiments do not show evidence for a primary central cardiovascular effect of SR 58611 A. The positive chronotropic effect of i.v. SR 58611 A is mainly of peripheral origin and can be attributed to a baroreceptor-mediated reflex due to the beta3-adrenoceptor mediated vasodilation with an increase in sympathetic tone and a reduction in vagal tone to the heart.

  17. Investigation of the causes of clinical symptom aggravation in process of intravenous thrombolysis with alteplase

    Directory of Open Access Journals (Sweden)

    LI Chen-hua


    Full Text Available Objective To explore the causes of aggravation of microcirculation disorders in the process of intravenous thrombolysis with alteplase and the clinical outcomes. Methods The clinical data of the aggravated signs and symptoms of 13 cases treated by alteplase were reported, and the onset characteristics and clinical outcomes were analysed to summarize emergency experiences. Results There were 13 patients with stenosis of intracranial large arteries occurred perforating branch infarctions caused by the blocking of carried arteries (8 cases in internal carotid system, 5 cases in vertebral-basilar system. In the process of thrombolytic therapy, main aggravated presentations including cortical ischemic symptom, quadriplegia, exacerbated disturbance of consciousness were seen. Imaging examinations showed multiple new petechial ischemic foci in cortex and watershed region or increasing of infarct foci in cerebellum and brain stem. The prognosis was favorable after expectant treatment. NIHSS score was 8.69 ± 3.42 at 24 h after treatment, and mRS score was 0.94 ±0.37 at 3 month-follow-up. Neurologic deficit and quality of life were evidently improved. Conclusion In the course of intravenous thrombolytic therapy with alteplase. Aggravated clinical signs and symptoms may be related to various factors. Emboli disintegration inducing microcirculation disorder is inferred to be the main cause. For patients presenting aggravated signs and symptoms in thrombolysis process, favorable outcomes may occur as long as intensive care and timely treatment are performed.

  18. Cysteinyl leukotriene signaling aggravates myocardial hypoxia in experimental atherosclerotic heart disease

    DEFF Research Database (Denmark)

    Nobili, Elena; Salvado, M Dolores; Folkersen, Lasse Westergaard;


    Cysteinyl-leukotrienes (cys-LT) are powerful spasmogenic and immune modulating lipid mediators involved in inflammatory diseases, in particular asthma. Here, we investigated whether cys-LT signaling, in the context of atherosclerotic heart disease, compromises the myocardial microcirculation and ...

  19. Intrinsic renal cell and leukocyte-derived TLR4 aggravate experimental anti-MPO glomerulonephritis

    NARCIS (Netherlands)

    Summers, Shaun A.; van der Veen, Betty S.; O'Sullivan, Kim M.; Gan, Poh-Yi; Ooi, Joshua D.; Heeringa, Peter; Satchell, Simon C.; Mathieson, Peter W.; Saleem, Moin A.; Visvanathan, Kumar; Holdsworth, Stephen R.; Kitching, A. Richard


    Antimyeloperoxidase antibodies can cause crescentic glomerulonephritis and pulmonary hemorrhage. Toll-like receptors (TLRs) respond to infectious agents activating host defenses, whereas infections potentially initiate disease and provoke relapses. Neutrophils were found to be key effector cells of

  20. Cysteinyl leukotriene signaling aggravates myocardial hypoxia in experimental atherosclerotic heart disease.

    Directory of Open Access Journals (Sweden)

    Elena Nobili

    Full Text Available BACKGROUND: Cysteinyl-leukotrienes (cys-LT are powerful spasmogenic and immune modulating lipid mediators involved in inflammatory diseases, in particular asthma. Here, we investigated whether cys-LT signaling, in the context of atherosclerotic heart disease, compromises the myocardial microcirculation and its response to hypoxic stress. To this end, we examined Apoe(-/- mice fed a hypercholesterolemic diet and analysed the expression of key enzymes of the cys-LT pathway and their receptors (CysLT1/CysLT2 in normal and hypoxic myocardium as well as the potential contribution of cys-LT signaling to the acute myocardial response to hypoxia. METHODS AND PRINCIPAL FINDINGS: Myocardial biopsies from Apoe(-/- mice demonstrated signs of chronic inflammation with fibrosis, increased apoptosis and expression of IL-6, as compared to biopsies from C57BL/6J control mice. In addition, we found increased leukotriene C(4 synthase (LTC(4S and CysLT1 expression in the myocardium of Apoe(-/- mice. Acute bouts of hypoxia further induced LTC(4S expression, increased LTC(4S enzyme activity and CysLT1 expression, and were associated with increased extension of hypoxic areas within the myocardium. Inhibition of cys-LT signaling by treatment with montelukast, a selective CysLT1 receptor antagonist, during acute bouts of hypoxic stress reduced myocardial hypoxic areas in Apoe(-/- mice to levels equal to those observed under normoxic conditions. In human heart biopsies from 14 patients with chronic coronary artery disease mRNA expression levels of LTC(4S and CysLT1 were increased in chronic ischemic compared to non-ischemic myocardium, constituting a molecular basis for increased cys-LT signaling. CONCLUSION: Our results suggest that CysLT1 antagonists may have protective effects on the hypoxic heart, and improve the oxygen supply to areas of myocardial ischemia, for instance during episodes of sleep apnea.

  1. Intermittent hypoxia can aggravate motor neuronal loss and cognitive dysfunction in ALS mice.

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    Sung-Min Kim

    Full Text Available BACKGROUND: Patients with ALS may be exposed to variable degrees of chronic intermittent hypoxia. However, all previous experimental studies on the effects of hypoxia in ALS have only used a sustained hypoxia model and it is possible that chronic intermittent hypoxia exerts effects via a different molecular mechanism from that of sustained hypoxia. No study has yet shown that hypoxia (either chronic intermittent or sustained can affect the loss of motor neurons or cognitive function in an in vivo model of ALS. OBJECTIVE: To evaluate the effects of chronic intermittent hypoxia on motor and cognitive function in ALS mice. METHODS: Sixteen ALS mice and 16 wild-type mice were divided into 2 groups and subjected to either chronic intermittent hypoxia or normoxia for 2 weeks. The effects of chronic intermittent hypoxia on ALS mice were evaluated using the rotarod, Y-maze, and wire-hanging tests. In addition, numbers of motor neurons in the ventral horn of the spinal cord were counted and western blot analyses were performed for markers of oxidative stress and inflammatory pathway activation. RESULTS: Compared to ALS mice kept in normoxic conditions, ALS mice that experienced chronic intermittent hypoxia had poorer motor learning on the rotarod test, poorer spatial memory on the Y-maze test, shorter wire hanging time, and fewer motor neurons in the ventral spinal cord. Compared to ALS-normoxic and wild-type mice, ALS mice that experienced chronic intermittent hypoxia had higher levels of oxidative stress and inflammation. CONCLUSIONS: Chronic intermittent hypoxia can aggravate motor neuronal death, neuromuscular weakness, and probably cognitive dysfunction in ALS mice. The generation of oxidative stress with activation of inflammatory pathways may be associated with this mechanism. Our study will provide insight into the association of hypoxia with disease progression, and in turn, the rationale for an early non-invasive ventilation treatment in

  2. Migraine: etiology, risk, triggering, aggravating factors and clinical manifestations

    Directory of Open Access Journals (Sweden)

    Natalia Lindemann Carezzato


    Full Text Available This study aimed to identify the etiology and clinical manifestations of migraine. An integrative literature review was performed guided by the question: What is the evidence available in the literature about the etiology, signs and symptoms of migraine? The article search was conducted in the electronic databases PubMed and LILACS, considering publications in the period from 2006 to 2010. The selected articles were categorized and evaluated according to the level of evidence. One found 1,677 articles and 26 were selected for full reading. Most studies (84.6% consisted of a non-experimental design and were classified as evidence level IV. Although the clinical manifestations found in this study confirm the data available in the literature, it is noticed that migraine does not have well-established causes

  3. Moderate alcohol consumption aggravates high fat-diet induced steatohepatitis in rats (United States)

    Background: Nonalcoholic steatohepatitis (NASH) develops in the absence of chronic and excessive alcohol consumption. However, it remains unknown whether moderate alcohol consumption aggravates liver inflammation in pre-existing NASH condition. Methods: Sprague-Dawley rats were first fed ad libitum...

  4. Aggravation and Stress in Parenting: Associations with Coparenting and Father Engagement among Resident Fathers (United States)

    Bronte-Tinkew, Jacinta; Horowitz, Allison; Carrano, Jennifer


    This study uses a sample of 2,139 resident biological fathers from the Fragile Families and Child Wellbeing surveys (baseline and 12-month follow-up), to examine whether paternal aggravation and stress in parenting is associated with father engagement and coparenting and whether this association differs by father's socioeconomic status. Results of…

  5. Metabolic response to various beta-adrenoceptor agonists in beta3-adrenoceptor knockout mice: evidence for a new beta-adrenergic receptor in brown adipose tissue. (United States)

    Preitner, F; Muzzin, P; Revelli, J P; Seydoux, J; Galitzky, J; Berlan, M; Lafontan, M; Giacobino, J P


    The beta3-adrenoceptor plays an important role in the adrenergic response of brown and white adipose tissues (BAT and WAT). In this study, in vitro metabolic responses to beta-adrenoceptor stimulation were compared in adipose tissues of beta3-adrenoceptor knockout and wild type mice. The measured parameters were BAT fragment oxygen uptake (MO2) and isolated white adipocyte lipolysis. In BAT of wild type mice (-)-norepinephrine maximally stimulated MO2 4.1+/-0.8 fold. Similar maximal stimulations were obtained with beta1-, beta2- or beta3-adrenoceptor selective agonists (dobutamine 5.1+/-0.3, terbutaline 5.3+/-0.3 and CL 316,243 4.8+/-0.9 fold, respectively); in BAT of beta3-adrenoceptor knockout mice, the beta1- and beta2-responses were fully conserved. In BAT of wild type mice, the beta1/beta2-antagonist and beta3-partial agonist CGP 12177 elicited a maximal MO2 response (4.7+/-0.4 fold). In beta3-adrenoceptor knockout BAT, this response was fully conserved despite an absence of response to CL 316,243. This unexpected result suggests that an atypical beta-adrenoceptor, distinct from the beta1-, beta2- and beta3-subtypes and referred to as a putative beta4-adrenoceptor is present in BAT and that it can mediate in vitro a maximal MO2 stimulation. In isolated white adipocytes of wild type mice, (-)-epinephrine maximally stimulated lipolysis 12.1+/-2.6 fold. Similar maximal stimulations were obtained with beta1-, beta2- or beta3-adrenoceptor selective agonists (TO509 12+/-2, procaterol 11+/-3, CL 316,243 11+/-3 fold, respectively) or with CGP 12177 (7.1+/-1.5 fold). In isolated white adipocytes of beta3-adrenoceptor knockout mice, the lipolytic responses to (-)epinephrine, to the beta1-, beta2-, beta3-adrenoceptor selective agonists and to CGP 12177 were almost or totally depressed, whereas those to ACTH, forskolin and dibutyryl cyclic AMP were conserved.

  6. Immunohistochemical localization of integrin alpha V beta 3 and osteopontin suggests that they do not interact during embryo implantation in ruminants

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    MacLaren Leslie A


    Full Text Available Abstract Background It has been suggested that trophoblast attachment requires co-expression of integrin alpha V beta 3 and its ligand osteopontin at the fetal-maternal interface. Until now the expression patterns of integrin alpha V beta 3 and osteopontin in the pregnant bovine uterus were unknown. The objectives of this study were to localize integrin alpha V beta 3 and osteopontin in bovine and sheep endometrium during the periimplantation period and to compare the distribution patterns using antibodies that had not yet been tested in sheep. Methods Cell compartments within endometrial tissue sections were scored for immunohistochemical staining intensity and data were analyzed to determine the effects of day of pregnancy or cycle. Results In pregnant bovine endometrium, integrin alpha V beta 3 was detected in luminal epithelium, stroma, myometrium and smooth muscle. A strong band of immunoreactivity was observed in the subepithelial stroma of intercaruncular regions, but there was reduced reactivity in the caruncles and glands. Bovine trophoblast did not express integrin alpha V beta 3 at any stage of pregnancy. In ovine endometrium a different pattern of staining for integrin alpha V beta 3 was observed. Reactivity was not present in the luminal epithelium or trophoblast. There was strong staining of the deep glands and no reactivity in the superficial glands. Osteopontin distribution was similar for sheep and cattle. For both species, apical staining was present on the luminal epithelium and glands and on embryonic tissues. Conclusion In ruminants, integrin alpha V beta 3 and osteopontin do not co-localize at the fetal-maternal interface indicating that these proteins could not interact to facilitate embryo attachment as has been proposed in other species.

  7. Polymorphism at the ovine beta3-adrenergic receptor locus: associations with birth weight, growth rate, carcass composition and cold survival. (United States)

    Forrest, R H; Hickford, J G H; Hogan, A; Frampton, C


    The beta3-adrenergic receptors (ADRB3s) are predominantly found on the surface of adipocytes and are the major mediators of the lipolytic and thermogenic effects of high catecholamine concentrations. Polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) analysis of part of the ovine beta3-adrenergic receptor gene (ADRB3) intron was used to screen 12 large Merino half-sib families for sequence variation. Six different alleles that segregated in a Mendelian fashion were observed. The genetic basis for the allelic differences were identified by sequencing the ADRB3 (coding and non-coding regions) from animals that were homozygous for each of the alleles. Five sire lines (two Merino x Merino, two Merino x Coopworth, one Dorset Down x Coopworth) provided phenotypic and genotypic data used to ascertain the effects of allelic variation at the ADRB3 locus on birth weight, weaning weight, growth rate (up until weaning), carcass composition at 63 days post-weaning and cold survival. Statistical analyses within each half-sib family showed that in some sire lines (S13, S15, and S17) the inheritance of a particular allele was associated with increased birth weights and/or increased growth rates up until weaning. The inheritance of a particular sire allele was associated with fatter carcasses in sire line S16. Chi-squared analysis revealed the association of the E allele with cold survival and the D allele with cold-related mortality in sire line S14. Such associations support the hypothesis that ADRB3s are involved in energy homeostasis. With more research, the variation detected at the ADRB3 locus may assist in the genetic selection for desirable animal production traits.

  8. Residential characteristics aggravating infestation by Culex quinquefasciatus in a region of Northeastern Brazil

    Directory of Open Access Journals (Sweden)

    Juliana Cavalcanti Correia


    Full Text Available OBJECTIVE: Analyse how basic sanitation conditions, water supply and housing conditions affect the concentration of Culex quinquefasciatus METHODS: Populations of C. quinquefasciatus in 61 houses in the municipality of Olinda, PE, were monitored between October 2009 and October 2010. Observations were carried out in homes without the presence of preferred breeding sites in order to identify characteristics that may be aggravating factors for the development of the mosquito. Five aggravating factors were analysed: vegetation cover surrounding the home, number of residents/home, water storage, sewage drainage and water drainage. These characteristics were analysed in terms of presence or absence and as indicators of the degree of infestation, which was estimated through monitoring the concentration of eggs (oviposition traps - BR-OVT and adults (CDC light traps. RESULTS: Sewage drainage to a rudimentary septic tank or to the open air was the most frequent aggravating factor in the homes (91.8%, although the presence of vegetation was the only characteristic that significantly influenced the increase in the number of egg rafts (p = 0.02. The BR-OVT achieved positive results in 95.1% of the evaluations, with the presence of at least one egg raft per month. A total of 2,366 adults were caught, with a mosquito/room/night ratio of 32.9. No significant difference was found in the number of mosquitoes caught in the homes. CONCLUSIONS: Although the sanitation and water supply influence the population density of C. quinquefasciatus, residence features that are not usually considered in control measures can be aggravating factors in sustaining the mosquito population.

  9. Energy expenditure, body composition and insulin response to glucose in male twins discordant for the Trp64Arg polymorphism of the beta3-adrenergic receptor gene

    DEFF Research Database (Denmark)

    Højlund, K; Christiansen, C; Bjørnsbo, K S;


    and environmental background, the Trp64Arg polymorphism of the beta3AR gene is associated with lower fat mass, fasting insulin levels and an appropriate insulin response to glucose. Thus, heterozygosity for the Trp64Arg variant is unlikely to increase the risk of obesity, insulin resistance or type 2 diabetes.......AIM: The tryptophan to arginine change in position 64 (Trp64Arg) polymorphism of the beta3-adrenergic receptor (beta3AR) gene has been associated with an increased prevalence of obesity, insulin resistance and type 2 diabetes. In this, decreased rates of energy expenditure and impaired insulin......-ray absorptiometry scanning and energy expenditure by indirect and direct calorimetry. RESULTS: Twins heterozygous for the Trp64Arg polymorphism showed significantly lower fat mass independent of the method used, and significantly lower fasting insulin and glucose concentrations compared with their homozygous wild...

  10. Aggravation of nonalcoholic steatohepatitis by moderate alcohol consumption is associated with decreased SIRT1 activity in rats (United States)

    Chronic alcohol intake decreases adiponectin and sirtuin 1 (SIRT1) expressions, both of which have been implicated in various biological processes including inflammation, apoptosis and metabolism. We have previously shown that moderate consumption of alcohol aggravates liver inflammation and apoptos...

  11. Rhodamine-labeled 2beta-carbomethoxy-3beta-(3,4-dichlorophenyl)tropane analogues as high-affinity fluorescent probes for the dopamine transporter

    DEFF Research Database (Denmark)

    Cha, Joo Hwan; Zou, Mu-Fa; Adkins, Erika M


    Novel fluorescent ligands were synthesized to identify a high-affinity probe that would enable visualization of the dopamine transporter (DAT) in living cells. Fluorescent tags were extended from the N- or 2-position of 2beta-carbomethoxy-3beta-(3,4-dichlorophenyl)tropane, using an ethylamino lin...

  12. Lack of associations between serum leptin, a polymorphism in the gene for the beta(3)-adrenergic receptor and glucose tolerance in the Dutch population.

    NARCIS (Netherlands)

    Janssen, JAMJL; Koper, JW; Stolk, RP; Englaro, P; Uitterlinden, AG; Huang, Q; van Leeuwen, JPTM; Blum, WF; Attanasio, AMF; Pols, HAP; Grobbee, DE; de Jong, FH; Lamberts, SWJ


    BACKGROUND The associations between leptin levels and the prevalence of a polymorphism in the beta(3)-adrenergic receptor were studied in a cross-sectional analysis of 600 participants in a population-based study, which were stratified for glucose tolerance by an oral glucose tolerance test. METHODS

  13. Leptin upregulates beta3-integrin expression and interleukin-1beta, upregulates leptin and leptin receptor expression in human endometrial epithelial cell cultures. (United States)

    Gonzalez, R R; Leavis, P


    Human endometrium and endometrial epithelial cells (EECs) either cultured alone or cocultured with human embryos express leptin and leptin receptor. This study compares the effect of leptin with that of interleukin-1beta (IL-1beta) on the expression of beta3-EEC integrin, a marker of endometrial receptivity. Both cytokines increased the expression of beta3-EEC at concentrations in the range of 0.06-3 nM; however, leptin exhibited a significantly greater effect than IL-1beta. We also determined the regulatory effects of IL-1beta on leptin secretion and on the expression of leptin and leptin receptor at the protein level in both EEC and endometrial stromal cell (ESC) cultures. In EEC cultures, IL-1beta upregulated secretion of leptin and expression of both leptin and leptin receptors. No effect of IL-1beta was found in the ESC cultures. However, leptin exhibited marginal upregulation of leptin receptor. The upregulation of beta3-integrin and leptin/leptin receptor expression by IL-1beta in EEC cultures indicates that both cytokines may be implicated in embryonic-maternal cross-talk during the early phase of human implantation. Our present data also raise the possibility that leptin is an endometrial molecular effector of IL-1beta action on beta3-integrin upregulation. Thus, a new role for leptin in human reproduction as an autocrine/paracrine regulator of endometrial receptivity is proposed.

  14. Expression of the wild-type and the Cys-/Trp-less alpha 3 beta 3 gamma complex of thermophilic F1-ATPase in Escherichia coli. (United States)

    Matsui, T; Yoshida, M


    The alpha, beta and gamma subunits of F1-ATPase from thermophilic Bacillus PS3 were expressed in Escherichia coli cells simultaneously in large amounts. Most of the expressed subunits assembled into a form of alpha 3 beta 3 gamma complex in E. coli cells and this complex was easily purified to homogeneity. The recombinant alpha 3 beta 3 gamma complex thus obtained showed similar enzymatic properties to the alpha 3 beta 3 gamma complex obtained by in vitro reconstitution from individual subunits (Yokoyama, K. et al. (1989) J. Biol. Chem. 264, 21837-21841) except that the former had several-fold higher ATPase activity than the latter. Using this expression system, a mutant alpha 3 beta 3 gamma complex with no Trp and Cys was generated by replacing alpha Cys193 and alpha Trp463 with Ser and Phe, respectively. This mutant complex was functionally intact, indicating both residues are not essential for catalysis. The Cys-/Trp-less complex is a convenient 'second wild type' enzyme from which one can generate mutants with Trp (as a fluorescent probe) or Cys (as an acceptor of a variety of probes) at desired positions without concern for 'background' Trp and Cys residues.

  15. Role of beta-adrenoceptors in memory consolidation: beta3-adrenoceptors act on glucose uptake and beta2-adrenoceptors on glycogenolysis. (United States)

    Gibbs, Marie E; Hutchinson, Dana S; Summers, Roger J


    Noradrenaline, acting via beta(2)- and beta(3)-adrenoceptors (AR), enhances memory formation in single trial-discriminated avoidance learning in day-old chicks by mechanisms involving changes in metabolism of glucose and/or glycogen. Earlier studies of memory consolidation in chicks implicated beta(3)- rather than beta(2)-ARs in enhancement of memory consolidation by glucose, but did not elucidate whether stimulation of glucose uptake or of glycolysis was responsible. This study examines the role of glucose transport in memory formation using central injection of the nonselective facilitative glucose transporter (GLUT) inhibitor cytochalasin B, the endothelial/astrocytic GLUT-1 inhibitor phloretin and the Na(+)/energy-dependent endothelial glucose transporter (SGLT) inhibitor phlorizin. Cytochalasin B inhibited memory when injected into the mesopallium (avian cortex) either close to or between 25 and 45 min after training, whereas phloretin and phlorizin only inhibited memory at 30 min. This suggested that astrocytic/endothelial (GLUT-1) transport is critical at the time of consolidation, whereas a different transporter, probably the neuronal glucose transporter (GLUT-3), is important at the time of training. Inhibition of glucose transport by cytochalasin B, phloretin, or phlorizin also interfered with beta(3)-AR-mediated memory enhancement 20 min posttraining, whereas inhibition of glycogenolysis interfered with beta(2)-AR agonist enhancement of memory. We conclude that in astrocytes (1) activities of both GLUT-1 and SGLT are essential for memory consolidation 30 min posttraining; (2) neuronal GLUT-3 is essential at the time of training; and (3) beta(2)- and beta(3)-ARs consolidate memory by different mechanisms; beta(3)-ARs stimulate central glucose transport, whereas beta(2)-ARs stimulate central glycogenolysis.

  16. Sodium chloride promotes pro-inflammatory macrophage polarization thereby aggravating CNS autoimmunity. (United States)

    Hucke, Stephanie; Eschborn, Melanie; Liebmann, Marie; Herold, Martin; Freise, Nicole; Engbers, Annika; Ehling, Petra; Meuth, Sven G; Roth, Johannes; Kuhlmann, Tanja; Wiendl, Heinz; Klotz, Luisa


    The increasing incidence in Multiple Sclerosis (MS) during the last decades in industrialized countries might be linked to a change in dietary habits. Nowadays, enhanced salt content is an important characteristic of Western diet and increased dietary salt (NaCl) intake promotes pathogenic T cell responses contributing to central nervous system (CNS) autoimmunity. Given the importance of macrophage responses for CNS disease propagation, we addressed the influence of salt consumption on macrophage responses in CNS autoimmunity. We observed that EAE-diseased mice receiving a NaCl-high diet showed strongly enhanced macrophage infiltration and activation within the CNS accompanied by disease aggravation during the effector phase of EAE. NaCl treatment of macrophages elicited a strong pro-inflammatory phenotype characterized by enhanced pro-inflammatory cytokine production, increased expression of immune-stimulatory molecules, and an antigen-independent boost of T cell proliferation. This NaCl-induced pro-inflammatory macrophage phenotype was accompanied by increased activation of NF-kB and MAPK signaling pathways. The pathogenic relevance of NaCl-conditioned macrophages is illustrated by the finding that transfer into EAE-diseased animals resulted in significant disease aggravation compared to untreated macrophages. Importantly, also in human monocytes, NaCl promoted a pro-inflammatory phenotype that enhanced human T cell proliferation. Taken together, high dietary salt intake promotes pro-inflammatory macrophages that aggravate CNS autoimmunity. Together with other studies, these results underline the need to further determine the relevance of increased dietary salt intake for MS disease severity.

  17. Viola Playing May Be a Strong Aggravating Factor for Temporomandibular Disorder

    Directory of Open Access Journals (Sweden)

    Mahmut Alpayci


    Full Text Available Temporomandibular disorder (TMD is the general term used to describe the symptoms originated from temporomandibular joint region. The most common symptom of the disorder is pain during mandibular movement. Etiology of TMD is multifactorial. Several factors such as trauma, occlusal discrepancies, stress, parafunctions, hypermobility, and heredity can make one more vulnerable to this disorder. It has been reported that viola playing might be a predisposing factor for TMD. In this article, we present a 24 year old male patient suffering from TMD symptoms exacerbated by viola playing and emphasize that viola playing may be a powerful aggravating factor for TMD.

  18. Environmental air pollution is an aggravating event for sudden unexpected death in epilepsy

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    Carla A. Scorza


    Full Text Available It is extremely difficult to estimate the occurrence of sudden unexpected death in epilepsy (SUDEP. On the other hand, discovering and carefully evaluating new risk factors that may contribute to the onset of cardiovascular abnormalities in people with refractory epilepsy may prevent fatal events in these individuals. In this context, we should not ignore that urban air pollution is a leading problem for environmental health and is able to cause serious cardiovascular dysfunctions that culminate in sudden death. In this regard, we aimed to determine whether environmental exposure to air pollution is an aggravating event for SUDEP.

  19. Hyperglycemia Aggravates Hepatic Ischemia Reperfusion Injury by Inducing Chronic Oxidative Stress and Inflammation

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    Yihan Zhang


    Full Text Available Aim. To investigate whether hyperglycemia will aggravate hepatic ischemia reperfusion injury (HIRI and the underlying mechanisms. Methods. Control and streptozotocin-induced diabetic Sprague-Dawley rats were subjected to partial hepatic ischemia reperfusion. Liver histology, transferase, inflammatory cytokines, and oxidative stress were assessed accordingly. Similarly, BRL-3A hepatocytes were subjected to hypoxia/reoxygenation (H/R after high (25 mM or low (5.5 mM glucose culture. Cell viability, reactive oxygen species (ROS, and activation of nuclear factor-erythroid 2-related factor 2 (Nrf2 and nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-κB were determined. Results. Compared with control, diabetic rats presented more severe hepatic injury and increased hepatic inflammatory cytokines and oxidative stress. HIRI in diabetic rats could be ameliorated by pretreatment of N-acetyl-L-cysteine (NAC or apocynin. Excessive ROS generation and consequent Nrf2 and NF-κB translocation were determined after high glucose exposure. NF-κB translocation and its downstream cytokines were further increased in high glucose cultured group after H/R. While proper regulation of Nrf2 to its downstream antioxidases was observed in low glucose cultured group, no further induction of Nrf2 pathway by H/R after high glucose culture was identified. Conclusion. Hyperglycemia aggravates HIRI, which might be attributed to chronic oxidative stress and inflammation and potential malfunction of antioxidative system.

  20. Orally delivered β-glucans aggravate dextran sulfate sodium (DSS)-induced intestinal inflammation. (United States)

    Heinsbroek, Sigrid E M; Williams, David L; Welting, Olaf; Meijer, Sybren L; Gordon, Siamon; de Jonge, Wouter J


    β-Glucans have beneficial health effects due to their immune modulatory properties. Oral administration of β-glucans affects tumour growth, microbial infection, sepsis, and wound healing. We hypothesized that pre-treatment with orally delivered soluble and particulate β-glucans could ameliorate the development of aggravate dextran sulfate sodium (DSS) induced intestinal inflammation. To study this, mice were orally pre-treated with β-glucans for 14 days. We tested curdlan (a particulate β-(1,3)-glucan), glucan phosphate (a soluble β-(1,3)-glucan), and zymosan (a particle made from Saccharomyces cerevisiae, which contains around 55% β-glucans). Weight loss, colon weight, and feces score did not differ between β-glucan and vehicle treated groups. However, histology scores indicated that β-glucan-treated mice had increased inflammation at a microscopic level suggesting that β-glucan treatment worsened intestinal inflammation. Furthermore, curdlan and zymosan treatment led to increased colonic levels of inflammatory cytokines and chemokines, compared to vehicle. Glucan phosphate treatment did not significantly affect cytokine and chemokine levels. These data suggest that particulate and soluble β-glucans differentially affect the intestinal immune responses. However, no significant differences in other clinical colitis scores between soluble and particulate β-glucans were found in this study. In summary, β-glucans aggravate the course of dextran sulfate sodium (DSS)-induced intestinal inflammation at the level of the mucosa.

  1. Consumption of Mercury-contaminated Rice Induces Oxidative Stress and Free Radical Aggravation in Rats

    Institute of Scientific and Technical Information of China (English)



    Objective To study the oxidative stress induced by consumption of mercury-contaminated rice in rats, and to assess the possible public health risk of mercury contamination in Wanshan mining area. Methods Sprague Dawley rats were fed the mercury-contaminated rice produced from Wanshan area for 90 days. The antioxidant status and the free radicals in rat serum were evaluated. Results High mercury accumulation in organs of rats fed the mercury-contaminated rice confirmed the server pollution of mercury in Wanshan mining area. The intensity of electron spin resonance (ESR) signal increased by 87.38% in rats fed the rice from Wanshan compared with that in the control rats fed the rice from Shanghai, suggesting that chronic dietary consumption of rice from mercury mining area could induce an aggravation of free radicals. Feeding the mercury-contaminated rice was associated with significant decreases in the antioxidant enzymatic activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and concentration of serum nitric oxide (NO), but it had no effect on serum nitric oxide synthase (NOS) activity. Feeding the mercury-contaminated rice raised the level of serum malonyldialdehyde (MDA), indicating the occurrence of oxidative stress. Conclusion The long-term dietary consumption of mercury-contaminated rice induces the aggravation of free radicals and exerts oxidative stress.

  2. Chronic hypertension aggravates heat stress-induced brain damage: possible neuroprotection by cerebrolysin. (United States)

    Muresanu, Dafin Fior; Zimmermann-Meinzingen, Sibilla; Sharma, Hari Shanker


    Whole body hyperthermia (WBH) aggravates brain edema formation and cell damage in chronic hypertensive rats compared with normotensive animals. In this investigation, we examined the influence of cerebrolysin on WBH-induced edema formation and brain pathology in hypertensive and normotensive rats. Rats subjected to 4 h WBH at 38 degrees C in a biological oxygen demand (BOD) incubator showed breakdown of the blood-brain barrier (BBB), reduced cerebral blood flow (CBF), edema formation and cell injuries in several parts of the brain. These effects were further aggravated in chronic hypertensive rats (two-kidney one clip model (2K1C), for 4 weeks) subjected to WBH. Pretreatment with cerebrolysin (5 mL/kg, 24 h and 30 min before heat stress) markedly attenuated the BBB dysfunction and brain pathology in normal animals. However, in hypertensive animals, a high dose of cerebrolysin (10 mL/kg, 24 h and 30 min before heat stress) was needed to attenuate WBH-induced BBB dysfunction and brain pathology. These observations indicate that heat stress could affect differently in normal and hypertensive conditions. Furthermore, our results suggest that patients suffering from various chronic cardiovascular diseases may respond differently to hyperthermia and to neuroprotective drugs, e.g., cerebrolysin not reported earlier.

  3. Inhibition of caspase-9 aggravates acute liver injury through suppression of cytoprotective autophagy (United States)

    Guo, Rui; Lin, Bin; Pan, Jing Fei; Liong, Emily C.; Xu, Ai Min; Youdim, Moussa; Fung, Man Lung; So, Kwok Fai; Tipoe, George L.


    Acute liver disease is characterized by inflammation, oxidative stress and necrosis, which can greatly influence the long term clinical outcome and lead to liver failure or cancer. Here, we initially demonstrated the beneficial role of caspase-9-dependent autophagy in acute liver injury. Treatment with caspase-9 inhibitor z-LEHD-FMK in HepG2 cells, AML12 cells and C57BL/b6N mice exacerbated CCl4-induced acute hepatocellular damage, and also down-regulated autophagy markers expression levels, indicating that caspase-9 inhibition may aggravate acute liver damage by suppressing cytoprotective autophagy. CCl4 was used as an acute liver injury inducer which caused oxidative stress and apoptosis through up-regulation of HIF-1α, as well as triggered hepatic inflammation and necroptosis via TLR4/NF-κB pathway. Caspase-9 Thr125 site was firstly phosphorylated by ERK1/2 which subsequently activated the cytoprotective autophagy process to attenuate acute CCl4 injury. Caspase-9 inhibition further aggravated hepatic necroptosis through NF-κB expression, leading to increased pro-inflammatory mediators levels, suggesting a protective role of caspase-9-dependent autophagy in the inflammatory process as well as its possibility being a new therapeutic target for the treatment of acute liver injury. PMID:27580936

  4. An Atherogenic Paigen-Diet Aggravates Nephropathy in Type 2 Diabetic OLETF Rats.

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    Masanori Nozako

    Full Text Available Diabetic nephropathy develops in association with hyperglycemia, is aggravated by atherogenic factors such as dyslipidemia, and is sometimes initiated before obvious hyperglycemia is seen. However, the precise mechanisms of progression are still unclear. In this study, we investigated the influence of an atherogenic Paigen diet (PD on the progression of nephropathy in spontaneous type 2 diabetic OLETF rats. Feeding PD to male OLETF rats for 12 weeks caused an extensive increase in excretion of urinary albumin and markers of tubular injury such as KIM-1 and L-FABP, accompanied by mesangial expansion and tubular atrophy. PD significantly increased plasma total cholesterol concentration, which correlates well with increases in urine albumin excretion and mesangial expansion. Conversely, PD did not change plasma glucose and free fatty acid concentrations. PD enhanced renal levels of mRNA for inflammatory molecules such as KIM-1, MCP-1, TLR4 and TNF-α and promoted macrophage infiltration and lipid accumulation in the tubulointerstitium and glomeruli in OLETF rats. Intriguingly, PD had little effect on urine albumin excretion and renal morphology in normal control LETO rats. This model may be useful in studying the complex mechanisms that aggravate diabetic nephropathy in an atherogenic environment.

  5. An Atherogenic Paigen-Diet Aggravates Nephropathy in Type 2 Diabetic OLETF Rats (United States)

    Nozako, Masanori; Koyama, Takashi; Nagano, Chifumi; Sato, Makoto; Matsumoto, Satoshi; Mitani, Kiminobu; Yasufuku, Reiko; Kohashi, Masayuki; Yoshikawa, Tomohiro


    Diabetic nephropathy develops in association with hyperglycemia, is aggravated by atherogenic factors such as dyslipidemia, and is sometimes initiated before obvious hyperglycemia is seen. However, the precise mechanisms of progression are still unclear. In this study, we investigated the influence of an atherogenic Paigen diet (PD) on the progression of nephropathy in spontaneous type 2 diabetic OLETF rats. Feeding PD to male OLETF rats for 12 weeks caused an extensive increase in excretion of urinary albumin and markers of tubular injury such as KIM-1 and L-FABP, accompanied by mesangial expansion and tubular atrophy. PD significantly increased plasma total cholesterol concentration, which correlates well with increases in urine albumin excretion and mesangial expansion. Conversely, PD did not change plasma glucose and free fatty acid concentrations. PD enhanced renal levels of mRNA for inflammatory molecules such as KIM-1, MCP-1, TLR4 and TNF-α and promoted macrophage infiltration and lipid accumulation in the tubulointerstitium and glomeruli in OLETF rats. Intriguingly, PD had little effect on urine albumin excretion and renal morphology in normal control LETO rats. This model may be useful in studying the complex mechanisms that aggravate diabetic nephropathy in an atherogenic environment. PMID:26606054

  6. Mesenchymal stromal cell implantation for stimulation of long bone healing aggravates Staphylococcus aureus induced osteomyelitis. (United States)

    Seebach, Elisabeth; Holschbach, Jeannine; Buchta, Nicole; Bitsch, Rudi Georg; Kleinschmidt, Kerstin; Richter, Wiltrud


    Large bone defects requiring long-term osteosynthetic stabilization or repeated surgeries show a considerable rate of infection. Mesenchymal stromal cells (MSCs) have been successfully used to enhance bone regeneration, but their powerful immunomodulatory effects may impose an enhanced risk for osteomyelitis development. In order to unravel whether implantation of MSCs aggravates a simultaneous bone infection, a hydrogel-supported osteomyelitis ostectomy model was developed in which rats received a femoral bone defect with rigid plate-fixation. After fibrin-assisted transfer of Staphylococcus aureus (SA), effects of MSC implantation on osteomyelitis development were quantified over 3-4 weeks. All SA-infected animals developed an acute local osteomyelitis with significantly increased blood neutrophil count, abscess formation and bone destruction. MSC-treatment of infected defects aggravated osteomyelitis according to a significantly elevated osteomyelitis score and enhanced distal bone loss with spongy alteration of cortical bone architecture. Increased attraction of macrophages, osteoclasts and regulation of pro- and anti-inflammatory mediators were potential MSC actions. Overall trophic actions of MSCs implanted into non-sterile bone defects may enhance an infection and/or exacerbate osteomyelitis. Studies on antibiotic carrier augmentation or antibiotic treatment are warranted to decide whether MSC implantation is a safe and promising therapy for orthopedic implant-stabilized bone defects at high risk for development of infection.

  7. Serotonin Transporter (5-HTT) and gamma-Aminobutyric Acid Receptor Subunit beta3 (GABRB3) Gene Polymorphisms are not Associated with Autism in the IMGSA Families

    DEFF Research Database (Denmark)

    Maestrini, E.; Lai, C.; Marlow, A.;


    Previous studies have suggested that the serotonin transporter (5-HTT) gene and the gamma-aminobutyric acid receptor subunit beta3 (GABRB3) gene, or other genes in the 15q11-q13 region, are possibly involved in susceptibility to autism. To test this hypothesis we performed an association study...... and the GABRB3 genes are unlikely to play a major role in the aetiology of autism in our family data set....

  8. Endogenous IGF-I and alpha v beta3 integrin ligands regulate increased smooth muscle growth in TNBS-induced colitis. (United States)

    Hazelgrove, Krystina B; Flynn, Robert S; Qiao, Li-Ya; Grider, John R; Kuemmerle, John F


    Endogenous insulin-like growth factor-I (IGF-I) regulates intestinal smooth muscle growth by concomitantly stimulating proliferation and inhibiting apoptosis. IGF-I-stimulated growth is augmented by the alpha(v)beta(3) integrin ligands vitronectin and fibronectin. IGF-I expression in smooth muscle is increased in both TNBS-induced colitis and Crohn's disease. We hypothesized that intestinal inflammation increased vitronectin and fibronectin expression by smooth muscle and, along with IGF-I upregulation, increased intestinal muscle growth. Intestinal smooth muscle cells were examined 7 days following the induction of TNBS-induced colitis. Although alpha(v)beta(3) integrin expression was not altered by TNBS-induced colitis, vitronectin and fibronectin levels were increased by 80 +/- 10% and 90 +/- 15%, above control levels, respectively. Basal IGF-I receptor phosphorylation in inflamed muscle from TNBS-treated rats was increased by 86 +/- 8% over vehicle-treated controls. Basal ERK1/2, p70S6 kinase, and GSK-3beta phosphorylation in muscle cells of TNBS-treated rats were also increased by 140-180%. TNBS treatment increased basal muscle cell proliferation by 130 +/- 15% and decreased apoptosis by 20 +/- 2% compared with that in vehicle-treated controls. The changes in proliferation and apoptosis were reversed by an IGF-I receptor tyrosine kinase inhibitor or an alpha(v)beta(3) integrin antagonist. The results suggest that smooth muscle hyperplasia in TNBS-induced colitis partly results from the upregulation of endogenous IGF-I and ligands of alpha(v)beta(3) integrin that mediate increased smooth muscle cell proliferation and decreased apoptosis. This paper has identified one mechanism regulating smooth muscle hyperplasia, a feature of stricture formation that occurs in the chronically inflamed intestine of TNBS-induced colitis and potentially Crohn's disease.

  9. Effects of the perfusion of beta-, beta2-, or beta3-adrenergic agonists or epinephrine on in situ adipose tissue lipolysis measured by microdialysis in underfed ewes. (United States)

    Ferlay, A; Charret, C; Galitzky, J; Berlan, M; Chilliard, Y


    The effects of isoproterenol (ISO, a non-selective beta-agonist), terbutaline (TER, a selective beta2-agonist), CL316243 (CL, a selective beta3-agonist), and epinephrine (EPI, beta- and alpha2-agonist) on in situ lipolytic response of s.c. adipose tissue were investigated in vivo, using a microdialysis method to measure glycerol release, in 12 adult nonlactating and ovariectomized, underfed Lacaune ewes. All the adrenergic compounds were perfused for 120 min at 10(-6), 10(-5), and 10(-4) M. They had no lipolytic effect at 10(-6) M. Isoproterenol and EPI at 10(-5) and 10(-4) M enhanced, in the same way, maximal response and area under the concentration curve (AUC) of dialysate glycerol, thus suggesting that involvement of alpha2-adrenoceptors in the control of in situ lipolysis is of minor importance in underfed ewes. Terbutaline had only a slight lipolytic effect at 10(-5) M. This low effect could be due to a lower affinity of TER than of ISO for the beta2-adrenoceptors. The beta3-agonist, CL, had no lipolytic effect whatever the concentration perfused. Further studies are needed to prove the putative presence of beta3-adrenoceptors and their possible role in the ovine adipose tissue.

  10. Acute patellofemoral pain: aggravating activities, clinical examination, MRI and ultrasound findings

    DEFF Research Database (Denmark)

    Brushoj, C.; Holmich, P.; Nielsen, M.B.;


    Objective: To investigate acute anterior knee pain caused by overuse in terms of pain location, aggravating activities, findings on clinical examination and ultrasound/MRI examination. To determine if acute anterior knee pain caused by overuse should be classified as a subgroup of patellofemoral...... pain syndrome (PFPS). Methods: In a observational study design 30 army recruits with anterior knee pain (mean duration of pain 4 weeks) were examined using the PFPS pain severity scale (PSS), knee pain diagrams, standardised clinical examination, ultrasound and MRI examinations. Results: On PSS typical......%)), but other synovial covered structures including the fat pad of Hoffa (12 patients (40%)), the medial plica and the joint line (12 patients (40%)) were also involved. Only eight patients (27%) experienced pain on the patellofemoral compression test. Only discrete changes was detected on MRI...

  11. Obesity does not aggravate vitrification injury in mouse embryos: a prospective study

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    Ma Wenhong


    Full Text Available Abstract Background Obesity is associated with poor reproductive outcomes, but few reports have examined thawed embryo transfer in obese women. Many studies have shown that increased lipid accumulation aggravates vitrification injury in porcine and bovine embryos, but oocytes of these species have high lipid contents (63 ng and 161 ng, respectively. Almost nothing is known about lipids in human oocytes except that these cells are anecdotally known to be relatively lipid poor. In this regard, human oocytes are considered to be similar to those of the mouse, which contain approximately 4 ng total lipids/oocyte. To date, no available data show the impact of obesity on vitrification in mouse embryos. The aim of this study was to establish a murine model of maternal diet-induced obesity and to characterize the effect of obesity on vitrification by investigating the survival rate and embryo developmental competence after thawing. Methods Prospective comparisons were performed between six–eight-cell embryos from obese and normal-weight mice and between fresh and vitrified embryos. Female C57BL/6 mice were fed standard rodent chow (normal-weight group or a high-fat diet (obese group for 6 weeks. The mice were mated, zygotes were collected from oviducts and cultured for 3 days, and six–eight-cell embryos were then selected to assess lipid content in fresh embryos and to evaluate differences in apoptosis, survival, and development rates in response to vitrification. Results In fresh embryos from obese mice, the lipid content (0.044 vs 0.030, Pvs.9.3%, Pvs. 93.1%, P Conclusions This study demonstrated that differences in survival and developmental rates between embryos from obese and normal-weight mice were eliminated after vitrification. Thus, maternal obesity does not aggravate vitrification injury, but obesity alone greatly impairs pre-implantation embryo survival and development.

  12. Calreticulin Translocation Aggravates Endoplasmic Reticulum Stress-associated Apoptosis during Cardiomyocyte Hypoxia/Reoxygenation

    Institute of Scientific and Technical Information of China (English)

    Fei-Fei Xu; Xiu-Hua Liu


    Background:Calreticulin (CRT) is major Ca2+-binding chaperone mainly resident in the endoplasmic reticulum (ER) lumen.Recently,it has been shown that non-ER CRT regulates a wide array of cellular responses.We previously found that CRT was up-regulated during hypoxia/reoxygenation (H/R) and this study was aimed to investigate whether CRT nuclear translocation aggravates ER stress (ERS)-associated apoptosis during H/R injury in neonatal rat cardiomyocytes.Methods:Apoptosis rate and lactate dehydrogenase (LDH) leakage in culture medium were measured as indices of cell injury.Immunofluorescence staining showed the morphological changes of ER and intracellular translocation of CRT.Western blotting or reverse transcription polymerase chain reaction was used to detect the expression of target molecules.Results:Compared with control,H/R increased apoptosis rate and LDH activity.The ER became condensed and bubbled,and CRT translocated to the nucleus.Western blotting showed up-regulation of CRT,Nrf2,activating transcription factor 4 (ATF4),CHOP and caspase-12 expression after H/R.Exogenous CRT overexpression induced by plasmid transfection before H/R increased cell apoptosis,LDH leakage,ER disorder,CRT nuclear translocation and the expression of ERS-associated molecules.However,administration of the ERS inhibitor,taurine,or CRT siRNA alleviated cell injury,ER disorder,and inhibited ERS-associated apoptosis.Conclusions:Our results indicated that during H/R stress,CRT translocation increases cell apoptosis and LDH leakage,aggravates ER disorder,up-regulates expression of nuclear transcription factors,Nrf2 and ATF4,and activates ERS-associated apoptosis.

  13. Diabetes mellitus aggravates hemorrhagic transformation after ischemic stroke via mitochondrial defects leading to endothelial apoptosis.

    Directory of Open Access Journals (Sweden)

    Keisuke Mishiro

    Full Text Available Diabetes is a crucial risk factor for stroke and is associated with increased frequency and poor prognosis. Although endothelial dysfunction is a known contributor of stroke, the underlying mechanisms have not been elucidated. The aim of this study was to elucidate the mechanism by which chronic hyperglycemia may contribute to the worsened prognosis following stroke, especially focusing on mitochondrial alterations. We examined the effect of hyperglycemia on hemorrhagic transformation at 24 hours after middle cerebral artery occlusion (MCAO in streptozotocin (STZ -induced diabetic mice. We also examined the effects of high-glucose exposure for 6 days on cell death, mitochondrial functions and morphology in human brain microvascular endothelial cells (HBMVECs or human endothelial cells derived from induced pluripotent stem cells (iCell endothelial cells. Hyperglycemia aggravated hemorrhagic transformation, but not infarction following stroke. High-glucose exposure increased apoptosis, capase-3 activity, and release of apoptosis inducing factor (AIF and cytochrome c in HBMVECs as well as affected mitochondrial functions (decreased cell proliferation, ATP contents, mitochondrial membrane potential, and increased matrix metalloproteinase (MMP-9 activity, but not reactive oxygen species production. Furthermore, morphological aberration of mitochondria was observed in diabetic cells (a great deal of fragmentation, vacuolation, and cristae disruption. A similar phenomena were seen also in iCell endothelial cells. In conclusion, chronic hyperglycemia aggravated hemorrhagic transformation after stroke through mitochondrial dysfunction and morphological alteration, partially via MMP-9 activation, leading to caspase-dependent apoptosis of endothelial cells of diabetic mice. Mitochondria-targeting therapy may be a clinically innovative therapeutic strategy for diabetic complications in the future.

  14. Aggravation of clozapine-induced hepatotoxicity by glycyrrhetinic acid in rats. (United States)

    Jia, Ling-ling; Zhong, Ze-yu; Li, Feng; Ling, Zhao-li; Chen, Yang; Zhao, Wei-man; Li, Ying; Jiang, Shu-wen; Xu, Ping; Yang, Yang; Hu, Meng-yue; Liu, Li; Liu, Xiao-dong


    Clozapine (CLZ) was reported to be associated with hepatotoxicity. Glycyrrhetinic acid (GA) has a liver protective effect. Our preliminary experiments showed that GA aggravated rather than attenuated CLZ-induced hepatotoxicity in primary cultured rat hepatocytes. The study aimed to describe the enhancing effect of GA on CLZ-induced hepatotoxicity in vivo and in vitro. Data from primary cultured rat hepatocytes showed the decreased formation of metabolites demethylclozapine (nor-CLZ) and clozapine N-oxide (CLZ N-oxide). The results in vivo showed that 7-day CLZ treatment led to marked accumulation of triglyceride (TG) and increase in γ-glutamyl transpeptidase (γ-GT) activity, liver weight, and serum AST in rats. Co-administration of GA enhanced the increases in hepatic TG, γ-GT, liver weight, and serum total cholesterol induced by CLZ. GA decreased plasma concentrations of nor-CLZ and CLZ N-oxide. Compared with control rats, hepatic microsomes of GA rats exhibited the decreased formations of nor-CLZ and CLZ N-oxide, accompanied by decreases in activities of CYP2C11 and CYP2C19 and increased activity of CYP1A2. QT-PCR analysis demonstrated that GA enhanced expression of CYP1A2, but suppressed expression of CYP2C11 and CYP2C13. All these results support the conclusion that GA aggravated CLZ-induced hepatotoxicity, which was partly via inhibiting CYP2C11 and CYP2C13 or inducing CYP1A2.

  15. Noninvasive visualization and quantification of tumor {alpha}{sub V{beta}3} integrin expression using a novel positron emission tomography probe, {sup 64}Cu-cyclam-RAFT-c(-RGDfK-){sub 4}

    Energy Technology Data Exchange (ETDEWEB)

    Jin, Zhao-Hui [Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Furukawa, Takako, E-mail: tfuru@nirs.go.j [Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Biomedical Imaging Research Center, University of Fukui, Fukui 910-1193 (Japan); Galibert, Mathieu; Boturyn, Didier [Departement de Chimie Moleculaire, UMR 5250, CNRS-Universite Joseph Fourier, 38041 Grenoble Cedex 9 (France); Coll, Jean-Luc [INSERM U823, Institut Albert Bonniot and Universite Joseph Fourier, 38706 La Tronche Cedex, Grenoble (France); Fukumura, Toshimitsu; Saga, Tsuneo [Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Dumy, Pascal [Departement de Chimie Moleculaire, UMR 5250, CNRS-Universite Joseph Fourier, 38041 Grenoble Cedex 9 (France); Fujibayashi, Yasuhisa [Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Biomedical Imaging Research Center, University of Fukui, Fukui 910-1193 (Japan)


    Introduction: The {alpha}{sub V{beta}3} integrin is a well-known transmembrane receptor involved in tumor invasion, angiogenesis and metastasis. Our aim was to evaluate a novel positron emission tomography (PET) probe, {sup 64}Cu-cyclam-RAFT-c(-RGDfK-){sub 4}, for noninvasive visualization and quantification of {alpha}{sub V{beta}3} integrin expression. Methods: RAFT-c(-RGDfK-){sub 4}, a tetrameric cyclic Arg-Gly-Asp (RGD)-based peptide, was conjugated with a bifunctional chelator, 1,4,8,11-tetraazacyclotetradecane (cyclam), radiolabeled with the positron emitter {sup 64}Cu and evaluated in vitro by cell binding and competitive inhibition assays and in vivo by biodistribution and receptor blocking studies, and PET imaging. The following cell lines, human embryonic kidney HEK293({beta}{sub 1}) [{alpha}{sub V{beta}3}-negative] and HEK293({beta}{sub 3}) [{alpha}{sub V{beta}3}-overexpressing] and human glioblastoma U87MG [naturally expressing {alpha}{sub V{beta}3}], together with their subcutaneous xenografts in athymic nude mice, were used for the present study. The expression levels of {alpha}{sub V{beta}3} on these cell lines and tumor xenografts were analyzed by flow cytometry and sodium dodecyl sulfate-polyacrylamide gel electrophoresis/autoradiography, respectively. Results: {sup 64}Cu-cyclam-RAFT-c(-RGDfK-){sub 4} demonstrated the in vitro and in vivo specificity for the {alpha}{sub V{beta}3} integrin and displayed rapid blood clearance, predominantly renal excretion and low uptake in nontumor tissues. Tumor uptake of {sup 64}Cu-cyclam-RAFT-c(-RGDfK-){sub 4} (3 h postinjection) in HEK293({beta}{sub 3}) (high levels of {alpha}{sub V{beta}3}), U87MG (moderate levels of {alpha}{sub V{beta}3}) and HEK293({beta}{sub 1}) (undetectable levels of {alpha}{sub V{beta}3}) tumors was 9.35%{+-}1.19%, 3.46%{+-}0.45% and 1.18%{+-}0.30% injected dose per gram, respectively, with a strong and positive correlation with the tumor {alpha}{sub V{beta}3} expression levels

  16. Manganese-induced integrin affinity maturation promotes recruitment of alpha V beta 3 integrin to focal adhesions in endothelial cells: evidence for a role of phosphatidylinositol 3-kinase and Src. (United States)

    Dormond, Olivier; Ponsonnet, Lionel; Hasmim, Meriem; Foletti, Alessandro; Rüegg, Curzio


    Integrin activity is controlled by changes in affinity (i.e. ligand binding) and avidity (i.e. receptor clustering). Little is known, however, about the effect of affinity maturation on integrin avidity and on the associated signaling pathways. To study the effect of affinity maturation on integrin avidity, we stimulated human umbilical vein endothelial cells (HUVEC) with MnCl(2) to increase integrin affinity and monitored clustering of beta 1 and beta 3 integrins. In unstimulated HUVEC, beta 1 integrins were present in fibrillar adhesions, while alpha V beta 3 was detected in peripheral focal adhesions. Clustered beta 1 and beta 3 integrins expressed high affinity/ligand-induced binding site (LIBS) epitopes. MnCl(2)-stimulation promoted focal adhesion and actin stress fiber formation at the basal surface of the cells, and strongly enhanced mAb LM609 staining and expression of beta 3 high affinity/LIBS epitopes at focal adhesions. MnCl(2)-induced alpha V beta 3 clustering was blocked by a soluble RGD peptide, by wortmannin and LY294002, two pharmacological inhibitors of phosphatidylinositol 3-kinase (PI 3-K), and by over-expressing a dominant negative PI 3-K mutant protein. Conversely, over-expression of active PI 3-K and pharmacological inhibiton of Src with PP2 and CGP77675, enhanced basal and manganese-induced alpha V beta 3 clustering. Transient increased phosphorylation of protein kinase B/Akt, a direct target of PI 3K, occurred upon manganese stimulation. MnCl(2) did not alter beta 1 integrin distribution or beta1 high-affinity/LIBS epitope expression. Based on these results, we conclude that MnCl(2)-induced alpha V beta 3 integrin affinity maturation stimulates focal adhesion and actin stress fiber formation, and promotes recruitment of high affinity alpha V beta 3 to focal adhesions. Affinity-modulated alpha V beta 3 clustering requires PI3-K signaling and is negatively regulate by Src.

  17. Effect of lysozyme chloride on betel quid chewing aggravated gastric oxidative stress and hemorrhagic ulcer in diabetic rats

    Institute of Scientific and Technical Information of China (English)

    Chen-Road Hung


    AIM: To evaluate the protective effect of lysozyme chloride on betel quid chewing (BQC) aggravated gastric oxidative stress and hemorrhagic ulcer in rats with diabetes mellitus (DM).METHODS: Male Wistar rats were challenged intravenously with streptozotocin (65 mg/kg) to induce DM. Rats were fed with regular pellet food or BQC-containing diets. After 90 d, rats were deprived of food for 24 h. Rat stomachs were irrigated for 3 h with normal saline or simulated gastric juice. Rats were killed and gastric specimens were harvested.RESULTS: An enhancement of various gastric ulcerogenic parameters, including acid back-diffusion, mucosal lipid peroxide generation, as well as decreased glutathione levels and mucus content, were observed in DM rats. After feeding DM rats with BQC, an exacerbation of these ulcerogenic parameters was achieved. Gastric juice caused a further aggravation of these ulcerogenic parameters. Daily intragastric lysozyme chloride dose-dependently inhibited exacerbation of various ulcerogenic parameters in those BQC-fed DM rats.CONCLUSION: (1) Gastric juice could aggravate both DM and BQC-fed DM rat hemorrhagic ulcer; (2) BQC exacerbated gastric hemorrhagic ulcer in DM rats via enhancing oxidative stress and reducing defensive factors; (3) lysozyme chloride effectively protected BQC aggravated gastric damage in DM rats.

  18. Aggravation of Risk and Precautionary Measures in Non-Life Insurance: A Tricky Scope for the Insurer?

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    Olavi-Jüri Luik


    Full Text Available Aggravation of risk and failure to take precautionary measures are focal issues in non-life insurance in terms of potential partial or full release of the insurer from the duty to perform. Not infrequently, it is difficult to draw a line between the aggravation of risk on the one hand, and non-compliance with precautionary measures on the other, since a particular action by a policyholder may present both situations. At the same time, the legal remedies available to the insurer regarding these two situations are different in scope. The aggravation of risk and non-compliance with precautionary measures are precisely the bases on which insurers actually reduce indemnity or refuse to compensate for damages. This article explores the differences between insurance laws in the Baltic states—specifically, the Estonian Law of Obligations Act, the Latvian Insurance Contract Law and Lithuanian rules contained in the Civil Code and Insurance Law. The article explores the differences between the Baltic states’ insurance laws and the Principles of European Insurance Contract Law (PEICL with regard to a policyholder’s duty in relation to aggravation of risk and precautionary measures, as the rights and obligations of policyholders do change where the optional instrument is applied. The article also includes comparisons to German, Finnish and Russian insurance law.

  19. Contributions of Streptococcus mutans Cnm and PA antigens to aggravation of non-alcoholic steatohepatitis in mice (United States)

    Naka, Shuhei; Hatakeyama, Rina; Takashima, Yukiko; Matsumoto-Nakano, Michiyo; Nomura, Ryota; Nakano, Kazuhiko


    Streptococcus mutans, a major pathogen of dental caries, can cause infective endocarditis after invading the bloodstream. Recently, intravenous administration of specific S. mutans strains was shown to aggravate non-alcoholic steatohepatitis (NASH) in a mouse model fed a high-fat diet. Here, we investigated the mechanism of this aggravation in a NASH mouse model by focusing on the S. mutans cell surface collagen-binding protein (Cnm) and the 190-kDa protein antigen (PA). Mice that were intravenously administered a S. mutans strain with a defect in Cnm (TW871CND) or PA (TW871PD) did not show clinical or histopathological signs of NASH aggravation, in contrast to those administered the parent strain TW871. The immunochemical analyses demonstrated higher levels of interferon-γ and metallothionein expression in the TW871 group than in the TW871CND and TW871PD groups. Analysis of bacterial affinity to cultured hepatic cells in the presence of unsaturated fatty acids revealed that the incorporation rate of TW871 was significantly higher than those of TW871CND and TW871PD. Together, our results suggest that Cnm and PA are important cell surface proteins for the NASH aggravation caused by S. mutans adhesion and affinity for hepatic cells. PMID:27833139

  20. Neuronal chloride accumulation and excitatory GABA underlie aggravation of neonatal epileptiform activities by phenobarbital. (United States)

    Nardou, Romain; Yamamoto, Sumii; Chazal, Geneviève; Bhar, Asma; Ferrand, Nadine; Dulac, Olivier; Ben-Ari, Yehezkel; Khalilov, Ilgam


    Phenobarbital produces its anti-epileptic actions by increasing the inhibitory drive of γ-aminobutyric acid. However, following recurrent seizures, γ-aminobutyric acid excites neurons because of a persistent increase of chloride raising the important issue of whether phenobarbital could aggravate persistent seizures. Here we compared the actions of phenobarbital on initial and established ictal-like events in an in vitro model of mirror focus. Using the in vitro three-compartment chamber preparation with the two hippocampi and their commissural fibres placed in three different chambers, kainate was applied to one hippocampus and phenobarbital contralaterally, either after one ictal-like event or after many recurrent ictal-like events that produce an epileptogenic mirror focus. Field, perforated patch and single-channel recordings were used to determine the effects of γ-aminobutyric acid and their modulation by phenobarbital, and alterations of the chloride cotransporters were investigated using sodium-potassium-chloride cotransporter 1 and potassium chloride cotransporter 2 antagonists, potassium chloride cotransporter 2 immunocytochemistry and sodium-potassium-chloride cotransporter 1 knockouts. Phenobarbital reduced initial ictal-like events and prevented the formation of a mirror focus when applied from the start. In contrast, phenobarbital aggravated epileptiform activities when applied after many ictal-like events by enhancing the excitatory actions of γ-aminobutyric acid due to increased chloride. The accumulation of chloride and the excitatory actions of γ-aminobutyric acid in mirror foci neurons are mediated by the sodium-potassium-chloride cotransporter 1 chloride importer and by downregulation and internalization of the chloride-exporter potassium-chloride cotransporter 2. Finally, concomitant applications of the sodium-potassium-chloride cotransporter 1 antagonist bumetanide and phenobarbital decreased excitatory actions of γ-aminobutyric acid and

  1. ERK5 knock down aggravates detrimental effects of hypothermal stimulation on cardiomyocytes via Bim upregulation. (United States)

    Wang, Yao-Sheng; Zhou, Jing; Liang, Chun; Hong, Kui; Cheng, Xiao-Shu; Wu, Zong-Gui


    Mechanism of cold induced myocardial injury remained unclear. Our study investigated the role of ERK5/Bim pathway in hypothermal stimulation-induced apoptosis or damage of cardiomyocytes (CMs). Results showed that in CMs which under hypothermal stimulation, ERK5 siRNA promoted expression of Bim protein. Bim siRNA did not influence ERK5 expression but attenuated production of p-ERK5. ERK5 siRNA induced higher apoptosis rate; intracellular Ca(2+) overload; ROS activity; ΔΨm damage in hypothermia stimulated CMs, when compared with hypothermal stimulation solely treated group, while Bim siRNA effected oppositely and canceled pro-apoptotic effect of ERK5 siRNA. In conclusion, ERK5 knock down releases inhibition to Bim expression, induces aggravated apoptosis in CMs under hypothermal stimulation, which related to higher intracellular Ca(2+) overload, ROS activity, and more severe ΔΨm damage. Results revealed regulative role of ERK5/Bim pathway in hypothermal stimulation-induced injure or apoptosis of cardiomyocytes.

  2. Nlrp3-inflammasome activation in non-myeloid-derived cells aggravates diabetic nephropathy. (United States)

    Shahzad, Khurrum; Bock, Fabian; Dong, Wei; Wang, Hongjie; Kopf, Stefan; Kohli, Shrey; Al-Dabet, Moh'd Mohanad; Ranjan, Satish; Wolter, Juliane; Wacker, Christian; Biemann, Ronald; Stoyanov, Stoyan; Reymann, Klaus; Söderkvist, Peter; Groß, Olaf; Schwenger, Vedat; Pahernik, Sascha; Nawroth, Peter P; Gröne, Herman-Josef; Madhusudhan, Thati; Isermann, Berend


    Diabetic nephropathy is a growing health concern with characteristic sterile inflammation. As the underlying mechanisms of this inflammation remain poorly defined, specific therapies targeting sterile inflammation in diabetic nephropathy are lacking. Intriguingly, an association of diabetic nephropathy with inflammasome activation has recently been shown, but the pathophysiological relevance of this finding remains unknown. Within glomeruli, inflammasome activation was detected in endothelial cells and podocytes in diabetic humans and mice and in glucose-stressed glomerular endothelial cells and podocytes in vitro. Abolishing Nlrp3 or caspase-1 expression in bone marrow-derived cells fails to protect mice against diabetic nephropathy. Conversely, Nlrp3-deficient mice are protected against diabetic nephropathy despite transplantation of wild-type bone marrow. Pharmacological IL-1R antagonism prevented or even reversed diabetic nephropathy in mice. Mitochondrial reactive oxygen species (ROS) activate the Nlrp3 inflammasome in glucose or advanced glycation end product stressed podocytes. Inhibition of mitochondrial ROS prevents glomerular inflammasome activation and nephropathy in diabetic mice. Thus, mitochondrial ROS and Nlrp3-inflammasome activation in non-myeloid-derived cells aggravate diabetic nephropathy. Targeting the inflammasome may be a potential therapeutic approach to diabetic nephropathy.

  3. Carbon monoxide pollution aggravates ischemic heart failure through oxidative stress pathway (United States)

    Reboul, Cyril; Boissière, Julien; André, Lucas; Meyer, Gregory; Bideaux, Patrice; Fouret, Gilles; Feillet-Coudray, Christine; Obert, Philippe; Lacampagne, Alain; Thireau, Jérôme; Cazorla, Olivier; Richard, Sylvain


    Risk of hospital readmission and cardiac mortality increases with atmospheric pollution for patients with heart failure. The underlying mechanisms are unclear. Carbon monoxide (CO) a ubiquitous environmental pollutant could be involved. We explored the effect of daily exposure of CO relevant to urban pollution on post-myocardial infarcted animals. Rats with ischemic heart failure were exposed 4 weeks to daily peaks of CO mimicking urban exposure or to standard filtered air. CO exposure worsened cardiac contractile dysfunction evaluated by echocardiography and at the cardiomyocyte level. In line with clinical reports, the animals exposed to CO also exhibited a severe arrhythmogenic phenotype with numerous sustained ventricular tachycardias as monitored by surface telemetric electrocardiograms. CO did not affect cardiac β–adrenergic responsiveness. Instead, mitochondrial dysfunction was exacerbated leading to additional oxidative stress and Ca2+ cycling alterations. This was reversed following acute antioxidant treatment of cardiomyocytes with N-acetylcysteine confirming involvement of CO-induced oxidative stress. Exposure to daily peaks of CO pollution aggravated cardiac dysfunction in rats with ischemic heart failure by specifically targeting mitochondria and generating ROS-dependent alterations. This pathway may contribute to the high sensibility and vulnerability of individuals with cardiac disease to environmental outdoor air quality. PMID:28045070

  4. Glucocorticoids aggravate retrograde memory deficiency associated with traumatic brain injury in rats. (United States)

    Chen, Xin; Zhang, Ke-Li; Yang, Shu-Yuan; Dong, Jing-Fei; Zhang, Jian-Ning


    Administration of glucocorticoid to patients with head injury has previously been demonstrated to impair memory. We hypothesize that glucocorticoids promote post-traumatic hippocampal apoptosis, resulting in retrograde memory deficiency associated with traumatic brain injury (TBI). In the present study, we tested this hypothesis by measuring spatial memory deficiency in rats subjected to fluid percussion injury (FPI) and receiving dexamethasone (DXM at 0.5-10 mg/kg) or methylprednisolone (MP at 5-30 mg/kg); we also examined neuronal apoptosis in hippocampus. Adult male Wistar rats were trained for the acquisition of spatial memory, then subjected to FPI and tested for spatial reference memory on post-injury days 7 and 14 using the Morris Water Maze. Brain tissue from injured rats was examined 24 h to 2 weeks after injury. The percent time in the goal quadrant, which measures spatial reference memory, was significantly lower in injured rats receiving either high-dose DXM or MP than in control groups. TUNEL-positive cells in hippocampus were first detected 24 h post-injury, plateauing at 48h. The number of TUNEL-positive cells was significantly higher in injured rats treated with either DXM or MP. The data suggest that glucocorticoid therapy for TBI may increase neuronal apoptosis in hippocampus and, as a result, aggravate retrograde memory deficits induced by TBI.

  5. Absence of intestinal PPARγ aggravates acute infectious colitis in mice through a lipocalin-2-dependent pathway.

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    Parag Kundu


    Full Text Available To be able to colonize its host, invading Salmonella enterica serovar Typhimurium must disrupt and severely affect host-microbiome homeostasis. Here we report that S. Typhimurium induces acute infectious colitis by inhibiting peroxisome proliferator-activated receptor gamma (PPARγ expression in intestinal epithelial cells. Interestingly, this PPARγ down-regulation by S. Typhimurium is independent of TLR-4 signaling but triggers a marked elevation of host innate immune response genes, including that encoding the antimicrobial peptide lipocalin-2 (Lcn2. Accumulation of Lcn2 stabilizes the metalloproteinase MMP-9 via extracellular binding, which further aggravates the colitis. Remarkably, when exposed to S. Typhimurium, Lcn2-null mice exhibited a drastic reduction of the colitis and remained protected even at later stages of infection. Our data suggest a mechanism in which S. Typhimurium hijacks the control of host immune response genes such as those encoding PPARγ and Lcn2 to acquire residence in a host, which by evolution has established a symbiotic relation with its microbiome community to prevent pathogen invasion.

  6. Cedar Pollen Aggravates Atopic Dermatitis in Childhood Monozygotic Twin Patients with Allergic Rhino Conjunctivitis

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    Yukako Murakami


    Full Text Available We report a case of 7-year-old monozygotic twin patients with atopic dermatitis. The HLA haplotypes were HLA A2, A11, B27, B61, DR1, and DR4. Both serum IgE levels and cedar pollen radioallergosorbent test (RAST scores were high in the twins (elder/younger sister: IgE: 5170/3980 IU/ml and Japansese cedar pollen: >100/64.0 in contrast to low mite and food RAST scores (Dermatophagoides Pterygonium; 0.59/0.4 and egg white 9.24/4.6. The patients showed positive immediate (20 min in both sisters and delayed (24 hours in elder sister, 24, 48, 72 hours in younger sister reactions to a scratch test with Japanese cedar pollen. Skin lesions on the face were aggravated and extended to the trunk and extremities during the Japanese cedar pollen season and gradually subsided in summer. Oral provocation with egg white or cow milk showed no exacerbations, and topical corticosteroid did not improve the eczema. In contrast, successful protection from severe scratching behaviors was achieved by use of topical anti-allergic eye drops and wearing nightgowns made by the mother.

  7. Dietary fructose aggravates the pathobiology of traumatic brain injury by influencing energy homeostasis and plasticity. (United States)

    Agrawal, Rahul; Noble, Emily; Vergnes, Laurent; Ying, Zhe; Reue, Karen; Gomez-Pinilla, Fernando


    Fructose consumption has been on the rise for the last two decades and is starting to be recognized as being responsible for metabolic diseases. Metabolic disorders pose a particular threat for brain conditions characterized by energy dysfunction, such as traumatic brain injury. Traumatic brain injury patients experience sudden abnormalities in the control of brain metabolism and cognitive function, which may worsen the prospect of brain plasticity and function. The mechanisms involved are poorly understood. Here we report that fructose consumption disrupts hippocampal energy homeostasis as evidenced by a decline in functional mitochondria bioenergetics (oxygen consumption rate and cytochrome C oxidase activity) and an aggravation of the effects of traumatic brain injury on molecular systems engaged in cell energy homeostasis (sirtuin 1, peroxisome proliferator-activated receptor gamma coactivator-1alpha) and synaptic plasticity (brain-derived neurotrophic factor, tropomyosin receptor kinase B, cyclic adenosine monophosphate response element binding, synaptophysin signaling). Fructose also worsened the effects of traumatic brain injury on spatial memory, which disruption was associated with a decrease in hippocampal insulin receptor signaling. Additionally, fructose consumption and traumatic brain injury promoted plasma membrane lipid peroxidation, measured by elevated protein and phenotypic expression of 4-hydroxynonenal. These data imply that high fructose consumption exacerbates the pathology of brain trauma by further disrupting energy metabolism and brain plasticity, highlighting the impact of diet on the resilience to neurological disorders.

  8. 147 Mitigating and Aggravating Circumstances. Their Impact on Judicial Individualization of Punishment

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    Cosmin Peonaşu


    Full Text Available For an act to fall under criminal law it is sufficient for it to meet the minimum conditions to achieve constitutive content of the offense. However, committing a criminal act takes place, in most cases, in a complex set of variables specific to each case, variables that, without characterizing the act as an offense or the perpetrator's person as subject of that offence, helps determining, on one hand, the social danger of the committed crime and, on the other hand, knowing the offender as an individual and its social dangerousness. Mitigating and aggravating circumstances are such variables and they have a specific impact on criminal responsibility of the perpetrator. These circumstances have a major influence on judicial individualization of punishment because their effect is preset by the Law and acts separately on the length or amount of punishment. This study aims both students and practitioners or academics and highlights on one hand, the legislative solutions of the new Criminal Code and on the other hand, the differences between the old and the new Criminal Code.

  9. Homocysteine Aggravates Cortical Neural Cell Injury through Neuronal Autophagy Overactivation following Rat Cerebral Ischemia-Reperfusion

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    Yaqian Zhao


    Full Text Available Elevated homocysteine (Hcy levels have been reported to be involved in neurotoxicity after ischemic stroke. However, the underlying mechanisms remain incompletely understood to date. In the current study, we hypothesized that neuronal autophagy activation may be involved in the toxic effect of Hcy on cortical neurons following cerebral ischemia. Brain cell injury was determined by hematoxylin-eosin (HE staining and TdT-mediated dUTP Nick-End Labeling (TUNEL staining. The level and localization of autophagy were detected by transmission electron microscopy, western blot and immunofluorescence double labeling. The oxidative DNA damage was revealed by immunofluorescence of 8-Hydroxy-2′-deoxyguanosine (8-OHdG. Hcy treatment aggravated neuronal cell death, significantly increased the formation of autophagosomes and the expression of LC3B and Beclin-1 in the brain cortex after middle cerebral artery occlusion-reperfusion (MCAO. Immunofluorescence analysis of LC3B and Beclin-1 distribution indicated that their expression occurred mainly in neurons (NeuN-positive and hardly in astrocytes (GFAP-positive. 8-OHdG expression was also increased in the ischemic cortex of Hcy-treated animals. Conversely, LC3B and Beclin-1 overexpression and autophagosome accumulation caused by Hcy were partially blocked by the autophagy inhibitor 3-methyladenine (3-MA. Hcy administration enhanced neuronal autophagy, which contributes to cell death following cerebral ischemia. The oxidative damage-mediated autophagy may be a molecular mechanism underlying neuronal cell toxicity of elevated Hcy level.

  10. Cardiac Fibroblasts Aggravate Viral Myocarditis: Cell Specific Coxsackievirus B3 Replication

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    Diana Lindner


    Full Text Available Myocarditis is an inflammatory disease caused by viral infection. Different subpopulations of leukocytes enter the cardiac tissue and lead to severe cardiac inflammation associated with myocyte loss and remodeling. Here, we study possible cell sources for viral replication using three compartments of the heart: fibroblasts, cardiomyocytes, and macrophages. We infected C57BL/6j mice with Coxsackievirus B3 (CVB3 and detected increased gene expression of anti-inflammatory and antiviral cytokines in the heart. Subsequently, we infected cardiac fibroblasts, cardiomyocytes, and macrophages with CVB3. Due to viral infection, the expression of TNF-α, IL-6, MCP-1, and IFN-β was significantly increased in cardiac fibroblasts compared to cardiomyocytes or macrophages. We found that in addition to cardiomyocytes cardiac fibroblasts were infected by CVB3 and displayed a higher virus replication (132-fold increase compared to cardiomyocytes (14-fold increase between 6 and 24 hours after infection. At higher virus concentrations, macrophages are able to reduce the viral copy number. At low virus concentration a persistent virus infection was determined. Therefore, we suggest that cardiac fibroblasts play an important role in the pathology of CVB3-induced myocarditis and are another important contributor of virus replication aggravating myocarditis.

  11. Cardiomyocyte Overexpression of FABP4 Aggravates Pressure Overload-Induced Heart Hypertrophy.

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    Ji Zhang

    Full Text Available Fatty acid binding protein 4 (FABP4 is a member of the intracellular lipid-binding protein family, responsible for the transportation of fatty acids. It is considered to express mainly in adipose tissues, and be strongly associated with inflammation, obesity, diabetes and cardiovasculardiseases. Here we report that FABP4 is also expressed in cardiomyocytes and plays an important role in regulating heart function under pressure overload. We generated heart-specific transgenic FABP4 (FABP4-TG mice using α myosin-heavy chain (α-MHC promoter and human FABP4 sequence, resulting in over-expression of FABP4 in cardiomyocytes. The FABP4-TG mice displayed normal cardiac morphology and contractile function. When they were subjected to the transverse aorta constriction (TAC procedure, the FABP4-TG mice developed more cardiac hypertrophy correlated with significantly increased ERK phosphorylation, compared with wild type controls. FABP4 over-expression in cardiomyocytes activated phosphor-ERK signal and up-regulate the expression of cardiac hypertrophic marker genes. Conversely, FABP4 induced phosphor-ERK signal and hypertrophic gene expressions can be markedly inhibited by an ERK inhibitor PD098059 as well as the FABP4 inhibitor BMS309403. These results suggest that FABP4 over-expression in cardiomyocytes can aggravate the development of cardiac hypertrophy through the activation of ERK signal pathway.

  12. Liver Cholesterol Overload Aggravates Obstructive Cholestasis by Inducing Oxidative Stress and Premature Death in Mice

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    Natalia Nuño-Lámbarri


    Full Text Available Nonalcoholic steatohepatitis is one of the leading causes of liver disease. Dietary factors determine the clinical presentation of steatohepatitis and can influence the progression of related diseases. Cholesterol has emerged as a critical player in the disease and hence consumption of cholesterol-enriched diets can lead to a progressive form of the disease. The aim was to investigate the impact of liver cholesterol overload on the progression of the obstructive cholestasis in mice subjected to bile duct ligation surgery. Mice were fed with a high cholesterol diet for two days and then were subjected to surgery procedure; histological, biochemical, and molecular analyses were conducted to address the effect of cholesterol in liver damage. Mice under the diet were more susceptible to damage. Results show that cholesterol fed mice exhibited increased apoptosis and oxidative stress as well as reduction in cell proliferation. Mortality following surgery was higher in HC fed mice. Liver cholesterol impairs the repair of liver during obstructive cholestasis and aggravates the disease with early fatal consequences; these effects were strongly associated with oxidative stress.

  13. Norepinephrine as a Potential Aggravator of Symptomatic Cerebral Vasospasm: Two Cases and Argument for Milrinone Therapy

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    F. A. Zeiler


    Full Text Available Background. During hypertensive therapy for post-subarachnoid hemorrhage (SAH symptomatic vasospasm, norepinephrine is commonly used to reach target blood pressures. Concerns over aggravation of vasospasm with norepinephrine exist. Objective. To describe norepinephrine temporally related deterioration in neurological examination of two post-SAH patients in vasospasm. Methods. We retrospectively reviewed two charts of patients with delayed cerebral ischemia (DCI post-SAH who deteriorated with norepinephrine infusions. Results. We identified two patients with DCI post-SAH who deteriorated during hypertensive therapy with norepinephrine. The first, a 43-year-old male presented to hospital with DCI, failed MABP directed therapy with rapid deterioration in exam with high dose norepinephrine and MABP of 140–150 mm Hg. His exam improved on continuous milrinone and discontinuation of norepinephrine. The second, a 39-year-old female who developed DCI on postbleed day 8 responded to milrinone therapy upfront. During further deterioration and after angioplasty, norepinephrine was utilized to drive MABP to 130–140 mm Hg. Progressive deterioration in examination occurred after angioplasty as norepinephrine doses escalated. After discontinuation of norepinephrine and continuation of milrinone, function dramatically returned but not to baseline. Conclusions. The potential exists for worsening of DCI post-SAH with hypertensive therapy directed by norepinephrine. A potential role exists for vasodilation and inotropic directed therapy with milrinone in the setting of DCI post-SAH.

  14. Carbon monoxide pollution aggravates ischemic heart failure through oxidative stress pathway. (United States)

    Reboul, Cyril; Boissière, Julien; André, Lucas; Meyer, Gregory; Bideaux, Patrice; Fouret, Gilles; Feillet-Coudray, Christine; Obert, Philippe; Lacampagne, Alain; Thireau, Jérôme; Cazorla, Olivier; Richard, Sylvain


    Risk of hospital readmission and cardiac mortality increases with atmospheric pollution for patients with heart failure. The underlying mechanisms are unclear. Carbon monoxide (CO) a ubiquitous environmental pollutant could be involved. We explored the effect of daily exposure of CO relevant to urban pollution on post-myocardial infarcted animals. Rats with ischemic heart failure were exposed 4 weeks to daily peaks of CO mimicking urban exposure or to standard filtered air. CO exposure worsened cardiac contractile dysfunction evaluated by echocardiography and at the cardiomyocyte level. In line with clinical reports, the animals exposed to CO also exhibited a severe arrhythmogenic phenotype with numerous sustained ventricular tachycardias as monitored by surface telemetric electrocardiograms. CO did not affect cardiac β-adrenergic responsiveness. Instead, mitochondrial dysfunction was exacerbated leading to additional oxidative stress and Ca(2+) cycling alterations. This was reversed following acute antioxidant treatment of cardiomyocytes with N-acetylcysteine confirming involvement of CO-induced oxidative stress. Exposure to daily peaks of CO pollution aggravated cardiac dysfunction in rats with ischemic heart failure by specifically targeting mitochondria and generating ROS-dependent alterations. This pathway may contribute to the high sensibility and vulnerability of individuals with cardiac disease to environmental outdoor air quality.

  15. Polymorphism Trp64Arg of beta 3 adrenoreceptor gene: allelic frequencies and influence on insulin resistance in a multicenter study of Castilla-León Polimorfismo TRP64ARG del gen receptor beta 3: frecuencia alélica e influencia en la resistencia a la insulina en un estudio multicéntrico de Castilla y León

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    D. A. de Luis


    Full Text Available Background and objective: The genetic variant (Trp64Arg is a missense mutation located within the beta3 adrenoreceptor (Beta3AR. The aim of our study was to investigate the influence of Trp64Arg polymorphism in the Beta3AR gene on insulin resistance in obese patients and the allelic distribution of this polymorphismin a geographic area of Spain. Design: A population of 264 obese patients was analyzed. A bioimpedance, blood pressure, an assessment of nutritional intake, and biochemical parameters were measured. The beta 3 adrenoreceptor gene polymorphism(Trp64Arg was genotyped. Results: Two hundred and twenty six patients (77 males/149 females (85.6% had the genotype Trp64/Trp64 (wild type group with and average age of 41.12 ± 13.1 years and 38 patients (16 males/22 females Trp64/Arg64 (14.4% (mutant type group with an average age of 40.5 ± 12.7 years. High frequencies of Arg64 allele were observed in Salamanca and Valladolid. In the mutant type group, HOMA (3.75 ± 2.77 vs 5.27 ± 5.4; p Introducción y objetivos: La variante genética (Trp64Arg es una mutación localizada en el adrenoreceptor Beta 3 (Beta3AR. El objetivo de nuestro trabajo es evaluar la influencia de el polimorfismo Trp64Arg del gen de Beta3AR sobre la resistencia a la insulina en pacientes obesos, así como la distribución alélica de este polimorfismo en un área geográfica de España. Diseño: Una muestra de 264 pacientes obesos fue analizada. Se realizó una bioimpedancia, evaluación nutricional y análisis bioquímico. Se genotiparon a los pacientes en función delpolimorfismos Tr64Arg del gen adrenoreceptor-beta 3. Resultados: Un total de 227 pacientes (77 varones/149 mujeres (85,6% presentaron el genotipo Trp64/Trp64 (grupo genotipo salvaje, con una media de edad de 41,12 ± 13,1 años y un total de 38 pacientes (16 varones/22 mujeres Trp64/Arg64 (14,4% (grupo genotipo mutante con una edad media de 40,5 ± 12,7 años. Se detectó una alta frecuencia alélica (Arg64

  16. Cobalamin inactivation by nitrous oxide produces severe neurological impairment in fruit bats: protection by methionine and aggravation by folates

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    van der Westhuyzen, J.; Fernandes-Costa, F.; Metz, J.


    Nitrous oxide, which inactivates cobalamin when administered to fruit bats, results in severe neurological impairment leading to ataxia, paralysis and death. This occurs after about 6 weeks in animals depleted of cobalamin by dietary restriction, and after about 10 weeks in cobalamin replete bats. Supplementation of the diet with pteroylglutamic acid caused acceleration of the neurological impairment--the first unequivocal demonstration of aggravation of the neurological lesion in cobalamin deficiency by pteroylglutamic acid. The administration of formyltetrahydropteroylglutamic acid produced similar aggravation of the neurological lesion. Supplementation of the diet with methionine protected the bats from neurological impairment, but failed to prevent death. Methionine supplementation protected against the exacerbating effect of folate, preventing the development of neurological changes. These findings lend support to the hypothesis that the neurological lesion in cobalamin deficiency may be related to a deficiency in the methyl donor S-adenosylmethionine which follows diminished synthesis of methionine.

  17. Charges for criminal exposure to HIV and aggravated prostitution filed in the Nashville, Tennessee Prosecutorial Region 2000-2010. (United States)

    Galletly, Carol L; Lazzarini, Zita


    This paper examines comprehensive data on arrests for HIV-specific crimes within a single jurisdiction, the Nashville Tennessee prosecutorial region, over 11 years. There were 25 arrests for HIV exposure and 27 for aggravated prostitution. Eleven of the arrests for HIV exposure involved nonsexual behaviors; none alleged transmission. Sixteen of the arrests for HIV exposure involved sexual behavior; three alleged transmission. Aggravated prostitution cases (i.e. prostitution while knowing one has HIV) often involved solicitation of oral sex; none alleged transmission. Maximum sentences for HIV-specific crimes ranged from 5 to 8 years. We conclude that enforcement of US HIV-specific laws is underestimated. Fifty-two arrests over 11 years were recorded in one jurisdiction. Over half of the arrests involved behaviors posing minimal or no HIV transmission risk. Despite concerns about malicious, intentional HIV transmission, no cases alleged malice or intention.

  18. Aggravated bone density decline following symptomatic osteonecrosis in children with acute lymphoblastic leukemia. (United States)

    den Hoed, Marissa A H; Pluijm, Saskia M F; te Winkel, Mariël L; de Groot-Kruseman, Hester A; Fiocco, Martha; Hoogerbrugge, Peter; Leeuw, Jan A; Bruin, Marrie C A; van der Sluis, Inge M; Bresters, Dorien; Lequin, Maarten H; Roos, Jan C; Veerman, Anjo J P; Pieters, Rob; van den Heuvel-Eibrink, Marry M


    Osteonecrosis and decline of bone density are serious side effects during and after treatment of childhood acute lymphoblastic leukemia. It is unknown whether osteonecrosis and low bone density occur together in the same patients, or whether these two osteogenic side-effects can mutually influence each other's development. Bone density and the incidence of symptomatic osteonecrosis were prospectively assessed in a national cohort of 466 patients with acute lymphoblastic leukemia (4-18 years of age) who were treated according to the dexamethasone-based Dutch Child Oncology Group-ALL9 protocol. Bone mineral density of the lumbar spine (BMDLS) (n=466) and of the total body (BMDTB) (n=106) was measured by dual X-ray absorptiometry. Bone density was expressed as age- and gender-matched standard deviation scores. Thirty patients (6.4%) suffered from symptomatic osteonecrosis. At baseline, BMDLS and BMDTB did not differ between patients who did or did not develop osteonecrosis. At cessation of treatment, patients with osteonecrosis had lower mean BMDLS and BMDTB than patients without osteonecrosis (respectively, with osteonecrosis: -2.16 versus without osteonecrosis: -1.21, Posteonecrosis: -1.73 versus without osteonecrosis: -0.57, Posteonecrosis had steeper BMDLS and BMDTB declines during follow-up than patients without osteonecrosis (interaction group time, Posteonecrosis. Bone density declines from the time that osteonecrosis is diagnosed; this suggests that the already existing decrease in bone density during acute lymphoblastic leukemia therapy is further aggravated by factors such as restriction of weight-bearing activities and destruction of bone architecture due to osteonecrosis. Osteonecrosis can, therefore, be considered a risk factor for low bone density in children with acute lymphoblastic leukemia.

  19. Vitamin D deficiency aggravates chronic kidney disease progression after ischemic acute kidney injury.

    Directory of Open Access Journals (Sweden)

    Janaína Garcia Gonçalves

    pathways and involvement of TGF-β1 growth factor, VDD could be considered as an aggravating factor for tubulointerstitial damage and fibrosis progression following acute kidney injury induced by ischemia/reperfusion.

  20. Chemerin aggravates DSS-induced colitis by suppressing M2 macrophage polarization. (United States)

    Lin, Yuli; Yang, Xuguang; Yue, Wenjie; Xu, Xiaofei; Li, Bingji; Zou, Linlin; He, Rui


    Chemerin is present in various inflammatory sites and is closely involved in tissue inflammation. Recent studies have demonstrated that chemerin treatment can cause either anti-inflammatory or pro-inflammatory effects according to the disease model being investigated. Elevated circulating chemerin was recently found in patients with inflammatory bowel disease (IBD); however, the role of chemerin in intestinal inflammation remains unknown. In this study, we demonstrated that the administration of exogenous chemerin (aa17-156) aggravated the severity of dextran sulfate sodium (DSS)-induced colitis, which was characterized by higher clinical scores, extensive mucosal damage and significantly increased local and systemic production of pro-inflammatory cytokines, including IL-6, TNF-α and interferon (IFN-γ). Interestingly, chemerin did not appear to influence the magnitudes of inflammatory infiltrates in the colons, but did result in significantly decreased colonic expression of M2 macrophage-associated genes, including Arginase 1 (Arg-1), Ym1, FIZZ1 and IL-10, following DSS exposure, suggesting an impaired M2 macrophage skewing in vivo. Furthermore, an in vitro experiment showed that the addition of chemerin directly suppressed M2 macrophage-associated gene expression and STAT6 phosphorylation in IL-4-stimulated macrophages. Significantly elevated chemerin levels were found in colons from DSS-exposed mice and from ulcerative colitis (UC) patients and appeared to positively correlate with disease severity. Moreover, the in vivo administration of neutralizing anti-chemerin antibody significantly improved intestinal inflammation following DSS exposure. Taken together, our findings reveal a pro-inflammatory role for chemerin in DSS-induced colitis and the ability of chemerin to suppress the anti-inflammatory M2 macrophage response. Our study also suggests that upregulated chemerin in inflamed colons may contribute to the pathogenesis of IBD.

  1. Disinhibition of Cathepsin C Caused by Cystatin F Deficiency Aggravates the Demyelination in a Cuprizone Model (United States)

    Liang, Junjie; Li, Ning; Zhang, Yanli; Hou, Changyi; Yang, Xiaohan; Shimizu, Takahiro; Wang, Xiaoyu; Ikenaka, Kazuhiro; Fan, Kai; Ma, Jianmei


    Although the precise mechanism underlying initial lesion development in multiple sclerosis (MS) remains unclear, CNS inflammation has long been associated with demyelination, and axonal degeneration. The activation of microglia/macrophages, which serve as innate immune cells in the CNS, is the first reaction to even minor pathologic changes in the CNS and is considered an initial pathogenic event in MS. Microglial activation accompanies a variety of gene expressions, including cystatin F (Cys F), which belongs to the cystatin superfamily and is one of the cathepsin inhibitors. In our previous study we showed that Cys F has a unique expression pattern in microglia/macrophages in the demyelination process. Specifically, the timing of Cys F induction correlated with ongoing demyelination, and the sites of Cys F expression overlapped with areas of remyelination. Cys F induction ceased in chronic demyelination when remyelination capacity was lost, suggesting that Cys F expressed by microglia/macrophages may play an important role in demyelination and/or remyelination. The functional role of Cys F in demyelinating disease of the CNS, however, is unclear. Cys F gene knockout mice were used in the current study to clarify the functional role of Cys F in the demyelination process in a cuprizone-induced demyelination animal model. We demonstrated that absence of the Cys F gene and the resulting disinhibition of cathepsin C (Cat C) aggravates the demyelination, and this finding may be related to the increased expression of the glia-derived chemokine, CXCL2, which may attract inflammatory cells to sites of myelin sheath damage. This effect was reversed by knock down of the Cat C gene. The findings gain further insight to function of Cat C in pathophysiology of MS, which may have implications for therapeutics for the prevention of neuroinflammation-involved neurological disorders in the future. PMID:28066178

  2. High Potassium Aggravates the Oxidative Stress Inducedy by Magnesium Deficiency in Rice Leaves

    Institute of Scientific and Technical Information of China (English)

    DING Yu-Chuan; CHANG Chun-Rong; LUO Wen; WU Yan-Shou; REN Xiao-Li; WANG Ping; XU Guo-Hua


    Magnesium (Mg) deficiency in plant affects photosynthesis and many other metabolic processes.Rice (Oryza sativa'Wuyunjing 7') plants were grown in hydroponics culture at three Mg and two potassium (K) levels under greenhouse conditions to examine the induction of oxidative stress and consequent antioxidant responses in rice leaves due to Mg deficiency.At low Mg (0.2 mmol L-1 Mg supply for two weeks after transplanting) and high K (6 mmol L-1) for 21days,the rice plants showed severe Mg deficiency and a significant decreases in the dry matter production. The Mg deficiency in leaves decreased chlorophyll concentrations,photosynthetic activity,and soluble protein,but significantly increased the concentrations of soluble sugars and malondialdehyde (MDA) and the activities of superoxide dismutase (SOD,EC,catalase (CAT,EC and peroxidase (POD,EC addition,Mg concentrations in the leaves and in the shoot biomass were negatively related to the activities of the three antioxidative enzymes and the concentration of MDA in leaves.There were very significant interactive effects between Mg and K supplied in the culture solution on shoot biomass yield,chlorophyll content,photosynthesis rate,the activities of SOD,CAT and POD,and MDA content in the leaves of rice.It is suggested that the high K level in the nutrient solution aggravated the effect of low Mg supply-induced Mg deficiency and created the oxidative damage in rice plants.

  3. Cigarette smoke exposure aggravates air space enlargement and alveolar cell apoptosis in Smad3 knockout mice. (United States)

    Farkas, Laszlo; Farkas, Daniela; Warburton, David; Gauldie, Jack; Shi, Wei; Stampfli, Martin R; Voelkel, Norbert F; Kolb, Martin


    The concept of genetic susceptibility factors predisposing cigarette smokers to develop emphysema stems from the clinical observation that only a fraction of smokers develop clinically significant chronic obstructive pulmonary disease. We investigated whether Smad3 knockout mice, which develop spontaneous air space enlargement after birth because of a defect in transforming growth factor-β (TGF-β) signaling, develop enhanced alveolar cell apoptosis and air space enlargement following cigarette smoke exposure. We investigated Smad3(-/-) and Smad3(+/+) mice at different adult ages and determined air space enlargement, alveolar cell proliferation, and apoptosis. Furthermore, laser-capture microdissection and real-time PCR were used to measure compartment-specific gene expression. We then compared the effects of cigarette smoke exposure on Smad3(-/-) and littermate controls. Smad3 knockout resulted in the development of air space enlargement in the adult mouse and was associated with decreased alveolar VEGF levels and activity and increased alveolar cell apoptosis. Cigarette smoke exposure aggravated air space enlargement and alveolar cell apoptosis. We also found increased Smad2 protein expression and phosphorylation, which was enhanced following cigarette smoke exposure, in Smad3-knockout animals. Double immunofluorescence analysis revealed that endothelial apoptosis started before epithelial apoptosis. Our data indicate that balanced TGF-β signaling is not only important for regulation of extracellular matrix turnover, but also for alveolar cell homeostasis. Impaired signaling via the Smad3 pathway results in alveolar cell apoptosis and alveolar destruction, likely via increased Smad2 and reduced VEGF expression and might represent a predisposition for accelerated development of emphysema due to cigarette smoke exposure.

  4. Hepatocyte nuclear factor 4α suppresses the aggravation of colon carcinoma. (United States)

    Yao, Hou Shan; Wang, Juan; Zhang, Xiao Ping; Wang, Liang Zhe; Wang, Yi; Li, Xin Xing; Jin, Kai Zhou; Hu, Zhi Qian; Wang, Wei Jun


    Hepatocyte nuclear factor 4-α (HNF4α), a nuclear receptor, is expressed at lower levels in colon carcinoma tissues than in adjacent normal tissues. However, the relation between HNF4α and colon cancer progression and the underlying molecular mechanisms remain unclear. Here, we investigated the role of HNF4α in the progression of colon carcinoma. We showed that HNF4α mRNA and protein were downregulated in colon carcinoma specimens. HNF4α expression was related to pT classification (P colon carcinoma patients. Patients with low or negative HNF4α expression had worse 3-year progression-free survival (PFS, P = 0.006) and overall survival (OS, P = 0.005) than patients with high HNF4α expression. Low HNF4α expression was an independent prognostic factor for 3-year PFS (hazard ratio 2.94; 95% confidence interval 1.047-8.250; P = 0.041). Ectopic expression of HNF4α inhibited colon carcinoma cell (HT29, LoVo, and SW480) proliferation, migration, and invasion, induced G2/M phase arrest and promoted apoptosis. Ectopic expression of HNF4α upregulated E-cadherin and downregulated vimentin in vitro, and suppressed SW480 xenograft tumor growth and liver metastasis in vivo. Furthermore, HNF4α overexpression downregulated the expression of snail, slug and twist. HNF4α inhibited EMT through its effect on the Wnt/β-catenin signaling pathway, and HNF4α downregulation may be mediated by promoter methylation in cancer tissues. Our results suggest that downregulation of HNF4α plays a critical role in the aggravation of colon carcinoma possibly by promoting EMT via the Wnt/β-catenin signaling pathway and by affecting apoptosis and cell cycle progression.

  5. The thyroid function of Graves' disease patients is aggravated by depressive personality during antithyroid drug treatment

    Directory of Open Access Journals (Sweden)

    Miyauchi Akira


    thyrotoxicosis and that it aggravates hyperthyroidism. Psychosomatic therapeutic approaches including antipsychiatric drugs and/or psychotherapy appears to be useful for improving the prognosis of hyperthyroidism.

  6. Respiratory Syncytial Virus Aggravates Renal Injury through Cytokines and Direct Renal Injury

    Directory of Open Access Journals (Sweden)

    Songhui Zhai


    Full Text Available The purpose of this study was to investigate the relationship between renal injury and reinfection that is caused by respiratory syncytial virus (RSV and to analyze the mechanism of renal injury. Rats were repeatedly infected with RSV on days 4, 8, 14, and 28, then sacrificed and examined on day 56 after the primary infection. Renal injury was examined by transmission electron microscopy and histopathology. The F protein of RSV was detected in the renal tissue by indirect immunofluorescence. Proteinuria and urinary glycosaminoglycans (GAGs, serum levels of albumin, urea nitrogen, and creatinine, secretion of cytokines, T lymphocyte population and subsets, and dendritic cell (DC activation state were examined. The results showed that renal injury was more serious in the reinfection group than in the primary infection group. At a higher infection dose, 6×106 PFU, the renal injury was more severe, accompanied by higher levels of proteinuria and urinary GAGs excretion, and lower levels of serum albumin. Podocyte foot effacement was more extensive, and hyperplasia of mesangial cells and proliferation of mesangial matrix were observed. The maturation state of DCs was specific, compared with the primary infection. There was also a decrease in the ratio of CD4+ to CD8+T lymphocytes, due to an increase in the percentage of CD8+T lymphocytes and a decrease in the percentage of CD4+T lymphocytes, and a dramatic increase in the levels of IL-6 and IL-17. In terms of the different reinfection times, the day 14 reinfection group yielded the most serious renal injury and the most significant change in immune function. RSV F protein was still expressed in the glomeruli 56 days after RSV infection. Altogether, these results reveal that RSV infection could aggravate renal injury, which might be due to direct renal injury caused by RSV and the inflammatory lesions caused by the anti-virus response induced by RSV.

  7. Right Cervical Vagotomy Aggravates Viral Myocarditis in Mice Via the Cholinergic Anti-inflammatory Pathway (United States)

    Li-Sha, Ge; Xing-Xing, Chen; Lian-Pin, Wu; De-Pu, Zhou; Xiao-Wei, Li; Jia-Feng, Lin; Yue-Chun, Li


    The autonomic nervous system dysfunction with increased sympathetic activity and withdrawal of vagal activity may play an important role in the pathogenesis of viral myocarditis. The vagus nerve can modulate the immune response and control inflammation through a ‘cholinergic anti-inflammatory pathway’ dependent on the α7-nicotinic acetylcholine receptor (α7nAChR). Although the role of β-adrenergic stimulation on viral myocarditis has been investigated in our pervious studies, the direct effect of vagal tone in this setting has not been yet studied. Therefore, in the present study, we investigated the effects of cervical vagotomy in a murine model of viral myocarditis. In a coxsackievirus B3 murine myocarditis model (Balb/c), effects of right cervical vagotomy and nAChR agonist nicotine on echocardiography, myocardial histopathology, viral RNA, and proinflammatory cytokine levels were studied. We found that right cervical vagotomy inhibited the cholinergic anti-inflammatory pathway, aggravated myocardial lesions, up-regulated the expression of TNF-α, IL-1β, and IL-6, and worsened the impaired left ventricular function in murine viral myocarditis, and these changes were reversed by co-treatment with nicotine by activating the cholinergic anti-inflammatory pathway. These results indicate that vagal nerve plays an important role in mediating the anti-inflammatory effect in viral myocarditis, and that cholinergic stimulation with nicotine also plays its peripheral anti-inflammatory role relying on α7nAChR, without requirement for the integrity of vagal nerve in the model. The findings suggest that vagus nerve stimulation mediated inhibition of the inflammatory processes likely provide important benefits in myocarditis treatment. PMID:28197102

  8. Aggravation of Allergic Airway Inflammation by Cigarette Smoke in Mice Is CD44-Dependent.

    Directory of Open Access Journals (Sweden)

    Smitha Kumar

    Full Text Available Although epidemiological studies reveal that cigarette smoke (CS facilitates the development and exacerbation of allergic asthma, these studies offer limited information on the mechanisms involved. The transmembrane glycoprotein CD44 is involved in cell adhesion and acts as a receptor for hyaluronic acid and osteopontin. We aimed to investigate the role of CD44 in a murine model of CS-facilitated allergic airway inflammation.Wild type (WT and CD44 knock-out (KO mice were exposed simultaneously to house dust mite (HDM extract and CS. Inflammatory cells, hyaluronic acid (HA and osteopontin (OPN levels were measured in bronchoalveolar lavage fluid (BALF. Proinflammatory mediators, goblet cell metaplasia and peribronchial eosinophilia were assessed in lung tissue. T-helper (Th 1, Th2 and Th17 cytokine production was evaluated in mediastinal lymph node cultures.In WT mice, combined HDM/CS exposure increased the number of inflammatory cells and the levels of HA and OPN in BALF and Th2 cytokine production in mediastinal lymph nodes compared to control groups exposed to phosphate buffered saline (PBS/CS, HDM/Air or PBS/Air. Furthermore, HDM/CS exposure significantly increased goblet cell metaplasia, peribronchial eosinophilia and inflammatory mediators in the lung. CD44 KO mice exposed to HDM/CS had significantly fewer inflammatory cells in BALF, an attenuated Th2 cytokine production, as well as decreased goblet cells and peribronchial eosinophils compared to WT mice. In contrast, the levels of inflammatory mediators were similar or higher than in WT mice.We demonstrate for the first time that the aggravation of pulmonary inflammation upon combined exposure to allergen and an environmental pollutant is CD44-dependent. Data from this murine model of concomitant exposure to CS and HDM might be of importance for smoking allergic asthmatics.

  9. Aggravation of fatigue by steroid therapy in terminally ill patients with cancer. (United States)

    Matsuo, Naoki; Yomiya, Kinomi


    Steroids are commonly used for fatigue relief in terminally ill cancer patients. However, steroid-induced adverse effects including depression, myopathy, and hyperglycemia may contribute to fatigue. We report our experiences with aggravation of fatigue with steroid use in three cases. Case 1 was a 65-year-old man with advanced gastric cancer. He was started on betamethasone (2 mg/d) for fatigue, but the fatigue worsened due to steroid-induced depression. Discontinuation of steroids and initiation of an antidepressant ameliorated the fatigue. Case 2 was a 68-year-old man with advanced lung cancer. He complained of fatigue. Betamethasone (1 mg/d) was started and alleviated the fatigue. However, when the betamethasone dose was increased to 2 mg/d, the fatigue, with muscle weakness and myalgia, worsened due to steroid-induced myopathy. We therefore switched from betamethasone (2 mg/d) to prednisolone (10 mg /d). The fatigue resolved and the patient returned to his previous condition. Case 3 was a 73-year-old man with recurrent bile duct cancer. He also had diabetes mellitus. He developed fatigue, anorexia and fever. We started betamethasone (1.5 mg/d) for these symptoms, but the fatigue and anorexia worsened due to steroid-induced hyperglycemia. Blood glucose rose to 532 mg/dL. Therefore, insulin therapy was started, and the dose of betamethasone was reduced to 0.5 mg/d. His glucose level decreased to less than 320 mg/dL and he recovered from the fatigue while achieving moderate oral intake. In conclusion, the possibility of steroid-induced secondary fatigue in terminally ill cancer patients should be taken into consideration.

  10. Cathepsin K Deficiency Prevents the Aggravated Vascular Remodeling Response to Flow Cessation in ApoE-/- Mice


    Marjo M P C Donners; Bai, Lili; Lutgens, Suzanne P. M.; Wijnands, Erwin; Johnson, Jason; Schurgers, Leon J.; Liu, Cong-Lin; Daemen, Mat; Cleutjens, Kitty B.J.M.; Shi, Guo-Ping; BIESSEN, Erik; Heeneman, Sylvia


    Cathepsin K (catK) is a potent lysosomal cysteine protease involved in extracellular matrix (ECM) degradation and inflammatory remodeling responses. Here we have investigated the contribution of catK deficiency on carotid arterial remodeling in response to flow cessation in apoE-/- and wild type (wt) background. Ligation-induced hyperplasia is considerably aggravated in apoE-/- versus wt mice. CatK protein expression was significantly increased in neointimal lesions of apoE-/- compared with w...

  11. Quantitative gene-expression of the tumor angiogenesis markers vascular endothelial growth factor, integrin alphaV and integrin beta3 in human neuroendocrine tumors

    DEFF Research Database (Denmark)

    Oxboel, Jytte; Binderup, Tina; Knigge, Ulrich;


    Anti-angiogenesis treatment is a promising new therapy for cancer that recently has also been suggested for patients with neuroendocrine tumors. The aim of the present study was therefore to investigate the level of tumor angiogenesis, and thereby the molecular basis for anti-angiogenesis treatment......, in neuroendocrine tumors. We used quantitative real-time PCR for measuring mRNA gene-expression of vascular endothelial growth factor (VEGF), integrin alphaV, and integrin beta3, and CD34 for a group of patients with neuroendocrine tumors (n=13). Tissue from patients with colorectal cancer liver metastases (n=14......) and normal liver tissues (n=16) was used as control. We found a lower mRNA level of VEGF in neuroendocrine tumors compared to both colorectal liver metastases (ptumors...

  12. Suggestive association between the C825T polymorphism of the G-protein beta3 subunit gene (GNB3) and clinical improvement with antipsychotics in schizophrenia. (United States)

    Müller, Daniel J; De Luca, Vincenzo; Sicard, Tricia; King, Nicole; Hwang, Rudi; Volavka, Jan; Czobor, Pal; Sheitman, Brian B; Lindenmayer, Jean-Pierre; Citrome, Leslie; McEvoy, Joseph P; Lieberman, Jeffrey A; Meltzer, Herbert Y; Kennedy, James L


    G-proteins are composed of alpha, beta and gamma subunits. Once activated, these subunits play a major role in the conversion of external receptor activation into intracellular signals. The functional C825T polymorphism of the beta3 subunit gene (GNB3) has recently been shown to modulate antidepressant response, with the T-allele conferring an increased signaling and being associated with favorable antidepressant response. We hypothesized that this polymorphism may be associated with response to antipsychotics in a population of 145 chronic schizophrenic patients deriving from two study-samples and being mainly treated with clozapine for up to 6 months. Overall, the C/C genotype was significantly associated with relative clinical improvement as measured by Brief Psychiatric Rating Scale (BPRS) change scores after 6 and 12 weeks (ppoint to the role of intracellular mechanisms in antipsychotic response.

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

    Directory of Open Access Journals (Sweden)

    Suri SS


    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

  14. Loss of p120 catenin aggravates alveolar edema of ventilation induced lung injury

    Institute of Scientific and Technical Information of China (English)

    DAI Chen-yang; DAI Guo-feng; SUN Yu; WANG Yue-lan


    Background p120 catenin (p120ctn) is an adheren junction protein that regulates barrier function,but its role has not been explored in alveolar edema induced by ventilation.We measured stretch-induced cell gap formation in MLE 12 cells due to the loss of p120.We hypothesized that alveolar permeability was increased by high lung inflation associated with alveolar epithelia cell tight junctions being destroyed,which resulted from the loss of p120.Methods Cultured MLE12 cells were subjected to being stretched or un-stretched (control) and some cells were pretreated with pp2 (c-src inhibitor).After the end of stretching for 0,1,2,and 4 hours,the cells were lysed,and p120 expression and c-src activation was determined by Western blotting analysis.In vivo,SD rats were taken to different tidal volumes (Vt 7 ml/kg or 40 ml/kg,PEEP=0,respiratory rate 30-40 betas/min) for 0,1,2,and 4 hour and some were pretreated with pp2,and alveolar edema was calculated.Rerults It was found that p120 expression was reduced and c-src activation increased in a time-dependent and strain-dependent manner due to cyclic-stretch of the alveolar epithelial cells.These changes could be reversed by inhibition of c-src.We obtained similar changes in rats when they were subjected to large tidal volumes and the alveolar edema increased more than in rats in the low Vt group.Pretreated the rats with inhibition of c-src had less pulmonary edema induced by the high tidal volume ventilation.Conclusions Cyclic stretch MLE 12 cells induced the loss of p120 and may be the same reason by high tidal volume ventilation in rats can aggravate alveolar edema.Maintenance of p120 expression may be a novel therapeutic strategy for the prevention and treatment of ventilation induced lung injury (VILI).

  15. Statins activate the canonical hedgehog-signaling and aggravate non-cirrhotic portal hypertension, but inhibit the non-canonical hedgehog signaling and cirrhotic portal hypertension. (United States)

    Uschner, Frank E; Ranabhat, Ganesh; Choi, Steve S; Granzow, Michaela; Klein, Sabine; Schierwagen, Robert; Raskopf, Esther; Gautsch, Sebastian; van der Ven, Peter F M; Fürst, Dieter O; Strassburg, Christian P; Sauerbruch, Tilman; Diehl, Anna Mae; Trebicka, Jonel


    Liver cirrhosis but also portal vein obstruction cause portal hypertension (PHT) and angiogenesis. This study investigated the differences of angiogenesis in cirrhotic and non-cirrhotic PHT with special emphasis on the canonical (Shh/Gli) and non-canonical (Shh/RhoA) hedgehog pathway. Cirrhotic (bile duct ligation/BDL; CCl4 intoxication) and non-cirrhotic (partial portal vein ligation/PPVL) rats received either atorvastatin (15 mg/kg; 7d) or control chow before sacrifice. Invasive hemodynamic measurement and Matrigel implantation assessed angiogenesis in vivo. Angiogenesis in vitro was analysed using migration and tube formation assay. In liver and vessel samples from animals and humans, transcript expression was analyzed using RT-PCR and protein expression using Western blot. Atorvastatin decreased portal pressure, shunt flow and angiogenesis in cirrhosis, whereas atorvastatin increased these parameters in PPVL rats. Non-canonical Hh was upregulated in experimental and human liver cirrhosis and was blunted by atorvastatin. Moreover, atorvastatin blocked the non-canonical Hh-pathway RhoA dependently in activated hepatic steallate cells (HSCs). Interestingly, hepatic and extrahepatic Hh-pathway was enhanced in PPVL rats, which resulted in increased angiogenesis. In summary, statins caused contrary effects in cirrhotic and non-cirrhotic portal hypertension. Atorvastatin inhibited the non-canonical Hh-pathway and angiogenesis in cirrhosis. In portal vein obstruction, statins enhanced the canonical Hh-pathway and aggravated PHT and angiogenesis.

  16. A case of aggravation of hemolytic anemia, elevated liver enzymes and low platelet count syndrome after delivery

    Institute of Scientific and Technical Information of China (English)

    JIANG Yuan-hui; WANG Yong-qing; WANG Jing; YE Rong-hua


    Background Hemolytic anemia, elevated liver enzymes and low platelet count (HELLP) syndrome is a severe obstetric complication which usually resolves in most patients after delivery.Methods We report a rare case of aggravation of HELLP syndrome after delivery.Results The patient underwent the treatment for HELLP syndrome,.including glucocorticoid therapy. The symptoms of HELLP syndrome reappeared and became more severe than before the termination of pregnancy. The patient also had severe and persistent hypoproteinemia, hyponatremia and hypocalcemia.Conclusions HELLP syndrome is an acute and critical obstetric syndrome which can have heterogeneous presentations and variable prognosis. We should be fully aware of the diverse clinical characteristics of this condition.

  17. 严重暴力犯罪概念解析%Analyzing the Concept of Aggravated Violent Crime

    Institute of Scientific and Technical Information of China (English)



      Compared with a traditional violent crime, an aggravated violent crime has endangered public security, which is its essential characteristic. The article starts from confusing terms like“a violent crime”, “an aggravated violent crime”, “an unexpected public event” and “a terrorist attack event”, distinguishing each connotation and nature, and then proposes that the nature of an unexpected event should be defined with the combination of the behavioral means and the endangering public security. The fundamental difference between an aggravated violent crime and a common violent crime lies in the factor of with or without “willful and malicious destruction, and endangering public security”. Aggravated violent crimes, as one of the most serious in unexpected events, have to be dealt immediately with special means rather than relying on the sole way through criminal punishment.%  与传统暴力犯罪相比,严重暴力犯罪已经危害公共安全,这是其本质特征。文章从“暴力犯罪”、“严重暴力犯罪”、“突发公共事件”、“恐怖袭击事件”等易混淆的概念入手,从认识层面理清各自内涵属性,提出应从行为手段与危害公共安全二者的结合来界定突发事件的性质,认为是否内含“人为恶意破坏、危害公共安全”要素是严重暴力犯罪与一般暴力犯罪的根本差别。严重暴力犯罪案件作为突发事件中性质最为严重的一种,其发生、发展的控制不能寄刑罚手段一途,须动用特别手段紧急处置。

  18. Basis of aggravated hepatic lipid metabolism by chronic stress in high-fat diet-fed rat. (United States)

    Han, Ying; Lin, Min; Wang, Xiaobin; Guo, Keke; Wang, Shanshan; Sun, Mengfei; Wang, Jiao; Han, Xiaoyu; Fu, Ting; Hu, Yang; Fu, Jihua


    Our previous study has demonstrated that long-term stress, known as chronic stress (CS), can aggravate nonalcoholic fatty liver disease in high-fat diet (HFD)-fed rat. In this study, we tried to figure out which lipid metabolic pathways were impacted by CS in the HFD-fed rat. Male Sprague-Dawley rats (6 weeks of age, n = 8 per group) were fed with either standard diet or HFD with or without CS exposure for 8 weeks. Hepatic lipidosis, biochemical, hormonal, and lipid profile markers in serum and liver, and enzymes involved in de novo lipogenesis (DNL) of fatty acids (FAs) and cholesterol, β-oxidation, FAs uptake, triglycerides synthesis, and very low-density lipoprotein (VLDL) assembly in the liver were detected. CS exposure reduced hepatic lipidosis but further elevated hepatic VLDL content with aggravated dyslipidemia in the HFD-fed rats. There was a synergism between CS and HFD on VLDL production and dyslipidemia. PCR and western blot assays showed that CS exposure significantly promoted hepatic VLDL assembly in rats, especially in the HFD-fed rats, while it had little impact on DNL, β-oxidation, FAs uptake, and triglycerides synthesis in the HFD-fed rats. This phenomenon was in accordance with elevated serum glucocorticoid level. The critical influence of CS exposure on hepatic lipid metabolism in the HFD-fed rats is VLDL assembly which might be regulated by glucocorticoid.

  19. Oral exposure to low-dose bisphenol A aggravates testosterone-induced benign hyperplasia prostate in rats. (United States)

    Wu, Jian-Hui; Jiang, Xiu-Rong; Liu, Gui-Ming; Liu, Xiang-Yun; He, Gui-Lin; Sun, Zu-Yue


    The declining level of androgen during aging, associated with an inclining level of estrogen, has been hypothesized to be important in the development of benign prostatic hyperplasia (BPH). Within physiologic range, increasing estrogen levels can stimulate prostate to develop and permanently increase prostate size. As an estrogenic endocrine disruptor, bisphenol A (BPA) might be stimulatory to prostate development. We further hypothesized that low dose BPA could induce hyperplasia prostate to proliferate and aggravate the symptom of BPH in male SD rats. BPH was induced by testosterone and then treated with BPA (10, 30, or 90 μg/kg, i.g., daily), 17β-estradiol (E(2); 50.0 μg/kg, s.c., daily), or vehicle for 4 weeks. We found that weight and volume in rats treated with low dose BPA (10 μg/kg) was higher than that of model control, and BPA significantly increased the relative weight of prostate (p prostate lobes, BPA 10 μg/kg/day significantly increased relative weight of ventral prostate (VP), weight and relative weight of dorsolateral prostate (DLP) (p prostate-specific antigen level. E(2) treatment also showed an obvious effect on relative weight of VP and DLP, HEC, and hormone levels. We concluded that environment exposure to low dose of BPA may induce prostate to proliferate and aggravate testosterone-induced benign hyperplasia prostate in rats.

  20. Acrolein, a highly toxic aldehyde generated under oxidative stress in vivo, aggravates the mouse liver damage after acetaminophen overdose. (United States)

    Arai, Tomoya; Koyama, Ryo; Yuasa, Makoto; Kitamura, Daisuke; Mizuta, Ryushin


    Although acetaminophen-induced liver injury in mice has been extensively studied as a model of human acute drug-induced hepatitis, the mechanism of liver injury remains unclear. Liver injury is believed to be initiated by metabolic conversion of acetaminophen to the highly reactive intermediate N-acetyl p-benzoquinoneimine, and is aggravated by subsequent oxidative stress via reactive oxygen species (ROS), including hydrogen peroxide (H2O2) and the hydroxyl radical (•OH). In this study, we found that a highly toxic unsaturated aldehyde acrolein, a byproduct of oxidative stress, has a major role in acetaminophen-induced liver injury. Acetaminophen administration in mice resulted in liver damage and increased acrolein-protein adduct formation. However, both of them were decreased by treatment with N-acetyl-L-cysteine (NAC) or sodium 2-mercaptoethanesulfonate (MESNA), two known acrolein scavengers. The specificity of NAC and MESNA was confirmed in cell culture, because acrolein toxicity, but not H2O2 or •OH toxicity, was inhibited by NAC and MESNA. These results suggest that acrolein may be more strongly correlated with acetaminophen-induced liver injury than ROS, and that acrolein produced by acetaminophen-induced oxidative stress can spread from dying cells at the primary injury site, causing damage to the adjacent cells and aggravating liver injury.

  1. Oral Candida as an aggravating factor of mucositis Induced by radiotherapy; Candida Oral como fator agravante da mucosite radioinduzida

    Energy Technology Data Exchange (ETDEWEB)

    Simoes, Cristiane Araujo; Castro, Jurema Freire Lisboa de; Cazal, Claudia [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil). Dept. de odontologia


    Antineoplastic treatment induces some undesirable consequences in head and neck cancer patients. Often, the emergence of major clinical manifestations, such as oral mucositis, results in temporary interruption of the treatment, decreasing the patients' quality of life, and increasing hospital costs. Radio-induced or chemo-induced oral mucositis is possibly aggravated by opportunist fungal infections, which turn the mucositis more resistant to the conventional treatments. Objective: this study aims to identify the presence of Candida sp. as a possible aggravating factor of oral mucositis in patients with head and neck cancer under antineoplastic treatment. Method: all patients with radio- or chemo-induced oral mucositis from the Cancer Hospital of Pernambuco, treated between October 2008 and April 2009, were selected for the study. The prevalence of Candida sp was measured through the cytological analysis of oral mucosa in patients with oral mucositis. The fungal presence was correlated with the mucositis severity. Results: the results showed a positive association between fungal colonization and more several lesions (degrees III and IV of mucositis). Conclusion: The outcomes shown may contribute to a solution for unconventional mucosites, which do not respond to the usual treatment. (author)

  2. Long-term management of sevelamer hydrochloride-induced metabolic acidosis aggravation and hyperkalemia in hemodialysis patients. (United States)

    Sonikian, Macroui; Metaxaki, Polyxeni; Iliopoulos, Anastasios; Marioli, Stamatia; Vlassopoulos, Dimosthenis


    Sevelamer hydrochloride use in hemodialysis patients is complicated by metabolic acidosis aggravation and hyperkalemia. Rare reports about a short-term correction of this complication have been published. The current authors investigated the long-term correction of metabolic acidosis and hyperkalemia in sevelamer hydrochloride-treated patients at doses adequate to achieve serum phosphate levels within K/DOQI recommendations. The authors followed 20 hemodialysis patients for 24 months in an open-label prospective study. The dialysate bicarbonate concentration was increased stepwise to a maximum 40 mEq/L and adjusted to reach patient serum bicarbonate levels of 22 mEq/L, according to K/DOQI recommendations. Laboratory results for serum bicarbonate, potassium, calcium, phosphate, albumin, alkaline phosphatase, iPTH, cholesterol (HDL-LDL), triglycerides, Kt/V, systolic-diastolic arterial pressure were recorded. Sevelamer hydrochloride-induced metabolic acidosis aggravation and hyperkalemia in hemodialysis patients were corrected, on the long-term, by an increase in dialysate bicarbonate concentration. Further improvement in bone biochemistry was noted with this adequate acidosis correction and parallel sevelamer hydrochloride administration, in sufficiently large doses to achieve K/DOQI phosphate recommendations.

  3. Introduction of silencing-inducing transgene against Fgf19 does not affect expression of Tbx5 and beta3-tubulin in the developing chicken retina. (United States)

    Okamoto, Mayumi; Tomonari, Sayuri; Naito, Yuki; Saigo, Kaoru; Noji, Sumihare; Ui-Tei, Kumiko; Ohuchi, Hideyo


    Fgf19 is known to be expressed in the developing chicken eye but its functions during retinal development have remained elusive. Since Fgf19 is expressed in the dorsal portion of the optic cup, it is intriguing to know whether FGF19 is required for expression of dorso-ventral morphogenetic genes in the eye. To clarify this, expression patterns of Tbx5 and Vax were examined in the developing eye after in ovo RNA interference targeted against Fgf19. Quantitative polymerase chain reaction (PCR) analysis showed that the short-hairpin RNAs (shRNAs) targeted against Fgf19 could reduce its expression in the eye to less than 50% of a relative amount of mRNA, compared with contralateral or untreated control eyes. However, no obvious alteration in expression domains of Tbx5 or Vax was observed. Misexpression of Tbx5 or Tbx5-RNAi did not alter the Fgf19 expression either. Furthermore, although Fgf19 is expressed in the central retina before neurogenesis occurs, beta3-tubulin, a marker for early retinal differentiation was still detected in the central retina after knockdown of Fgf19. Thus, knockdown of Fgf19 supports no obvious regulations between Fgf19 and Tbx5, or exhibits no phenotypes that perturb early retinal differentiation.

  4. Alkaline ceramidase 3 deficiency aggravates colitis and colitis-associated tumorigenesis in mice by hyperactivating the innate immune system. (United States)

    Wang, K; Xu, R; Snider, A J; Schrandt, J; Li, Y; Bialkowska, A B; Li, M; Zhou, J; Hannun, Y A; Obeid, L M; Yang, V W; Mao, C


    Increasing studies suggest that ceramides differing in acyl chain length and/or degree of unsaturation have distinct roles in mediating biological responses. However, still much remains unclear about regulation and role of distinct ceramide species in the immune response. Here, we demonstrate that alkaline ceramidase 3 (Acer3) mediates the immune response by regulating the levels of C18:1-ceramide in cells of the innate immune system and that Acer3 deficiency aggravates colitis in a murine model by augmenting the expression of pro-inflammatory cytokines in myeloid and colonic epithelial cells (CECs). According to the NCBI Gene Expression Omnibus (GEO) database, ACER3 is downregulated in immune cells in response to lipopolysaccharides (LPS), a potent inducer of the innate immune response. Consistent with these data, we demonstrated that LPS downregulated both Acer3 mRNA levels and its enzymatic activity while elevating C(18:1)-ceramide, a substrate of Acer3, in murine immune cells or CECs. Knocking out Acer3 enhanced the elevation of C(18:1)-ceramide and the expression of pro-inflammatory cytokines in immune cells and CECs in response to LPS challenge. Similar to Acer3 knockout, treatment with C(18:1)-ceramide, but not C18:0-ceramide, potentiated LPS-induced expression of pro-inflammatory cytokines in immune cells. In the mouse model of dextran sulfate sodium-induced colitis, Acer3 deficiency augmented colitis-associated elevation of colonic C(18:1)-ceramide and pro-inflammatory cytokines. Acer3 deficiency aggravated diarrhea, rectal bleeding, weight loss and mortality. Pathological analyses revealed that Acer3 deficiency augmented colonic shortening, immune cell infiltration, colonic epithelial damage and systemic inflammation. Acer3 deficiency also aggravated colonic dysplasia in a mouse model of colitis-associated colorectal cancer. Taken together, these results suggest that Acer3 has an important anti-inflammatory role by suppressing cellular or tissue C(18

  5. Pseudomonas aeruginosa biofilm aggravates skin inflammatory response in BALB/c mice in a novel chronic wound model

    DEFF Research Database (Denmark)

    Trøstrup, Hannah; Thomsen, Kim; Christophersen, Lars J


    bacteria organized in clusters, resembling biofilms, and inflammation located adjacent to the PA. The chronic wound infection showed a higher number of PAO1 in the BALB/c mice at day 4 after infection as compared to C3H/HeN mice (p ... in the chronic wounds of BALB/c mice was observed at day 7 (p biofilm infection in mice. The results showed an aggravating impact of local inflammation induced by PA biofilms......Chronic wounds are presumed to persist in the inflammatory state, preventing healing. Emerging evidence indicates a clinical impact of bacterial biofilms in soft tissues, including Pseudomonas aeruginosa (PA) biofilms. To further investigate this, we developed a chronic PA biofilm wound infection...

  6. Human-specific SNP in obesity genes, adrenergic receptor beta2 (ADRB2, Beta3 (ADRB3, and PPAR γ2 (PPARG, during primate evolution.

    Directory of Open Access Journals (Sweden)

    Akiko Takenaka

    Full Text Available UNLABELLED: Adrenergic-receptor beta2 (ADRB2 and beta3 (ADRB3 are obesity genes that play a key role in the regulation of energy balance by increasing lipolysis and thermogenesis. The Glu27 allele in ADRB2 and the Arg64 allele in ADRB3 are associated with abdominal obesity and early onset of non-insulin-dependent diabetes mellitus (NIDDM in many ethnic groups. Peroxisome proliferator-activated receptor γ (PPARG is required for adipocyte differentiation. Pro12Ala mutation decreases PPARG activity and resistance to NIDDM. In humans, energy-expense alleles, Gln27 in ADRB2 and Trp64 in ADRB3, are at higher frequencies than Glu27 and Arg64, respectively, but Ala12 in PPARG is at lower frequency than Pro12. Adaptation of humans for lipolysis, thermogenesis, and reduction of fat accumulation could be considered by examining which alleles in these genes are dominant in non-human primates (NHP. All NHP (P. troglodytes, G. gorilla, P. pygmaeus, H. agilis and macaques had energy-thrifty alleles, Gly16 and Glu27 in ADRB2, and Arg64 in ADRB3, but did not have energy-expense alleles, Arg16, Gln27 and Trp64 alleles. In PPARG gene, all NHP had large adipocyte accumulating type, the Pro12 allele. CONCLUSIONS: These results indicate that a tendency to produce much more heat through the energy-expense alleles developed only in humans, who left tropical rainforests for savanna and developed new features in their heat-regulation systems, such as reduction of body hair and increased evaporation of water, and might have helped the protection of entrails from cold at night, especially in glacial periods.

  7. Human-Specific SNP in Obesity Genes, Adrenergic Receptor Beta2 (ADRB2), Beta3 (ADRB3), and PPAR γ2 (PPARG), during Primate Evolution (United States)

    Takenaka, Akiko; Nakamura, Shin; Mitsunaga, Fusako; Inoue-Murayama, Miho; Udono, Toshifumi; Suryobroto, Bambang


    Adrenergic-receptor beta2 (ADRB2) and beta3 (ADRB3) are obesity genes that play a key role in the regulation of energy balance by increasing lipolysis and thermogenesis. The Glu27 allele in ADRB2 and the Arg64 allele in ADRB3 are associated with abdominal obesity and early onset of non-insulin-dependent diabetes mellitus (NIDDM) in many ethnic groups. Peroxisome proliferator-activated receptor γ (PPARG) is required for adipocyte differentiation. Pro12Ala mutation decreases PPARG activity and resistance to NIDDM. In humans, energy-expense alleles, Gln27 in ADRB2 and Trp64 in ADRB3, are at higher frequencies than Glu27 and Arg64, respectively, but Ala12 in PPARG is at lower frequency than Pro12. Adaptation of humans for lipolysis, thermogenesis, and reduction of fat accumulation could be considered by examining which alleles in these genes are dominant in non-human primates (NHP). All NHP (P. troglodytes, G. gorilla, P. pygmaeus, H. agilis and macaques) had energy-thrifty alleles, Gly16 and Glu27 in ADRB2, and Arg64 in ADRB3, but did not have energy-expense alleles, Arg16, Gln27 and Trp64 alleles. In PPARG gene, all NHP had large adipocyte accumulating type, the Pro12 allele. Conclusions These results indicate that a tendency to produce much more heat through the energy-expense alleles developed only in humans, who left tropical rainforests for savanna and developed new features in their heat-regulation systems, such as reduction of body hair and increased evaporation of water, and might have helped the protection of entrails from cold at night, especially in glacial periods. PMID:22937051

  8. Systematic determination of the peptide acceptor preferences for the human UDP-Gal:glycoprotein-alpha-GalNAc beta 3 galactosyltransferase (T-synthase). (United States)

    Perrine, Cynthia; Ju, Tongzhong; Cummings, Richard D; Gerken, Thomas A


    Mucin-type protein O-glycosylation is initiated by the addition of alpha-GalNAc to Ser/Thr residues of a polypeptide chain. The addition of beta-Gal to GalNAc by the UDP-Gal:glycoprotein-alpha-GalNAc beta 3 galactosyltransferase (T-synthase), forming the Core 1 structure (beta-Gal(1-3)-alpha-GalNAc-O-Ser/Thr), is a common and biologically significant subsequent step in O-glycan biosynthesis. What dictates the sites of Core 1 glycosylation is poorly understood; however, the peptide sequence and neighboring glycosylation effects have been implicated. To systematically address the role of the peptide sequence on the specificity of T-synthase, we used the oriented random glycopeptide: GAGAXXXX(T-O-GalNAc)XXXXAGAG (where X = G, A, P, V, I, F, Y, S, N, D, E, H, R, and K) as a substrate. The Core 1 glycosylated product was isolated on immobilized PNA (Arachis hypogaea) lectin and its composition determined by Edman amino acid sequencing for comparison with the initial substrate composition, from which transferase preferences were obtained. From these studies, elevated preferences for Gly at the +1 position with moderately high preferences for Phe and Tyr in the +3 position relative to the acceptor Thr-O-GalNAc were found. A number of smaller Pro enhancements were also observed. Basic residues, i.e., Lys, Arg, and His, in any position were disfavored, suggesting electrostatic interactions as an additional important component modulating transferase specificity. This work suggests that there are indeed subtle specific and nonspecific protein-targeting sequence motifs for this transferase.

  9. [Case of distal renal tubular acidosis complicated with renal diabetes insipidus, showing aggravation of symptoms with occurrence of diabetes mellitus]. (United States)

    Liu, Hexing; Tomoda, Fumihiro; Koike, Tsutomu; Ohara, Maiko; Nakagawa, Taizo; Kagitani, Satoshi; Inoue, Hiroshi


    We report herein a 27-year-old male case of inherited distal renal tubular acidosis complicated with renal diabetes insipidus, the symptoms of which were aggravated by the occurrence of diabetes mellitus. At 2 months after birth, he was diagnosed as having inherited distal renal tubular acidosis and thereafter supplementation of both potassium and alkali was started to treat his hypokalemia and metabolic acidosis. At the age of 4 years, calcification of the bilateral renal medulla was detected by computed tomography. Subsequently his urinary volume gradually increased and polyuria of approximately 4 L/day persisted. At the age of 27 years, he became fond of sugar-sweetened drinks and also often forgot to take the medicine. He was admitted to our hospital due to polyuria of more than 10 L day, muscle weakness and gait disturbance. Laboratory tests disclosed worsening of both hypokalemia and metabolic acidosis in addition to severe hyperglycemia. It seemed likely that occurrence of diabetes mellitus and cessation of medications can induce osmotic diuresis and aggravate hypokalemia and metabolic acidosis. Consequently, severe dehydration, hypokalemia-induced damage of his urinary concentration ability and enhancement of the renin angiotensin system occurred and thereby possibly worsened his hypokalemia and metabolic acidosis. As normalization of hyperglycemia and metabolic acidosis might have exacerbated hypokalemia further, dehydration and hypokalemia were treated first. Following intensive treatment, these abnormalities were improved, but polyuria persisted. Elevated plasma antidiuretic hormone (12.0 pg/mL) and deficit of renal responses to antidiuretic hormone suggested that the polyuria was attributable to the preexisting renal diabetes insipidus possibly caused by bilateral renal medulla calcification. Thiazide diuretic or nonsteroidal anti-inflammatory drugs were not effective for the treatment of diabetes insipidus in the present case.

  10. TNF-Like Weak Inducer of Apoptosis Aggravates Left Ventricular Dysfunction after Myocardial Infarction in Mice

    Directory of Open Access Journals (Sweden)

    Kai-Uwe Jarr


    Full Text Available Background. TNF-like weak inducer of apoptosis (TWEAK has recently been shown to be potentially involved in adverse cardiac remodeling. However, neither the exact role of TWEAK itself nor of its receptor Fn14 in this setting is known. Aim of the Study. To analyze the effects of sTWEAK on myocardial function and gene expression in response to experimental myocardial infarction in mice. Results. TWEAK directly suppressed the expression of PGC-1α and genes of oxidative phosphorylation (OXPHOS in cardiomyocytes. Systemic sTWEAK application after MI resulted in reduced left ventricular function and increased mortality without changes in interstitial fibrosis or infarct size. Molecular analysis revealed decreased phosphorylation of PI3K/Akt and ERK1/2 pathways associated with reduced expression of PGC-1α and PPARα. Likewise, expression of OXPHOS genes such as atp5O, cycs, cox5b, and ndufb5 was also reduced. Fn14 -/- mice showed significantly improved left ventricular function and PGC-1α levels after MI compared to their respective WT littermates (Fn14 +/+. Finally, inhibition of intrinsic TWEAK with anti-TWEAK antibodies resulted in improved left ventricular function and survival. Conclusions. TWEAK exerted maladaptive effects in mice after myocardial infarction most likely via direct effects on cardiomyocytes. Analysis of the potential mechanisms revealed that TWEAK reduced metabolic adaptations to increased cardiac workload by inhibition of PGC-1α.

  11. G-protein beta3 subunit gene variant is unlikely to have a significant influence on serum uric acid level in Japanese workers. (United States)

    Suwazono, Yasushi; Kobayashi, Etsuko; Uetani, Mirei; Miura, Katsuyuki; Morikawa, Yuko; Ishizaki, Masao; Kido, Teruhiko; Nakagawa, Hideaki; Nogawa, Koji


    The C825T variant of the G-protein beta3 subunit (GNB3) gene has attracted renewed attention as a candidate gene for obesity, hypertension and hyperuricemia. The main role of G-protein is to translate signals from the cell surface into a cellular response. The 825T allele is associated with a splice variant of GNB3 protein and enhanced G-protein activation. We examined the relationship between this variant and the risk of hyperuricemia in Japanese workers. The study subjects were 1,452 men and 1,169 women selected from 3,834 men and 2,591 women in 1997. On the basis of common clinical criteria, hyperuricemia I was defined as serum uric acid >or= 7.0 mg/dl in men and 6.0 mg/dl in women or taking antihyperuricemic medication. The hyperuricemia I group consisted of 186 men and 20 women and its control of 1,266 men and 1,149 women. Hyperuricemia II was defined as serum uric acid > 5.7 mg/dl (median) in men and 3.9 mg/dl (median) in women or taking antihyperuricemic medication. The hyperuricemic II group consisted of 684 men and 570 women and its control of 768 men and 599 women. To replicate previous significant results in young Caucasian men, we selected these criteria because the authors of the study in young Caucasian men adopted the median in their subjects as a cut-off. The statistical power was estimated as 99% based on the significant results in Caucasians. Genotype and allele distributions in men and women with hyperuricemia I and II were not significantly different from those in the corresponding control groups. Logistic regression analysis on hyperuricemia I and II, and multiple regression on serum uric acid level demonstrated no significant effect of the C825T genotype. Despite the sufficient statistical power, this study could not demonstrate the significant influence of C825T on hyperuricemia or serum uric acid. The targeting of this polymorphism is unlikely to be beneficial in the prevention of hyperuricemia in the general Japanese population.

  12. High-NaCl Diet Aggravates Cardiac Injury in Rats with Adenine-Induced Chronic Renal Failure and Increases Serum Troponin T Levels

    DEFF Research Database (Denmark)

    Kashioulis, Pavlos; Hammarsten, Ola; Marcussen, Niels


    correlation between the degree of LV fibrosis and serum cTnT levels in ACRF rats (r = 0.81, p produces LV injury and aggravates increases in serum cTnT levels, presumably by causing hypertension-induced small artery lesions leading...

  13. Prostacyclin inhibition by indomethacin aggravates hepatic damage and encephalopathy in rats with thioacetamide-induced fulminant hepatic failure

    Institute of Scientific and Technical Information of China (English)

    Chi-Jen Chu; Shou-Dong Lee; Ching-Chin Hsiao; Teh-Fang Wang; Cho-Yu Chan; Fa-Yauh Lee; Full-Young Chang; Yi-Chou Chen; Hui-Chun Huang; Sun-Sang Wang


    AIM: Vasodilatation and increased capillary permeability have been proposed to be involved in the pathogenesis of acute and chronic form of hepatic encephalopathy.Prostacyclin (PGI2) and nitric oxide (NO) are important contributors to hyperdynamic circulation in portal hypertensive states. Our previous study showed that chronic inhibition of NO had detrimental effects on the severity of encephalopathy in thioacetamide (TAA)-treated rats due to aggravation of liver damage. To date, there are no detailed data concerning the effects of PGI2 inhibition on the severity of hepatic encephalopathy during fulminant hepatic failure.METHODS: Male Sprague-Dawley rats weighing 300-350 g were used. Fulminant hepatic failure was induced by were divided into two groups to receive intraperitoneal saline (N/S, n = 20) for 5 d, starting 2 d before TAA administration. Severity of encephalopathy was assessed by the counts of motor activity measured with Opto-Varimex animal activity meter. Plasma tumor necrosis factor-α(TNF-α, an index of liver injury) and 6-keto-PGF1α (a metabolite of PGI2) levels were measured by enzyme-linked immunosorbent assay.RESULTS: As compared with N/S-treated rats, the mortality rate was significantly higher in rats receiving indomethacin (20% vs5%, P<0.01). Inhibition of PGI2 created detrimental effects on total movement counts (indomethacin vs N/S:438±102 vs841±145 counts/30 min, P<0.05). Rats treated with indomethacin had significant higher plasma levels of TNF-α (indomethacin vsN/S: 22±5 vs 10±1 pg/mL, P<0.05)and lower plasma levels of 6-keto-PGF1α (P<0.001), but not total bilirubin or creatinine (P>0.05), as compared with rats treated with N/S.CONCLUSION: Chronic indomethacin administration has detrimental effects on the severity of encephalopathy in TAA-treated rats and this phenomenon may be attributed to the aggravation of liver injury. This study suggests that PGI2 may provide a protective role in the development of fulminant

  14. IL-33 Aggravates DSS-Induced Acute Colitis in Mouse Colon Lamina Propria by Enhancing Th2 Cell Responses. (United States)

    Zhu, Junfeng; Yang, Fangli; Sang, Lixuan; Zhai, Jingbo; Zhang, Xiaoqing; Yue, Dan; Li, Shengjun; Li, Yan; Lu, Changlong; Sun, Xun


    Interleukin- (IL-) 33, a member of the IL-1 cytokine family, is an important modulator of the immune system associated with several immune-mediated diseases. IL-33 was expressed in high level on epithelial cells of intestinal tract. It suggested that IL-33 plays a potential role in inflammatory bowel diseases (IBD). We investigated the role of interleukin- (IL-) 33 in dextran sulphate sodium- (DSS-) induced acute colitis in mice using recombinant mouse IL-33 protein (rIL-33). We found that DSS-induced acute colitis was aggravated by rIL-33 treatment. rIL-33-treated DSS mice showed markedly reduced levels of interferon- (IFN-)γ and IL-17A in their colon lamina propria lymphocytes (LPL), but the levels of Th2 cytokines, such as IL-5 and IL-13, in these cells were significantly increased, compared to DSS mice treated with PBS. Our results suggested that IL-33 stimulated CD4(+)T cells and caused the cell to adopt a Th2-type response but at the same time suppressed Th17 and Th1 cell responses. Therefore, IL-33 may be involved in pathogenesis of DSS-induced acute colitis by promoting Th2 cell response in intestinal mucosa of mice. Modulation of IL-33/ST2 signaling by monoclonal antibody (mAb) could be a novel biological therapy in DSS-induced acute colitis.

  15. Accelerated dysbiosis of gut microbiota during aggravation of DSS-induced colitis by a butyrate-producing bacterium. (United States)

    Zhang, Qianpeng; Wu, Yanqiu; Wang, Jing; Wu, Guojun; Long, Wenmin; Xue, Zhengsheng; Wang, Linghua; Zhang, Xiaojun; Pang, Xiaoyan; Zhao, Yufeng; Zhao, Liping; Zhang, Chenhong


    Butyrate-producing bacteria (BPB) are potential probiotic candidates for inflammatory bowel diseases as they are often depleted in the diseased gut microbiota. However, here we found that augmentation of a human-derived butyrate-producing strain, Anaerostipes hadrus BPB5, significantly aggravated colitis in dextran sulphate sodium (DSS)-treated mice while exerted no detrimental effect in healthy mice. We explored how the interaction between BPB5 and gut microbiota may contribute to this differential impact on the hosts. Butyrate production and severity of colitis were assessed in both healthy and DSS-treated mice, and gut microbiota structural changes were analysed using high-throughput sequencing. BPB5-inoculated healthy mice showed no signs of colitis, but increased butyrate content in the gut. In DSS-treated mice, BPB5 augmentation did not increase butyrate content, but induced significantly more severe disease activity index and much higher mortality. BPB5 didn't induce significant changes of gut microbiota in healthy hosts, but expedited the structural shifts 3 days earlier toward the disease phase in BPB5-augmented than DSS-treated animals. The differential response of gut microbiota in healthy and DSS-treated mice to the same potentially beneficial bacterium with drastically different health consequences suggest that animals with dysbiotic gut microbiota should also be employed for the safety assessment of probiotic candidates.

  16. Absence of Intestinal PPARγ Aggravates Acute Infectious Colitis in Mice through a Lipocalin-2–Dependent Pathway (United States)

    Kundu, Parag; Ling, Teo Wei; Korecka, Agata; Li, Yinghui; D'Arienzo, Rossana; Bunte, Ralph M.; Berger, Thorsten; Arulampalam, Velmurugesan; Chambon, Pierre; Mak, Tak Wah; Wahli, Walter; Pettersson, Sven


    To be able to colonize its host, invading Salmonella enterica serovar Typhimurium must disrupt and severely affect host-microbiome homeostasis. Here we report that S. Typhimurium induces acute infectious colitis by inhibiting peroxisome proliferator-activated receptor gamma (PPARγ) expression in intestinal epithelial cells. Interestingly, this PPARγ down-regulation by S. Typhimurium is independent of TLR-4 signaling but triggers a marked elevation of host innate immune response genes, including that encoding the antimicrobial peptide lipocalin-2 (Lcn2). Accumulation of Lcn2 stabilizes the metalloproteinase MMP-9 via extracellular binding, which further aggravates the colitis. Remarkably, when exposed to S. Typhimurium, Lcn2-null mice exhibited a drastic reduction of the colitis and remained protected even at later stages of infection. Our data suggest a mechanism in which S. Typhimurium hijacks the control of host immune response genes such as those encoding PPARγ and Lcn2 to acquire residence in a host, which by evolution has established a symbiotic relation with its microbiome community to prevent pathogen invasion. PMID:24465207

  17. Partial pyruvate kinase deficiency aggravates the phenotypic expression of band 3 deficiency in a family with hereditary spherocytosis. (United States)

    van Zwieten, Rob; van Oirschot, Brigitte A; Veldthuis, Martijn; Dobbe, Johannes G; Streekstra, Geert J; van Solinge, Wouter W; Schutgens, Roger E G; van Wijk, Richard


    In a family with mild dominant spherocytosis, affected members showed partial band 3 deficiency. The index patient showed more severe clinical symptoms than his relatives, and his red blood cells displayed concomitant low pyruvate kinase activity. We investigated the contribution of partial PK deficiency to the phenotypic expression of mutant band 3 in this family. Pyruvate kinase deficiency and band 3 deficiency were characterized by DNA analysis. Results of red cell osmotic fragility testing, the results of cell deformability obtained by the Automated Rheoscope and Cell Analyzer and the results obtained by Osmotic Gradient Ektacytometry, which is a combination of these tests, were related to the red cell ATP content. Spherocytosis in this family was due to a novel heterozygous mutation in SLC4A1, the gene for band 3. Reduced PK activity of the index patient was attributed to a novel mutation in PKLR inherited from his mother, who was without clinical symptoms. Partial PK deficiency was associated with decreased red cell ATP content and markedly increased osmotic fragility. This suggests an aggravating effect of low ATP levels on the phenotypic expression of band 3 deficiency.

  18. A new update for radiocontrast-induced nephropathy aggravated with glycerol in rats: the protective potential of epigallocatechin-3-gallate. (United States)

    Palabiyik, Saziye Sezin; Dincer, Busra; Cadirci, Elif; Cinar, Irfan; Gundogdu, Cemal; Polat, Beyzagul; Yayla, Muhammed; Halici, Zekai


    Contrast media (CM) is known to have nephrotoxic adverse effects. Epigallocatechin-3-gallate (EGCG) is the most abundant and active catechin in green tea, and has strong antioxidant and anti-inflammatory properties. This study investigated whether EGCG can reduce contrast-induced nephrotoxicity (CIN), alone or with glycerol (GLY)-induced renal damage, and to understand its mechanisms of protection against toxicity, using models of GLY and CIN in rats. The rats were separated into eight groups (n = 6 in each), as follows: Healthy, GLY, CM, GLY + CM, CM + EGCG 50 mg/kg (po), GLY + CM + EGCG 50 mg/kg (po), CM + EGCG 100 mg/kg (po), and GLY + CM + EGCG 100 mg/kg (po). Both doses of EGCG protected against CM-induced renal dysfunction, as measured by serum creatinine and blood urea nitrogen (BUN). In addition, EGCG treatment markedly improved CIN-induced oxidative stress, and resulted in a significant down-regulatory effect on tumor necrosis factor (TNF)-α and nuclear factor (NF)-κB mRNA expression. Moreover, histopathological analysis showed that EGCG also attenuated CM-induced kidney damage. Considering the potential clinical use of CM and the numerous health benefits of EGCG, this study showed the protective role of multi-dose EGCG treatment on CIN and GLY-aggravated CIN through different mechanisms.

  19. Aggravation of brain infarction through an increase in acrolein production and a decrease in glutathione with aging. (United States)

    Uemura, Takeshi; Watanabe, Kenta; Ishibashi, Misaki; Saiki, Ryotaro; Kuni, Kyoshiro; Nishimura, Kazuhiro; Toida, Toshihiko; Kashiwagi, Keiko; Igarashi, Kazuei


    We previously reported that tissue damage during brain infarction was mainly caused by inactivation of proteins by acrolein. This time, it was tested why brain infarction increases in parallel with aging. A mouse model of photochemically induced thrombosis (PIT) was studied using 2, 6, and 12 month-old female C57BL/6 mice. The size of brain infarction in the mouse PIT model increased with aging. The volume of brain infarction in 12 month-old mice was approximately 2-fold larger than that in 2 month-old mice. The larger brain infarction in 12 month-old mice was due to an increase in acrolein based on an increase in the activity of spermine oxidase, together with a decrease in glutathione (GSH), a major acrolein-detoxifying compound in cells, based on the decrease in one of the subunits of glutathione biosynthesizing enzymes, γ-glutamylcysteine ligase modifier subunit, with aging. The results indicate that aggravation of brain infarction with aging was mainly due to the increase in acrolein production and the decrease in GSH in brain.

  20. Continuing Exposure to Low-Dose Nonylphenol Aggravates Adenine-Induced Chronic Renal Dysfunction and Role of Rosuvastatin Therapy

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    Yen Chia-Hung


    Full Text Available Abstract Background Nonylphenol (NP, an environmental organic compound, has been demonstrated to enhance reactive-oxygen species (ROS synthesis. Chronic exposure to low-dose adenine (AD has been reported to induce chronic kidney disease (CKD. Methods In this study, we tested the hypothesis that chronic exposure to NP will aggravate AD-induced CKD through increasing generations of inflammation, ROS, and apoptosis that could be attenuated by rosuvastatin. Fifty male Wistar rats were equally divided into group 1 (control, group 2 (AD in fodder at a concentration of 0.25%, group 3 (NP: 2 mg/kg/day, group 4 (combined AD & NP, and group 5 (AD-NP + rosuvastatin: 20 mg/kg/day. Treatment was continued for 24 weeks for all animals before being sacrificed. Results By the end of 24 weeks, serum blood urea nitrogen (BUN and creatinine levels were increased in group 4 than in groups 1–3, but significantly reduced in group 5 as compared with group 4 (all p  Conclusion NP worsened AD-induced CKD that could be reversed by rosuvastatin therapy.

  1. Food-advanced glycation end products aggravate the diabetic vascular complications via modulating the AGEs/RAGE pathway. (United States)

    Lv, Xing; Lv, Gao-Hong; Dai, Guo-Ying; Sun, Hong-Mei; Xu, Hui-Qin


    The aim of this study was to investigate the effects of high-advanced glycation end products (AGEs) diet on diabetic vascular complications. The Streptozocin (STZ)-induced diabetic mice were fed with high-AGEs diet. Diabetic characteristics, indicators of renal and cardiovascular functions, and pathohistology of pancreas, heart and renal were evaluated. AGEs/RAGE/ROS pathway parameters were determined. During the experiments, the diabetic mice exhibited typical characteristics including weight loss, polydipsia, polyphagia, polyuria, high-blood glucose, and low-serum insulin levels. However, high-AGEs diet effectively aggravated these diabetic characteristics. It also increased the 24-h urine protein levels, serum levels of urea nitrogen, creatinine, c-reactive protein (CRP), low density lipoprotein (LDL), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in the diabetic mice. High-AGEs diet deteriorated the histology of pancreas, heart, and kidneys, and caused structural alterations of endothelial cells, mesangial cells and podocytes in renal cortex. Eventually, high-AGEs diet contributed to the high-AGE levels in serum and kidneys, high-levels of reactive oxygen species (ROS) and low-levels of superoxide dismutase (SOD) in serum, heart, and kidneys. It also upregulated RAGE mRNA and protein expression in heart and kidneys. Our results showed that high-AGEs diet deteriorated vascular complications in the diabetic mice. The activation of AGEs/RAGE/ROS pathway may be involved in the pathogenesis of vascular complications in diabetes.

  2. Genetic predisposition to essential hypertension in a Mongolian population Detecting the C825T polymorphism of the G-protein beta 3 subunit gene

    Institute of Scientific and Technical Information of China (English)

    Chunyu Zhang; Shigang Zhao; Guangming Niu; Rile Hu; Zhiguang Wang; Mingfang Jiang; Rile Hu


    BACKGROUND: The prevalences of hypertension, cerebrovascular diseases, etc. are higher in Mongolian population because of the influence of various factors including genetics, geography, diet, etc. Therefore, it is helpful for prevention to develop researches on the genetics of various diseases including hypertension in Mongolian population.OBJECTIVE: To analyze the association between C825T polymorphisms of G-protein beta 3 subunit gene (GNB3), the important candidate gene of various disease of cardiovascular system, and Mongolian patients with essential hypertension.DESIGN: A comparative observation.SETTINGS: Department of Neurology, the First Affiliated Hospital of Inner Mongolia Medical College;Wulate Houqi Red Cross Society.PARTICIPANTS: Totally 267 Mongolian residents, whose blood relations of 3 generations were all Mongolians, were selected from Wulate Houqi, Inner Mongolia. The patients were screened based on the diagnostic standard of hypertension set by WHO in 1999, and the enrolled subjects were divided into two groups according to the level of blood pressure: ① Normal blood pressure group (n =124): 64 males and 60 females, systolic blood pressure (SBP) < 140 mm Hg (1 mm Hg=0.133 kPa), diastolic blood pressure (DBP) <90 mm Hg; ② Essential hypertension group (n =143): 71 males and 72 females, including 60 patients with simple high SBP (SBP ranged 145 to 195 mm Hg, whereas DBP < 90 mm Hg).METHODS: Peripheral venous blood (5 mL) was drawn from all the subjects, the genome DNA was extracted, and the polymorphisms of the GNB3 C825T genotype were detected with the Sequenom system.Polymerase chain reaction (PCR) experiment and SNP detection were performed in Beijing Huada gene laboratory. Then the univariate analysis of variance was applied in the sample comparison among groups, and the chi-square test was used to compare the genotypes and allele frequencies. The odd ratio (OR) and 95% confidence interval (CI)were calculated.MAIN OUTCOME MEASURES: The

  3. Over-starvation aggravates intestinal injury and promotes bacterial and endotoxin translocation under high-altitude hypoxic environment

    Institute of Scientific and Technical Information of China (English)

    Qi-Quan Zhou; Ding-Zhou Yang; Yong-Jun Luo; Su-Zhi Li; Fu-Yu Liu; Guan-Song Wang


    AIM: To study whether over-starvation aggravates intestinal mucosal injury and promotes bacterial and endotoxin translocation in a high-altitude hypoxic environment. METHODS: Sprague-Dawley rats were exposed to hypobaric hypoxia at a simulated altitude of 7000 m for 72 h. Lanthanum nitrate was used as a tracer to detect intestinal injury. Epithelial apoptosis was observed with terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Serum levels of diamino oxidase (DAO), malondialdehyde (MDA), glutamine (Gln), superoxide dismutase (SOD) and endotoxin were measured in intestinal mucosa. Bacterial translocation was detected in blood culture and intestinal homogenates. In addition, rats were given Gln intragastrically to observe its protective effect on intestinal injury. RESULTS: Apoptotic epithelial cells, exfoliated villi and inflammatory cells in intestine were increased with edema in the lamina propria accompanying effusion of red blood cells. Lanthanum particles were found in the intercellular space and intracellular compartment. Bacterial translocation to mesenteric lymph nodes (MLN) and spleen was evident. The serum endotoxin, DAO and MDA levels were significantly higher while the serum SOD, DAO and Gln levels were lower in intestine (P < 0.05). The bacterial translocation number was lower in the high altitude hypoxic group than in the high altitude starvation group (0.47 ± 0.83 vs 2.38 ± 1.45, P < 0.05). The bacterial translocation was found in each organ, especially in MLN and spleen but not in peripheral blood. The bacterial and endotoxin translocations were both markedly improved in rats after treatment with Gln. CONCLUSION: High-altitude hypoxia and starvation cause severe intestinal mucosal injury and increase bacterial and endotoxin translocation, which can be treated with Gln.

  4. Aggravation of north channels' shrinkage and south channels' development in the Yangtze Estuary under dam-induced runoff discharge flattening (United States)

    Zhu, Bo-yuan; Li, Yi-tian; Yue, Yao; Yang, Yun-ping


    Construction of dams on rivers has progressively affected the seasonal variability of runoff discharge, which has consequently produced remarkable impacts on the morphology of estuarine channels. This paper considers four-typical-order bifurcations of the Yangtze Estuary and adopts an ebb partition ratio (defined as the diversion ratio of ebb flow in a given branch divided by the total ebb tidal discharge immediately upstream of the river node where the bifurcation occurs) as a measure of water excavating force in the bifurcation channels. Results show that the seasonal variability of runoff discharge at Datong Hydrological Station (Datong) is flattened, being mainly driven by upstream runoff flattening observed at Yichang Hydrological Station (Yichang) and the tributary rivers. Yearly ebb partition ratios of the channels located to the north and south of the islands present decreasing and increasing trends respectively, and as also do the yearly north and south channel volume of the bifurcations. Yearly ebb partition ratio is proved to be an effective index to represent the water excavating force considering the stability of yearly ebb tidal discharge and its relationship with the channel erosion-deposition. River dams are the driving factors behind the runoff flattening at Datong because of their flattening effects on its main contributors (Yichang and tributary rivers). This flattening significantly helps reduce and enlarge the yearly ebb partition ratios of the north and south channels respectively, and then aggravates the shrinkage and development of the north and south channels separately. Yearly ebb partition ratio of the North Passage (NP) must be enlarged in order for the NP to maintain its function as a shipping channel.

  5. Erosive arthritis and hepatic granuloma formation induced by peptidoglycan polysaccharide in rats is aggravated by prasugrel treatment.

    Directory of Open Access Journals (Sweden)

    Analia E Garcia

    Full Text Available Administration of the thienopyridine P2Y12 receptor antagonist, clopidogrel, increased the erosive arthritis induced by peptidoglycan polysaccharide (PG-PS in rats or by injection of the arthritogenic K/BxN serum in mice. To determine if the detrimental effects are caused exclusively by clopidogrel, we evaluated prasugrel, a third-generation thienopyridine pro-drug, that contrary to clopidogrel is mostly metabolized into its active metabolite in the intestine. Prasugrel effects were examined on the PG-PS-induced arthritis rat model. Erosive arthritis was induced in Lewis rats followed by treatment with prasugrel for 21 days. Prasugrel treated arthritic animals showed a significant increase in the inflammatory response, compared with untreated arthritic rats, in terms of augmented macroscopic joint diameter associated with significant signs of inflammation, histomorphometric measurements of the hind joints and elevated platelet number. Moreover, fibrosis at the pannus, assessed by immunofluorescence of connective tissue growth factor, was increased in arthritic rats treated with prasugrel. In addition to the arthritic manifestations, hepatomegaly, liver granulomas and giant cell formation were observed after PG-PS induction and even more after prasugrel exposure. Cytokine plasma levels of IL-1 beta, IL-6, MIP1 alpha, MCP1, IL-17 and RANTES were increased in arthritis-induced animals. IL-10 plasma levels were significantly decreased in animals treated with prasugrel. Overall, prasugrel enhances inflammation in joints and liver of this animal model. Since prasugrel metabolites inhibit neutrophil function ex-vivo and the effects of both clopidogrel and prasugrel metabolites on platelets are identical, we conclude that the thienopyridines metabolites might exert non-platelet effects on other immune cells to aggravate inflammation.

  6. Iron as a possible aggravating factor for osteopathy in itai-itai disease, a disease associated with chronic cadmium intoxication

    Energy Technology Data Exchange (ETDEWEB)

    Noda, M.; Yasuda, M.; Kitagawa, M. (Toyama Medical and Pharmaceutical Univ. (Japan))


    Itai-itai disease is thought to be the result of chronic cadmium (Cd) intoxication. We examined 23 autopsy cases of itai-itai disease and 18 cases of sudden death as controls. Urine and blood samples from 10 patients were collected before they died and revealed the presence of severe anemia and renal tubular injuries. Undecalcified sections of iliac bone were stained with Aluminon reagent, and ammonium salt of aurintricarboxylic acid, and Prussian blue reagent in all cases of itai-itai disease. These two reagents reacted at the same mineralization fronts. X-ray microanalysis revealed the presence of iron at mineralization fronts in itai-itai disease. Five patients showed evidence of hemosiderosis in the liver, spleen, and pancreas, probably as a result of post transfusion iron overload. Renal calculi and calcified aortic walls were also stained with Prussian blue reagent in several patients. Neither ferritin nor transferrin were visualized at mineralization fronts in itai-itai disease by immunohistochemical staining. These results suggest that iron is bound to calcium or to calcium phosphate by a physicochemical reaction. A marked osteomalacia was observed in 10 cases of itai-itai disease by histomorphometry. Regression analyses of data from cases of itai-itai disease suggested that an Aluminon-positive metal inhibited mineralization and that renal tubules were injured. Since bone Cd levels were increased in itai-itai disease, it is likely that renal tubules were injured by exposure to Cd. Therefore, stainable bone iron is another possible aggravating factor for osteopathy in itai-itai disease, and a synergistic effect between iron and Cd on mineralization is proposed.

  7. Extracellular heat-shock protein 70 aggravates cerulein-induced pancreatitis through toll-like receptor-4 in mice

    Institute of Scientific and Technical Information of China (English)

    SONG Jun-min; WANG Rong; LIU Hong-xiang; LI Yuan; ZENG Yu-jian; ZHOU Zong-guang; LIU Hai-yi; XU Bing; WANG Ling; ZHOU Bin


    Background In patients suffering from acute pancreatitis, the pathogenesis is not completely understood, and several recent studies in vitro suggested that heat shock proteins might play an important role in cell signaling. To investigate the possible role of extracellular heat shock protein 70 (Hsp70) in pancreatitis, toll-like receptor-4 (TLR4)-deficient and wild-type mice were administered with exogenous Hsp70 during the course of cerulein-induced pancreatitis (CIP).Methods Acute pancreatitis was induced by 5 intraperitoneal injections of cerulein at hourly intervals, and then treated with recombinant Hsp70 through the caudal vein 4 hours after the start of cerulein injections. Subsequently serum amylase and serum cytokines levels were detected. Histologic alteration of the pancreas was evaluated. Tumor necrosis factor alpha (TNF-a) concentrations and myeloperoxidase (MPO) activity in both pancreas and lungs were analyzed. The nuclear factor kappa B (NF-KB) activation in pancreatic tissue was measured using a sensitive RelA enzyme-linked immunosorbent assay.Results Treatment with recombinant Hsp70 to wild-type mice in CIP resulted in significant aggravation of inflammation in pancreas, elevated levels of serum cytokines, up-regulation of pulmonary MPO activity and increase of lung tissues TNF-α concentrations. In contrast, treatment with Hsp70 to TLR4-deficient mice had little effect on serum cytokines levels, pancreatic inflammation, pulmonary MPO activity and TNF-a concentrations.Conclusions The results suggest that extracellular HspTO might induce systemic inflammatory response syndrome (SIRS)-Iike response in vivo and TLR4 might be involved in the Hsp70-mediated activation of inflammatory reaction in the progression of CIP without infection.

  8. Inhibition of JNK aggravates the recovery of rat hearts after global ischemia: the role of mitochondrial JNK.

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    Sehwan Jang

    Full Text Available c-Jun N-terminal kinase (JNK, a stress-activated MAPK, is activated during cardiac ischemia-reperfusion (IR. The role of JNK inhibitors in cardioprotection against IR still remains controversial, in part, due to spill-over effects of non-specific inhibitors. In the present study, we sought to examine whether inhibition of JNK by SU3327, a specific JNK inhibitor that inhibits upstream JNK signaling rather than the kinase activity of JNK, improves cardiac function and reduces heart damage during IR. Hearts of male Sprague-Dawley rats perfused by Langendorff were subjected to 25 min of global ischemia followed by 30 min reperfusion in the presence or absence of SU3327. Cardiac function was monitored throughout the perfusion period. Myocardial damage was extrapolated from LDH activity in the coronary effluent. At the end of reperfusion, mitochondria were isolated and used to measure respiration rates and mitochondrial permeability transition pore opening. Protein analysis of mitochondria predictably revealed that SU3327 inhibited JNK phosphorylation. Although SU3327 significantly reduced cell damage during the first minutes of reperfusion, it did not improve cardiac function and, furthermore, reduced the mitochondrial respiratory control index. Interestingly, SU3327 activated the other stress-related MAPK, p38, and greatly increased its translocation to mitochondria. Mitochondrial P-JNK and P-p38 were co-immunoprecipitated with complex III of the electron transfer chain. Thus, JNK plays an essential role in cardiac signaling under both physiological and pathological conditions. Its inhibition by SU3327 during IR aggravates cardiac function. The detrimental effects of JNK inhibition are associated with reciprocal p38 activation and mitochondrial dysfunction.

  9. High-sodium intake aggravates myocardial injuriesinduced by aldosterone via oxidative stress inSprague-Dawley rats

    Institute of Scientific and Technical Information of China (English)

    Jing-yi LI; Shao-ling ZHANG; Meng REN; Yan-ling WEN; Li YAN; Hua CHENG


    To evaluate the effects of aldosterone with or without high sodium intake on blood pressure,myocardial structure and left ventricular function in rats,and to investigate the mechanisms underlying the effects.Methods:Eight-week-old male Sprague-Dawley rats were randomly divided into 3 groups:(1) control (CON) group fed a normal sodium diet,(2) aldosterone (ALD) group receiving aldosterone infusion and a normal sodium diet,and (3) high sodium plus aldosterone (HS-ALD) group receiving 1% NaCl diet in conjunction with aldosterone infusion.Aldosterone was administered through continuously subcutaneous infusion with osmotic minipump at the rate of 0.75 μg/h for 8 weeks.The myocardium structure was observed using transt-horacic echocardiography and transmission electron microscopy.The collagen deposition in left ventricle was evaluated with Masson'strichrome staining.The expression of IL-18,p22phox,and p47phox proteins was examined using Western blot analysis.Results:The systolic blood pressure in the ALD and HS-ALD groups was significantly higher than that in the CON group after 2-week treatment.But the blood pressure showed no significant difference between the HS-ALD and ALD groups.The left ventricular hyper-trophy,myocardial collagen deposition and oxidative stress were predominantly found in the HS-ALD and ALD group.Furthermore,the breakdown of myocardial structure and oxidative stress were more apparent in the HS-ALD group as compared with those in the ALDgroup.Conclusion:Long-term infusion of aldosterone results in hypertension and profibrotic cardiovascular responses in rats fed a normal sodium diet,which were mediated by oxidative stress.High-sodium intake could aggravate myocardial injuries induced by aldosterone.

  10. In situ assessment of the role of the beta 1-, beta 2- and beta 3-adrenoceptors in the control of lipolysis and nutritive blood flow in human subcutaneous adipose tissue. (United States)

    Barbe, P.; Millet, L.; Galitzky, J.; Lafontan, M.; Berlan, M.


    1. The involvement of beta 1-, beta 2- and beta 3-adrenoceptors in the control of lipolysis and nutritive blood flow was investigated in abdominal subcutaneous adipose tissue of healthy young adults by use of an in situ microdialysis technique. 2. Dialysis probes were infused either with isoprenaline (non-selective beta-adrenoceptor agonist), CGP 12,177 (selective beta 3-adrenoceptor agonist having beta 1-/beta 2-antagonist properties), dobutamine (selective beta 1-adrenoceptor agonist) or terbutaline (selective beta 2-adrenoceptor agonist). The recovery of each probe used for perfusion was calculated by an in vivo calibration method. The local blood flow was estimated through the measurement of the escape of ethanol infused simultaneously with the drugs included in the probe. 3. Isoprenaline infusion at 0.01 microM had a weak effect while higher concentrations of isoprenaline (0.1 and 1 microM) caused a rapid, sustained and concentration-dependent increase of glycerol outflow; the maximum increase was 306 +/- 34% with 1 microM. Isoprenaline also increased the nutritive blood flow in adipose tissue; a significant effect appeared at 0.1 microM isoprenaline and was greater at 1 microM. 4. CGP 12,177 (10 and 100 microM) increased the glycerol concentration in the dialysate (128 +/- 8 and 149 +/- 12%, respectively) and nutritive blood flow. Terbutaline and dobutamine (100 microM) both provoked rapid and similar increases in glycerol outflow (252 +/- 18 and 249 +/- 18%, respectively). Both, terbutaline and dobutamine increased nutritive blood flow. 5. It is concluded that beta 1- and beta 2-adrenoceptor subtypes are both mainly involved in the mobilization of lipids and in the control of nutritive blood flow. beta 3-Adrenoceptors play a weaker role in the control of lipolysis and nutritive blood flow in human subcutaneous abdominal adipose tissue. PMID:8851509

  11. Synthesis, radiolabeling and baboon SPECT imaging of 2{beta}-carbomethoxy-3{beta}-(3'-[{sup 123}I]iodophenyl)tropane ([{sup 123}I]YP256) as a serotonin transporter radiotracer

    Energy Technology Data Exchange (ETDEWEB)

    Bois, Frederic; Baldwin, Ronald M.; Amici, Louis; Al-Tikriti, Mohammed S. [Yale University, School of Medicine, VA Connecticut HCS (116A2), West Haven, CT 06516 (United States); Kula, Nora; Baldessarini, Ross [Department of Psychiatry and Neuroscience Program, Harvard Medical School, Mailman Research Center McLean Division of Massachusetts General Hospital, Belmont, MA 02478 (United States); Innis, Robert B.; Staley, Julie K. [Yale University, School of Medicine, VA Connecticut HCS (116A2), West Haven, CT 06516 (United States); Tamagnan, Gilles D. [Yale University, School of Medicine, VA Connecticut HCS (116A2), West Haven, CT 06516 (United States); Institute for Neurodegenerative Disorders, New Haven, CT 06510 (United States)], E-mail:


    To develop a potential SPECT probe to evaluate the integrity of the serotoninergic system (5-HTT) whose dysfunction is linked to several disease conditions such as Parkinson's disease, Alzheimer's disease and depression, we report the synthesis, radiolabeling and in vivo baboon imaging of 2{beta}-carbomethoxy-3{beta}-(3'-[{sup 123}I]iodophenyl) tropane (YP256, ). The radiolabeling was performed by iododestannylation using sodium [{sup 123}I]iodide and peracetic acid. Although the ligand displayed high selectivity for 5-HTT over dopamine transporter in vitro, SPECT imaging in baboons did not reveal selective 5-HTT accumulation in brain in vivo.

  12. Libraries of RGD analogs, labeled through ReO{sup 3+} or TcO{sup 3+} coordination, targeting {alpha}V{beta}3 integrin: development of tracers for the early detection of tumor neo-angiogenesis; Chimiotheques de complexes du technetium et du rhenium ciblant l'integrine {alpha}V{beta}3: developpement de traceurs pour la detection precoce de la neoangiogenese tumorale

    Energy Technology Data Exchange (ETDEWEB)

    Aufort, M.


    Integrins form a family of hetero-dimeric integral glycoproteins which play a central role in cell-cell adhesion and cell-matrix interactions. In particular, they are over expressed during tumor neo-angiogenesis. About 10 of them recognize a structured RGD (Arg-Gly-Asp) sequence. Analogs of this sequence can be used for the early detection of tumors and metastases. We developed new tracers, labeled with {sup 99m}Tc, for the molecular imaging of {alpha}{sub V{beta}3} integrin. Until recently, there was no reliable ab initio structure prediction of complex molecules containing Re and Tc chelates. Therefore, we preferred a combinatorial approach to develop potential ligands of {alpha}{sub V{beta}3} integrin and we attempted to identify efficient tracers by in vivo screening. This method would account for biodistribution and pharmacokinetics properties in the early steps of the study. Tracers were obtained according two strategies: i) cyclization of linear RGD analogs; ii) combinatorial assembling of independent modules through metal core coordination by the well-known NS{sub 2}+S motif. After synthesis and labeling, the stability of the tracers was investigated in presence of glutathione and in murine plasma. In vitro screening on purified integrin showed that a cyclic rhenium coordinate binds specifically {alpha}{sub V{beta}3}. A tumor model (U87-MG tumor on nude mice) was validated in the laboratory and a method was developed to analyze in vivo experiments. Biodistribution data and percentage of activity found in tumors are encouraging for cyclic compounds though identification of efficient tracers is difficult due to their instability in the conditions of analyses. (author)

  13. Inducible chondrocyte-specific overexpression of BMP2 in young mice results in severe aggravation of osteophyte formation in experimental OA without altering cartilage damage

    NARCIS (Netherlands)

    Davidson, E.N.; Vitters, E.L.; Bennink, M.B.; Lent, P.L. van; Caam, A.P. van; Blom, A.B.; Berg, W.B. van den; Loo, F.A.J. van de; Kraan, P.M. van der


    OBJECTIVES: In osteoarthritis (OA) chondrocytes surrounding lesions express elevated bone morphogenetic protein 2 (BMP2) levels. To investigate the functional consequence of chondrocyte-specific BMP2 expression, we made a collagen type II dependent, doxycycline (dox)-inducible BMP2 transgenic mouse

  14. The in-vivo use of superparamagnetic iron oxide nanoparticles to detect inflammation elicits a cytokine response but does not aggravate experimental arthritis

    NARCIS (Netherlands)

    Vermeij, E.A.; Koenders, M.I.; Bennink, M.B.; Crowe, L.A.; Maurizi, L.; Vallee, J.P.; Hofmann, H.; Berg, W.B. van den; Lent, P.L. van; Loo, F.A. van de


    BACKGROUND: Superparamagnetic Iron Oxide Nanoparticles (SPION) are used in diagnostic imaging of a variety of different diseases. For such in-vivo application, an additional coating with a polymer, for example polyvinyl alcohol (PVA), is needed to stabilize the SPION and prevent aggregation. As the

  15. Acute cold exposure-induced down-regulation of CIDEA, cell death-inducing DNA fragmentation factor-alpha-like effector A, in rat interscapular brown adipose tissue by sympathetically activated beta3-adrenoreceptors. (United States)

    Shimizu, Takahiro; Yokotani, Kunihiko


    The thermogenic activity of brown adipose tissue (BAT) largely depends on the mitochondrial uncoupling protein 1 (UCP1), which is up-regulated by environmental alterations such as cold. Recently, CIDEA (cell death-inducing DNA fragmentation factor-alpha-like effector A) has also been shown to be expressed at high levels in the mitochondria of BAT. Here we examined the effect of cold on the mRNA and protein levels of CIDEA in interscapular BAT of conscious rats with regard to the sympathetic nervous system. Cold exposure (4 degrees C for 3h) elevated the plasma norepinephrine level and increased norepinephrine turnover in BAT. Cold exposure resulted in down-regulation of the mRNA and protein levels of CIDEA in BAT, accompanied by up-regulation of mRNA and protein levels of UCP1. The cold exposure-induced changes of CIDEA and UCP1 were attenuated by intraperitoneal pretreatment with propranolol (a non-selective beta-adrenoreceptor antagonist) (2mg/animal) or SR59230A (a selective beta(3)-adrenoreceptor antagonist) (2mg/animal), respectively. These results suggest that acute cold exposure resulted in down-regulation of CIDEA in interscapular BAT by sympathetically activated beta(3)-adrenoreceptor-mediated mechanisms in rats.

  16. Interactions between an alpha2-adrenergic antagonist and a beta3-adrenergic agonist on the expression of UCP2 and UCP3 in rats.



    This experimental trial was devised to assess whether selective β3-adrenergic receptor (AR) stimulation and simultaneous blockade of α2-AR would affect thermoregulation. With this purpose, the individual and combined administration of a β3-AR agonist, trecadrine, and an α2-AR antagonist, yohimbine, were evaluated. Yohimbine produced a marked decrease (p < 0.001) in body temperature one hour after administration (5 mg kg−1, i.p.) and blocked the thermogenic effect of trecadrine (1 mg kg−1, i.p...

  17. Glucocerebrosidase deficiency accelerates the accumulation of proteinase K-resistant α-synuclein and aggravates neurodegeneration in a Drosophila model of Parkinson's disease. (United States)

    Suzuki, Mari; Fujikake, Nobuhiro; Takeuchi, Toshihide; Kohyama-Koganeya, Ayako; Nakajima, Kazuki; Hirabayashi, Yoshio; Wada, Keiji; Nagai, Yoshitaka


    Alpha-synuclein (αSyn) plays a central role in the pathogenesis of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Recent multicenter genetic studies have revealed that mutations in the glucocerebrosidase 1 (GBA1) gene, which are responsible for Gaucher's disease, are strong risk factors for PD and DLB. However, the mechanistic link between the functional loss of glucocerebrosidase (GCase) and the toxicity of αSyn in vivo is not fully understood. In this study, we employed Drosophila models to examine the effect of GCase deficiency on the neurotoxicity of αSyn and its molecular mechanism. Behavioral and histological analyses showed that knockdown of the Drosophila homolog of GBA1 (dGBA1) exacerbates the locomotor dysfunction, loss of dopaminergic neurons and retinal degeneration of αSyn-expressing flies. This phenotypic aggravation was associated with the accumulation of proteinase K (PK)-resistant αSyn, rather than with changes in the total amount of αSyn, raising the possibility that glucosylceramide (GlcCer), a substrate of GCase, accelerates the misfolding of αSyn. Indeed, in vitro experiments revealed that GlcCer directly promotes the conversion of recombinant αSyn into the PK-resistant form, representing a toxic conformational change. Similar to dGBA1 knockdown, knockdown of the Drosophila homolog of β-galactosidase (β-Gal) also aggravated locomotor dysfunction of the αSyn flies, and its substrate GM1 ganglioside accelerated the formation of PK-resistant αSyn. Our findings suggest that the functional loss of GCase or β-Gal promotes the toxic conversion of αSyn via aberrant interactions between αSyn and their substrate glycolipids, leading to the aggravation of αSyn-mediated neurodegeneration.

  18. Enhanced formation of secondary air pollutants and aggravation of urban smog due to crop residue burning emissions in North India (United States)

    Sarkar, Chinmoy; Kumar, Vinod; Sinha, Vinayak


    Biomass burning causes intense perturbations to regional atmospheric chemistry and air quality and is a significant global source of reactive pollutants to the atmosphere (Andreae and Merlet, 2001). In November 2012, large areas in North India including New Delhi experienced several weeks of aggravated smog and poor air quality due to the impact of crop residue burning, which is a biannual post harvest activity that occurs during Oct-Nov and April-May every year in the agricultural belts of North western India. In-situ high temporal resolution (1 measurement every minute) measurements of a suite of volatile organic compounds measured using proton transfer reaction mass spectrometry (PTR-MS) such as acetonitrile (biomass burning tracer) and aromatic hydrocarbons were performed simultaneously with carbon monoxide, nitrogen oxides, ozone and aerosol mass concentrations (PM 2.5 and PM 10) at a suburban site (30.667°N, 76.729°E and 310 m asl), impacted by air masses that had passed over the burning fields less than 72 hours ago. By using data from the same season but before the post harvest crop residue burning activity had commenced, we were able to quantify enhancements in ambient levels of the measured species due to the crop residue burning activity. When air masses influenced by the fire emissions reached the measurement site, peak values of about 8 ppbV acetonitrile, 4 ppmV CO, 100 ppbV NOx , 30 ppbV toluene and 15 ppbV benzene were observed which represented a factor of 2-5 increase over their ambient levels in the non-fire influenced period. Emission ratios of aromatic hydrocarbons/CO also showed a marked increase. Non fire event (N.F. E.) influenced and fire event (F.E.) influenced air masses had the following emission ratio enhancements: benzene/CO (N.F.E = 3; F.E. = 5), toluene/CO (N.F.E = 4; F.E. = 8.7) and sum of C8 aromatics/CO (N.F.E = 4; F.E. = 7.3) and sum of C9 aromatics/CO (N.F.E = 2.6; F.E. = 3.4). The OH reactivity of air masses which has strong

  19. Expression of TGF-beta1, TGF-beta2, TGF-beta3 and the receptors TGF-betaRI and TGF-betaRII in placentomes of artificially inseminated and nuclear transfer derived bovine pregnancies. (United States)

    Ravelich, S R; Shelling, A N; Wells, D N; Peterson, A J; Lee, R S F; Ramachandran, A; Keelan, J A


    Bovine nuclear transfer pregnancies are characterized by a high incidence of placental abnormalities, notably, increased placentome size and deficiencies in trophoblast cell function and establishment of placental vasculature. Alterations in gene expression during placental growth and development may contribute to the appearance of large placentomes in pregnancies derived from nuclear transfer. The placenta synthesizes a number of cytokines and growth factors, including the transforming growth factor-betas (TGF-betas) that are involved in the establishment, maintenance and/or regulation of pregnancy. All forms of TGF-beta and their receptors are present at the fetal-maternal interface of the bovine placentome, where they are thought to play an important role in regulating growth, differentiation, and function of the placenta. Using real-time RT-PCR, we have examined the expression of TGF-beta1, TGF-beta2, TGF-beta3 and the receptors TGF-betaRI and TGF-betaRII in placentomes of artificially inseminated (AI) and nuclear transfer (NT)-derived bovine pregnancies at days 50, 100 and 150 of gestation. TGF-beta1, TGF-beta2 and TGF-beta3 mRNA expression increased by 2.0-2.8-fold, while TGF-betaRI and TGF-betaRII mRNA expression decreased by 1.7-2.0-fold in NT placentomes compared to AI controls at all gestational ages examined. These findings indicate that NT placentomes may be resistant to the growth suppressive effects of TGF-betas and could contribute to the placental proliferative abnormalities observed in NT-derived placentas. Alternatively, deficiencies in placentation may provide a mechanism whereby TGF-betas are dysregulated in NT pregnancies.

  20. Carboxylated multi-walled carbon nanotubes aggravated biochemical and subcellular damages in leaves of broad bean (Vicia faba L.) seedlings under combined stress of lead and cadmium

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Chengrun, E-mail: [School of Life Science, Huainan Normal University, Huainan 232001 (China); Liu, Haitao; Chen, Jinyun [School of Life Science, Huainan Normal University, Huainan 232001 (China); Tian, Yuan [Department of Plant, Soil and Microbial Sciences, Michigan State University, East Lansing, MI 48824 (United States); Shi, Jian; Li, Dongdong; Guo, Chen; Ma, Qingping [School of Life Science, Huainan Normal University, Huainan 232001 (China)


    Highlights: • MWCNTs-COOH disturb mineral elements and cause oxidative damages in the leaves. • Cd and Pb combination result in reduction of mineral elements and enrichment of Na, involving in toxicity mechanisms. • MWCNTs-COOH facilitate Cd and Pb uptake, and aggravate biochemical and subcellular damages. - Abstract: Increasing industrialization of multi-walled carbon nanotubes (MWCNTs) would inevitably lead to their release into the environment and combination with heavy metals. However, studies concerning the combined effects of MWCNTs and heavy metals on agricultural crops are limited. Herein, effects and mechanisms of carboxylated MWCNTs (MWCNTs-COOH) (2.5, 5 and 10 mg/L) and their combination with 20 μM Pb and 5 μM Cd (shortened as Pb + Cd) on Vicia faba L. seedlings were investigated. The results showed that the MWCNTs-COOH disturbed the imbalance of nutrient elements, and caused oxidative stress and damages in the leaves. Additionally, the combination of MWCNTs-COOH with Pb + Cd resulted in enrichment of Pb and Cd, and deterioration of oxidative damages compared with the treatments of MWCNTs-COOH or Pb + Cd alone in the leaves. As the results, the concentrations of MWCNTs-COOH not only caused oxidative stress, but also exacerbated the biochemical and subcellular damages due to the treatment of Pb + Cd in the leaves. It also suggests that persistent release of MWCNTs-COOH into the environment may cause phytotoxicity and aggravate ecological risks due to combination of heavy metals.

  1. Effects of Kanlijian (坎离煎) on Exercise Tolerance, Quality of Life, and Frequency of Heart Failure Aggravation in Patients with Chronic Heart Failure

    Institute of Scientific and Technical Information of China (English)

    JIANG Mei-xian; RUAN Xiao-fen; XU Yan


    Objective: To observe the effects of conventional therapy combined with Kanlijian (坎离煎,KLJ) on exercise tolerance, quality of life and frequency of heart failure aggravation in patients with chronic heart failure(CHF). Methods: Sixty. CHF patients differentiated as sufferring from the syndrome of Xin-Shen Yang deficiency were included in the study and randomly assigned at the ratio of 2: 1 into the KLJ group (n=39) and the control group(n = 21). All the patients were treated with conventional therapy of Western medicine, but to those in the KLJ group, KLJ was medicated additionally one dose daily with 24 wks as one therapeutic course. The efficacy on TCM syndrome and changes of scores on TCM syndrome were observed after treatment. The indexes, including 6-minute walking distance (6MWD), quality of life (QOL, accessed by LHFQ scoring), NYHA grade, hemodynamic indexes and reducing/withdrawal rate of diuretic and digoxin before and after treatment were recorded and compared. Also the frequency of re-admission due to aggravation of heart failure in one year's time were observed. Results: ( 1 ) The efficacy on TCM syndrome, improvement on scores of TCM syndrome, therapeutic effects on 6MWD, QOL, and NYHA grade in the KLJ group were superior to those in the control group. (2) Hemodynamic indexes after treatment, left ventricular fractional shortening (LVFS) and E peak/A peak (E/A), between the two groups had no significant difference, while left ventricular ejection fraction (LVEF) was increased significantly in the KLJ group, but with no obvious change in the control group. (3) The reducing/withdrawal rate of diuretic and digoxin in the KLJ group was significantly higher than that in the control group. (4) The 1-year frequency of re-admission significantly decreased in the KLJ group. Conclusion: The adjuvant treatment of KLJ on the basis of Western conventional therapy can significantly improve CHF patients' exercise tolerance, quality of life and cardiac function

  2. Impaired removal of Vβ8(+) lymphocytes aggravates colitis in mice deficient for B cell lymphoma-2-interacting mediator of cell death (Bim). (United States)

    Leucht, K; Caj, M; Fried, M; Rogler, G; Hausmann, M


    We investigated the role of B cell lymphoma (BCL)-2-interacting mediator of cell death (Bim) for lymphocyte homeostasis in intestinal mucosa. Lymphocytes lacking Bim are refractory to apoptosis. Chronic colitis was induced in Bim-deficient mice (Bim(-/-) ) with dextran sulphate sodium (DSS). Weight loss and colonoscopic score were increased significantly in Bim(-/-) mice compared to wild-type mice. As Bim is induced for the killing of autoreactive cells we determined the role of Bim in the regulation of lymphocyte survival at mucosal sites. Upon chronic dextran sulphate sodium (DSS)-induced colitis, Bim(-/-) animals exhibited an increased infiltrate of lymphocytes into the mucosa compared to wild-type mice. The number of autoreactive T cell receptor (TCR) Vβ8(+) lymphocytes was significantly higher in Bim(-/-) mice compared to wild-type controls. Impaired removal of autoreactive lymphocytes in Bim(-/-) mice upon chronic DSS-induced colitis may therefore contribute to aggravated mucosal inflammation.

  3. Conditioned medium from mesenchymal stem cells induces cell death in organotypic cultures of rat hippocampus and aggravates lesion in a model of oxygen and glucose deprivation. (United States)

    Horn, Ana Paula; Frozza, Rudimar Luiz; Grudzinski, Patrícia Benke; Gerhardt, Daniéli; Hoppe, Juliana Bender; Bruno, Alessandra Nejar; Chagastelles, Pedro; Nardi, Nance Beyer; Lenz, Guido; Salbego, Christianne


    Cell therapy using bone marrow-derived mesenchymal stem cells (MSC) seems to be a new alternative for the treatment of neurological diseases, including stroke. In order to investigate the response of hippocampal tissue to factors secreted by MSC and if these factors are neuroprotective in a model of oxygen and glucose deprivation (OGD), we used organotypic hippocampal cultures exposed to conditioned medium from bone marrow-derived MSC. Our results suggest that the conditioned medium obtained from these cells aggravates lesion caused by OGD. In addition, the presence of the conditioned medium alone was toxic mainly to cells in the CA1, CA2 and CA3 areas of the hippocampal organotypic culture even in basal conditions. GABA stimulation and NMDA and AMPA receptors antagonists were able to reduce propidium iodide staining, suggesting that the cell death induced by the toxic factors secreted by MSC could involve these receptors.

  4. Chronic administration of recombinant IL-6 upregulates lipogenic enzyme expression and aggravates high-fat-diet-induced steatosis in IL-6-deficient mice

    Directory of Open Access Journals (Sweden)

    Margarita Vida


    Full Text Available Interleukin-6 (IL-6 has emerged as an important mediator of fatty acid metabolism with paradoxical effects in the liver. Administration of IL-6 has been reported to confer protection against steatosis, but plasma and tissue IL-6 concentrations are elevated in chronic liver diseases, including fatty liver diseases associated with obesity and alcoholic ingestion. In this study, we further investigated the role of IL-6 on steatosis induced through a high-fat diet (HFD in wild-type (WT and IL-6-deficient (IL-6−/− mice. Additionally, HFD-fed IL-6−/− mice were also chronically treated with recombinant IL-6 (rIL-6. Obesity in WT mice fed a HFD associated with elevated serum IL-6 levels, fatty liver, upregulation of carnitine palmitoyltransferase 1 (CPT1 and signal transducer and activator of transcription-3 (STAT3, increased AMP kinase phosphorylation (p-AMPK, and downregulation of the hepatic lipogenic enzymes fatty acid synthase (FAS and stearoyl-CoA desaturase 1 (SCD1. The HFD-fed IL-6−/− mice showed severe steatosis, no changes in CPT1 levels or AMPK activity, no increase in STAT3 amounts, inactivated STAT3, and marked downregulation of the expression of acetyl-CoA carboxylase (ACCα/β, FAS and SCD1. The IL-6 chronic replacement in HFD-fed IL-6−/− mice restored hepatic STAT3 and AMPK activation but also increased the expression of the lipogenic enzymes ACCα/β, FAS and SCD1. Furthermore, rIL-6 administration was associated with aggravated steatosis and elevated fat content in the liver. We conclude that, in the context of HFD-induced obesity, the administration of rIL-6 might contribute to the aggravation of fatty liver disease through increasing lipogenesis.

  5. Chronic IL-6 Administration Desensitizes IL-6 Response in Liver, Causes Hyperleptinemia and Aggravates Steatosis in Diet-Induced-Obese Mice (United States)

    Gavito, Ana Luisa; Bautista, Dolores; Suarez, Juan; Badran, Samir; Arco, Rocío; Pavón, Francisco Javier; Serrano, Antonia; Rivera, Patricia; Decara, Juan; Cuesta, Antonio Luis; Rodríguez-de-Fonseca, Fernando


    High-fat diet-induced obesity (DIO) is associated with fatty liver and elevated IL-6 circulating levels. IL-6 administration in rodents has yielded contradictory results regarding its effects on steatosis progression. In some models of fatty liver disease, high doses of human IL-6 ameliorate the liver steatosis, whereas restoration of IL-6 in DIO IL-6-/- mice up-regulates hepatic lipogenic enzymes and aggravates steatosis. We further examined the effects of chronic low doses of murine IL-6 on hepatic lipid metabolism in WT mice in DIO. IL-6 was delivered twice daily in C57BL/6J DIO mice for 15 days. The status and expression of IL-6-signalling mediators and targets were investigated in relation to the steatosis and lipid content in blood and in liver. IL-6 administration in DIO mice markedly raised circulating levels of lipids, glucose and leptin, elevated fat liver content and aggravated steatosis. Under IL-6 treatment there was hepatic Stat3 activation and increased gene expression of Socs3 and Tnf-alpha whereas the gene expression of endogenous IL-6, IL-6-receptor, Stat3, Cpt1 and the enzymes involved in lipogenesis was suppressed. These data further implicate IL-6 in fatty liver disease modulation in the context of DIO, and indicate that continuous stimulation with IL-6 attenuates the IL-6-receptor response, which is associated with high serum levels of leptin, glucose and lipids, the lowering levels of lipogenic and Cpt1 hepatic enzymes and with increased Tnf-alpha hepatic expression, a scenario evoking that observed in IL-6-/- mice exposed to DIO and in obese Zucker rats. PMID:27333268

  6. Imbalance between pro and anti-oxidant mechanisms in perivascular adipose tissue aggravates long-term high-fat diet-derived endothelial dysfunction.

    Directory of Open Access Journals (Sweden)

    Marta Gil-Ortega

    Full Text Available BACKGROUND: The hypothesis of this study is that long-term high-fat diets (HFD induce perivascular adipose tissue (PVAT dysfunction characterized by a redox imbalance, which might contribute to aggravate endothelial dysfunction in obesity. METHODS AND RESULTS: C57BL/6J mice were fed either control or HFD (45% kcal from fat for 32 weeks. Body weight, lumbar and mesenteric adipose tissue weights were significantly higher in HFD animals compared to controls. The anticontractile effect of PVAT in mesenteric arteries (MA was lost after 32 week HFD and mesenteric endothelial-dependent relaxation was significantly impaired in presence of PVAT in HFD mice (Emax = 71.0±5.1 vs Emax = 58.5±4.2, p<0.001. The inhibitory effect of L-NAME on Ach-induced relaxation was less intense in the HFD group compared with controls suggesting a reduction of endothelial NO availability. Expression of eNOS and NO bioavailability were reduced in MA and almost undetectable in mesenteric PVAT of the HFD group. Superoxide levels and NOX activity were higher in PVAT of HFD mice. Apocynin only reduced contractile responses to NA in HFD animals. Expression of ec-SOD and total SOD activity were significantly reduced in PVAT of HFD mice. No changes were observed in Mn-SOD, Cu/Zn-SOD or catalase. The ratio [GSSG]/([GSH]+[GSSG] was 2-fold higher in the mesenteric PVAT from HFD animals compared to controls. CONCLUSIONS: We suggest that the imbalance between pro-oxidant (NOX, superoxide anions, hydrogen peroxide and anti-oxidant (eNOS, NO, ecSOD, GSSG mechanisms in PVAT after long-term HFD might contribute to the aggravation of endothelial dysfunction.

  7. Expression of transforming growth factor beta (TGF beta) receptors and expression of TGF beta 1, TGF beta 2 and TGF beta 3 in human small cell lung cancer cell lines

    DEFF Research Database (Denmark)

    Damstrup, L; Rygaard, K; Spang-Thomsen, M;


    A panel of 21 small cell lung cancer cell (SCLC) lines were examined for the presence of Transforming growth factor beta receptors (TGF beta-r) and the expression of TGF beta mRNAs. By the radioreceptor assay we found high affinity receptors to be expressed in six cell lines. scatchard analysis...... of the binding data demonstrated that the cells bound between 4.5 and 27.5 fmol mg-1 protein with a KD ranging from 16 to 40 pM. TGF beta 1 binding to the receptors was confirmed by cross-linking TGF beta 1 to the TGF beta-r. Three classes of TGF beta-r were demonstrated, type I and type II receptors with M......(r) = 65,000 and 90,000 and the betaglycan (type III) with M(r) = 280,000. Northern blotting showed expression of TGF beta 1 mRNA in ten, TGF beta 2 mRNA in two and TGF beta 3 mRNA in seven cell lines. Our results provide, for the first time, evidence that a large proportion of a broad panel of SCLC cell...

  8. Exogenous administration of a recombinant variant of TWEAK impairs healing after myocardial infarction by aggravation of inflammation.

    Directory of Open Access Journals (Sweden)

    Christina Pachel

    Full Text Available BACKGROUND: Tumor necrosis factor-like weak inducer of apoptosis (TWEAK and its receptor fibroblast growth factor-inducible 14 (Fn14 are upregulated after myocardial infarction (MI in both humans and mice. They modulate inflammation and the extracellular matrix, and could therefore be important for healing and remodeling after MI. However, the function of TWEAK after MI remains poorly defined. METHODS AND RESULTS: Following ligation of the left coronary artery, mice were injected twice per week with a recombinant human serum albumin conjugated variant of TWEAK (HSA-Flag-TWEAK, mimicking the activity of soluble TWEAK. Treatment with HSA-Flag-TWEAK resulted in significantly increased mortality in comparison to the placebo group due to myocardial rupture. Infarct size, extracellular matrix remodeling, and apoptosis rates were not different after MI. However, HSA-Flag-TWEAK treatment increased infiltration of proinflammatory cells into the myocardium. Accordingly, depletion of neutrophils prevented cardiac ruptures without modulating all-cause mortality. CONCLUSION: Treatment of mice with HSA-Flag-TWEAK induces myocardial healing defects after experimental MI. This is mediated by an exaggerated neutrophil infiltration into the myocardium.

  9. Progressive Seizure Aggravation in the Repeated 6-Hz Corneal Stimulation Model Is Accompanied by Marked Increase in Hippocampal p-ERK1/2 Immunoreactivity in Neurons (United States)

    Giordano, Carmela; Costa, Anna M.; Lucchi, Chiara; Leo, Giuseppina; Brunel, Luc; Fehrentz, Jean-Alain; Martinez, Jean; Torsello, Antonio; Biagini, Giuseppe


    the third session. The vast majority of p-ERK1/2 immunopositive cells were co-labeled with FosB/ΔFosB antibodies, suggesting the existence of a relationship between the investigated markers in a subpopulation of neurons activated by seizures. These findings suggest that p-ERK1/2 are useful markers to define the aggravation of seizures and the response to anticonvulsant treatments. In particular, p-ERK1/2 expression clearly identified the involvement of hippocampal regions during seizure aggravation in the 6-Hz model. PMID:28018175

  10. The mtDNA nt7778 G/T polymorphism augments formation of lymphocytic foci but does not aggravate cerulein-induced acute pancreatitis in mice.

    Directory of Open Access Journals (Sweden)

    Sarah Müller

    Full Text Available A polymorphism in the ATP synthase 8 (ATP8 gene of the murine mitochondrial genome, G-to-T transversion at position 7778, has been suggested to increase susceptibility to multiple autoimmune diseases, including autoimmune pancreatitis (AIP. The polymorphism also induces mitochondrial reactive oxygen species generation, secretory dysfunction and β-cell mass adaptation. Here, we have used two conplastic mouse strains, C57BL/6N-mtAKR/J (B6-mtAKR; nt7778 G; control and C57BL/6N-mtFVB/N (B6-mtFVB; nt7778 T, to address the question if the polymorphism also affects the course of cerulein-induced acute pancreatitis in mice. Therefore, two age groups of mice (3 and 12-month-old, respectively were subjected to up to 7 injections of the secretagogue cerulein (50 µg/kg body weight at hourly intervals. Disease severity was assessed at time points from 3 hours to 7 days based on pancreatic histopathology, serum levels of α-amylase and activities of myeloperoxidase (MPO in lung tissue. A comparison of cerulein-induced pancreatic tissue damage and increases of α-amylase and MPO activities showed no differences between the age-matched groups of both strains. Interestingly, histological evaluation of pancreatic tissue of both untreated and cerulein-treated B6-mtAKR and B6-mtFVB mice also revealed the presence of infiltrates of immune cells surrounding ducts and vessels; a finding that is compatible with an early stage of AIP. After recovery from cerulein-induced pancreatitis (day 7 after the injections, 12-month-old B6-mtFVB mice but not B6-mtAKR mice displayed aggravated lymphocytic lesions. A comparison of 12-month-old mice with other age groups of both strains revealed that lymphocytic foci were largely absent in 3-month-old mice, while 24-month-old mice were more affected. Together, our data suggest that the mtDNA nt7778 G/T polymorphism does not aggravate cerulein-induced acute pancreatitis. Autoimmune-like lesions, however, may progress faster if

  11. Heterogeneity in hand veins responses to acetylcholine is not associated with polymorphisms in the G-protein beta3-subunit (C825T) and endothelial nitric oxide synthase (G894T) genes but with serum low density lipoprotein cholesterol. (United States)

    Grossmann, M; Dobrev, D; Siffert, W; Kirch, W


    Vascular responses to acetylcholine (ACh) are notoriously variable, the reason for this phenomenon is unknown. We tested the hypothesis that the variability in venous response to acetylcholine may be associated with two recently identified genetic polymorphisms for proteins involved in the signal transduction pathway, i.e. the G-protein beta3-subunit (GNB3) and endothelial nitric oxide synthase (eNOS). The dorsal hand vein technique was used in 37 healthy subjects. Hand veins were preconstricted with the alpha1-adrenoceptor agonist phenylephrine and the venodilator response to local ACh infusion was measured with and without comedication of acetylsalicylic acid or co-infusion of N(G)-monomethyl-L-arginine (L-NMMA). In addition, all subjects received routine laboratory tests and 26 of them were genotyped for the C825T polymorphism of the GNB3 gene and for the G894T polymorphism of the eNOS gene. A striking variability in venous response to ACh was found with dilation observed in the low ACh concentration range and reduced dilation or even constriction at high concentrations. ACh-induced venodilation was mediated by muscarinic receptors and abolished in the presence of both acetylsalicylic acid and L-NMMA suggesting dependence on endothelium. We did not find any association of the variability in ACh response with GNB3 or eNOS allele status. On the other hand, a significant positive correlation between ACh responsiveness and low density lipoprotein-cholesterol status was detected. Two recently discovered gene polymorphisms are not responsible for the profound heterogeneity in venodilator response to ACh. Surprisingly, this variability appears to relate to the lipid status of the subjects. The exact nature of this new finding requires further study.

  12. Antibiotic-induced imbalances in gut microbiota aggravates cholesterol accumulation and liver injuries in rats fed a high-cholesterol diet. (United States)

    Hu, Xu; Wang, Tao; Liang, Shan; Li, Wei; Wu, Xiaoli; Jin, Feng


    Increasing evidence suggests that maintenance of homeostasis between gut microbiota and host plays an important role in human health. Many diseases, such as those affecting the liver, have been linked to imbalances in gut microbial communities. However, it is not clear whether an imbalance in gut microbiota promotes the onset of liver injury or if the imbalance results from the pathological state. In the current study, antibiotics were used to disturb the gut microbiota of both rats fed a high-cholesterol diet and rats fed a normal diet (controls). The prevalence of Bacteroidetes and Firmicutes were reduced, and Proteobacteria was greatly increased in the guts of rats after antibiotic treatment. The antibiotic-induced perturbation of gut microbiota aggravated cholesterol accumulation and liver injury in rats fed a high-cholesterol diet. This may have been due to an increase in intestinal permeability and plasma lipopolysaccharide (LPS), which lead to an increase in LPS absorption and activation of TLR4 signaling, resulting in the synthesis of pro-inflammatory cytokines and chemokines in liver tissues. This study suggests that imbalances in gut microbiota may be a predisposing factor for the onset of metabolic diseases and liver injuries related to cholesterol and high-cholesterol diets. Modulation of gut microbiota could be a novel target for preventing cholesterol-related metabolic disorders.

  13. A saturated-fat diet aggravates the outcome of traumatic brain injury on hippocampal plasticity and cognitive function by reducing brain-derived neurotrophic factor. (United States)

    Wu, A; Molteni, R; Ying, Z; Gomez-Pinilla, F


    We have conducted studies to determine the potential of dietary factors to affect the capacity of the brain to compensate for insult. Rats were fed with a high-fat sucrose (HFS) diet, a popularly consumed diet in industrialized western societies, for 4 weeks before a mild fluid percussion injury (FPI) or sham surgery was performed. FPI impaired spatial learning capacity in the Morris water maze, and these effects were aggravated by previous exposure of the rats to the action of the HFS diet. Learning performance decreased according to levels of brain-derived neurotrophic factor (BDNF) in individual rats, such that rats with the worst learning efficacy showed the lowest levels of BDNF in the hippocampus. BDNF immunohistochemistry localized the decreases in BDNF to the CA3 and dentate gyrus of the hippocampal formation. BDNF has a strong effect on synaptic plasticity via the action of synapsin I and cAMP-response element-binding protein (CREB), therefore, we assessed changes in synapsin I and CREB in conjunction with BDNF. Levels of synapsin I and CREB decreased in relation to decreases in BDNF levels. The combination of FPI and the HFS diet had more dramatic effects on the active state (phosphorylated) of synapsin I and CREB. There were no signs of neurodegeneration in the hippocampus of any rat group assessed with Fluoro-Jade B staining. The results suggest that FPI and diet impose a risk factor to the molecular machinery in charge of maintaining neuronal function under homeostatic and challenging situations.

  14. 论聚众犯强制猥亵、侮辱妇女罪的加重犯%Aggravated Offense of Mass Compulsory Indecent Woman Crime

    Institute of Scientific and Technical Information of China (English)



    聚众犯罪是刑法分则特别规定的一种犯罪,与共同犯罪存在交叉关系,共同犯罪的制刑规则不能适用于聚众犯罪。聚众犯罪的特点和刑法体系内的协调性特征决定了聚众犯强制猥亵、侮辱妇女罪的加重犯限于首要分子,积极参加者和一般参加者不包含在内。%Mass crime is specifically stipulated by specific provisions of criminal law, which is interrelated with the joint crime, but the rule of joint crime cannot apply to the mass crime absolutely. On the basis of the difference characteristics of mass crime and coordination between the crime and the punishment, the aggravated offense just applies to the ringleaders of compulsory indecent woman crime.

  15. Monopoly experimentation



    This paper considers a firm facing an uncertain demand curve. The firm can experimentally adjust its output in order to gain information that willincrease expected future profits. We examine two basic questions. Under whatconditions is it worthwhile for the firm to experiment? How does the firmadjust its output away from the myopic optimism to exploit its ability to experiment? Two necessary conditions are established for experimentation tooccur, involving requirements that experimentation be...


    de Luis, Daniel Antonio; Aller, Rocío; Izaola, Olatz; de la Fuente, Beatriz; Romero, Enrique


    Introducción: la variante Trp64Arg del receptor Beta ha sido relacionada con un aumento del peso corporal y resistencia a la insulina. Objetivo: el objetivo de nuestro estudio fue investigar la influencia del polimorfismo (rs 4994) del gen del receptor adrenérgico-Beta-3 en la respuesta metabólica y la pérdida de peso en un estudio de intervención a medio plazo con una dieta con alto contenido en proteínas/baja en carbohidratos vs una dieta hipocalórica estándar (1.000 kcal / día). Material y métodos: se evaluó una muestra de 284 sujetos obesos con un diseño de ensayo aleatorio. Se realizó una evaluación nutricional al inicio y al final de un período de 9 meses en el que los sujetos recibieron una de las dos dietas (dieta HP: alta en proteínas/baja en carbohidratos vs dieta S: dieta estándar). Resultados: no hubo diferencias significativas entre los efectos positivos (sobre el peso, el índice de masa corporal, la circunferencia de la cintura, la masa grasa, la presión arterial sistólica y los niveles de leptina) en los dos genotipos con ambas dietas. Con ambas dietas y solo en el genotipo salvaje (dieta HP vs dieta S), colesterol total (-10,1 ± 3,9 mg / dl vs -10,1 ± 2,2 mg / dl; p> 0,05), colesterol LDL (-9,5 ± 2,1 mg / dl vs -8,5 ± 2,3 mg / dl; p> 0,05) y los triglicéridos (-19,1 ± 2,1 mg / dl vs -14,3 ± 2,1 mg / dl; p> 0,05) disminuyeron. La mejoría de estos parámetros fue similar en sujetos con dieta HP vs dieta HS. Con la dieta HP y solo en el genotipo salvaje, los niveles de insulina (-3,7 ± 1,9 UI / L; p.

  17. Bottlenecks aggravate rising construction costs

    Energy Technology Data Exchange (ETDEWEB)



    Rising demand for power in developing countries combined with concerns about carbon emissions from coal-fired power plants in developed countries have created a bonanza for carbon-light technologies, including nuclear, renewables and natural gas plants. This, in turn, has put upward pressure on the price of natural gas in key markets while resulting in shortages in critical components for building renewables and nuclear reactors. Globalization of the power industry means that pressures in one segment or one region translate into shortages and rising prices everywhere else.

  18. Impairment of insulin-stimulated Akt/GLUT4 signaling is associated with cardiac contractile dysfunction and aggravates I/R injury in STZ-diabetic Rats

    Directory of Open Access Journals (Sweden)

    Deng Jen-Ying


    Full Text Available Abstract In this study, we established systemic in-vivo evidence from molecular to organism level to explain how diabetes can aggravate myocardial ischemia-reperfusion (I/R injury and revealed the role of insulin signaling (with specific focus on Akt/GLUT4 signaling molecules. The myocardial I/R injury was induced by the left main coronary artery occlusion for 1 hr and then 3 hr reperfusion in control, streptozotocin (STZ-induced insulinopenic diabetes, and insulin-treated diabetic rats. The diabetic rats showed a significant decrease in heart rate, and a prolonged isovolumic relaxation (tau which lead to decrease in cardiac output (CO without changing total peripheral resistance (TPR. The phosphorylated Akt and glucose transporter 4 (GLUT 4 protein levels were dramatically reduced in both I/R and non-I/R diabetic rat hearts. Insulin treatment in diabetes showed improvement of contractile function as well as partially increased Akt phosphorylation and GLUT 4 protein levels. In the animals subjected to I/R, the mortality rates were 25%, 65%, and 33% in the control, diabetic, and insulin-treated diabetic group respectively. The I/R-induced arrhythmias and myocardial infarction did not differ significantly between the control and the diabetic groups. Consistent with its anti-hyperglycemic effects, insulin significantly reduced I/R-induced arrhythmias but had no effect on I/R-induced infarctions. Diabetic rat with I/R exhibited the worse hemodynamic outcome, which included systolic and diastolic dysfunctions. Insulin treatment only partially improved diastolic functions and elevated P-Akt and GLUT 4 protein levels. Our results indicate that cardiac contractile dysfunction caused by a defect in insulin-stimulated Akt/GLUT4 may be a major reason for the high mortality rate in I/R injured diabetic rats.

  19. Are droughts occurrence and severity aggravating? A study on SPI drought class transitions using loglinear models and ANOVA-like inference

    Directory of Open Access Journals (Sweden)

    E. E. Moreira


    Full Text Available Long time series (95 to 135 yr of the Standardized Precipitation Index (SPI computed with the 12-month time scale relative to 10 locations across Portugal were studied with the aim of investigating if drought frequency and severity are changing through time. Considering four drought severity classes, time series of drought class transitions were computed and later divided into 4 or 5 sub-periods according to length of time series. Drought class transitions were calculated to form a 2-dimensional contingency table for each period. Two-dimensional loglinear models were fitted to these contingency tables and an ANOVA-like inference was then performed in order to investigate differences relative to drought class transitions among those sub-periods, which were considered as treatments of only one factor. The application of ANOVA-like inference to these data allowed to compare the four or five sub-periods in terms of probabilities of transition between drought classes, which were used to detect a possible trend in time evolution of droughts frequency and severity that could be related to climate change. Results for a number of locations show some similarity between the first, third and fifth period (or the second and the fourth if there were only 4 sub-periods regarding the persistency of severe/extreme and sometimes moderate droughts. In global terms, results do not support the assumption of a trend for progressive aggravation of droughts occurrence during the last century, but rather suggest the existence of long duration cycles.

  20. GDNF pre-treatment aggravates neuronal cell loss in oxygen-glucose deprived hippocampal slice cultures: a possible effect of glutamate transporter up-regulation. (United States)

    Bonde, C; Sarup, A; Schousboe, A; Gegelashvili, G; Noraberg, J; Zimmer, J


    Besides its neurotrophic and neuroprotective effects on dopaminergic neurons and spinal motoneurons, glial cell line-derived neurotrophic factor (GDNF) has potent neuroprotective effects in cerebral ischemia. The protective effect has so far been related to reduced activation of N-methyl-D-aspartate receptors (NMDAr). This study tested the effects of GDNF on glutamate transporter expression, with the hypothesis that modulation of glutamate transporter activity would affect the outcome of cerebral ischemia. Organotypic hippocampal slice cultures, derived from 1-week-old rats, were treated with 100 ng/ml GDNF for either 2 or 5 days, followed by Western blot analysis of NMDAr subunit 1 (NR1) and two glutamate transporter subtypes, GLAST and GLT-1. After 5-day exposure to GDNF, expression of GLAST and GLT-1 was up-regulated to 169 and 181% of control values, respectively, whereas NR1 was down-regulated to 64% of control. However, despite these changes that potentially would support neuronal resistance to excitotoxicity, the long-term treatment with GDNF was found to aggravate the neuronal damage induced by oxygen-glucose deprivation (OGD). The increased cell death, assessed by propidium iodide (PI) uptake, occurred not only among the most susceptible CA1 pyramidal cells, but also in CA3 and fascia dentata. Given that glutamate transporters are able to release glutamate by reversed action during energy failure, it is suggested that the observed increase in OGD-induced cell death in the GDNF-pretreated cultures was caused by the build-up of excitotoxic concentrations of extracellular glutamate released through the glutamate transporters, which were up-regulated by GDNF. Although the extent and consequences of glutamate release via reversal of GLAST and GLT-1 transporters seem to vary in different energy failure models, the present findings should be taken into account in clinical trials of GDNF.

  1. Reinjury risk of nano-calcium oxalate monohydrate and calcium oxalate dihydrate crystals on injured renal epithelial cells: aggravation of crystal adhesion and aggregation (United States)

    Gan, Qiong-Zhi; Sun, Xin-Yuan; Bhadja, Poonam; Yao, Xiu-Qiong; Ouyang, Jian-Ming


    Background Renal epithelial cell injury facilitates crystal adhesion to cell surface and serves as a key step in renal stone formation. However, the effects of cell injury on the adhesion of nano-calcium oxalate crystals and the nano-crystal-induced reinjury risk of injured cells remain unclear. Methods African green monkey renal epithelial (Vero) cells were injured with H2O2 to establish a cell injury model. Cell viability, superoxide dismutase (SOD) activity, malonaldehyde (MDA) content, propidium iodide staining, hematoxylin–eosin staining, reactive oxygen species production, and mitochondrial membrane potential (Δψm) were determined to examine cell injury during adhesion. Changes in the surface structure of H2O2-injured cells were assessed through atomic force microscopy. The altered expression of hyaluronan during adhesion was examined through laser scanning confocal microscopy. The adhesion of nano-calcium oxalate monohydrate (COM) and calcium oxalate dihydrate (COD) crystals to Vero cells was observed through scanning electron microscopy. Nano-COM and COD binding was quantitatively determined through inductively coupled plasma emission spectrometry. Results The expression of hyaluronan on the cell surface was increased during wound healing because of Vero cell injury. The structure and function of the cell membrane were also altered by cell injury; thus, nano-crystal adhesion occurred. The ability of nano-COM to adhere to the injured Vero cells was higher than that of nano-COD crystals. The cell viability, SOD activity, and Δψm decreased when nano-crystals attached to the cell surface. By contrast, the MDA content, reactive oxygen species production, and cell death rate increased. Conclusion Cell injury contributes to crystal adhesion to Vero cell surface. The attached nano-COM and COD crystals can aggravate Vero cell injury. As a consequence, crystal adhesion and aggregation are enhanced. These findings provide further insights into kidney stone

  2. 二至天癸颗粒对克罗米芬诱导排卵小鼠子宫内膜整合素β3表达的影响%Effect of Erzhi Tiangui Granule on the expression of endometrial beta3-integrin in the mice of induced ovulation with clomifene citrate

    Institute of Scientific and Technical Information of China (English)

    连方; 李婷婷; 孙振高


    Objective: To explore the effect of Erzhi Tiangui Granules (ETG) on the expression of endometrial beta3-integrin in mice of induced ovulation with clomifene citrate (CC).Methods: Forty Kunming female mice with ovulation failure were randomized into TCM group (treated with CC and ETG) and CC group (treated with CC only), while other 20 healthy mice of the same age were as normal controls.Their implantation rate on the fourth day of pregnancy (PD4) and the morphological changes of endometrium were observed, and the expression of endometrial beta3-integrin was detected by immunohistochemistry.Results: More mice had their oestrous cycle recovered in TCM group than in CC group (P<0.05).The endometrial morphological changes on PD4 in TCM group were significantly more suitable for implantation(P<0.05).The immunostaining scores of beta3-integrin in luminal epithelium, glandular epithelium and stroma of endometrium were all higher in TCM group than in CC group (P<0.05).The number of implanted blastocysts, implantation rate, and the expression of beta3-integrin in glandular epithelium and stroma in TCM group were comparable to those in normal controls (P>0.05), while expression of beta3integrin in luminal epithelium was lower in TCM group than in normal controls (P<0.05).The expressions of beta3-integrin in luminal and glandular epithelium were both higher than that in stroma in all three groups (P<0.05).Conclusions: ETG can help to restore the oestrous cycle and improve the expression of endometrial beta3-integrin and implantation rate in the mouse with ovulation failure.%目的 探讨二至天癸颗粒对克罗米芬(CC)诱导排卵小鼠子宫内膜整合素β3表达的影响.方法 40只生育期排卵障碍模型小鼠分中药组及CC组两组,每组20只,中药组予二至天癸颗粒加CC,CC组单纯予CC,20只非模型鼠为空白组.观察三组胚泡着床率、子宫内膜形态学变化,并采用免疫组化方法测定子宫内膜整合素β3的表

  3. Single high-dose irradiation aggravates eosinophil-mediated fibrosis through IL-33 secreted from impaired vessels in the skin compared to fractionated irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Eun-Jung, E-mail: [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of); Kim, Jun Won, E-mail: [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of); Yoo, Hyun, E-mail: [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of); Kwak, Woori, E-mail: [Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul 151-747 (Korea, Republic of); Choi, Won Hoon, E-mail: [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of); Cho, Seoae, E-mail: [C& K Genomics, Seoul National University Mt.4-2, Main Bldg. #514, SNU Research Park, NakSeoungDae, Gwanakgu, Seoul 151-919 (Korea, Republic of); Choi, Yu Jeong, E-mail: [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of); Lee, Yoon-Jin, E-mail: [Division of Radiation Effects, Research Center for Radiotherapy, Korea Institute of Radiological & Medical Sciences, Seoul 139-760 (Korea, Republic of); Cho, Jaeho, E-mail: [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of)


    We have revealed in a porcine skin injury model that eosinophil recruitment was dose-dependently enhanced by a single high-dose irradiation. In this study, we investigated the underlying mechanism of eosinophil-associated skin fibrosis and the effect of high-dose-per-fraction radiation. The dorsal skin of a mini-pig was divided into two sections containing 4-cm{sup 2} fields that were irradiated with 30 Gy in a single fraction or 5 fractions and biopsied regularly over 14 weeks. Eosinophil-related Th2 cytokines such as interleukin (IL)-4, IL-5, and C–C motif chemokine-11 (CCL11/eotaxin) were evaluated by quantitative real-time PCR. RNA-sequencing using 30 Gy-irradiated mouse skin and functional assays in a co-culture system of THP-1 and irradiated-human umbilical vein endothelial cells (HUVECs) were performed to investigate the mechanism of eosinophil-mediated radiation fibrosis. Single high-dose-per-fraction irradiation caused pronounced eosinophil accumulation, increased profibrotic factors collagen and transforming growth factor-β, enhanced production of eosinophil-related cytokines including IL-4, IL-5, CCL11, IL-13, and IL-33, and reduced vessels compared with 5-fraction irradiation. IL-33 notably increased in pig and mouse skin vessels after single high-dose irradiation of 30 Gy, as well as in irradiated HUVECs following 12 Gy. Blocking IL-33 suppressed the migration ability of THP-1 cells and cytokine secretion in a co-culture system of THP-1 cells and irradiated HUVECs. Hence, high-dose-per-fraction irradiation appears to enhance eosinophil-mediated fibrotic responses, and IL-33 may be a key molecule operating in eosinophil-mediated fibrosis in high-dose-per fraction irradiated skin. - Highlights: • Single high-dose irradiation aggravates eosinophil-mediated fibrosis through IL-33. • Vascular endothelial cells damaged by high-dose radiation secrete IL-33. • Blocking IL-33 suppressed migration of inflammatory cells and cytokine secretion. • IL

  4. Social Factors to Aggravate Disasters in Yunnan in Late Imperial China%清末民初云南灾荒加剧的社会因素

    Institute of Scientific and Technical Information of China (English)



    云南的自然环境极具灾害性。明清以降至清末民初,由于人口急速膨胀、农田过度开垦和山林矿藏的掠夺式开发,云南生态环境迅速恶化,进而加速加剧了各类自然灾害的发生;农业与家庭手工业相结合的自然经济又从根本上限制了社会抗灾减荒能力的生成与提高。封建剥削、战乱兵祸及列强的经济掠夺、迷信赌毒等造成社会环境的全面恶化,各族民众极度贫困,加重了灾后饥荒疾疫的蔓延与流行。中央与地方政府的荒政长久缺失,导致云南赈灾救荒活动严重乏力。总之,清末民初的云南已完全陷入人为破坏生态环境加剧自然灾害频发、逢灾必荒的结果加速了社会环境的恶化、社会环境恶化又加重了饥荒的蔓延这一恶性循环过程。%Yunnan is prone to natural disasters due to its environment. From the Ming and Qing dynasties to late imperial China, population explosion, over-farming, predatory exploitation of forests and minerals, and ecological damages aggravated all kinds of natural disasters in Yunnan on one hand, and on the other hand, natural economy of agriculture and household handicrafts weakened the power of society to prevent and reduce disasters. Feudal exploitation, government's taxes, wars, bandits, economic plunder of imperialists, superstition, gambling and drugs deteriorated social environment, and extreme poverty of ethnic people speeded.up the wide spread of famine and epidemic after disasters. Neither the central government nor the local governments made policies to deal with natural disasters. As a result, disaster relief in Yunnan was seriously weak. All in all, Yunnan in late imperial China was ecological damages leading to frequent natural disasters which totally stuck into a vicious circle of man-made then would deteriorate social environment, and which in turn would result in prolonged famines.

  5. Reinjury risk of nano-calcium oxalate monohydrate and calcium oxalate dihydrate crystals on injured renal epithelial cells: aggravation of crystal adhesion and aggregation

    Directory of Open Access Journals (Sweden)

    Gan QZ


    , and cell death rate increased.Conclusion: Cell injury contributes to crystal adhesion to Vero cell surface. The attached nano-COM and COD crystals can aggravate Vero cell injury. As a consequence, crystal adhesion and aggregation are enhanced. These findings provide further insights into kidney stone formation. Keywords: nano-calcium oxalate crystals, cell injury, crystal adhesion, kidney stones

  6. Convenience experimentation. (United States)

    Krohs, Ulrich


    Systems biology aims at explaining life processes by means of detailed models of molecular networks, mainly on the whole-cell scale. The whole cell perspective distinguishes the new field of systems biology from earlier approaches within molecular cell biology. The shift was made possible by the high throughput methods that were developed for gathering 'omic' (genomic, proteomic, etc.) data. These new techniques are made commercially available as semi-automatic analytic equipment, ready-made analytic kits and probe arrays. There is a whole industry of supplies for what may be called convenience experimentation. My paper inquires some epistemic consequences of strong reliance on convenience experimentation in systems biology. In times when experimentation was automated to a lesser degree, modeling and in part even experimentation could be understood fairly well as either being driven by hypotheses, and thus proceed by the testing of hypothesis, or as being performed in an exploratory mode, intended to sharpen concepts or initially vague phenomena. In systems biology, the situation is dramatically different. Data collection became so easy (though not cheap) that experimentation is, to a high degree, driven by convenience equipment, and model building is driven by the vast amount of data that is produced by convenience experimentation. This results in a shift in the mode of science. The paper shows that convenience driven science is not primarily hypothesis-testing, nor is it in an exploratory mode. It rather proceeds in a gathering mode. This shift demands another shift in the mode of evaluation, which now becomes an exploratory endeavor, in response to the superabundance of gathered data.

  7. Experimental philosophy. (United States)

    Knobe, Joshua; Buckwalter, Wesley; Nichols, Shaun; Robbins, Philip; Sarkissian, Hagop; Sommers, Tamler


    Experimental philosophy is a new interdisciplinary field that uses methods normally associated with psychology to investigate questions normally associated with philosophy. The present review focuses on research in experimental philosophy on four central questions. First, why is it that people's moral judgments appear to influence their intuitions about seemingly nonmoral questions? Second, do people think that moral questions have objective answers, or do they see morality as fundamentally relative? Third, do people believe in free will, and do they see free will as compatible with determinism? Fourth, how do people determine whether an entity is conscious?

  8. Experimental Techniques

    CERN Document Server

    Engelfried, J


    In this course we will give examples for experimental techniques used in particle physics experiments. After a short introduction, we will discuss applications in silicon microstrip detectors, wire chambers, and single photon detection in Ring Imaging Cherenkov (RICH) counters. A short discussion of the relevant physics processes, mainly different forms of energy loss in matter, is enclosed.

  9. Animal experimentation. (United States)

    Kolar, Roman


    Millions of animals are used every year in often times extremely painful and distressing scientific procedures. Legislation of animal experimentation in modern societies is based on the supposition that this is ethically acceptable when certain more or less defined formal (e.g. logistical, technical) demands and ethical principles are met. The main parameters in this context correspond to the "3Rs" concept as defined by Russel and Burch in 1959, i.e. that all efforts to replace, reduce and refine experiments must be undertaken. The licensing of animal experiments normally requires an ethical evaluation process, often times undertaken by ethics committees. The serious problems in putting this idea into practice include inter alia unclear conditions and standards for ethical decisions, insufficient management of experiments undertaken for specific (e.g. regulatory) purposes, and conflicts of interest of ethics committees' members. There is an ongoing societal debate about ethical issues of animal use in science. Existing EU legislation on animal experimentation for cosmetics testing is an example of both the public will for setting clear limits to animal experiments and the need to further critically examine other fields and aspects of animal experimentation.

  10. 探讨慢性肺源性心脏病急性加重期的临床护理对策%Clinical nursing countermeasure of chronic cor pulmonale with acute aggravating period

    Institute of Scientific and Technical Information of China (English)



    目的:应用全面护理模式对急性加重期慢性肺源性心脏病患者实施的护理效果进行研究。方法选择在我院就诊的急性加重期慢性肺源性心脏病患者82例,随机分为对照组和观察组,各41例。对照组采用常规护理模式;观察组采用全面护理模式。结果观察组患者对慢性肺源性心脏病急性加重期护理模式的满意度明显高于对照组;治疗时间明显短于对照组。结论应用全面护理模式对急性加重期慢性肺源性心脏病患者实施的护理效果非常明显。%Objective To apply the comprehensive nursing mode on condition of patients with acute aggravating period of chronic cor pulmonale implementation of nursing clinical effect were studied. Methods In the condition of our hospital in 82 patients with acute aggravating period of chronic cor pulmonale patients, randomly divided into control group and observation group, an average of 41 cases in each group. The conventional nursing care model to control the implementation of nursing;Observation group to implement the comprehensive nursing pattern on the nursing care. Results The observation group of patients of chronic cor pulmonale with acute aggravating period of the nursing mode satisfaction is signiifcantly higher than control group;Cor pulmonale clinical treatment time signiifcantly shorter than the control group.Conclusion Comprehensive nursing model was applied to the illness of patients with acute aggravating period of chronic cor pulmonale implementation of nursing clinical effect is very obvious.

  11. Self-similar structure and experimental signatures of suprathermal ion distribution in inertial confinement fusion implosions

    CERN Document Server

    Kagan, Grigory; Rinderknecht, H G; Rosenberg, M J; Zylstra, A B; Huang, C -K


    The distribution function of suprathermal ions is found to be self-similar under conditions relevant to inertial confinement fusion hot-spots. By utilizing this feature, interference between the hydro-instabilities and kinetic effects is for the first time assessed quantitatively to find that the instabilities substantially aggravate the fusion reactivity reduction. The ion tail depletion is also shown to lower the experimentally inferred ion temperature, a novel kinetic effect that may explain the discrepancy between the exploding pusher experiments and rad-hydro simulations and contribute to the observation that temperature inferred from DD reaction products is lower than from DT at National Ignition Facility.

  12. Stress kinase inhibition modulates acute experimental pancreatitis

    Institute of Scientific and Technical Information of China (English)

    F. Fleischer; R. Dabew; B. Goke; ACC Wagner


    AIM To examine the role of p38 during acute experimental cerulein pancreatitis.METHODS Rats were treated with cerulein with or without a specific JNK inhibitor (CEP1347)andy or a specific p38 inhbitor (SB203380) and pancreatic stress kinase activity wasdetermined. Parameters to assess pancreatitis included trypsin, amylase, lipase, pancreatic weight and histology.RESULTS JNK inhibition with CEP1347ameliorated pancreatitis, reducing pancreatic edema. In contrast, p38 inhibition with SB203580aggravated pancreatitis with higher trypsinlevels and, with induction of acinar necrosis not normally found after cerulein hyperstimulation.Simultaneous treatment with both CEP1347 and SB203580 mutually abolished the effects of either compound on cerulein pancreatitis.CONCLUSION Stress kinases modulatepancreatitis differentially. JNK seems to promote pancreatitis development, possibly by supporting inflammatory reactions such as edema formation while its inhibition ameliorates pancreatitis. In contrast, p38 may help reduce organ destruction while inhibition of p38 during induction of cerulein pancreatitis leads to the occurrence of acinar necrosis.

  13. Experimental music for experimental physics

    CERN Multimedia

    Rosaria Marraffino


    Using the sonification technique, physicist and composer Domenico Vicinanza paid homage to CERN at its 60th anniversary ceremony. After months of hard work, he turned the CERN Convention and LHC data into music.   Click here to download the full score of the "LHChamber music". Every birthday deserves gifts and CERN’s 60th anniversary was no exception. Two gifts were very special, thanks to the hard work of Domenico Vicinanza, a physicist and composer. He created two experimental pieces by applying the sonification technique to the CERN Convention and to data recorded by the four LHC detectors during Run 1. “This technique allows us to ‘hear’ data using an algorithm that translates numbers or letters into notes. It keeps the same information enclosed in a graph or a document, but has a more aesthetic exposition,” explains Domenico Vicinanza. “The result is meant to be a metaphor for scientific cooperation, in which d...

  14. Aggravated unbundling in German energy industry (part 1). Basics: EU acceleration directive and economic monopoly theory; Verschaerftes Unbundling in der deutschen Energiewirtschaft (Teil 1). Grundlagen: EG-Beschleunigungsnovellen und volkswirtschaftliche Monopoltheorie

    Energy Technology Data Exchange (ETDEWEB)

    Wiedmann, K.P. [Hannover Univ. (Germany); Langerfeldt, M. [Lueneburg Univ. (Germany)


    The main innovations of the so-called acceleration directive are clearly aggravated regulations for divestiture of vertically integrated enterprises. This difficulty commonly known as unbundling is the topic of this two-part article. Part 1 reviews the process of European legislation. The unbundling regulations of the current and future laws are then presented systematically against the economic background. A microeconomic assessment of the regulations will follow in part 2. [German] Zu den wichtigsten Neuerungen der sog. Beschleunigungsrichtlinien zaehlen deutlich verschaerfte Entflechtungsregelungen fuer vertikal integrierte Versorger. Die gemeinhin mit dem Stichwort 'Unbundling' bezeichnete Problematik ist Gegenstand des vorliegenden zweiteiligen Beitrags. Der 1. Teil blickt kurz zurueck auf das Verfahren der europaeischen Rechtsetzung. Anschliessend werden die Unbundling-Vorschriften des bestehenden und des zukuenftigen Rechts systematisch im Spiegel ihres volkswirtschaftlichen Hintergrunds vorgestellt. Eine betriebswirtschaftliche Bewertung der Neuerungen folgt in Teil 2. (orig.)

  15. Research on Strategy of Foreign Trade Enterprises in Guangxi Based on the Aggravation of European Debt Crisis%欧债危机加剧下广西外贸企业对策探讨

    Institute of Scientific and Technical Information of China (English)



      The global economic, financial and trade situations deteriorate sharply with the European debt crisis erupting, spreading and upgrading. China's foreign trade is impacted tremendously and the development of foreign trade enterprises in Guangxi will inevitably be affected. In the paper, the aggravation of the European debt crisis is described. Its adverse effects on the development of foreign trade enterprises in Guangxi are analyzed through several aspects of the transmission mechanism in external demand, exchange rate fluctuations, exchange risk and trade frictions. And the development strategies coping with aggravation of the European debt crisis are proposed.%  欧债危机的爆发、蔓延和加剧,使全球经济、金融、贸易形势急剧恶化,我国外贸经济遭受巨大冲击,广西外贸企业的发展也不可避免地受到影响。文章就欧债危机加剧的态势,通过其外部需求、汇率变动、汇兑风险和贸易摩擦等几方面的传导机制,分析了欧债危机对广西对外贸易发展的不利影响,并相应地提出了外贸企业应对欧债危机日益加剧的策略。

  16. Co-administration of α-lipoic acid and cyclosporine aggravates colon ulceration of acetic acid-induced ulcerative colitis via facilitation of NO/COX-2/miR-210 cascade. (United States)

    El-Gowelli, Hanan M; Saad, Evan I; Abdel-Galil, Abdel-Galil A; Ibrahim, Einas R


    In this work, α-lipoic acid and cyclosporine demonstrated significant protection against acetic acid-induced ulcerative colitis in rats. We proposed that α-lipoic acid and cyclosporine co-administration might modulate their individual effects. Induction of ulcerative colitis in rats was performed by intra-rectal acetic acid (5% v/v) administration for 3 consecutive days. Effects of individual or combined used of α-lipoic acid (35 mg/kg ip) or cyclosporine (5mg/kg sc) for 6 days starting 2 days prior to acetic acid were assessed. Acetic acid caused colon ulceration, bloody diarrhea and weight loss. Histologically, there was mucosal atrophy and inflammatory cells infiltration in submucosa, associated with depletion of colon reduced glutathione, superoxide dismutase and catalase activities and elevated colon malondialdehyde, serum C-reactive protein (C-RP) and tumor necrosis factor-α (TNF-α). Colon gene expression of cyclooxygenase-2 and miR-210 was also elevated. These devastating effects of acetic acid were abolished upon concurrent administration of α-lipoic acid. Alternatively, cyclosporine caused partial protection against acetic acid-induced ulcerative colitis. Cyclosporine did not restore colon reduced glutathione, catalase activity, serum C-RP or TNF-α. Unexpectedly, co-administration of α-lipoic acid and cyclosporine aggravated colon ulceration. Concomitant use of α-lipoic acid and cyclosporine significantly increased nitric oxide production, cyclooxygenase-2 and miR-210 gene expression compared to all other studied groups. The current findings suggest that facilitation of nitric oxide/cyclooxygenase-2/miR-210 cascade constitutes, at least partially, the cellular mechanism by which concurrent use of α-lipoic acid and cyclosporine aggravates colon damage. Collectively, the present work highlights the probable risk of using α-lipoic acid/cyclosporine combination in ulcerative colitis patients.


    Directory of Open Access Journals (Sweden)

    L. D. Khidirova


    Full Text Available Aim. To study the role of hormonal and metabolic changes specific to myocardial infarction in the development of inflammatory reactions in the experimental non-coronarogenic myocardial damage. Material and methods. Wistar male rats weighing 180–220 g (n=80 were used in the study. Metabolic myocardial infarction in intact rats and rats with alloxan diabetes was induced by epinephrine injected subcutaneously as single dose or daily (7 days. Myocardial infarction was verified by ECG analysis, and by histological control. Nitroblue tetrazolium test (NBT-test both spontaneous and zymosan induced NBT-test was used to determine the oxygen-dependent functional activity of neutrophils and their biocidal reserve. Determination of cationic proteins in neutrophils of peripheral blood was performed using lysosomal-cationic test. Results. Increase in oxygen-dependent neutrophil biocidal activity was found as well as reduction in biocidal reserves. Indicators of zymosan induced NBT-test raised according to aggravation of hormonal changes much slower: alloxan increased them by 10% only , epinephrine single dose — by 35%, long-term epinephrine administration simultaneously with alloxan — by 54%. At the same time oxygen-independent neutrophil activity determined by intra-neutrophil cationic proteins level was significantly reduced. Blood levels of pro-inflammatory cytokines raised according to progression of the changes in myocardium: tumor necrosis factor-α (from 5.5±0.03 to 12.6±1.23 pg/ml and interleukin-1β (from 6.0±0.18 to 11.1±0.78 pg/ml. Conclusion. Experimental model of hormonal changes specific to myocardial infarction detected a relationship between inflammatory reactions accompanying myocardial damage and increased catecholamine production.

  18. 慢性耳鸣急性加重时的听阈改变及其对耳鸣预后的影响%Acute aggravation of chronic tinnitus: a study of the hearing characteristic and prognosis

    Institute of Scientific and Technical Information of China (English)

    曾祥丽; 王树芳; 黎志成; 岑锦添; 李源


    目的 探讨慢性耳鸣急性加重时患者的听阈改变及其对耳鸣预后的影响.方法 对32例在习服治疗过程中出现耳鸣急性加重的患者进行纯音听阈、声导抗、耳声发射、听性脑干反应、耳蜗电图及甘油试验等听力学检测,对新出现听阈提高者在习服治疗的同时,按照突发性聋方案治疗.对照组75例仅接受习服治疗.分析慢性耳鸣急性加重时的听阈改变,以及耳鸣加重组与对照组在习服治疗的第3、6、9、12个月时的耳鸣代偿情况.结果 慢性耳鸣急性加重时,出现3种类型的局部频率听阈提高:①既往为4~8 kHz高频下降型听力曲线,耳鸣加重时,相邻的中频区1~2个频率(含半倍频)听阈提高;②既往中频区单个频率听力损失,耳鸣加重时,紧邻的中频区新增单个频率听阈提高,听力曲线由锯齿型转变为凹槽型;③低频听力波动型,慢性耳鸣急性加重时,125~1000 Hz平均听阈较既往提高10~30 dB,而高频区听阈无改变.按照突发性聋方案治疗后,随着新出现听力损伤的恢复,25例随之实现耳鸣代偿.耳鸣加重组与对照组在习服治疗的第3、6、9个月,代偿率差异无统计学意义(X2值分别为0.005、0.005、2.587,P值均>0.05),12个月时,耳鸣加重组代偿率明显高于对照组,差异有统计学意义(X2=0.108,P<0.05).结论 慢性耳鸣急性加重时,出现了不同形式的局部频率听力损失,对新出现听力损失及时有效的治疗,在挽救听力的同时,加速了耳鸣的代偿.%Objective To ivestigate the hearing change when chronic tinnitus acute aggravated and the affect of prognosis due to hearing change. Methods The pure tone threshold and acoustic immittance were used for every case in the acute aggravation of chronic tinnitus(AACT)group, and for some of AACT group members the auditory brainstem response (ABR), distort-product otoacoustic emission (DPOAE), electrocochleogram (EcochG), glycerin test and

  19. Ferrous sulfate, but not iron polymaltose complex, aggravates local and systemic inflammation and oxidative stress in dextran sodium sulfate-induced colitis in rats

    Directory of Open Access Journals (Sweden)

    Toblli JE


    Full Text Available Jorge E Toblli, Gabriel Cao, Margarita Angerosa Laboratory of Experimental Medicine, Hospital Alemán, School of Medicine, University of Buenos Aires, Buenos Aires, Argentina Background and aims: Iron deficiency is common in inflammatory bowel disease, yet oral iron therapy may worsen the disease symptoms and increase systemic and local oxidative stress. The aim of this study was to compare the effects of oral ferrous sulfate and iron polymaltose complex on inflammatory and oxidative stress markers in colitic rats.Methods: Animals were divided into four groups with ten animals each. Rats of three groups received dextran sodium sulfate to induce colitis and animals of two of these groups received 5 mg iron/kg of body weight a day, as ferrous sulfate or iron polymaltose complex, for 7 days. Gross colon anatomy, histology of colon and liver, stainings of L-ferritin, Prussian blue, hepcidin, tumor necrosis factor-α, and interleukin-6, as well serum levels of liver enzymes, inflammatory markers, and iron markers, were assessed.Results: Body weight, gross anatomy, crypt injury and inflammation scores, inflammatory parameters in liver and colon, as well as serum and liver hepcidin levels were not significantly different between colitic animals without iron treatment and colitic animals treated with iron polymaltose complex. In contrast, ferrous sulfate treatment caused significant worsening of these parameters. As opposed to ferrous sulfate, iron polymaltose complex caused less or no additional oxidative stress in the colon and liver compared to colitic animals without iron treatment.Conclusion: Iron polymaltose complex had negligible effects on colonic tissue erosion, local or systemic oxidative stress, and local or systemic inflammation, even at high therapeutic doses, and may thus represent a valuable oral treatment of iron deficiency in inflammatory bowel disease. Keywords: preclinical, oral iron treatment, tolerability, colonic tissue erosion

  20. A rare aggravation of severe mucositis post chemotherapy in a child with acute lymphoblastic leukemia [v1; ref status: indexed,

    Directory of Open Access Journals (Sweden)

    Adlette Inati


    Full Text Available Oral mucositis is a debilitating manifestation in children undergoing chemotherapy and radiotherapy. Children with mucositis should be properly managed in order to prevent further exacerbation and adverse complications. We hereby present the first report of a severe chemotherapy-induced mucositis, plausibly aggravated by improper dental hygiene leading to shedding of the ventral part of the tongue in a child with pre-B acute lymphoblastic leukemia (ALL. The patient steadily and gradually recovered her oral maneuvers and ability to speak several months later. Her tongue underwent hypertrophy as a compensatory mechanism. We recommend that critical and regular assessment of the oral mucosa and proper dental care and oral hygiene be emphasized in all pediatric patients receiving chemotherapy. Families of affected children need to be educated about the benefits and modes of optimal oral hygiene for their children and the need to seek immediate care for mouth pain and or lesions. Optimal treatment for mucositis needs to be instituted without delay in this high risk pediatric population. Such a preventive and therapeutic approach may prevent associated life threatening oral and systemic complications, promote rapid and complete mucosal healing, alleviate pain and improve quality of life in children with cancer.

  1. Pancreatic acinar cells-derived cyclophilin A promotes pancreatic damage by activating NF-κB pathway in experimental pancreatitis

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Ge [Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai (China); Wan, Rong [Department of Gastroenterology, Shanghai First People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai (China); Hu, Yanling [Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai (China); Ni, Jianbo [Department of Gastroenterology, Shanghai First People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai (China); Yin, Guojian; Xing, Miao [Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai (China); Shen, Jie [Department of Gastroenterology, Shanghai First People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai (China); Tang, Maochun [Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai (China); Chen, Congying [Department of Gastroenterology, Shanghai First People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai (China); Fan, Yuting; Xiao, Wenqin; Zhao, Yan [Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai (China); Wang, Xingpeng, E-mail: [Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai (China); Department of Gastroenterology, Shanghai First People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai (China); and others


    Highlights: • CypA is upregulated in experimental pancreatitis. • CCK induces expression and release of CypA in acinar cell in vitro. • rCypA aggravates CCK-induced acinar cell death and inflammatory cytokine production. • rCypA activates the NF-κB pathway in acinar cells in vitro. - Abstract: Inflammation triggered by necrotic acinar cells contributes to the pathophysiology of acute pancreatitis (AP), but its precise mechanism remains unclear. Recent studies have shown that Cyclophilin A (CypA) released from necrotic cells is involved in the pathogenesis of several inflammatory diseases. We therefore investigated the role of CypA in experimental AP induced by administration of sodium taurocholate (STC). CypA was markedly upregulated and widely expressed in disrupted acinar cells, infiltrated inflammatory cells, and tubular complexes. In vitro, it was released from damaged acinar cells by cholecystokinin (CCK) induction. rCypA (recombinant CypA) aggravated CCK-induced acinar cell necrosis, promoted nuclear factor (NF)-κB p65 activation, and increased cytokine production. In conclusion, CypA promotes pancreatic damage by upregulating expression of inflammatory cytokines of acinar cells via the NF-κB pathway.

  2. 高通量测序探讨胰腺炎加重肝损伤的研究%Through high-throughput sequencing technologies to explore the mechanism of pancreatitis aggravating liver damage

    Institute of Scientific and Technical Information of China (English)

    王谦; 白槟; 赵占伟; 余鹏飞; 郝一鸣; 邱兆岩; 郭敏; 冯全新; 刘朝旭


    目的 探讨急性胰腺炎(AP)加重肝脏损伤的机制.方法 将SD大鼠随机分为AP组和对照组(NC),采用牛磺胆酸钠逆行胰胆管注射的方法建立AP模型,造模后6h经下腔静脉采血,检测血清淀粉酶、脂肪酶水平、胰腺水含量,同时收集肝脏组织,用于提取RNA.通过转录组测序(RNA-seq)的方法分析AP加重肝损害的相关基因和通路改变.结果 AP组与NC组比,其血清淀粉酶[(8 964.65 ±401.23) U/L]和脂肪酶[(2350.00 ±201.90) U/L]含量明显上升(P<0.05);胰腺水含量AP组[(79.42±1.21)%]显著高于NC组[(70.14±1.02)%];RNA-seq结果显示两组间共有2 249个差异表达基因,其中564个表达上调,1 685个表达下调.京都基因与基因组百科全书(KEGG)通路富集结果由高到低为代谢通路、炎性因子通路、趋化因子通路、Toll样受体通路等.结论 AP可能通过炎性因子、Toll样受体(TLR)等通路介导了对肝脏的损伤.%Objective To explore the mechanism of acute pancrea titis (AP) aggravating liver damage.Methods SD rats were randomly divided into negative control (NC) and AP group.We use the method of sodium taurocholate retrograde pancreatic duct injection to establish the model of AP.After 6 h of anesthesia,the blood were collected from the inferior vena cava to detect the levels of serum amylase and lipase.The liver tissue was collected imnediately in order to extract total RNA.The genes and related pathways were analyzed by RNA-seq.Results Compared to NC group,the levels of serum amylase [(8 964.65 ±401.23) U/L] and lipase [(2 350.00 ± 201.90) U/L] were significantly higher in AP group (P <0.05);the pancreatic water content in AP group [(79.42 ± 1.21) %] were significantly higher than NC group [(70.14 ± 1.02) %];RNA-seq results showed that there were 2249 differently expressed genes between AP and NC group,among which 564 genes were up-regulated and 1685 genes were down-regulated.Kyoto gene and genome encyclopedia (KEGG

  3. Exposure to multi-walled carbon nanotubes results in aggravation of airway inflammation and remodeling and in increased production of epithelium-derived innate cytokines in a mouse model of asthma. (United States)

    Ronzani, Carole; Casset, Anne; Pons, Françoise


    With the development of nanotechnologies, the potential adverse effects of nanomaterials such as multi-walled carbon nanotubes (MWCNT) on the respiratory tract of asthmatics are questioned. Furthermore, investigations are necessary to understand how these effects might arise. In the present study, we hypothesized that epithelium-derived innate cytokines that are considered as important promoting factors in allergy may contribute to an aggravating effect of MWCNT on asthma. We investigated in the mouse the effect of MWCNT on systemic immune response and airway inflammation and remodeling induced by the most frequent allergen so far associated with asthma, house dust mite (HDM), and we examined the production of the innate cytokines thymic stromal lymphopoietin (TSLP), IL-25, IL-33, and GM-CSF. Mice exposed to HDM exhibited specific IgG1 in serum and inflammatory cell infiltration, and increased Th2 cytokine production, mucus hyperproduction, and collagen deposition in the airways when compared to naïve animals. Levels of total IgG1 and HDM-specific IgG1, influx of macrophages, eosinophils and neutrophils, production of collagen, TGF-β1, and mucus, as well as levels of IL-13, eotaxin, and TARC, were dose-dependently increased in mice exposed to HDM and MWCNT compared to HDM alone. These effects were associated with an increased production of TSLP, IL-25, IL-33, and GM-CSF in the airways. Our data demonstrate that MWCNT increase in a dose-dependent manner systemic immune response, as well as airway allergic inflammation and remodeling induced by HDM in the mouse. Our data suggest also a role for airway epithelium and innate cytokines in these effects.

  4. Dimethyl Ether: New Advances in Wear Testing: Theoretical and Experimental Results

    DEFF Research Database (Denmark)

    Sivebæk, Ion Marius; Sorenson, Spencer C; Jakobsen, J.;


    ) on the ball. Up to now, all analyses indicated that fuel viscosity influences the wear scar size and fuel performance in full-scale pumps. The wear scar size could then be a result of hydrodynamic lubrication (at least a significant part of it) and not of boundary lubrication as it was the original intention...... viscosity sensibility issue is seriously aggravated for this fuel. Molecular dynamics calculations involving straight alkanes with lengths from 3 to 14 carbon atoms have been performed. The model is based on simple inter-atomic and surface interactions and it simulates an asperity contact between curved...... surfaces with long-range elasticity. This last property has enabled the model to correlate well with experimental results. The outcome of the alkane calculations indicates that the longer ones lubricate better than the shorts ones but not necessarily because of viscosity differences. The reason is more...

  5. The correlation analysis between environmental factors, bone morphogenetic protein-4 and transforming growth factor beta-3 polymorphisms in nonsyndromic cleft lip with or without cleft palate%BMP4、TGF-β3基因多态性与环境暴露在非综合征性唇腭裂发生中的交互作用

    Institute of Scientific and Technical Information of China (English)

    林健燕; 栾荣生; 郭泽强; 林新勤; 汤洪洋; 陈苑萍


    目的 探讨环境暴露因素、骨形态生成蛋白4(BMP4)基因、转化生长因子β3(transforming growth factor beta-3,TGF-β3)基因之间的交互作用在非综合征性唇腭裂(nonsyndromic cleft lip and cleft palate,NSCLP)发生中的可能作用.方法 通过问卷调查获取环境暴露资料.用聚合酶链反应(PCR)-限制性片段长度多态性(restriction fragment length polymorphism,RFLP)技术对对照组(200例)和NSCLP组(200例)各基因位点的多态性进行检测.采用多因子降维法(multifactor djmensionality reduction,MDR)分析基因之间、基因与环境之间的交互作用关系,并对筛选的交互作用关系用Logistic回归进行验证.结果 BMP4 T538C、TGF-β3 C641A和TGF-β3G15572-三个单核苷酸多态性(single nucleotide polymorphism,SNP)位点间的交互作用与NSCLP的发生无关联.基因与环境交互作用分析发现,BMP4 T538C与母亲妊娠早期被动吸烟、母亲妊娠早期感染史对NSCLP的发生具有交互作用;TGF-β3G15572-与母亲妊娠早期被动吸烟、母亲妊娠早期感染史、父亲知晓妊娠前吸烟、父亲知晓妊娠前饮酒、母亲妊娠早期补充维生素对NSCLP的发生具有交互作用.经Logistic回归验证,结果一致.结论 NSCLP是基因与环境因素共同作用的结果,易感基因多态性影响着个体对环境因素的反应,研究它们之间的相互关系对阐明NSCLP的病因及发病机制具有重要意义.%Objective To investigate the effects of interactions among environmental factors, bone morphogenetic protein-4 ( BMP4 ) and transforming growth factor beta-3 ( TGF-β3 ) polymorphisms on nonsyndromic cleft lip and cleft palate (NSCLP) . MethodsThe data of environmental exposures were collected with questionnaires.Genotypes were determined with techniques of polymerase chain reactionrestriction fragment length polymorphism. Interactions between genes, environmental factors and NSCLP were analyzed using multifactor dimensionality

  6. HIRENASD Experimental Data (United States)

    National Aeronautics and Space Administration — Experimental Data for HIRENASD configuration Zip files below contain the experimental data for the pressure coefficients, both the static and the forced oscillation...

  7. Ethics in Animal Experimentation

    Directory of Open Access Journals (Sweden)

    Yusuf Ergun


    Full Text Available Experimental animals are frequently used to obtain information for primarily scientific reasons. In the present review, ethics in animal experimentation is examined. At first, the history of animal experimentation and animal rights is outlined. Thereafter, the terms in relation with the topic are defined. Finally, prominent aspects of 3Rs constituting scientific and ethical basis in animal experimentation are underlined. [Archives Medical Review Journal 2010; 19(4.000: 220-235

  8. Ethics in Animal Experimentation


    Yusuf Ergun


    Experimental animals are frequently used to obtain information for primarily scientific reasons. In the present review, ethics in animal experimentation is examined. At first, the history of animal experimentation and animal rights is outlined. Thereafter, the terms in relation with the topic are defined. Finally, prominent aspects of 3Rs constituting scientific and ethical basis in animal experimentation are underlined. [Archives Medical Review Journal 2010; 19(4.000): 220-235

  9. Microexperiencia Educativa (Microeducational Experimentation). (United States)

    Burton Meis, Roberto


    Experimentation for educational reform in Argentina is limited to specifically designated schools which are to be in a permanent state of experimentation. This article presents the official statements designating the experimental schools and includes remarks covering administration, evaluation, and supervision. (VM)

  10. Experimental treatments for mitochondrial dysfunction in sepsis: A narrative review

    Directory of Open Access Journals (Sweden)

    Guilang Zheng


    Full Text Available Sepsis is a systemic inflammatory response to infection. Sepsis, which can lead to severe sepsis, septic shock, and multiple organ dysfunction syndrome, is an important cause of mortality. Pathogenesis is extremely complex. In recent years, cell hypoxia caused by mitochondrial dysfunction has become a hot research field. Sepsis damages the structure and function of mitochondria, conversely, mitochondrial dysfunction aggravated sepsis. The treatment of sepsis lacks effective specific drugs. The aim of this paper is to undertake a narrative review of the current experimental treatment for mitochondrial dysfunction in sepsis. The search was conducted in PubMed databases and Web of Science databases from 1950 to January 2014. A total of 1,090 references were retrieved by the search, of which 121 researches met all the inclusion criteria were included. Articles on the relationship between sepsis and mitochondria, and drugs used for mitochondrial dysfunction in sepsis were reviewed retrospectively. The drugs were divided into four categories: (1 Drug related to mitochondrial matrix and respiratory chain, (2 drugs of mitochondrial antioxidant and free radical scavengers, (3 drugs related to mitochondrial membrane stability, (4 hormone therapy for septic mitochondria. In animal experiments, many drugs show good results. However, clinical research lacks. In future studies, the urgent need is to develop promising drugs in clinical trials.

  11. Risk assessment of hand washing efficacy using literature and experimental data. (United States)

    Montville, Rebecca; Chen, Yuhuan; Schaffner, Donald W


    This study simulated factors that influence the levels of bacteria on foodservice workers' hands. Relevant data were collected from the scientific literature and from laboratory experiments. Literature information collected included: initial bacterial counts on hands and water faucet spigots, bacterial population changes during hand washing as effected by soap type, sanitizing agent, drying method, and the presence of rings. Experimental data were also collected using Enterobacter aerogenes as a surrogate for transient bacteria. Both literature and experimental data were translated into appropriate discrete or probability distribution functions. The appropriate statistical distribution for each phase of the hand washing process was determined. These distributions were: initial count on hands, beta (2.82, 2.32, 7.5); washing reduction using regular soap, beta (3.01, 1.91, -3.00, 0.60); washing reduction using antimicrobial soap, beta (4.19, 2.99, -4.50, 1.50); washing reduction using chlorhexidine gluconate (CHG), triangular (-4.75, -1.00, 0); reductions from hot air drying, beta (3.52, 1.92, -0.20, 1.00); reduction from paper towel drying, triangular (-2.25, -0.75, 0); reduction due to alcohol sanitizer, gamma (-1.23, 4.42) -5.8; reduction due to alcohol-free sanitizer, gamma (2.22, 5.38) -5.00; and the effect of rings, beta (8.55, 23.35, 0.10, 0.45). Experimental data were fit to normal distributions (expressed as log percentage transfer rate): hand-to-spigot transfer, normal (-0.80, 1.09); spigot to hand, normal (0.36, 0.90). Soap with an antimicrobial agent (in particular, CHG) was observed to be more effective than regular soap. Hot air drying had the capacity to increase the amount of bacterial contamination on hands, while paper towel drying caused a slight decrease in contamination. There was little difference in the efficacy of alcohol and alcohol-free sanitizers. Ring wearing caused a slight decrease in the efficacy of hand washing. The experimental data

  12. Is animal experimentation fundamental? (United States)

    d'Acampora, Armando José; Rossi, Lucas Félix; Ely, Jorge Bins; de Vasconcellos, Zulmar Acciolli


    The understanding about the utilization of experimental animals in scientific research and in teaching is many times a complex issue. Special attention needs to be paid to attain the understanding by the general public of the importance of animal experimentation in experimental research and in undergraduate medical teaching. Experimental teaching and research based on the availability of animals for experimentation is important and necessary for the personal and scientific development of the physician-to-be. The technological arsenal which intends to mimic experimentation animals and thus fully replace their use many times does not prove to be compatible with the reality of the living animal. The purpose of this paper is to discuss aspects concerning this topic, bringing up an issue which is complex and likely to arouse in-depth reflections.

  13. Transonic Experimental Research Facility (United States)

    Federal Laboratory Consortium — The Transonic Experimental Research Facility evaluates aerodynamics and fluid dynamics of projectiles, smart munitions systems, and sub-munitions dispensing systems;...

  14. Strength of Experimental Grouts

    DEFF Research Database (Denmark)

    Sørensen, Eigil V.

     The present report describes tests carried out on 5 experimental grouts developed by BASF Construction Materials and designed for use in grouted connections of offshore windmill foundations....... The present report describes tests carried out on 5 experimental grouts developed by BASF Construction Materials and designed for use in grouted connections of offshore windmill foundations....

  15. Introduction: Experimental Green Strategies

    DEFF Research Database (Denmark)

    Peters, Terri


    Defining new ways in which archietcts are responding to the challenge of creating sustainable architecture , Experimental Green Strategies present a state of the art in applied ecological architectural research.......Defining new ways in which archietcts are responding to the challenge of creating sustainable architecture , Experimental Green Strategies present a state of the art in applied ecological architectural research....

  16. The Experimental College. (United States)

    Meiklejohn, Alexander

    "The Experimental College" tells the story of a 4-year academic experiment at the University of Wisconsin established by Alexander Meiklejohn. Aimed at finding a method of teaching that would help students develop "intelligence in the conduct of their own lives," the Experimental College discarded major requirements,…

  17. Ansiedade experimental humana Human experimental anxiety

    Directory of Open Access Journals (Sweden)

    Frederico Guilherme Graeff


    Full Text Available CONTEXTO: A ansiedade experimental no ser humano constitui-se em ponte entre os modelos animais e os ensaios clínicos. OBJETIVO: Este artigo focaliza métodos químicos e psicológicos utilizados para provocar ansiedade experimental em seres humanos. MÉTODOS: Realizou-se revisão seletiva da literatura. RESULTADOS: Os desafios farmacológicos têm sido usados principalmente para induzir ataques de pânico em pacientes com transtorno de pânico, os quais são mais sensíveis a eles que indivíduos normais ou pacientes portadores de outros transtornos psiquiátricos. Uma das mais importantes contribuições deste método é a de ter mostrado que os agentes panicogênicos mais seletivos, como o lactato ou a inalação de CO2, não ativam o eixo hormonal do estresse. Entre os métodos psicológicos, destacam-se o condicionamento de respostas elétricas da condutância da pele, cujo perfil farmacológico se aproxima daquele do transtorno de ansiedade generalizada, e o teste da simulação do falar em público, cuja farmacologia é semelhante à do transtorno de pânico. CONCLUSÕES: Tais resultados salientam a diferença entre a neurobiologia da ansiedade e a do pânico.BACKGROUND: Human experimental anxiety methods bridge the gap between animal models and clinical assays. OBJECTIVE: This article is focused on chemical and psychological procedures used to generate experimental anxiety in human beings. METHODS: A selective review of the literature has been carried out. RESULTS: Pharmacological challenges have been mainly used to induce panic attacks in panic disorder patients, who are more susceptible than normal individuals or patients with other psychiatric disorders. One of the most important contributions of this method is to have shown that the most selective panicogenic agents, such as lactate or CO2 inhalation, do not activate the hormonal stress axis. Among the psychological methods stand the conditioning of the electrical skin conductance

  18. Hyperbaric oxygen therapy aggravates liver reperfusion injury in rats Oxigenoterapia hiperbárica agrava lesão de reperfusão hepática em ratos

    Directory of Open Access Journals (Sweden)

    Cristiano Xavier Lima


    Full Text Available PURPOSE: To evaluate the effects of hyperbaric oxygen (HO therapy in the protection against liver ischemia/reperfusion injury. METHODS: Thirty-two male Wistar rats were divided into four groups of eight animals each: group A - laparotomy and liver manipulation, group B - liver ischemia and reperfusion, group C - HO pretreatment for 60 min followed by liver ischemia and reperfusion, and group D - pretreatment with ambient air at 2.5 absolute atmospheres for 60 min followed by liver ischemia and reperfusion. Plasma was assayed for aspartate aminotransferase (AST, alanine aminotransferase (ALT and lactate dehydrogenase (LDH. Intra-arterial blood pressure was monitored continuously. Myeloperoxidase activity in the liver and lung was assessed 30 min after reperfusion. RESULTS: Plasma AST, ALT and LDH increased after reperfusion in all animals. Plasma ALT values and myeloperoxidase activity in the liver parenchyma were higher in HO-pretreated animals than in groups A, B and D. HO had a negative hemodynamic effect during liver reperfusion. CONCLUSION: Liver preconditioning with hyperbaric oxygen therapy aggravated liver ischemia/reperfusion injury in rats as demonstrated by plasma ALT and liver myeloperoxidase activity.OBJETIVO: Avaliar os efeitos da oxigenoterapia hiperbárica (OH como método preventivo da lesão de isquemia e reperfusão (LIR do fígado. MÉTODOS: Trinta e dois ratos machos Wistar foram distribuídos em quatro grupos de oito animais cada: A - laparotomia e manipulação hepática, B - isquemia e reperfusão hepática, C - pré-tratamento com OH por 60 minutos seguido de isquemia e reperfusão hepática e D - pré-tratamento com ar ambiente a 2,5 atmosferas absolutas por 60 minuto e isquemia e reperfusão hepática. Dosagens seriadas de AST, ALT e DHL foram realizadas. A pressão intra arterial foi monitorizada continuamente. O grau de infiltração leucocitária no fígado e pulmões foi inferido pela dosagem de mieloperoxidade

  19. Experimentally produced calf pneumonia. (United States)

    Gourlay, R N; Howard, C J; Thomas, L H; Stott, E J


    Experimental pneumonia was produced in calves by the endobronchial inoculation of pneumonic lung homogenates. Irradiated homogenates produced minimal pneumonia. Ampicillin treatment of the homogenates and the experimental calves reduced the extent of pneumonia. Treatment with tylosin tartrate prevented experimental pneumonia. These results suggest that the total pneumonia was due to organisms susceptible to tylosin tartrate and that the residual pneumonia remaining after ampicillin treatment was due to organisms susceptible to tylosin tartrate but not to ampicillin. Of the organisms isolated from the lungs, the ones in this latter category most likely to be responsible are Mycoplasma dispar and ureaplasmas (T-mycoplasmas).

  20. Experimental approaches and applications

    CERN Document Server

    Crasemann, Bernd


    Atomic Inner-Shell Processes, Volume II: Experimental Approaches and Applications focuses on the physics of atomic inner shells, with emphasis on experimental aspects including the use of radioactive atoms for studies of atomic transition probabilities. Surveys of modern techniques of electron and photon spectrometry are also presented, and selected practical applications of inner-shell processes are outlined. Comprised of six chapters, this volume begins with an overview of the general principles underlying the experimental techniques that make use of radioactive isotopes for inner-sh

  1. Experimental semiotics: a review. (United States)

    Galantucci, Bruno; Garrod, Simon


    In the last few years a new line of research has appeared in the literature. This line of research, which may be referred to as experimental semiotics (ES; Galantucci, 2009; Galantucci and Garrod, 2010), focuses on the experimental investigation of novel forms of human communication. In this review we will (a) situate ES in its conceptual context, (b) illustrate the main varieties of studies thus far conducted by experimental semioticians, (c) illustrate three main themes of investigation which have emerged within this line of research, and (d) consider implications of this work for cognitive neuroscience.

  2. Network Science Experimentation Vision (United States)


    Experimentation Ecosystem 3 2.1 Multi-thread Campaign of Experimentation 4 2.1.1 Need for a CAMPX 4 2.1.2 CAMPX Overview 5 2.1.3 Conceptual Model ...Collaborative Research Alliance (CS CRA) and Applied Research and Experimentation Partner (AREP) Programs 19 3.3 Researcher Empowerment and...Productivity 20 4. Composite Network CAMPX 21 4.1 Military Relevance 21 iv 4.2 Goals 22 4.3 Conceptual Model 23 4.3.1 Endeavor Space 23 4.3.2 Single

  3. Systems biology: experimental design. (United States)

    Kreutz, Clemens; Timmer, Jens


    Experimental design has a long tradition in statistics, engineering and life sciences, dating back to the beginning of the last century when optimal designs for industrial and agricultural trials were considered. In cell biology, the use of mathematical modeling approaches raises new demands on experimental planning. A maximum informative investigation of the dynamic behavior of cellular systems is achieved by an optimal combination of stimulations and observations over time. In this minireview, the existing approaches concerning this optimization for parameter estimation and model discrimination are summarized. Furthermore, the relevant classical aspects of experimental design, such as randomization, replication and confounding, are reviewed.

  4. Experimental Aspects of Synthesis

    CERN Document Server

    Ehlers, Rüdiger


    We discuss the problem of experimentally evaluating linear-time temporal logic (LTL) synthesis tools for reactive systems. We first survey previous such work for the currently publicly available synthesis tools, and then draw conclusions by deriving useful schemes for future such evaluations. In particular, we explain why previous tools have incompatible scopes and semantics and provide a framework that reduces the impact of this problem for future experimental comparisons of such tools. Furthermore, we discuss which difficulties the complex workflows that begin to appear in modern synthesis tools induce on experimental evaluations and give answers to the question how convincing such evaluations can still be performed in such a setting.


    Institute of Scientific and Technical Information of China (English)

    XUE Yang; XU Wei-lin; LUO Shu-jing; CHEN Hua-yong; LI Nai-wen; XU Ling-jun


    Dam break can cause a significant disaster in the downstream,especially,in a valley with cascade reservoirs,which would aggravate the disaster extent.The experimental studies of the dam-break flow of cascade reservoirs are few and far between at the present.Most of related studies concern the failure of a single dam..This article presents an experimental study of the characteristics of an instantly filled dam-break flow of cascade reservoirs in a rectangular glass flume with a steep bottom slope.A new method was used to simulate the sudden collapse of the dam.A series of sensors for automatic water-levels were deployed to record the rapid water depth fluctuation.The experimental results show that,the ratio of the initial water depth of the downstream reservoir to that of the upstream reservoir would greatly affect the flood peak water depth in the downstream reservoir area and in the stream channel behind the downstream dam,while the influence of the dam spacing is insignificant.In addition,the comparison between the single reservoir and the cascade reservoirs shows some difference in the dam-break flow pattern and the stage hydrograph at the corresponding gauging points.

  6. Nuclear test experimental science

    Energy Technology Data Exchange (ETDEWEB)

    Struble, G.L.; Middleton, C.; Bucciarelli, G.; Carter, J.; Cherniak, J.; Donohue, M.L.; Kirvel, R.D.; MacGregor, P.; Reid, S. (eds.)


    This report discusses research being conducted at Lawrence Livermore Laboratory under the following topics: prompt diagnostics; experimental modeling, design, and analysis; detector development; streak-camera data systems; weapons supporting research.

  7. Experimental modal analysis

    Energy Technology Data Exchange (ETDEWEB)

    Ibsen, Lars Bo; Liingaard, M.


    This technical report concerns the basic theory and principles for experimental modal analysis. The sections within the report are: Output-only modal analysis software, general digital analysis, basics of structural dynamics and modal analysis and system identification. (au)

  8. The Experimental Art School

    DEFF Research Database (Denmark)

    Ørum, Tania


    The article describes the Experimental Art School from its early beginnings, its development from formal experiments to political action, the question of gender and politics, and the power of the self-organised......The article describes the Experimental Art School from its early beginnings, its development from formal experiments to political action, the question of gender and politics, and the power of the self-organised...

  9. Generalizing Experimental Findings (United States)


    Generalizing Experimental Findings Judea Pearl University of California, Los Angeles Computer Science Department Los Angeles, CA, 90095-1596, USA...Selection Bias The classical problem of generalizing experimental findings from the trial sample to the population as a whole, also known as the problem...of “sample selection-bias” (Heckman, 1979; Bareinboim et al., 2014), has received renewed attention in the past decade, as more researchers come to

  10. Software Reliability Experimentation and Control

    Institute of Scientific and Technical Information of China (English)

    Kai-Yuan Cai


    This paper classifies software researches as theoretical researches, experimental researches, and engineering researches, and is mainly concerned with the experimental researches with focus on software reliability experimentation and control. The state-of-the-art of experimental or empirical studies is reviewed. A new experimentation methodology is proposed, which is largely theory discovering oriented. Several unexpected results of experimental studies are presented to justify the importance of software reliability experimentation and control. Finally, a few topics that deserve future investigation are identified.

  11. Experimental Research in Marketing

    Directory of Open Access Journals (Sweden)

    Jose Mauro Hernandez


    Full Text Available Considering the growing number of scientific studies published in the marketing field and the development of unique theories of the area (Hunt, 2010, using experimental designs seems increasingly appropriate to investigate marketing phenomena. This article aims to discuss the main elements in conducting experimental studies and also to stimulate researchers to adopt this research method. Several international journals (e.g., JCR, JCP, JMR, JR, JBR have been publishing articles based on experiments that not only demonstrate a relationship between two events, but also elucidate how they occur by means of mediation and moderation analyses. This article intents to be a roadmap for novice researchers on how to conduct experiments and to offer new perspectives in experimental research for experienced researchers.  

  12. Knockout reactions: experimental aspects

    Energy Technology Data Exchange (ETDEWEB)

    Cortina Gil, D. [Santiago de Compostela Univ. (Spain)


    The availability of radioactive beams has given rise to intense activity in the field of direct reactions. The removal of one(two)-nucleon (referred to as nucleon knockout in this text) from a fast exotic projectile has been extensively investigated. This lecture provides a general overview of the experimental results achieved using this technique. The sensitivity of the method to different experimental aspects is illustrated with a few examples. Special attention is given to the application of nucleon-knockout reactions as a general purpose spectroscopic tool. (author)

  13. SPHINX experimenters information package

    Energy Technology Data Exchange (ETDEWEB)

    Zarick, T.A. [Sandia National Lab., Albuquerque, NM (United States). Radiation Effects Experimentation Dept.


    This information package was prepared for both new and experienced users of the SPHINX (Short Pulse High Intensity Nanosecond X-radiator) flash X-Ray facility. It was compiled to help facilitate experiment design and preparation for both the experimenter(s) and the SPHINX operational staff. The major areas covered include: Recording Systems Capabilities,Recording System Cable Plant, Physical Dimensions of SPHINX and the SPHINX Test cell, SPHINX Operating Parameters and Modes, Dose Rate Map, Experiment Safety Approval Form, and a Feedback Questionnaire. This package will be updated as the SPHINX facilities and capabilities are enhanced.

  14. Experimental fully contextual correlations

    CERN Document Server

    Amselem, Elias; Lopez-Tarrida, Antonio J; Portillo, Jose R; Bourennane, Mohamed; Cabello, Adan


    Quantum correlations are contextual yet, in general, nothing prevents the existence of even more contextual correlations. We identify and test a simple noncontextual inequality in which the quantum violation cannot be improved by any hypothetical post-quantum resource, and use it to experimentally obtain correlations in which the maximum noncontextual content, defined as the maximum fraction of noncontextual correlations, is less than 0.06. Our correlations are experimentally generated from the outcomes of sequential compatible measurements on a four-state quantum system encoded in the polarization and path of a single photon.

  15. Experimental probes of axions

    Energy Technology Data Exchange (ETDEWEB)

    Chou, Aaron S.; /Fermilab


    Experimental searches for axions or axion-like particles rely on semiclassical phenomena resulting from the postulated coupling of the axion to two photons. Sensitive probes of the extremely small coupling constant can be made by exploiting familiar, coherent electromagnetic laboratory techniques, including resonant enhancement of transitions using microwave and optical cavities, Bragg scattering, and coherent photon-axion oscillations. The axion beam may either be astrophysical in origin as in the case of dark matter axion searches and solar axion searches, or created in the laboratory from laser interactions with magnetic fields. This note is meant to be a sampling of recent experimental results.

  16. Experimental Blade Research

    DEFF Research Database (Denmark)

    Eder, Martin Alexander; Branner, Kim; Berring, Peter

    This report is a summary of the results obtained in the project: Experimental Blade Research – phase 2 (EBR2). The project was supported by the Danish Energy Authority through the 2010 Energy Technology Development and Demonstration Program (EUDP 2010-II) and has journal no. 64011-0006. The project...

  17. Experimental Focal Cerebral Ischemia

    DEFF Research Database (Denmark)

    Christensen, Thomas


    of the middle cerebral artery (MCAO) was used as an experimental model of ischemic stroke. MCAO produces an acute lesion consisting of an ischemic core or focus with severely reduced blood flow surrounded by a borderzone or ischemic penumbra with less pronounced blood flow reduction. Cells in the ischemic focus...

  18. Semiconductor Research Experimental Techniques

    CERN Document Server

    Balkan, Naci


    The book describes the fundamentals, latest developments and use of key experimental techniques for semiconductor research. It explains the application potential of various analytical methods and discusses the opportunities to apply particular analytical techniques to study novel semiconductor compounds, such as dilute nitride alloys. The emphasis is on the technique rather than on the particular system studied.

  19. Communicating Uncertain Experimental Evidence (United States)

    Davis, Alexander L.; Fischhoff, Baruch


    Four experiments examined when laypeople attribute unexpected experimental outcomes to error, in foresight and in hindsight, along with their judgments of whether the data should be published. Participants read vignettes describing hypothetical experiments, along with the result of the initial observation, considered as either a possibility…

  20. Outsourcing of experimental work

    DEFF Research Database (Denmark)

    Nielsen, Henrik


    With the development of new technologies for simultaneous analysis of many genes, transcripts, or proteins (the "omics" revolution), it has become common to outsource parts of the experimental work. In order to maintain the integrity of the research projects, it is important that the interphase...

  1. Experimental Autonomous Vehicle Systems

    DEFF Research Database (Denmark)

    Ravn, Ole; Andersen, Nils Axel


    The paper describes the requirements for and a prototype configuration of a software architecture for control of an experimental autonomous vehicle. The test bed nature of the system is emphasised in the choice of architecture making re-configurability, data logging and extendability simple...

  2. Experimental Design Research

    DEFF Research Database (Denmark)

    of experimental approaches and their utility in this domain, and brings together analytical approaches to promote an integrated understanding. The book also investigates where these approaches lead to and how they link design research more fully with other disciplines (e.g. psychology, cognition, sociology...

  3. Experimental modal analysis

    DEFF Research Database (Denmark)

    Ibsen, Lars Bo; Liingaard, Morten

    This technical report concerns the basic theory and principles for experimental modal analysis. The sections within the report are: Output-only modal analysis software (section 1.1), general digital analysis (section 1.2), basics of structural dynamics and modal analysis (section 1.3) and system ...

  4. Administrative Aspects of Human Experimentation. (United States)

    Irvine, George W.


    The following administrative aspects of scientific experimentation with human subjects are discussed: the definition of human experimentation; the distinction between experimentation and treatment; investigator responsibility; documentation; the elements and principles of informed consent; and the administrator's role in establishing and…

  5. Teaching experimental design. (United States)

    Fry, Derek J


    Awareness of poor design and published concerns over study quality stimulated the development of courses on experimental design intended to improve matters. This article describes some of the thinking behind these courses and how the topics can be presented in a variety of formats. The premises are that education in experimental design should be undertaken with an awareness of educational principles, of how adults learn, and of the particular topics in the subject that need emphasis. For those using laboratory animals, it should include ethical considerations, particularly severity issues, and accommodate learners not confident with mathematics. Basic principles, explanation of fully randomized, randomized block, and factorial designs, and discussion of how to size an experiment form the minimum set of topics. A problem-solving approach can help develop the skills of deciding what are correct experimental units and suitable controls in different experimental scenarios, identifying when an experiment has not been properly randomized or blinded, and selecting the most efficient design for particular experimental situations. Content, pace, and presentation should suit the audience and time available, and variety both within a presentation and in ways of interacting with those being taught is likely to be effective. Details are given of a three-day course based on these ideas, which has been rated informative, educational, and enjoyable, and can form a postgraduate module. It has oral presentations reinforced by group exercises and discussions based on realistic problems, and computer exercises which include some analysis. Other case studies consider a half-day format and a module for animal technicians.

  6. Effects of Bifidobacterium Breve Feeding Strategy and Delivery Modes on Experimental Allergic Rhinitis Mice.

    Directory of Open Access Journals (Sweden)

    Jian-jun Ren

    Full Text Available Different delivery modes may affect the susceptibility to allergic diseases. It is still unknown whether early intervention with probiotics would counteract this effect.The effect of different delivery modes on immune status and nasal symptoms was investigated on established allergic rhinitis (AR mouse model. In addition, the immunoregulatory effects and mechanisms of different feeding manners with Bifidobacterium breve(B. breve were examined.Live lyophilized B. breve was orally administered to BALB/c mice born via vaginal delivery(VD or cesarean delivery (CD for 8 consecutive weeks, after which they were sensitized by ovalbumin(OVA to establish experimental AR. Nasal symptoms, serum immunoglobulins, cytokines, splenic percentages of CD4(+CD25(+Foxp3(+ regulatory T(Treg cells and nasal eosinophil infiltration were evaluated.Compared with VD mice, mice delivered via CD demonstrated more serious nasal symptoms, higher concentrations of OVA-specific immunoglobulin (Ig E, more nasal eosinophils and lower percentages of splenic CD4(+CD25(+Foxp3(+Treg cells after establishing experimental AR. These parameters were reversed by administering B. breves hortly after birth. However, the effect of B. breve did not differ between different delivery modes.CD aggravates the nasal symptoms of AR mice compared to VD. This is the first report that oral administration of B. breve shortly after birth can significantly alleviate the symptoms of AR mice born via both deliveries, probably via activation of the regulatory capacity of CD4(+CD25(+Foxp3(+Treg cells.

  7. Role of inducible nitric oxide synthase in the pathogenesis of experimental leptospirosis. (United States)

    Prêtre, Gabriela; Olivera, Noelia; Cédola, Maia; Haase, Santiago; Alberdi, Lucrecia; Brihuega, Bibiana; Gómez, Ricardo M


    Nitric oxide (NO) produced by inducible nitric oxide synthase (iNOS) is a radical effector molecule of the innate immune system that can directly inhibit pathogen replication. In order to study subsequent iNOS kidney expression in experimental leptospirosis, Golden Syrian hamsters and C3H/HeJ mice were infected intraperitoneally with 10(2) or 10(7) virulent Leptospira interrogans serovar Copenhageni (LIC) strain Fiocruz L1-130. Results showed increased levels of iNOS mRNA and protein in kidneys of infected animals when compared to that in mock-infected animals. To get a deeper insight into the role of iNOS in experimental leptospirosis, both subject species were treated or not treated with 4-aminopyridine (4-AP, 0.3mg/kg), an iNOS inhibitor. Treatment of infected hamsters with 4-AP accelerated the mortality rate to 100% by one day and increased the mortality rate from 20 to 60% in mice at 14 days post-infection. In kidney tissues, 4-AP treatment increased the bacterial burden, as demonstrated through leptospiral DNA quantification by real-time PCR, and aggravated tubulointerstitial nephritis. In addition, iNOS inhibition reduced the specific humoral response against LIC when compared to that in untreated infected animals. According to these results, iNOS expression and the resulting NO have an important role in leptospirosis.

  8. 氧化应激 DNA 损伤在重症肺炎中的作用研究%Key factor of pneumonia′s occurrence and aggravation:oxidative stress-DNA damage

    Institute of Scientific and Technical Information of China (English)

    杨小琼; 李国平; 王孝芸; 戴曦; 王媛媛; 陈媛媛; 谢桃; 伍娟


    was significantly negative correlation with ROS average fluorescent intensity(r =-0.847,P <0.01)、ROS average optical density(r =-0.952,P <0.01) respectively.Conclusions ①There existes oxidative stress in airway tissue and peripheral blood of pneumonia patients;oxidation/anti-oxidation imbalance;oxidative stress takes part in cells DNA damage.②Oxidative stress-DNA damage may be one of the important reasons of pneumonia′s occurrence and aggravation.%目的:研究肺炎患者机体中氧化应激程度、抗氧化能力及其细胞 DNA 损伤情况的相应改变,探讨氧化应激-DNA 损伤在肺炎中可能发生的作用。方法收集2011年6月至2012年3月泸州医学院附属医院呼吸内科住院部肺炎患者67例(肺炎组35例,重症肺炎组32例),招募32名健康志愿者作为正常对照组。对其中3名志愿者及3例肺炎组患者分别行经纤维支气管镜气道组织钳取活检观察气道组织氧化应激及炎症细胞浸润情况,对剩余64例患者及32名志愿者分别行无菌静脉取血2 ml,分离外周血单个核细胞(peripheral blood mononuclear cell,PBMC)测定各组细胞氧化应激程度,DNA 损伤情况,留取血清测定各组抗氧化水平。结果①肺炎组支气管气道组织炎症细胞浸润明显多于正常对照组;②肺炎组支气管气道组织 ROS 红色荧光强度明显强于正常对照组;③肺炎组、重症肺炎组细胞 ROS 平均荧光强度均高于正常对照组,分别为3.308±0.240、6.628±0.349、1.505±0.352(P <0.01);肺炎组、重症肺炎组细胞 ROS 平均光密度值均高于正常对照组,分别为0.913±0.065、1.260±0.023、0.390±0.031(P <0.01);④肺炎组、重症肺炎组细胞平均拖尾长度均高于正常对照组,分别为6.783±5.015、30.363±7.436、0.095±0.123(P <0.05);⑤肺炎组、重症肺炎组血清 SOD 平均光密度值均低于正常对照组,分别为0.225±0.030、0.159±0.033、0.456±0.024(P <0.01)。人外周血单个核细

  9. Th17细胞在慢性乙型肝炎及其重症化中的变化%The changes of Th17 cells in the pathogenesis and aggravation of chronic hepatitis B

    Institute of Scientific and Technical Information of China (English)

    杨波; 赵彩彦; 王亚东; 车宏浩; 阎文昭; 赵萌


    Objective To explore the changes of Th17 cells in the pathogenesis and aggravation of chronic hepatitis B (CHB).Methods Thirty-two CHB patients,44 hepatitis B virus (HBV)related acute-on-chronic liver [ailure (ACLF) patients and 20 healthy controls (HC) were involved in our research. The frequencies of circulating Th17 cells were detected by flow cyrometry. The interleukin 17 (IL-17) mRNA expressions in the peripheral blood mononuclear cells (PBMC) were detected by quantitative real-time polymerase chain reaction (PCR).Immunohistochemical staining was performed to determine the expressions of IL-17+ cells in the liver tissues.The serum IL-17 concentrations were detected by enzyme-linked immunosorhent assay (ELISA),and the dynamic changes in ACLF patients with different prognosis were also observed.Normal distribution data were used by analysis of variance and non-normal distribution data were used by Kruskal-Wallis H test or Mann-Whitney U test.Results In CHB,ACLF and healthy control groups,Th17 cells frequencies in PBMC were (1.47 ± 0.60) %,(3.20 ± 1.08) % and (0.86 ± 0.43) %,respectively ; IL-17 mRNA were 4.32±11.77,18.32±8.21 and 1.00,respectively; IL-17+ cells in the liver tissues were (10.6±4.8),(21.1±6.6) and (0.5±0.2)/high power field; the level of IL-17 in serum were (15.88±6.51),(35.03±11.54) and (10.04±4.06) ng/L,respectively (all P<0.05).Moreover,the frequencies of circulating Th17 cells and the levels of serum IL-17 in medium-stage and end-stage ACLF patients were higher than that in early-stage ACLF patients (both P < 0.01). In ACLF patients,the circulating Th17 cells frequencies were positively correlated with international normalized ratio (INR,r=0.44,P<0.01) and model of end-stage liver disease (MELD) score (r=0.44,P<0.01).And the frequencies of circulating Th17 cells were positively associated with the serum alanine transaminase (ALT) levels in CHB patients (r=0.51,P<0.01).Moreover,the survival ACLF patients had an

  10. Experimental temporal quantum steering (United States)

    Bartkiewicz, Karol; Černoch, Antonín; Lemr, Karel; Miranowicz, Adam; Nori, Franco


    Temporal steering is a form of temporal correlation between the initial and final state of a quantum system. It is a temporal analogue of the famous Einstein-Podolsky-Rosen (spatial) steering. We demonstrate, by measuring the photon polarization, that temporal steering allows two parties to verify if they have been interacting with the same particle, even if they have no information about what happened with the particle in between the measurements. This is the first experimental study of temporal steering. We also performed experimental tests, based on the violation of temporal steering inequalities, of the security of two quantum key distribution protocols against individual attacks. Thus, these results can lead to applications for secure quantum communications and quantum engineering. PMID:27901121

  11. Experimental higher dimensional entanglement

    Energy Technology Data Exchange (ETDEWEB)

    Richart, Daniel L.; Wieczorek, Witlef; Weinfurter, Harald [MPI fuer Quantenoptik, Hans Kopfermannstr. 1, 85748 Garching (Germany); Ludwig-Maximilians-Universitaet, Schellingstr. 4, D-80797 Muenchen (Germany)


    Higher dimensional states (qudits) allow to implement quantum communication schemes of increasing complexity, as e.g. superdense coding. Similarly, qudits allow further research into the fundaments of quantum theory. Here we report on first steps towards the implementation of states with correlated photon pairs in a 2 x 8 dimensional Hilbert space. To this end the photon pairs are prepared in the energy-time basis, as initially proposed in: Using unbalanced interferometers, information can be encoded in the different arrival times of the photon pairs, early and late, as was experimentally realized in. Here, we extend this scheme by proposing and characterizing a scalable multiple time delay interferometer. This interferometer system allows an exponential increase in the dimensionality of the entangled state with only a linear increase in the optical components used. Using the proposed interferometer system, first experimental tests on a two-dimensional state yielded a violation of a Bell inequality by four standard deviations.

  12. Geoengineering as Collective Experimentation. (United States)

    Stilgoe, Jack


    Geoengineering is defined as the 'deliberate and large-scale intervention in the Earth's climatic system with the aim of reducing global warming'. The technological proposals for doing this are highly speculative. Research is at an early stage, but there is a strong consensus that technologies would, if realisable, have profound and surprising ramifications. Geoengineering would seem to be an archetype of technology as social experiment, blurring lines that separate research from deployment and scientific knowledge from technological artefacts. Looking into the experimental systems of geoengineering, we can see the negotiation of what is known and unknown. The paper argues that, in renegotiating such systems, we can approach a new mode of governance-collective experimentation. This has important ramifications not just for how we imagine future geoengineering technologies, but also for how we govern geoengineering experiments currently under discussion.

  13. Experimental status of physics

    Indian Academy of Sciences (India)

    H Yamamoto


    In a short period of time, we will have a large amount of results from -factories including ones on CP violation. In this talk, we briefly review the current experimental status of -physics. After a quick description of -facilities, we divide this vast field into two categories: (1) weak interaction and QCD, (2) unitarity triangle and CP violation. Only a few critical items are selected in each category for the sake of time and space.





    The article provides an overview of experimental studies of charoite and charoite-containing rock formation hypotheses. The authors conducted experiments to clarify charoite and host rocks interaction and study charoite transformation processes at high temperatures. A series of experiments was aimed at improving the substandard charoite samples. The experiments show the formation of polymineral reaction zones due to the contact interaction between charoite and microcline-arfvedsonite lamproph...

  15. Experimental chronic periodontitis morphogenesis


    Schneider S.A.


    Morphogenesis of periodontium tissue in a model of chronic periodontitis was studied. Adult Wistar rats wereused in a model; chronic periodontitis was developed through mastication-related loading decrease. Histological assessmentof periodontium tissue was conducted at Days 7, 14, 21 and 30. It was demonstrated that dystrophic tissue changes prevailover the inflammatory one in this particular experimental model. The structural elements of periodontium were involved intothe pathologic process ...

  16. Blois V: Experimental summary

    Energy Technology Data Exchange (ETDEWEB)

    Albrow, M.G.


    The author gives a summary talk of the best experimental data given at the Vth Blois Workshop on Elastic and Diffractive Scattering. He addresses the following eight areas in his talk: total and elastic cross sections; single diffractive excitation; electron-proton scattering; di-jets and rapidity gaps; areas of future study; spins and asymmetries; high-transverse momentum and masses at the Tevatron; and disoriented chiral condensates and cosmic radiation.

  17. SAA drift: Experimental results (United States)

    Grigoryan, O. R.; Romashova, V. V.; Petrov, A. N.

    According to the paleomagnetic analysis there are variations of Earth’s magnetic field connected with magnetic moment changing. These variations affect on the South Atlantic Anomaly (SAA) location. Indeed different observations approved the existence of the SAA westward drift rate (0.1 1.0 deg/year) and northward drift rate (approximately 0.1 deg/year). In this work, we present the analysis of experimental results obtained in Scobeltsyn Institute of Nuclear Physics, Moscow State University (SINP MSU) onboard different Earth’s artificial satellites (1972 2003). The fluxes of protons with energy >50 MeV, gamma quanta with energy >500 keV and neutrons with energy 0.1 1.0 MeV in the SAA region have been analyzed. The mentioned above experimental data were obtained onboard the orbital stations Salut-6 (1979), MIR (1991, 1998) and ISS (2003) by the similar experimental equipment. The comparison of the data obtained during these two decades of investigations confirms the fact that the SAA drifts westward. Moreover the analysis of fluxes of electrons with energy about hundreds keV (Cosmos-484 (1972) and Active (Interkosmos-24, 1991) satellites) verified not only the SAA westward drift but northward drift also.

  18. Woodward Effect Experimental Verifications (United States)

    March, Paul


    The work of J. F. Woodward (1990 1996a; 1996b; 1998; 2002a; 2002b; 2004) on the existence of ``mass fluctuations'' and their use in exotic propulsion schemes was examined for possible application in improving space flight propulsion and power generation. Woodward examined Einstein's General Relativity Theory (GRT) and assumed that if the strong Machian interpretation of GRT as well as gravitational / inertia like Wheeler-Feynman radiation reaction forces hold, then when an elementary particle is accelerated through a potential gradient, its rest mass should fluctuate around its mean value during its acceleration. Woodward also used GRT to clarify the precise experimental conditions necessary for observing and exploiting these mass fluctuations or ``Woodward effect'' (W-E). Later, in collaboration with his ex-graduate student T. Mahood, they also pushed the experimental verification boundaries of these proposals. If these purported mass fluctuations occur as Woodward claims, and his assumption that gravity and inertia are both byproducts of the same GRT based phenomenon per Mach's Principle is correct, then many innovative applications such as propellantless propulsion and gravitational exotic matter generators may be feasible. This paper examines the reality of mass fluctuations and the feasibility of using the W-E to design propellantless propulsion devices in the near to mid-term future. The latest experimental results, utilizing MHD-like force rectification systems, will also be presented.

  19. Experimental computer tomograph

    Directory of Open Access Journals (Sweden)

    Heinemann D.


    Full Text Available The computed tomography is one of the most important medical instruments, allowing the non-invasive visualization of cross sections which are free from superpositions. Since 2000 an experimental computer tomo-graph of the third generation for the purpose of education and research was set up and further developed. Besides the mechanical construction design reconstruction algorithms, including certain corrections of the measured data were developed and implemented. In 2013 iterative reconstruction methods were investigated and implemented for advanced reconstructions and dose reduction using various ray tracing algorithms. The new reconstruction technique leads to improvements in image quality and low dose reconstructions.

  20. Experimental Axion Review

    CERN Document Server

    CERN. Geneva


    Axions are a natural consequence of the Peccei-Quinn mechanism, the most compelling solution to the strong-CP problem. Similar axion-like particles (ALPs) also appear in a number of possible extensions of the Standard Model, notably in string theories. Both axions and ALPs are very well motivated candidates for the Dark Matter, and in addition would be copiously produced at the stellar cores. Some anomalous astrophysical observations could be hinting the existence of these particles. They are object of increasing interest by experimentalists. I will briefly review the motivation to search for axions and ALPs, as well as the current status and future prospects of the experimental landscape.

  1. Teatro experimental en Almagro




    El objeto del proyecto es la construcción de un teatro experimental en el Centro de Arte Dramático en Almagro. En este proyecto se opta por un edificio único, no fragmentario, que puede recorrerse de forma continua. Se busca que el patio sea el centro alrededor del que se organiza el edificio; es el espacio susceptible de ser ocupado y se utiliza también para la representación. Una parte de este patio se particulariza cubriéndose para construir la sala, que se convierte en el centro de refere...

  2. Experimental unsaturated soil mechanics

    CERN Document Server

    Delage, Pierre


    In this general report, experimental systems and procedures of investigating the hydro-mechanical behaviour of unsaturated soils are presented. The water retention properties of unsaturated soils are commented and linked to various physical parameters and properties of the soils. Techniques of controlling suction are described together with their adaptation in various laboratory testing devices. Some typical features of the mechanical behaviour of unsaturated soils are presented within an elasto-plastic framework. An attempt to describe the numerous and significant recent advances in the investigation of the behaviour of unsaturated soils, including the contributions to this Conference, is proposed.

  3. Outsourcing of experimental work. (United States)

    Nielsen, Henrik


    With the development of new technologies for simultaneous analysis of many genes, transcripts, or proteins (the "omics" revolution), it has become common to outsource parts of the experimental work. In order to maintain the integrity of the research projects, it is important that the interphase between the researcher and the service is further developed. This involves robust protocols for sample preparation, an informed choice of analytical tool, development of standards for individual technologies, and transparent data analysis. This chapter introduces some of the problems related to analysis of RNA samples in the "omics" context and gives a few hints and key references related to sample preparation for the non-specialist.

  4. The electroconvulsive shock can aggravate the cognitive impairment of the depression model rats though up-regulate the hyperphosphorylation of protein tau%电休克通过上调tau蛋白过度磷酸化程度加重抑郁模型大鼠认知障碍

    Institute of Scientific and Technical Information of China (English)

    陈安; 刘鸿章; 刘超


    Objective To explore the change of the cognitive ability after a course of Electroconvulsive therapy (ECT) in depressed rats.Methods The depression model rats whose olfactory bulbs were removed were established.The analysis of variance of factorial design was done to set up two intervention factors:the electric current groups (three levels:25,50,and 75 mA) and the duration groups (three levels:3 times,6 times,and 9 times electroconvulsive shock).Fifty-four adult depression model rats whose olfactory bulbs were removed were randomly divided into nine experimental groups (n =6 in each group).The morris water maze test started within 1 day after the course of electroconvulsive shock finished in order to evaluate learning-memory.The hippocampus was removed from rats within 1 day after the morris water maze test finished.The content of glutamate (Glu) in the hippocampus of rats was determined by high performance liquid chromatography.The expression levels of tau protein including p-AT8Ser202 and GSK-3β1H8 in the hippocampus of rats were detected by Westem blotting.Results With the increase of ECT current,the escape latency is prolonged and space exploration time is shortened.With the extension of ECT time,the escape latency is prolonged and space exploration time is shortened.In 75 mA and the 9 ECT group,the escape latency was longest [(100.51 ± 6.64) s],and the space exploration time is the shortest [(10.02 ± 1.20) s].With the increase of ECT current,the concentration of Glu increased.With the increase of ECT,the concentration of Glu was increased.In 75 mA and the 9 ECT group,Glu concentration was the highest [(184.39 ±20.86) μmol/gprot].With the increase of ECT current,the expression of target protein was increased.With the prolongation of ECT time,the expression of target protein was increased.In 75 mA and the 9 ECT group,the expression of target protein was the highest (p-AT8Ser202:1 771.50 ± 278.26,GSK-3β1H8:1 747.13 ± 162.23).Conclusion Our results

  5. [Animal experimentation in Israel]. (United States)

    Epstein, Yoram; Leshem, Micah


    In 1994 the Israeli parliament (Knesset) amended the Cruelty to Animals Act to regulate the use of experimental animals. Accordingly, animal experiments can only be carried out for the purposes of promoting health and medical science, reducing suffering, advancing scientific research, testing or production of materials and products (excluding cosmetics and cleaning products) and education. Animal experiments are only permitted if alternative methods are not possible. The National Board for Animal Experimentation was established to implement the law. Its members are drawn from government ministries, representatives of doctors, veterinarians, and industry organizations, animal rights groups, and academia. In order to carry out an animal experiment, the institution, researchers involved, and the specific experiment, all require approval by the Board. To date the Board has approved some 35 institutions, about half are public institutions (universities, hospitals and colleges) and the rest industrial firms in biotechnology and pharmaceutics. In 2000, 250,000 animals were used in research, 85% were rodents, 11% fowls, 1,000 other farm animals, 350 dogs and cats, and 39 monkeys. Academic institutions used 74% of the animals and industry the remainder. We also present summarized data on the use of animals in research in other countries.

  6. Clinical Study on Whether Cold-aggravated Joint Pain Is the Key Indicator to Cold Bi in the Syndrome Differentiation of Rheumatoid Arthritis%关节遇冷痛增是否类风湿关节炎中医证候寒痹关键指标的临床研究

    Institute of Scientific and Technical Information of China (English)

    张子扬; 娄玉钤


    Objective:To investigate whether cold-aggravated joint pain is the key indicator to cold bi in the syndrome differentiation of rheumatoid arthritis.Methods:Four hundred cases with Rheumatoid Arthritis from the HFRA Database of the Henan Rheumatism Hospital were divided into a cold-aggravated group and a control group.SPSS 19.0 was used to analyze the difference and relationship on the aspects of joint and extra articular manifestations of the 2 groups.Results:In the clustering analysis result 3 of the cold-aggravated group,heat manifestations such as heat pain,dry mouth,dry throat,bitter taste of mouth and dry nose appeared. This analysis was not carried out for the control group since it was not suitable.After the X2 test for 82 joints and extra articular manifestations,cold manifestations such as aggravation due to coldness,cold pain,aversion to cold,cold limbs and hot drink preference appeared more frequently in the cold-aggravated group than the control group,the difference between them being signiifcant(P< 0.05).In the cold-aggravated group,294 cases had heat manifestations:151 cases(51.36%)with dry mouth,122 cases(36.75%)with dreaminess,103 cases(35.03%) with bitter taste of mouth,87 cases(29.59%) with yellow urine,78 cases(26.53%)with burning sensation of five centres,77 cases (26.19%)with dry throat,57(19.39%)cases with heat pain,33 cases(11.22%)with hot drink preference,and 32 cases with sore throat(10.88%).In the control group,115 cases had cold manifestations:61 cases(53.04%) with aversion to coldness,38 cases(33.04%)with aversion to coldness and cold limbs,23 Cases(20%)with hot drink preference,21 cases(18.26%)with cold limbs,and 15 cases(4.35%)with cold diarrhea.Conclusion:The increase of pain due to coldness cannot be seen as a key indicator for arthritis rheumatoid.%目的:探讨关节遇冷痛增是否是类风湿关节炎中医证候寒痹的关键指标。方法:将河南风湿病医院RA数据库(HFRA数据库)中收录的409例RA患者

  7. The Experimental Turn in Economics : A History of Experimental Economics

    NARCIS (Netherlands)

    Svorencik, A.


    The emergence of experimental economics in the last third of the 20th century revisited the long standing belief that economics is a non-experimental discipline. By experimental economics I denote the field within economics that from its beginnings in the 1960s and early 1970s has continuously studi

  8. Experimental adaptive process tomography (United States)

    Pogorelov, I. A.; Struchalin, G. I.; Straupe, S. S.; Radchenko, I. V.; Kravtsov, K. S.; Kulik, S. P.


    Adaptive measurements were recently shown to significantly improve the performance of quantum state tomography. Utilizing information about the system for the online choice of optimal measurements allows one to reach the ultimate bounds of precision for state reconstruction. In this article we generalize an adaptive Bayesian approach to the case of process tomography and experimentally show its superiority in the task of learning unknown quantum operations. Our experiments with photonic polarization qubits cover all types of single-qubit channels. We also discuss instrumental errors and the criteria for evaluation of the ultimate achievable precision in an experiment. It turns out that adaptive tomography provides a lower noise floor in the presence of strong technical noise.

  9. Experimental particle physics (United States)

    Steinberg, R. I.; Lane, C. E.


    The goals of this research are the experimental testing of fundamental theories of physics beyond the standard model and the exploration of cosmic phenomena through the techniques of particle physics. We are working on the MACRO experiment, which employs a large-area underground detector to search for grand unification magnetic monopoles and dark matter candidates and to study cosmic ray muons as well as low- and high-energy neutrinos; the Chooz experiment to search for reactor neutrino oscillations at a distance of 1 km from the source; a new proposal (the Perry experiment) to construct a one-kiloton liquid scintillator in the Fairport, Ohio underground facility IMB to study neutrino oscillations with a 13 km baseline; and development of technology for improved liquid scintillators and for very-low-background materials in support of the MACRO and Perry experiments and for new solar neutrino experiments.

  10. Future Experimental Programs

    CERN Document Server

    Murayama, Hitoshi


    I was asked to discuss future experimental programs even though I'm a theorist. As a result, I present my own personal views on where the field is, and where it is going, based on what I myself have been working on. In particular, I discuss why we need expeditions into high energies to find clues to where the relevant energy scale is for dark matter, baryon asymmetry, and neutrino mass. I also argue that the next energy frontier machine should be justified on the basis of what we know, namely the mass of the Higgs boson, so that we will learn what energy we should aim at once we nail the Higgs sector. Finally I make remarks on dark energy.

  11. Experimental techniques; Techniques experimentales

    Energy Technology Data Exchange (ETDEWEB)

    Roussel-Chomaz, P. [GANIL CNRS/IN2P3, CEA/DSM, 14 - Caen (France)


    This lecture presents the experimental techniques, developed in the last 10 or 15 years, in order to perform a new class of experiments with exotic nuclei, where the reactions induced by these nuclei allow to get information on their structure. A brief review of the secondary beams production methods will be given, with some examples of facilities in operation or under project. The important developments performed recently on cryogenic targets will be presented. The different detection systems will be reviewed, both the beam detectors before the targets, and the many kind of detectors necessary to detect all outgoing particles after the reaction: magnetic spectrometer for the heavy fragment, detection systems for the target recoil nucleus, {gamma} detectors. Finally, several typical examples of experiments will be detailed, in order to illustrate the use of each detector either alone, or in coincidence with others. (author)

  12. Experimental impact crater morphology (United States)

    Dufresne, A.; Poelchau, M. H.; Hoerth, T.; Schaefer, F.; Thoma, K.; Deutsch, A.; Kenkmann, T.


    The research group MEMIN (Multidisciplinary Experimental and Impact Modelling Research Network) is conducting impact experiments into porous sandstones, examining, among other parameters, the influence of target pore-space saturation with water, and projectile velocity, density and mass, on the cratering process. The high-velocity (2.5-7.8 km/s) impact experiments were carried out at the two-stage light-gas gun facilities of the Fraunhofer Institute EMI (Germany) using steel, iron meteorite (Campo del Cielo IAB), and aluminium projectiles with Seeberg Sandstone as targets. The primary objectives of this study within MEMIN are to provide detailed morphometric data of the experimental craters, and to identify trends and characteristics specific to a given impact parameter. Generally, all craters, regardless of impact conditions, have an inner depression within a highly fragile, white-coloured centre, an outer spallation (i.e. tensile failure) zone, and areas of arrested spallation (i.e. spall fragments that were not completely dislodged from the target) at the crater rim. Within this general morphological framework, distinct trends and differences in crater dimensions and morphological characteristics are identified. With increasing impact velocity, the volume of craters in dry targets increases by a factor of ~4 when doubling velocity. At identical impact conditions (steel projectiles, ~5km/s), craters in dry and wet sandstone targets differ significantly in that "wet" craters are up to 76% larger in volume, have depth-diameter ratios generally below 0.19 (whereas dry craters are almost consistently above this value) at significantly larger diameters, and their spallation zone morphologies show very different characteristics. In dry craters, the spall zone surfaces dip evenly at 10-20° towards the crater centre. In wet craters, on the other hand, they consist of slightly convex slopes of 10-35° adjacent to the inner depression, and of sub-horizontal tensile

  13. Experimental Particle Physics

    Energy Technology Data Exchange (ETDEWEB)

    Rosenfeld, Carl [Univ of South Carolina; Mishra, Sanjib R. [Univ of South Carolina; Petti, Roberto [Univ of South Carolina; Purohit, Milind V. [Univ of South Carolina


    The high energy physics group at the University of South Carolina, under the leadership of Profs. S.R. Mishra, R. Petti, M.V. Purohit, J.R. Wilson (co-PI's), and C. Rosenfeld (PI), engaged in studies in "Experimental Particle Physics." The group collaborated with similar groups at other universities and at national laboratories to conduct experimental studies of elementary particle properties. We utilized the particle accelerators at the Fermi National Accelerator Laboratory (Fermilab) in Illinois, the Stanford Linear Accelerator Center (SLAC) in California, and the European Center for Nuclear Research (CERN) in Switzerland. Mishra, Rosenfeld, and Petti worked predominantly on neutrino experiments. Experiments conducted in the last fifteen years that used cosmic rays and the core of the sun as a source of neutrinos showed conclusively that, contrary to the former conventional wisdom, the "flavor" of a neutrino is not immutable. A neutrino of flavor "e," "mu," or "tau," as determined from its provenance, may swap its identity with one of the other flavors -- in our jargon, they "oscillate." The oscillation phenomenon is extraordinarily difficult to study because neutrino interactions with our instruments are exceedingly rare -- they travel through the earth mostly unimpeded -- and because they must travel great distances before a substantial proportion have made the identity swap. Three of the experiments that we worked on, MINOS, NOvA, and LBNE utilize a beam of neutrinos from an accelerator at Fermilab to determine the parameters governing the oscillation. Two other experiments that we worked on, NOMAD and MIPP, provide measurements supportive of the oscillation experiments. Good measurements of the neutrino oscillation parameters may constitute a "low energy window" on related phenomena that are otherwise unobservable because they would occur only at energies way above the reach of conceivable accelerators. Purohit and Wilson participated in the Ba

  14. [Intramural nervous apparatus of jejunum and rectum in experimental portal hypertension]. (United States)

    Gaĭvoronskiĭ, I V; Tikhonova, L P; Chepur, S V; Nichiporuk, G I


    Using histological and electron microscopical methods, the state of intramural nervous structures of jejunum and rectum was studied in 92 dogs with experimental portal hypertension. Three phases of changes of portal pressure were detected and its influence upon the intramural nervous apparatus was observed. In phase 1 (first 4-5 days after the surgery) the reactive changes of the nervous apparatus were shown that were more pronounced in jejunum. In phase 2 (day 5 to 2.5 months) the portal pressure was shown to drop; this was accompanied by some signs of regeneration in jejunum and by an aggravation of destructive processes in rectum. In phase 3 of the repeated rise of portal pressure (2.5 to 6.5 months after the surgery), destructive changes in the nervous apparatus were demonstrated that were similar to those found in phase 1. However, the differences in the reaction of nervous structures in different layers of intestinal tube and the heterogeneity of the changes of the nervous apparatus in jejunum and rectum were absent. The association of time of appearance and of severity of structural changes with the elevation of portal pressure suggests the significant role of vascular factor in the morphogenesis of alterations observed in phase 3 of hemodynamic changes.

  15. Experimental quantum data locking (United States)

    Liu, Yang; Cao, Zhu; Wu, Cheng; Fukuda, Daiji; You, Lixing; Zhong, Jiaqiang; Numata, Takayuki; Chen, Sijing; Zhang, Weijun; Shi, Sheng-Cai; Lu, Chao-Yang; Wang, Zhen; Ma, Xiongfeng; Fan, Jingyun; Zhang, Qiang; Pan, Jian-Wei


    Classical correlation can be locked via quantum means: quantum data locking. With a short secret key, one can lock an exponentially large amount of information in order to make it inaccessible to unauthorized users without the key. Quantum data locking presents a resource-efficient alternative to one-time pad encryption which requires a key no shorter than the message. We report experimental demonstrations of a quantum data locking scheme originally proposed by D. P. DiVincenzo et al. [Phys. Rev. Lett. 92, 067902 (2004), 10.1103/PhysRevLett.92.067902] and a loss-tolerant scheme developed by O. Fawzi et al. [J. ACM 60, 44 (2013), 10.1145/2518131]. We observe that the unlocked amount of information is larger than the key size in both experiments, exhibiting strong violation of the incremental proportionality property of classical information theory. As an application example, we show the successful transmission of a photo over a lossy channel with quantum data (un)locking and error correction.

  16. Experimental thermodynamics experimental thermodynamics of non-reacting fluids

    CERN Document Server

    Neindre, B Le


    Experimental Thermodynamics, Volume II: Experimental Thermodynamics of Non-reacting Fluids focuses on experimental methods and procedures in the study of thermophysical properties of fluids. The selection first offers information on methods used in measuring thermodynamic properties and tests, including physical quantities and symbols for physical quantities, thermodynamic definitions, and definition of activities and related quantities. The text also describes reference materials for thermometric fixed points, temperature measurement under pressures, and pressure measurements. The publicatio

  17. Knockout of the c-Jun N-terminal Kinase 2 aggravates the development of mild chronic dextran sulfate sodium colitis independently of expression of intestinal cytokines TNFα, TGFB1, and IL-6

    Directory of Open Access Journals (Sweden)

    Kersting S


    Full Text Available Sabine Kersting,1 Kirstin Reinecke,2 Christoph Hilgert,1 Monika S Janot,1 Elisabeth Haarmann,1 Martin Albrecht,1 Annette M Müller,3 Thomas Herdegen,2 Ulrich Mittelkötter,1 Waldemar Uhl,1 Ansgar M Chromik11Department of General and Visceral Surgery, St Josef Hospital, Ruhr-University of Bochum, Bochum, Germany; 2Institute of Experimental and Clinical Pharmacology, University Hospital of Schleswig-Holstein, Campus Kiel, Germany; 3Department of Pediatric Pathology, Rheinische Friedrich-Wilhems-University of Bonn, Bonn, GermanyIntroduction: The c-Jun N-terminal kinases (JNKs are involved in signal transduction of inflammatory bowel diseases. The aim of this study was to examine the function of JNKs by using a low-dose dextran sulfate sodium (DSS model in JNK1 knockout mice (Mapk8–/–, JNK2 knockout mice (Mapk9–/–, and wild-type controls (WT1, WT2.Methods: The animals were evaluated daily using a disease activity index. After 30 days, the intestine was evaluated histologically with a crypt damage score. CD4+ and CD8+ cells were quantified using immunofluorescence. Analysis of tumor necrosis factor-a (TNFα, interleukin-6 (IL-6, and transforming growth factor ß1 (TGFB1 expression was carried out using LightCycler® real-time polymerase chain reaction.Results: Cyclic administration of low-dose DSS (1% was not able to induce features of chronic colitis in Mapk8–/– WT2 mice. By contrast, DSS administration significantly increased the disease activity index in WT1 and Mapk9–/– mice. In Mapk9–/– mice, the crypt damage score and the number of CD4+ and CD8+ cells as features of chronic colitis/inflammation were also significantly elevated. Expression of TNFα, IL-6, and TGFB1 was not altered by the JNK knockout.Conclusion: Administering DSS at a defined low concentration that is unable to induce colitis in WT animals leads to clinically and histologically detectable chronic colitis in Mapk9–/– mice. The reason for this disease

  18. Closed headpiece of integrin [alpah]IIb[beta]3 and its complex with an [alpha]IIb[beta]3-specific antagonist that does not induce opening

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Jieqing; Zhu, Jianghai; Negri, Ana; Provasi, Davide; Filizola, Marta; Coller, Barry S.; Springer, Timothy A. (Sinai); (Rockefeller); (CH-Boston)


    The platelet integrin {alpha}{sub IIb}{beta}{sub 3} is essential for hemostasis and thrombosis through its binding of adhesive plasma proteins. We have determined crystal structures of the {alpha}{sub IIb}{beta}{sub 3} headpiece in the absence of ligand and after soaking in RUC-1, a novel small molecule antagonist. In the absence of ligand, the {alpha}{sub IIb}{beta}{sub 3} headpiece is in a closed conformation, distinct from the open conformation visualized in presence of Arg-Gly-Asp (RGD) antagonists. In contrast to RGD antagonists, RUC-1 binds only to the {alpha}{sub IIb} subunit. Molecular dynamics revealed nearly identical binding. Two species-specific residues, {alpha}{sub IIb} Y190 and {alpha}{sub aIIb} D232, in the RUC-1 binding site were confirmed as important by mutagenesis. In sharp contrast to RGD-based antagonists, RUC-1 did not induce {alpha}{sub IIb}{beta}{sub 3} to adopt an open conformation, as determined by gel filtration and dynamic light scattering. These studies provide insights into the factors that regulate integrin headpiece opening, and demonstrate the molecular basis for a novel mechanism of integrin antagonism.

  19. Exclusion of the phosphatidylinositol-specific phospholipase C beta 3 (PLC beta 3) gene as candidate for the multiple endocrine neoplasia type 1 (MEN 1) gene

    NARCIS (Netherlands)

    de Wit, M J; Landsvater, R M; Sinke, R J; Geurts van Kessel, A; Lips, C J; Höppener, J W


    Multiple endocrine neoplasia type 1 (MEN 1) is inherited as an autosomal dominant disorder, characterized by hyperplasia and neoplasia in several endocrine organs. The MEN 1 gene, which is most probably a tumor suppressor gene, has been localized to a 900-kb region on chromosome 11q13. The human pho

  20. Experimental Object-Oriented Modelling

    DEFF Research Database (Denmark)

    Hansen, Klaus Marius

    and discuss techniques for handling and representing uncertainty when modelling in experimental system development. These techniques are centred on patterns and styles for handling uncertainty in object-oriented software architectures. Tools We present the Knight tool designed for collaborative modelling...... in experimental system development and discuss its design, implementation, and evaluation. The tool has subsequently been successfully commercialized. In summary, this thesis presents techniques and tools that advance the effectiveness and efficiency of experimental modelling.......This thesis examines object-oriented modelling in experimental system development. Object-oriented modelling aims at representing concepts and phenomena of a problem domain in terms of classes and objects. Experimental system development seeks active experimentation in a system development project...

  1. 高压喷射氧雾化吸入沐舒坦对慢性阻塞性肺疾病急性加重期痰液性状的影响%The Effects of Ambroxol Mucosolvan Inhalated by High-pressure Jet Oxygen Atomization to Sputum Properties in Patients with Chronic Obstructive Pulmonary Disease During Acute Aggravating Period

    Institute of Scientific and Technical Information of China (English)

    杨玉平; 周向东


    Objective To observe the effects of Ambroxol mucosolvan inhalated by High-pressure jet oxygen atomization to the physical and chemical properties of sputum in patients with chronic obstructive pulmonary disease during acute aggravating period. Method 72 cases of COPD patients with acute aggravating period to give an easy high-pressure jet oxygen atomization inhalation,bathing separately col ected before detect atomization,1 hours after atomization sputum volume,wet/dry weight and viscosity. Results After oxygen atomization,oxygen atomization before amount of sputum,sputum viscosity,sputum dry/wet weight had significant dif erence (p<0.05), and inflammatory biomarkers of neutrophil (PMN) combined with elastic enzyme membrane(HLE) has no obvious change. Conclusion High-pressure jet oxygen atomization inhalation of Ambroxol mucosolvan with dilute sputum and increased sputum volume effect,so as to ease of airway obstruction caused by high mucus secretion,relieve the patient's clinical symptoms,but the inhibition effect of the inflammatory response in the airways of has yet to be further research.%目的:观察高压喷射氧雾化吸入沐舒坦对慢性阻塞性肺疾病(COPD)急性加重期患者痰液理化性质的作用。方法72例COPD急性加重期患者给予沐舒坦高压喷射氧雾化吸入,分别收集检测雾化前、雾化后1h痰液量、干/湿重及黏度。结果氧雾化前与雾化后的痰液量、痰液黏度、痰液干/湿重均有明显差异(P<0.05)。而炎症指标中性粒细胞(PMN)膜结合弹力酶(HLE)无明显改变。结论高压喷射氧雾化吸入沐舒坦有稀释痰液、增加排痰量的作用。从而缓解黏液高分泌所致的气道阻塞、减轻患者的临床症状,但抑制气道炎症反应的作用尚无明确证据。

  2. Does Population Ageing Aggravate Income Inequality? Evidence from China 1996 -2009%人口老龄化是否加剧收入不平等?——基于中国(1996~2009)的实证研究

    Institute of Scientific and Technical Information of China (English)

    董志强; 魏下海; 汤灿晴


    Since inequality differs cross population groups, changing population age structure may have an effect on overall income inequality. This paper develops an analytical (statistical) model to describe conditions under which population ageing could aggravate income inequality, and show theoretically and empirically that the conditions are true in China. Thus, it is hypothesized that population ageing aggravates inequality in China. With Gini coefficient as measurement of income inequality, and employing provincial level panel data over 1996 -2009, this paper confirms that population ageing (i. e. an increasing aged dependency ratio and a decreasing child dependency ratio) is a positive and significant factor contributing to income inequality. This suggests that inequality studies need to incorporate population ageing, as it conveys different policy implications as compared to other factors.%不同年龄群体内部的收入程度通常存在差异,因而人口年龄结构变迁会影响整个经济的收入不平等程度。文章建立了一个(统计性)分析框架,刻画出老龄化导致收入不平等加剧的条件,并从经济理论和经验证据上说明该条件在中国成立,从而提出假说:中国的老龄化加剧了经济中的收入不平等。运用1996—2009年省级面板数据,以基尼系数衡量收入不平等,从经验上证实老龄化(老年抚养比上升和少儿抚养比下降)对我国收入不平等有显著的正向影响。这一结论表明,研究收入不平等问题时,应注意老龄化这一长期被研究者们忽视的因素,因为它蕴含着与其他因素大不相同的政策含义。

  3. BCG and BCG/DNAhsp65 Vaccinations Promote Protective Effects without Deleterious Consequences for Experimental Autoimmune Encephalomyelitis

    Directory of Open Access Journals (Sweden)

    Sofia Fernanda Gonçalves Zorzella-Pezavento


    Full Text Available A prime-boost strategy conserving BCG is considered the most promising vaccine to control tuberculosis. A boost with a DNA vaccine containing the mycobacterial gene of a heat shock protein (pVAXhsp65 after BCG priming protected mice against experimental tuberculosis. However, anti-hsp65 immunity could worsen an autoimmune disease due to molecular mimicry. In this investigation, we evaluated the effect of a previous BCG or BCG/pVAXhsp65 immunization on experimental autoimmune encephalomyelitis (EAE development. Female Lewis rats were immunized with BCG or BCG followed by pVAXhsp65 boosters. The animals underwent EAE induction and were daily evaluated for weight loss and clinical score. They were euthanized during recovery phase to assess immune response and inflammatory infiltration at the central nervous system. Previous immunization did not aggravate or accelerate clinical score or weight loss. In addition, this procedure clearly decreased inflammation in the brain. BCG immunization modulated the host immune response by triggering a significant reduction in IL-10 and IFN-γ levels induced by myelin basic protein. These data indicated that vaccination protocols with BCG or BCG followed by boosters with pVAXhsp65 did not trigger a deleterious effect on EAE evolution.

  4. Global cities and cultural experimentation

    DEFF Research Database (Denmark)

    Rojas Gaviria, Pilar; Emontspool, Julie


    an ethnographic perspective, combining observations of rehearsals and performances, in-depth interviews with actors, directors and audience, and secondary data. Findings: The fluidity of global cities allows their inhabitants to engage in collective creative processes of cultural experimentation, performing...... of the research community to the collective, reflexive, and experimental aspects of symbolic consumption. It does this by introducing the concept of cultural experimentation. Finally, it shows how arts and cultural products can function as valuable contexts for international marketing research, providing original...

  5. Experimental Data Processing. Part 2

    Directory of Open Access Journals (Sweden)

    Wilhelm LAURENZI


    Full Text Available This paper represents the second part of a study regarding the processing of experimental monofactorialdata, and it presents the original program developed by the author for processing experimental data.Using consecrated methods and relations, this program allows establishing the number of samples,generating the experimental plan, entering and saving the measured data, identifying the data corrupted byaberrant errors, verifying the randomness, verifying the normality of data repartition, calculating the mainstatistical parameters and exporting the experimental data to Excel or to other programs for statistical dataprocessing.

  6. Experimental Volcanology: 2010 and 2020 (United States)

    Dingwell, D. B.


    The advent of an experimental approach to volcanology has its roots in decades-old laboratory based approaches to characterising the properties of magmas and analog materials, together with the attempts at simulating volcanic processes in the lab. A little over ten years ago many new thrusts of experimental advance led to a new dawn for experimental science applied to volcanic eruptions. Along with that, new expectations, new goals and new strategies emerged about ten years ago. Ten years later, in 2010, many fruits have been born of this labour, and new frontiers are being unfolded as we meet here. Here are some of the youngest captivating themes being explored in experimental programs today: 1) interfacing volcanic monitoring systems to experimentally generated eruptions. 2) elucidating the physicochemical behavior of experimentally generated volcanic ash as an agent in the earth system. 3) blending experimental rock deformation and magmatology studies to understand the strength and stability of volcanic materials and volcanic structures 4) exploiting the kinematics of experimentally-generated versus natural volcanic products to understand flow style and strain history. The past ten years of experimental developments in volcanology have prepared us for great advances in the future, most of which were not perceived as likely avenues of investigation as little as ten years ago! The situation is likely to repeat itself in 2020.

  7. Experimental Design and Some Threats to Experimental Validity: A Primer (United States)

    Skidmore, Susan


    Experimental designs are distinguished as the best method to respond to questions involving causality. The purpose of the present paper is to explicate the logic of experimental design and why it is so vital to questions that demand causal conclusions. In addition, types of internal and external validity threats are discussed. To emphasize the…

  8. Experimental Mathematics and Computational Statistics

    Energy Technology Data Exchange (ETDEWEB)

    Bailey, David H.; Borwein, Jonathan M.


    The field of statistics has long been noted for techniques to detect patterns and regularities in numerical data. In this article we explore connections between statistics and the emerging field of 'experimental mathematics'. These includes both applications of experimental mathematics in statistics, as well as statistical methods applied to computational mathematics.

  9. Aterosclerose experimental em coelhos Experimental atherosclerosis in rabbits

    Directory of Open Access Journals (Sweden)

    Waleska C. Dornas


    Full Text Available Numerosas pesquisas têm sido realizadas utilizando modelos experimentais para estudar o desenvolvimento da aterosclerose com dieta induzindo hiperlipidemia. Devido ao fato de que coelhos são muito sensíveis a dietas ricas em colesterol e acumulam grandes quantidades no plasma, a utilização destes animais como modelo experimental para avaliar o desenvolvimento de aterosclerose é de grande relevância, trazendo informação sobre fatores que contribuem para progressão e regressão aplicadas a situações humanas. Sendo assim, nessa revisão a função aterogênica do colesterol é mostrada em trabalhos que incluem o coelho como modelo experimental, uma vez que este animal tornou-se o mais popular modelo experimental de aterosclerose.Many researches have been conducted in experimental models in order to study the development of atherosclerosis from hyperlipidemia-inducing diets. Since rabbits are very sensitive to cholesterol-rich diets and accumulate large amounts of cholesterol in their plasma, their use as experimental models to evaluate the development of atherosclerosis is highly relevant and brings information on factors that contribute to the progression and regression of this condition that can be applied to humans. As such, this review includes studies on the atherogenic function of cholesterol based on rabbits as the experimental model, since they have become the most largely used experimental model of atherosclerosis.

  10. Residential characteristics aggravating infestation by Culex quinquefasciatus in a region of Northeastern Brazil Características agravantes por infestación residencial de Culex quinquefasciatus, en una región del Noreste de Brasil Características agravantes por infestação residencial de Culex quinquefasciatus, em Olinda, PE

    Directory of Open Access Journals (Sweden)

    Juliana Cavalcanti Correia


    Full Text Available OBJECTIVE: Analyse how basic sanitation conditions, water supply and housing conditions affect the concentration of Culex quinquefasciatus METHODS: Populations of C. quinquefasciatus in 61 houses in the municipality of Olinda, PE, were monitored between October 2009 and October 2010. Observations were carried out in homes without the presence of preferred breeding sites in order to identify characteristics that may be aggravating factors for the development of the mosquito. Five aggravating factors were analysed: vegetation cover surrounding the home, number of residents/home, water storage, sewage drainage and water drainage. These characteristics were analysed in terms of presence or absence and as indicators of the degree of infestation, which was estimated through monitoring the concentration of eggs (oviposition traps - BR-OVT and adults (CDC light traps. RESULTS: Sewage drainage to a rudimentary septic tank or to the open air was the most frequent aggravating factor in the homes (91.8%, although the presence of vegetation was the only characteristic that significantly influenced the increase in the number of egg rafts (p = 0.02. The BR-OVT achieved positive results in 95.1% of the evaluations, with the presence of at least one egg raft per month. A total of 2,366 adults were caught, with a mosquito/room/night ratio of 32.9. No significant difference was found in the number of mosquitoes caught in the homes. CONCLUSIONS: Although the sanitation and water supply influence the population density of C. quinquefasciatus, residence features that are not usually considered in control measures can be aggravating factors in sustaining the mosquito population.OBJETIVO: Analizar como las condiciones de saneamiento básico, abastecimiento de agua y habitaciones afectan la densidad de Culex quinquefasciatus MÉTODOS: se monitoreó la población de C. quinquefasciatus en 61 residencias del municipio de Olinda, PE, Brasil, de octubre de 2009 a octubre de

  11. Psychopharmacology's debt to experimental psychology. (United States)

    Schmied, Lori A; Steinberg, Hannah; Sykes, Elizabeth A B


    The role of experimental psychology in the development of psychopharmacology has largely been ignored in recent historical accounts. In this article the authors attempt to redress that gap by outlining work in early experimental psychology that contributed significantly to the field. While psychiatrists focused on the therapeutic nature of drugs or their mimicry of psychopathology, experimental psychologists used psychoactive drugs as tools to study individual differences in normal behavior as well as to develop methodologies using behavior to study mechanisms of drug action. Experimental work by Kraepelin, Rivers, and Hollingworth was particularly important in establishing drug-screening protocols still used today. Research on nitrous oxide and on the effects of drug combinations is discussed to illustrate the importance of experimental psychology to psychopharmacology.

  12. Experimental design a chemometric approach

    CERN Document Server

    Deming, SN


    Now available in a paperback edition is a book which has been described as `` exceptionally lucid, easy-to-read presentation... would be an excellent addition to the collection of every analytical chemist. I recommend it with great enthusiasm.'' (Analytical Chemistry). Unlike most current textbooks, it approaches experimental design from the point of view of the experimenter, rather than that of the statistician. As the reviewer in `Analytical Chemistry' went on to say: ``Deming and Morgan should be given high praise for bringing the principles of experimental design to the level of the p

  13. Experimentation on humans and nonhumans. (United States)

    Pluhar, Evelyn B


    In this article, I argue that it is wrong to conduct any experiment on a nonhuman which we would regard as immoral were it to be conducted on a human, because such experimentation violates the basic moral rights of sentient beings. After distinguishing the rights approach from the utilitarian approach, I delineate basic concepts. I then raise the classic "argument from marginal cases" against those who support experimentation on nonhumans but not on humans. After next replying to six important objections against that argument, I contend that moral agents are logically required to accord basic moral rights to every sentient being. I conclude by providing criteria for distinguishing ethical from unethical experimentation.

  14. HIRENASD Experimental Data - matlab format (United States)

    National Aeronautics and Space Administration — This resource contains the experimental data that was included in tecplot input files but in matlab files. dba1_cp has all the results is dimensioned (7,2) first...

  15. Strongly correlated systems experimental techniques

    CERN Document Server

    Mancini, Ferdinando


    The continuous evolution and development of experimental techniques is at the basis of any fundamental achievement in modern physics. Strongly correlated systems (SCS), more than any other, need to be investigated through the greatest variety of experimental techniques in order to unveil and crosscheck the numerous and puzzling anomalous behaviors characterizing them. The study of SCS fostered the improvement of many old experimental techniques, but also the advent of many new ones just invented in order to analyze the complex behaviors of these systems. Many novel materials, with functional properties emerging from macroscopic quantum behaviors at the frontier of modern research in physics, chemistry and materials science, belong to this class of systems. The volume presents a representative collection of the modern experimental techniques specifically tailored for the analysis of strongly correlated systems. Any technique is presented in great detail by its own inventor or by one of the world-wide recognize...

  16. Animal Experimentation in High Schools (United States)

    Ansevin, Kystyna D.


    Recommends that teacher and student be provided with the broadest possible spectrum of meaningful and feasible experiments in which the comfort of the experimental animal is protected by the design of the experiment. (BR)

  17. Persuasion in experimental ultimatum games

    DEFF Research Database (Denmark)

    Andersson, Ola; Galizzi, Matteo M.; Hoppe, Tim


    We study persuasion effects in experimental ultimatum games and find that Proposers' payoffs significantly increase if, along with offers, they can send messages which Responders read before deciding. Higher payoffs are driven by both lower offers and higher acceptance rates....

  18. Multi-Directional Experimental Facility (United States)

    Federal Laboratory Consortium — The ATLSS Multi-directional Experimental Laboratory was constructed in 1987 under funding from the National Science Foundation to be a major facility for large-scale...

  19. HIRENASD Experimental Data, Individual Plots (United States)

    National Aeronautics and Space Administration — The HIRENASD data produced by analyzing the experimental data is repeated on this website, for those who can not download the information in the zip format found on...

  20. General footage ISOLDE experimental hall

    CERN Multimedia


    Overview of the ISOLDE experimental hall. Equipment and experiments. Taken from the WITCH / EBIS platform: ISOLDE hall infrastructure, GHM line, LA1, LA2, LA0, central beamline, COLLAPS experiment, CRIS experiment, ISOLTRAP experiment, laser guidance from building 508 into the hall for laser spectroscopy COLLAPS and CRIS. Taken from the HIE ISOLDE shielding tunnel roof: ISOLDE hall infrastructure, WITCH experiment, VITO line, TAS experiment. General footage: High Tension room entrance and EBIS platform, staircases and passages in the experimental hall.

  1. [The ethics of animal experimentation]. (United States)

    Goffi, Jean-Yves


    The paper starts with a short definition of animal experimentation, then three main approaches to the practice are considered: unconditional approval (as advocated by Claude Bernard), conditional and restricted approval (as advocated by Peter Singer) and strict prohibition (as advocated by Tom Regan and Gary Francione). It is argued that what is actually approved or condemned in animal experimentation is the value of the scientific enterprise.

  2. Aggregation without the Aggravation? Nonparametric Analysis of the Representative Consumer

    NARCIS (Netherlands)

    Cherchye, L.J.H.; Crawford, I.; de Rock, B.; Vermeulen, F.M.P.


    Abstract: In the tradition of Afriat (1967), Diewert (1973) and Varian (1982), we provide a revealed preference characterisation of the representative consumer. Our results are simple and complement those of Gorman (1953, 1961), Samuelson (1956) and others. They can also be applied to data very read

  3. Inflammation aggravates disease severity in Marfan syndrome patients.

    Directory of Open Access Journals (Sweden)

    Teodora Radonic

    Full Text Available BACKGROUND: Marfan syndrome (MFS is a pleiotropic genetic disorder with major features in cardiovascular, ocular and skeletal systems, associated with large clinical variability. Numerous studies reveal an involvement of TGF-β signaling. However, the contribution of tissue inflammation is not addressed so far. METHODOLOGY/PRINCIPAL FINDINGS: Here we showed that both TGF-β and inflammation are up-regulated in patients with MFS. We analyzed transcriptome-wide gene expression in 55 MFS patients using Affymetrix Human Exon 1.0 ST Array and levels of TGF-β and various cytokines in their plasma. Within our MFS population, increased plasma levels of TGF-β were found especially in MFS patients with aortic root dilatation (124 pg/ml, when compared to MFS patients with normal aorta (10 pg/ml; p = 8×10(-6, 95% CI: 70-159 pg/ml. Interestingly, our microarray data show that increased expression of inflammatory genes was associated with major clinical features within the MFS patients group; namely severity of the aortic root dilatation (HLA-DRB1 and HLA-DRB5 genes; r = 0.56 for both; False Discovery Rate(FDR = 0%, ocular lens dislocation (RAET1L, CCL19 and HLA-DQB2; Fold Change (FC = 1.8; 1.4; 1.5, FDR = 0% and specific skeletal features (HLA-DRB1, HLA-DRB5, GZMK; FC = 8.8, 7.1, 1.3; FDR = 0%. Patients with progressive aortic disease had higher levels of Macrophage Colony Stimulating Factor (M-CSF in blood. When comparing MFS aortic root vessel wall with non-MFS aortic root, increased numbers of CD4+ T-cells were found in the media (p = 0.02 and increased number of CD8+ T-cells (p = 0.003 in the adventitia of the MFS patients. CONCLUSION/SIGNIFICANCE: In conclusion, our results imply a modifying role of inflammation in MFS. Inflammation might be a novel therapeutic target in these patients.

  4. Arteriovenous fistulas aggravate the hemodynamic effect of vein bypass stenoses

    DEFF Research Database (Denmark)

    Nielsen, T G; Djurhuus, C; Pedersen, Erik Morre;


    PURPOSE: The purpose of this study was to assess the impact of arteriovenous fistulas combined with varying degrees of stenosis on distal bypass hemodynamics and Doppler spectral parameters. METHODS: In an in vitro flow model bypass stenoses causing 30%, 55%, and 70% diameter reduction were induced...... 10 cm upstream of a fistula with low outflow resistance. Flow and intraluminal pressure were measured proximal to the stenosis and downstream of the fistula. The waveform parameters peak systolic velocity, end-diastolic velocity, pulsatility index, and pulse rise time were determined from midstream...... Doppler spectra obtained 10 cm downstream of the fistula. All measurements were carried out with open and clamped fistula. RESULTS: At 30% diameter reducing stenosis opening of the fistula induced a 12% systolic pressure drop across the stenosis but had no adverse effect on the Doppler waveform parameters...

  5. TLR2 deficiency aggravates lung injury caused by mechanical ventilation

    NARCIS (Netherlands)

    Kuipers, Maria Theresa; Jongsma, Geartsje; Hegeman, Maria A; Tuip-de Boer, Anita M; Wolthuis, Esther K; Choi, Goda; Bresser, Paul; van der Poll, Tom; Schultz, Marcus J; Wieland, Catharina W


    Innate immunity pathways are found to play an important role in ventilator-induced lung injury. We analyzed pulmonary expression of Toll-like receptor 2 (TLR2) in humans and mice and determined the role of TLR2 in the pathogenesis of ventilator-induced lung injury in mice. Toll-like receptor 2 gene

  6. PP005. Vitamin D depletion aggravates hypertension in transgenic rats

    DEFF Research Database (Denmark)

    Bjørkholt Andersen, Louise; Herse, Florian; Christesen, Henrik Thybo


    overexpressing the human renin and angiotensinogen genes, group 1 (n=18) received vitamin D depleted chow; group 2 (n=15) standard chow and intraperitoneal paricalcitol at 800ng/kg thrice weekly; and group 3 (n=15) standard chow and vehicle injections. Blood pressure (tail cuff) and 24-h albuminuria were...... determined once weekly. After three weeks, animals were sacrificed. Heart tissue was examined for atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) by RT-PCR. RESULTS: The vitamin D depleted group had higher blood pressure at week 1 (mean difference 23.4mmHg, 95% CI 9.1-37.7) and tended...... to have higher blood pressure in weeks 2 and 3 (mean difference 14.3mmHg 95% CI -0.02-28.7 and 15.2mmHg 95% CI -1.5-33). The depletion group had higher heart-to-body weight ratio, and a trend towards higher ANP and BNP levels. The group receiving paricalcitol did not perform better. No differences were...

  7. Chronic kidney disease aggravates arteriovenous fistula damage in rats. (United States)

    Langer, Stephan; Kokozidou, Maria; Heiss, Christian; Kranz, Jennifer; Kessler, Tina; Paulus, Niklas; Krüger, Thilo; Jacobs, Michael J; Lente, Christina; Koeppel, Thomas A


    Neointimal hyperplasia (NIH) and impaired dilatation are important contributors to arteriovenous fistula (AVF) failure. It is unclear whether chronic kidney disease (CKD) itself causes adverse remodeling in arterialized veins. Here we determined if CKD specifically triggers adverse effects on vascular remodeling and assessed whether these changes affect the function of AVFs. For this purpose, we used rats on a normal diet or on an adenine-rich diet to induce CKD and created a fistula between the right femoral artery and vein. Fistula maturation was followed noninvasively by high-resolution ultrasound (US), and groups of rats were killed on 42 and 84 days after surgery for histological and immunohistochemical analyses of the AVFs and contralateral femoral vessels. In vivo US and ex vivo morphometric analyses confirmed a significant increase in NIH in the AVFs of both groups with CKD compared to those receiving a normal diet. Furthermore, we found using histological evaluation of the fistula veins in the rats with CKD that the media shrank and their calcification increased significantly. Afferent artery dilatation was significantly impaired in CKD and the downstream fistula vein had delayed dilation after surgery. These changes were accompanied by significantly increased peak systolic velocity at the site of the anastomosis, implying stenosis. Thus, CKD triggers adverse effects on vascular remodeling in AVFs, all of which contribute to anatomical and/or functional stenosis.

  8. Inflammation Aggravates Disease Severity in Marfan Syndrome Patients

    NARCIS (Netherlands)

    Radonic, Teodora; de Witte, Piet; Groenink, Maarten; de Waard, Vivian; Lutter, Rene; van Eijk, Marco; Jansen, Marnix; Timmermans, Janneke; Kempers, Marlies; Scholte, Arthur J.; Hilhorst-Hofstee, Yvonne; van den Berg, Maarten P.; van Tintelen, J. Peter; Pals, Gerard; Baars, Marieke J. H.; Mulder, Barbara J. M.; Zwinderman, Aeilko H.


    Background: Marfan syndrome (MFS) is a pleiotropic genetic disorder with major features in cardiovascular, ocular and skeletal systems, associated with large clinical variability. Numerous studies reveal an involvement of TGF-beta signaling. However, the contribution of tissue inflammation is not ad

  9. Public Administration Efficiency and the Aggravation of Public Health Issues

    Directory of Open Access Journals (Sweden)

    Vladimir Aleksandrovich Ilyin


    Full Text Available December 3, 2015, the President of Russia Vladimir Putin delivered his annual Address to the Federal Assembly. Having analyzed the Address, experts pointed out the President’s worries and concerns about the efficiency of execution of development priorities he had set out. Vladimir Putin repeatedly urged the Government to implement effective measures on specific issues in the shortest time possible. However, it has not been done so far; therefore, we think that the President’s concern is reasonable. Recent research carried out by ISEDT RAS reveals certain alarming trends in the social health of the regional society

  10. Fibrogenic Cell Plasticity Blunts Tissue Regeneration and Aggravates Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    Patrizia Pessina


    Full Text Available Preservation of cell identity is necessary for homeostasis of most adult tissues. This process is challenged every time a tissue undergoes regeneration after stress or injury. In the lethal Duchenne muscular dystrophy (DMD, skeletal muscle regenerative capacity declines gradually as fibrosis increases. Using genetically engineered tracing mice, we demonstrate that, in dystrophic muscle, specialized cells of muscular, endothelial, and hematopoietic origins gain plasticity toward a fibrogenic fate via a TGFβ-mediated pathway. This results in loss of cellular identity and normal function, with deleterious consequences for regeneration. Furthermore, this fibrogenic process involves acquisition of a mesenchymal progenitor multipotent status, illustrating a link between fibrogenesis and gain of progenitor cell functions. As this plasticity also was observed in DMD patients, we propose that mesenchymal transitions impair regeneration and worsen diseases with a fibrotic component.

  11. Lack of Galanin 3 Receptor Aggravates Murine Autoimmune Arthritis. (United States)

    Botz, Bálint; Kemény, Ágnes; Brunner, Susanne M; Locker, Felix; Csepregi, Janka; Mócsai, Attila; Pintér, Erika; McDougall, Jason J; Kofler, Barbara; Helyes, Zsuzsanna


    Neurogenic inflammation mediated by peptidergic sensory nerves has a crucial impact on the pathogenesis of various joint diseases. Galanin is a regulatory sensory neuropeptide, which has been shown to attenuate neurogenic inflammation, modulate neutrophil activation, and be involved in the development of adjuvant arthritis, but our current understanding about its targets and physiological importance is incomplete. Among the receptors of galanin (GAL1-3), GAL3 has been found to be the most abundantly expressed in the vasculature and on the surface of some immune cells. However, since there are minimal in vivo data on the role of GAL3 in joint diseases, we analyzed its involvement in different inflammatory mechanisms of the K/BxN serum transfer-model of autoimmune arthritis employing GAL 3 gene-deficient mice. After arthritis induction, GAL3 knockouts demonstrated increased clinical disease severity and earlier hindlimb edema than wild types. Vascular hyperpermeability determined by in vivo fluorescence imaging was also elevated compared to the wild-type controls. However, neutrophil accumulation detected by in vivo luminescence imaging or arthritic mechanical hyperalgesia was not altered by the lack of the GAL3 receptor. Our findings suggest that GAL3 has anti-inflammatory properties in joints by inhibiting vascular hyperpermeability and consequent edema formation.

  12. Seawater Immersion Aggravates Burn Injury Causing Severe Blood Coagulation Dysfunction



    This study aimed to investigate the endothelial function in a canine model of burn injury combined with seawater immersion. The model of burn injury was established. The dogs were randomly divided into four groups including dogs with burn injury (B group), or burn injury combined with seawater immersion (BI group), or only immersion in seawater (I group), or control animals with no injury or immersion (C group). The circulating endothelial cell (CEC) count and coagulation-fibrinolysis paramet...

  13. Fibrogenic Cell Plasticity Blunts Tissue Regeneration and Aggravates Muscular Dystrophy. (United States)

    Pessina, Patrizia; Kharraz, Yacine; Jardí, Mercè; Fukada, So-ichiro; Serrano, Antonio L; Perdiguero, Eusebio; Muñoz-Cánoves, Pura


    Preservation of cell identity is necessary for homeostasis of most adult tissues. This process is challenged every time a tissue undergoes regeneration after stress or injury. In the lethal Duchenne muscular dystrophy (DMD), skeletal muscle regenerative capacity declines gradually as fibrosis increases. Using genetically engineered tracing mice, we demonstrate that, in dystrophic muscle, specialized cells of muscular, endothelial, and hematopoietic origins gain plasticity toward a fibrogenic fate via a TGFβ-mediated pathway. This results in loss of cellular identity and normal function, with deleterious consequences for regeneration. Furthermore, this fibrogenic process involves acquisition of a mesenchymal progenitor multipotent status, illustrating a link between fibrogenesis and gain of progenitor cell functions. As this plasticity also was observed in DMD patients, we propose that mesenchymal transitions impair regeneration and worsen diseases with a fibrotic component.

  14. Some necessary criminalist methods for the investigation of aggravated murders

    Directory of Open Access Journals (Sweden)

    Valon Brahimi


    Full Text Available Crime is a negative, complex and dynamic occurrence that fits to the social changes. So in order to fight the crime and prevent it in society, it is very important to know some social disciplines which clearly help to understand the aim of this phenomenon. To reach this aim we must use different techniques which are based on the proceedings pair. The investigations are based on the scene, witnesses, police, criminalist experts, medicine, processes and the treatment of cases in the most correct form through a structure of investigation.

  15. Esporotricose experimental sistêmica em ratos Wistar: avaliação hematológica e perfil hepático Systemic experimental sporotrichosis in Wistar rats: hematological evaluation and hepatic profile

    Directory of Open Access Journals (Sweden)

    A.R.M. Meinerz


    Full Text Available Alanine aminotransferase (ALT and alkaline phosphatase (AP hepatic enzymes, hematological values, and total plasmatic proteins (TPP of 12 Wistar rats with systemic experimental sporotrichosis were evaluated. Inoculation was performed at 2x10³ cells of S. schenckii/ml. The values ranged from 35 to 48UI/l for ALT and 67 to 251.3UI/l for AP. Fifty percent of the AP values were above the physiological limits. TPP was elevated in 66.7% (8/12 of the rats with values varying from 7.9 to 8.5g%. In 75% (9/12 of the animals, it was observed that hemoglobin and red blood cells count were below the physiologic limits, and 8.3% (1/12 of the animals showed anemia masked by dehydration. At the necropsy, it was observed local and/or disseminated nodular lesions. At the histological analysis, cells compatible to S. schenckii were found. The observed alterations are aggravating factors for the recurrence and treatment of the mycosis.

  16. NaCl胁迫加重强光胁迫下超大甜椒叶片的光系统Ⅱ和光系统Ⅰ的光抑制%NaCl stress aggravates photoinhibition of photosystem Ⅱ and photosystem Ⅰ in Capsicum annuum leaves under high irradiance stress

    Institute of Scientific and Technical Information of China (English)

    宋旭丽; 胡春梅; 孟静静; 侯喜林; 何启伟; 李新国


    快速叶绿素荧光动力学可以在无损情况下探知叶片光合机构的损伤程度,快速叶绿素荧光测定和分析技术(JIP-test)将测量值转化为多种具有生物学意义的参数,因而被广泛应用于植物光合机构对环境的响应机制研究.该文研究了超大甜椒(Capsicum annuum)幼苗在强光及不同NaCl浓度胁迫下的荧光响应情况.与单纯强光胁迫相比,NaCl胁迫引起了叶绿素荧光诱导曲线的明显改变,光系统Ⅱ(PSⅡ)光抑制加重,同时PSⅡ反应中心和受体侧受到明显影响,而且高NaCl浓度胁迫下PSⅡ供体侧受伤害明显,同时PSⅠ反应中心活性(P700+)在盐胁迫下明显降低.这些结果表明,NaCl胁迫会增强强光对超大甜椒光系统的光抑制,并且浓度越高抑制越明显,但对PSⅠ的抑制作用低于PSⅡ.高NaCl浓度胁迫易对PSⅡ供体侧造成破坏,且PSⅠ光抑制严重.%Aims Our aim was to study effects of salt stress and high irradiance on photoinhibition of photosystem Ⅱ (PSⅡ)and Ⅰ (PSⅠ) in leaves of sweet pepper (Capsicum annuum).Methods We used the chlorophyll a fluorescence technique and the JIP-test to study the responses of sweet pepper leaves to salt stress with different NaCl concentrations and under high irradiance (1 000 μmol.m-2·s-l).Important findings The chlorophyll a fluorescence induction curves changed greatly as induced by NaCI stress under high irradiance, and photoinhibition of PSⅡ was aggravated with apparent effects on PSⅡ reaction centers and the acceptor side. Also, the donor side of PSⅡ was damaged by high NaCl concentration under high irradiance. Additionally, the activity of PSⅠ reaction centers (P700+) was inhibited by NaCl stress under high irradiance.Therefore, NaCl stress could aggravate photoinhibition of sweet pepper photosystem under high irradiance, and photoinhibition was greater with higher NaCl concentration. However, PSI photoinhibition was less than PSⅡ photoinhibition

  17. Clinical Observation of Chronic Obstructive Pulmonary Disease at Acute Aggravation Stage Treated with Yiqi Huoxue Formula%益气活血方治疗急性加重期慢性阻塞性肺疾病临床观察

    Institute of Scientific and Technical Information of China (English)



    目的 观察益气活血方治疗急性加重期慢性阻塞性肺疾病(COPD)的临床疗效.方法 首先将符合诊断标准的患者分为男、女两组,每组60例,按照入组时间先后顺序,男、女两组中单号入治疗组,双号入对照组.对照组60例,采用吸氧联合西药治疗;治疗组60例,在对照组治疗基础上加用益气活血方治疗.两组均以治疗2周为1个疗程,比较两组治疗前后第一秒用力呼气容积占预计值百分比(FEV1%),并评价中医症状积分,判定疗效.结果 治疗后治疗组中医症状积分为(6.3± 5.3)分,对照组中医症状积分为(9.8±7.2)分,两组比较,差异有统计学意义(P<0.05);治疗组有效27例,对照组有效15例,两组比较,差异有统计学意义(P<0.01).结论 益气活血方治疗急性加重期慢性阻塞性肺疾病,针对病因病机,结合患者多为老年人的特点,遣方用药,取得了良好的临床疗效.%Objective To observe the clinical efficacy of yiqi huoxue formula on chronic obslruclive pulmonary disease ( COPD) at acute aggravation stage. Methods The palienls who were complied with the diagnostic criteria were divided into a male group and a female group, 60 cases in each one. In accordance with the inclusive sequence, of the cases in male group and female group, those with single number in the sequence were classified into a trial group and those with double number were into a control group. 60 cases in control group were treated with oxygen combined with western medicine therapy. 60 cases in trial group were treated with yiqi huoxue formula supplemented on the basis of the treatment as control group. The cases in either group were treated for 2 weeks as 1 session. The forced expiration volume in one second/predicted value (FEV1%)was compared before and after treatment between two groups. The symptom score of traditional Chinese medicine ( TCM ) and the efficacy were assessed. Results After treatment, the symptom score of TCM was(6

  18. Risk minimization by experimental mechanics

    Energy Technology Data Exchange (ETDEWEB)


    Experimental mechanics has to undertake new functions to confirm theoretical perceptions and to check results of numerical analysis, because such results are dependent on the validity of assumptions and suppositions which generally are necessary to enable mathematical analysis of complex problems. Methods of experimental mechanics have become essential to design structures and products of a large variety to save raw materials and energy, to improve safety against failure and reliability of products, structures and even complex technical systems. Experimental methods are applied in system identification of complex structures. They are developed also as tools for supervising operating systems, machinery and installations as well as engineering structures, in order to get reliable informations on the life-time, to guarantee a higher degree of safety and to minimize risks. Therefore, methods of experimental mechanics are quite essential in developing strategies of riskmanagement. The contributions to this report are dealing with new theoretical perceptions, practical applications and experiences according to the objectives of the international symposium on 'Risk Minimization by Experimental Mechanics'. (orig.).

  19. Effect of Mesalamine and Prednisolone on TNBS Experimental Colitis, following Various Doses of Orally Administered Iron

    Directory of Open Access Journals (Sweden)

    John K. Triantafillidis


    Full Text Available Background. Experimental data suggest that oral iron (I. supplementation can worsen colitis in animals. Aim. To investigate the influence of various concentrations of orally administered I. in normal gut mucosa and mucosa of animals with TNBS colitis, as well as the influence of Mesalamine (M. and Prednisolone (P. on the severity of TNBS colitis following orally administered I. Methods and Materials. 156 Wistar rats were allocated into 10 groups. Colitis was induced by TNBS. On the 8th day, all animals were euthanatized. Activity of colitis and extent of tissue damage were assessed histologically. The levels of tissue tumor necrosis factor-α (t-TNF-α and tissue malondialdehyde (t-MDA were estimated in all animal groups. Results. Moderate and high I. supplementation induced inflammation in the healthy colon and increased the activity of the experimentally induced TNBS colitis. Administration of M. on TNBS colitis following moderate iron supplementation (0.3 g/Kg diet resulted in a significant improvement in the overall histological score as well as in two individual histological parameters. M. administration, however, did not significantly reduce the t-TNF-α levels (17.67±4.92 versus 14.58±5.71, P=0.102, although it significantly reduced the t-MDA levels (5.79±1.55 versus 3.67±1.39, P=0.000. Administration of M. on TNBS colitis following high iron supplementation (3.0 g/Kg diet did not improve the overall histological score and the individual histological parameters, neither reduced the levels of t-TNF-α (16.57 ± 5.61 versus 14.65±3.88, P=0.296. However, M. significantly reduced the t-MDA levels (5.99±1.37 versus 4.04±1.41, P=0.000. Administration of P. on TNBS colitis after moderate iron supplementation resulted in a significant improvement in the overall histological score as well as in three individual histological parameters. P. also resulted in a significant reduction in the t-TNF-α levels (17.67±4.92 versus 12.64±3

  20. Experimental Approach to Teaching Fluids (United States)

    Stern, Catalina


    For the last 15 years we have promoted experimental work even in the theoretical courses. Fluids appear in the Physics curriculum of the National University of Mexico in two courses: Collective Phenomena in their sophomore year and Continuum Mechanics in their senior year. In both, students are asked for a final project. Surprisingly, at least 85% choose an experimental subject even though this means working extra hours every week. Some of the experiments were shown in this congress two years ago. This time we present some new results and the methodology we use in the classroom. I acknowledge support from the Physics Department, Facultad de Ciencias, UNAM.

  1. Understanding experimentally-observed fluctuations

    CERN Document Server

    Kitazawa, Masakiyo


    We discuss two topics on the experimental measurements of fluctuation observables in relativistic heavy-ion collisions. First, we discuss the effects of the thermal blurring, i.e. the blurring effect arising from the experimental measurement of fluctuations in momentum space as a proxy of the thermal fluctuations defined in coordinate space, on higher order cumulants. Second, we discuss the effect of imperfect efficiency of detectors on the measurement of higher order cumulants. We derive effective formulas which can carry out the correction of this effect for higher order cumulants based on the binomial model.

  2. Experimentation and Bricolage on Institutions

    DEFF Research Database (Denmark)

    Cartel, Melodie; Boxenbaum, Eva; Aggeri, Franck

    a qualitative study of institutional bricolage in the context of the making of the European carbon market. We suggest that, during episodes of experimental bricolage, alternative arrangements may be tested and evaluated inside experimental spaces named platforms. We identify three selection mechanisms......This paper examines how innovative institutional arrangements are generated during processes of institutional bricolage. The aim of the paper is to highlight how an arrangement is selected among the others when many alternatives exist or are imaginable. To address this question, we present...

  3. Experimental techniques in hadron spectroscopy

    Directory of Open Access Journals (Sweden)

    Gianotti P.


    Full Text Available Quantum Chromodynamics (QCD is the theory of the strong interaction, but the properties of the hadrons cannot be directly calculated from the QCD Lagrangian and alternative approaches are then used. In order to test the different models, precise measurements of hadron properties are of extreme importance. This is the main motivation for the hadron spectroscopy experimental program carried out since many years with different probes and different detectors. A survey of some recent results in the field is here presented and commented, together with the opportunities offered by the forthcoming experimental programs.

  4. Experimental application of QCD antennas

    Energy Technology Data Exchange (ETDEWEB)

    Bobrovskyi, Sergei


    A serious problem in searches for new physics at the LHC is the rejection of QCD induced multijet events. In this thesis the formalism of QCD antenna variables based on the SPHEL approximation of QCD matrix elements is applied for the rst time on experimentally reconstructed jets in order to discriminate QCD from supersymmetric processes. The new observables provide additional information with respect to traditional event shape variables. Albeit correlated with experimentally measured missing transverse energy, the variables can be used to improve the signal to background ratio. (orig.)

  5. Graphical Models for Quasi-Experimental Designs (United States)

    Kim, Yongnam; Steiner, Peter M.; Hall, Courtney E.; Su, Dan


    Experimental and quasi-experimental designs play a central role in estimating cause-effect relationships in education, psychology, and many other fields of the social and behavioral sciences. This paper presents and discusses the causal graphs of experimental and quasi-experimental designs. For quasi-experimental designs the authors demonstrate…

  6. Histological and ultrastructural changes induced by selenium in early experimental gastric carcinogenesis

    Institute of Scientific and Technical Information of China (English)

    Yan-Ping Su; Jun-Min Tang; Yan Tang; Hui-Ying Gao


    AIM: To investigate the effect and significance of selenium in early experimental gastric carcinogenesis.METHODS: Weaning male Wistar rats were divided randomly into normal control group, experiment control group, low selenium (2 mg/L) group and high selenium (4 mg/L) group. Wistar rat gastric carcinogenesis was induced by N-methyl-N-nitro-N-nitroso guanidine (MNNG) (20 mg/kg) gavage daily for 10 d. Na2SeO3 was given by piped drinking 1 wk prior to MNNG gavage. The rats were killed at the 43rd wk. The surface characteristics of gastric mucosa were observed with naked eyes. Histopathologic changes of rat gastric mucosa were observed by HE staining and AB-PAS methods. The changes of cellular ultrastructure were observed under transmission electron microscope. Statistical analysis was carried out by SPSS.RESULTS: The incidence rate of gastric mucosa erosion,hemorrhage and intestinal metaplasia was 0, 45.5%,66.7%, and 92.9%, respectively (92.9% vs45.5%, P<0.05)in the normal control group, experiment control group,low selenium group, and high selenium group. Leiomyoma formed in the process of inducement of rat gastric carcinoma. Dietary Na2SeO3 (2 and 4 mg/L) slightly increased the incidence rate of leiomyoma (0, 23%, 46.6%, and 46.6%). gastric mucosa did not change in the course of rat gastric carcinogenesis. Dietary Na2SeO3 by pipe drinking could expand the intracellular secretory canaliculus of parietal cells and increase the number of endocrine cells and lysosomes.CONCLUSION: Dietary Na2SeO3 by pipe drinking aggravates gastric erosion, hemorrhage and promotes intestinal metaplasia of gastric mucosa. The mechanism may be related with the function of parietal cells.

  7. Coupled plasma filtration adsorption in experimental peritonitis-induced septic shock. (United States)

    Sykora, Roman; Chvojka, Jiri; Krouzecky, Ales; Radej, Jaroslav; Kuncova, Jitka; Varnerova, Veronika; Karvunidis, Thomas; Novak, Ivan; Matejovic, Martin


    The coupled plasma filtration adsorption (CPFA) was developed as an adsorptive hemopurification method aimed at nonselective removal of circulating soluble mediators potentially involved in the pathogenesis of sepsis. We hypothesized that this nonselective hemopurification could protect from detrimental consequences of long-term, volume-resuscitated porcine septic shock. In 16 anesthetized, mechanically ventilated, and instrumented pigs, the hyperdynamic septic shock secondary to peritonitis was induced by intraperitoneally inoculating feces and maintained for 22 h with fluid resuscitation and norepinephrine infusion as needed to maintain MAP above 65 mmHg. After 12 h of peritonitis, animals were randomized to receive either supportive treatment (control, n = 8) or CPFA treatment (CPFA, n = 8). Systemic, hepatosplanchnic, and renal hemodynamics; oxygen exchange; energy metabolism (lactate/pyruvate and ketone body ratios); ileal mucosal and renal cortex microcirculation; systemic inflammation (TNF-alpha, IL-6); nitrosative/oxidative stress (thiobarbituric acid reactive species, nitrates + nitrites); and endothelial/coagulation dysfunction (asymmetric dimethylarginine, von Willebrand factor, thrombin-antithrombin complexes, platelet count) were assessed before and 12, 18, and 22 h of peritonitis. Coupled plasma filtration adsorption neither delayed the development of hypotension nor reduced the dose of norepinephrine. The treatment failed to attenuate sepsis-induced alterations in microcirculation, surrogate markers of cellular energetics, endothelial injury, and systemic inflammation. Similarly, CPFA did not protect from lung and liver dysfunction and even aggravated sepsis-induced disturbances in coagulation and oxidative/nitrosative stress. In this porcine model of septic shock, the early treatment with CPFA was not capable of reversing the sepsis-induced disturbances in various biological pathways and organ systems. Both the efficacy and safety of this method


    Directory of Open Access Journals (Sweden)

    Romanova OA


    Full Text Available Introduction. With the transport links development there is rather important issue respiratory viral infections spread, especially influenza. The only method controlling influenza is vaccination. Search and development effective and safe vaccines is important. Material and methods. In base SO "Mechnikov Institute Microbiology and Immunology National Ukrainian Academy Medical Sciences" in the scientific theme "Developing new approaches to creating viral vaccines and study specific activity depending of type and degree component`s modification" was created several experimental influenza vaccine with subsequent component`s modification for selecting the most optimal pattern of safety and immunogenicity. In assessing the influenza vaccine safety is using a few criteria, including, reactivity, as measured by the frequency of local and systemic adverse (negative effects, which due to its introduction, and for lipid content drugs, ability to influence oxidation processes. At present study phase was determined: a systemic reaction and local reaction of delayed-type hypersensitivity (foot pad swelling assay;b lipids and proteins peroxidation processes after administration officinal and experimental vaccines (content protein’s carbonyl groups, lipid’s hydroperoxides, activity of glutathione-peroxidase.Study objects were trivalent seasonal influenza vaccine, "Vaxigrip" (Sanofi Pasteur, S.A., France, "Inflexal V" (Biotech Ltd. Berne, Switzerland and experimental vaccine samples. Highest immunogenicity vaccines had undergone improvements and modifications using adjuvant systems and acylation influenza proteins. Liposomes 2 – the experimental influenza vaccine with a liposome negative charge and antigenic composition like split vaccines "Vaksihryp". Liposomes 2.1 - the adjuvantexperimental influenza vaccine with modifications liposomal components (etoniy and chlorophyllipt molecules embedded in liposomal membrane. Liposomes 2.2 - the adjuvant

  9. Experimental Blade Research - phase 2

    DEFF Research Database (Denmark)

    Eder, Martin Alexander; Branner, Kim; Berring, Peter

    This report is a summary of the results obtained in the project: Experimental Blade Research – phase 2 (EBR2). The project was supported by the Danish Energy Authority through the 2010 Energy Technology Development and Demonstration Program (EUDP 2010-II) and has journal no. 64011-0006. The project...

  10. Digging the CMS experimental cavern

    CERN Multimedia

    Laurent Guiraud


    The huge CMS experimental cavern is located 100 m underground and has two access shafts through which the experiment's components will be lowered. Initially assembled on the surface, each part of the 12 500 tonne machine must be lowered individually with very little clearance.

  11. Persuasion in Experimental Ultimatum Games

    DEFF Research Database (Denmark)

    Andersson, Ola; Galizzi, Matteo; Hoppe, Tim;


     This paper experimentally studies persuasion effects in ultimatum games and finds that Proposers' payoffs significantly increase if, along with offers, they can send messages which Responders read before their acceptance decision. Higher payoffs are due to higher acceptance rates as well as more...

  12. [Ethical issue in animal experimentation]. (United States)

    Parodi, André-Laurent


    In the 1970s, under pressure from certain sections of society and thanks to initiatives by several scientific research teams, committees charged with improving the conditions of laboratory animals started to be created, first in the United States and subsequently in Europe. This led to the development of an ethical approach to animal experimentation, taking into account new scientific advances. In addition to the legislation designed to provide a legal framework for animal experimentation and to avoid abuses, this ethical approach, based on the concept that animals are sentient beings, encourages greater respect of laboratory animals and the implementation of measures designed to reduce their suffering. Now, all animal experiments must first receive ethical approval--from in-house committees in the private sector and from regional committees for public institutions. Very recently, under the impetus of the French ministries of research and agriculture, the National committee for ethical animal experimentation published a national ethical charter on animal experimentation, setting the basis for responsible use of animals for scientific research and providing guidelines for the composition and functioning of ethics committees. Inspired by the scientific community itself this ethical standardization should help to assuage--but not eliminate--the reticence and hostility expressed by several sections of society.

  13. Persuasion in Experimental Ultimatum Games

    DEFF Research Database (Denmark)

    Andersson, Ola; Galizzi, Matteo; Hoppe, Tim


     This paper experimentally studies persuasion effects in ultimatum games and finds that Proposers' payoffs significantly increase if, along with offers, they can send messages which Responders read before their acceptance decision. Higher payoffs are due to higher acceptance rates as well as more...... aggressive offers by Proposers....

  14. Experimental Neutrino Physics: Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Lane, Charles E.; Maricic, Jelena


    Experimental studies of neutrino properties, with particular emphasis on neutrino oscillation, mass and mixing parameters. This research was pursued by means of underground detectors for reactor anti-neutrinos, measuring the flux and energy spectra of the neutrinos. More recent investigations have been aimed and developing detector technologies for a long-baseline neutrino experiment (LBNE) using a neutrino beam from Fermilab.

  15. Rotavirus enterotoxin NSP4 binds to the extracellular matrix proteins laminin-beta3 and fibronectin.

    NARCIS (Netherlands)

    J.A. Boshuizen; J.W. Rossen (John); C.K. Sitaram; F.F.P. Kimenai; Y. Simons-Oosterhuis (Ytje); C. Laffeber; H.A. Büller (Hans); A.W.C. Einerhand (Sandra)


    textabstractRotavirus is the most important cause of viral gastroenteritis and dehydrating diarrhea in young children. Rotavirus nonstructural protein 4 (NSP4) is an enterotoxin that was identified as an important agent in symptomatic rotavirus infection. To identify cellular prote

  16. Rotavirus enterotoxin NSP4 binds to the extracellular matrix proteins laminin-beta3 and fibronectin

    NARCIS (Netherlands)

    Boshuizen, J A; Rossen, J W A; Sitaram, C K; Kimenai, F F P; Simons-Oosterhuis, Y; Laffeber, C; Büller, H A; Einerhand, A W C


    Rotavirus is the most important cause of viral gastroenteritis and dehydrating diarrhea in young children. Rotavirus nonstructural protein 4 (NSP4) is an enterotoxin that was identified as an important agent in symptomatic rotavirus infection. To identify cellular proteins that interact with NSP4, a

  17. A macroporous bioreactor super activated by the recombinant human transforming growth factor-beta 3

    Directory of Open Access Journals (Sweden)

    Ugo eRipamonti


    Full Text Available Macroporous single-phase hydroxyapatite (HA and biphasic HA/β-tricalcium phosphate with 33% post-sinter hydroxyapatite (HA/β-TCP were combined with 25 or 125 µg recombinant human transforming growth factor-β3 (hTGF-β3 to engineer a super activated bioreactor implanted in orthotopic calvarial and heterotopic rectus abdominis muscle sites and harvested on day 30 and 90. Coral-derived calcium carbonate fully converted (100% and partially converted to 5% and 13% hydroxyapatite/calcium carbonate (HA/CC preloaded with 125 and 250 µg hTGF-β3, and 1:5 and 5:1 binary applications of hTGF-β3: hOP-1 by weight, were implanted in the rectus abdominis and harvested on day 20 and 30, respectively, to monitor spatial/temporal morphogenesis by high doses of hTGF-β3. Bone formation was assessed on decalcified paraffin-embedded sections by measuring the fractional volume of newly-formed bone. On day 30 and 90, single phase HA implants showed greater amounts of bone when compared to biphasic specimens; 5 % and 13 % HA/CC pre-loaded with 125 and 250 µg hTGF-β3 showed substantial induction of bone formation; 250 µg hTGF-β3 induced as yet unreported massive induction of bone formation as early as 20 days prominently outside the profile of the macroporous constructs. The induction of bone formation is controlled by the implanted ratio of the recombinant morphogens, i.e. the 1:5 hTGF-β3:hOP-1 ratio by weight was greater than the inverse ratio. The unprecedented tissue induction by single doses of 250 µg hTGF-β3 resulting in rapid bone morphogenesis of vast mineralized ossicles with multiple trabeculations surfaced by contiguous secreting osteoblasts is the novel molecular and morphological frontier for the induction of bone formation in clinical contexts.

  18. Sizeable beta-strength in 31Ar (beta 3p) decay

    DEFF Research Database (Denmark)

    T. Koldste, G.; Blank, B.; J. G. Borge, M.


    We present for the first time precise spectroscopic information on the recently discovered decay mode beta-delayed 3p-emission. The detection of the 3p events gives an increased sensitivity to the high energy part of the Gamow-Teller strength distribution from the decay of 31Ar revealing that as ...

  19. Perspectives on mirabegron in the treatment of overactive bladder syndrome: A new beta-3 adrenoceptor agonist

    Directory of Open Access Journals (Sweden)

    Chia-Hao Kuei


    Full Text Available Mirabegron, the first β3-adrenoceptor agonist introduced for use in clinical practice, differs from antimuscarinic agents in terms of mechanism of action. This review discusses various perspectives on mirabegron in terms of efficacy, mechanism of action, pharmacokinetics, safety, and tolerability for overactive bladder syndrome in studies conducted thus far. Mirabegron administered at daily doses of 25 mg, 50 mg, and 100 mg demonstrated significant improvements in micturition frequency, urgency incontinence, and mean volume voided/micturition as early as the first assessment, and these were maintained throughout the treatment course. Mirabegron seemed well tolerated. The most common adverse events observed with mirabegron in clinical trials were hypertension, nasopharyngitis, and urinary tract infection. The incidence of dry mouth was similar to that with placebo, between 3- and 5-fold lower than with 4 mg tolterodine extended release. Considering that dry mouth is the most bothersome adverse event associated with antimuscarinic drugs and often a reason for treatment discontinuation, mirabegron may be a valuable treatment option for these patients. The benefit of mirabegron (at doses of 50 mg and 100 mg was also evident in elderly patients and in both treatment-naive patients and those who previously discontinued antimuscarinic therapy. Mirabegron can also be used in combination with antimuscarinics or in addition to alpha blockers. Mirabegron may quickly become a standard treatment of overactive bladder syndrome.

  20. Transforming growth factor Beta 3 is required for excisional wound repair in vivo.

    Directory of Open Access Journals (Sweden)

    Mark Le

    Full Text Available Wound healing is a complex process that relies on proper levels of cytokines and growth factors to successfully repair the tissue. Of particular interest are the members of the transforming growth factor family. There are three TGF-ß isoforms-TGF- ß 1, 2, and 3, each isoform showing a unique expression pattern, suggesting that they each play a distinct function during development and repair. Previous studies reported an exclusive role for TGF-ß 3 in orofacial development and a potent anti-scarring effect. However, the role of TGF- ß 3 in excisional wound healing and keratinocyte migration remains poorly understood. We tested the effect of TGF-ß 3 levels on excisional cutaneous wounds in the adult mouse by directly injecting recombinant TGF-ß 3 or neutralizing antibody against TGF-ß 3 (NAB in the wounds. Our results demonstrate that TGF-ß 3 does not promote epithelialization. However, TGF-ß 3 is necessary for wound closure as wounds injected with neutralizing antibody against TGF-ß 3 showed increased epidermal volume and proliferation in conjunction with a delay in keratinocyte migration. Wild type keratinocytes treated with NAB and Tgfb3-deficient keratinocytes closed an in vitro scratch wound with no delay, suggesting that our in vivo observations likely result from a paracrine effect.

  1. Dystroglycans and laminin 'BETA' 3 features on the prostate of mdx mice


    Leslie Cristina Pinto


    Resumo: A distroglicana (DG) é uma importante proteína estrutural a qual está envolvida no desenvolvimento celular epitelial, formação de membrana basal e manutenção da integridade de diferentes tecidos. Estudos indicaram que a alteração na expressão da DG é um evento freqüente nas malignecências humanas e sugerem que esta molécula tem um papel importante no desenvolvimento de tumor. No câncer de próstata, verificou-se expressiva redução das distroglicanas, especialmente da _-DG, acarre...

  2. Changes of hard dental and bone tissue of alveolar process in rats on the orthodontic tooth movement on the background of an experimental goiter

    Directory of Open Access Journals (Sweden)

    Kamila A. Kolesnik


    Full Text Available Aim of this study was to study the state of dental hard and bone tissues of alveolar process in rats with the model of orthodontic tooth movement at the experimental goiter based on the analysis of bone phosphatases and proteases activity. Material and Methods —Experimental study with the model of goiter and orthodontic tooth movement in rats. The experiment was carried out with 30 Wistar rats of gregarious breeding. During the first stage of the experiment the goitre was being simulated by giving 1% solution of potassium perchlorate with drinking water for 20 days. During the second experimental stage using thiopental the orthodontic model of tooth movement (OMtM was being reproduced for 21 days. The lower jaw in rats served to reveal carious cavities and atrophy rate of alveolar process, the upper jaw served for determining the common activity of alkaline, acid phosphatase, elastase and total proteolytic activity (OPA, the pulp of incisors served to determine the activity of bone phosphatases. Statistical analysis — One way analysis of variance (ANOVA. Сomparison between experimental groups was carried out with the help of t-Student U and Mann-Whitney test (p.asymp.sig<0.05 was considered significant. Results — in animals under experiment the orthodontic tooth movement together with thyroid disorders is accompanied by increased proteases activity of bone tissue and impaired activity of bone phosphatases. Conclusions — sudden aggravation in the resorption processes of bone tissue of alveolar process, demineralization of hard dental tissue during the orthodontic tooth movement in relation to experimental goiter show that child with the thyroid gland disorders are in need of active treatment and preventive measures during active apparatus treatment of dentoalveolar anomalies.

  3. Experimental unconditionally secure bit commitment (United States)

    Liu, Yang; Cao, Yuan; Curty, Marcos; Liao, Sheng-Kai; Wang, Jian; Cui, Ke; Li, Yu-Huai; Lin, Ze-Hong; Sun, Qi-Chao; Li, Dong-Dong; Zhang, Hong-Fei; Zhao, Yong; Chen, Teng-Yun; Peng, Cheng-Zhi; Zhang, Qiang; Cabello, Adan; Pan, Jian-Wei


    Quantum physics allows unconditionally secure communication between parties that trust each other. However, when they do not trust each other such as in the bit commitment, quantum physics is not enough to guarantee security. Only when relativistic causality constraints combined, the unconditional secure bit commitment becomes feasible. Here we experimentally implement a quantum bit commitment with relativistic constraints that offers unconditional security. The commitment is made through quantum measurements in two quantum key distribution systems in which the results are transmitted via free-space optical communication to two agents separated with more than 20 km. Bits are successfully committed with less than 5 . 68 ×10-2 cheating probability. This provides an experimental proof of unconditional secure bit commitment and demonstrates the feasibility of relativistic quantum communication.

  4. Human parallels to experimental myopia?

    DEFF Research Database (Denmark)

    Fledelius, Hans C; Goldschmidt, Ernst; Haargaard, Birgitte


    Raviola and Wiesel's monkey eyelid suture studies of the 1970s laid the cornerstone for the experimental myopia science undertaken since then. The aim has been to clarify the basic humoral and neuronal mechanisms behind induced myopization, its eye tissue transmitters in particular. Besides...... of the present PubMed literature-based review is to evaluate apparent similarities between experience from disturbed imaging in experimental laboratory science and varieties within the spectrum of childhood human myopia. So far, the main impression is that macroscopical optical deprivation appears absent...... in the prevalent types of human myopia, nor is myopia a regular sequel where early eye pathology has led to poor imaging and optical deprivation. Optical aberrations of a higher order are a relatively new issue in myopia research, and microstructural deprivation is only marginally dealt within the survey. Links...

  5. Experimental lithium system. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Kolowith, R.; Berg, J.D.; Miller, W.C.


    A full-scale mockup of the Fusion Materials Irradiation Test (FMIT) Facility lithium system was built at the Hanford Engineering Development Laboratory (HEDL). This isothermal mockup, called the Experimental Lithium System (ELS), was prototypic of FMIT, excluding the accelerator and dump heat exchanger. This 3.8 m/sup 3/ lithium test loop achieved over 16,000 hours of safe and reliable operation. An extensive test program demonstrated satisfactory performance of the system components, including the HEDL-supplied electromagnetic lithium pump, the lithium jet target, the purification and characterization hardware, as well as the auxiliary argon and vacuum systems. Experience with the test loop provided important information on system operation, performance, and reliability. This report presents a complete overview of the entire Experimental Lithium System test program and also includes a summary of such areas as instrumentation, coolant chemistry, vapor/aerosol transport, and corrosion.

  6. PEMFC modeling and experimental validation

    Energy Technology Data Exchange (ETDEWEB)

    Vargas, J.V.C. [Federal University of Parana (UFPR), Curitiba, PR (Brazil). Dept. of Mechanical Engineering], E-mail:; Ordonez, J.C.; Martins, L.S. [Florida State University, Tallahassee, FL (United States). Center for Advanced Power Systems], Emails:,


    In this paper, a simplified and comprehensive PEMFC mathematical model introduced in previous studies is experimentally validated. Numerical results are obtained for an existing set of commercial unit PEM fuel cells. The model accounts for pressure drops in the gas channels, and for temperature gradients with respect to space in the flow direction, that are investigated by direct infrared imaging, showing that even at low current operation such gradients are present in fuel cell operation, and therefore should be considered by a PEMFC model, since large coolant flow rates are limited due to induced high pressure drops in the cooling channels. The computed polarization and power curves are directly compared to the experimentally measured ones with good qualitative and quantitative agreement. The combination of accuracy and low computational time allow for the future utilization of the model as a reliable tool for PEMFC simulation, control, design and optimization purposes. (author)

  7. Experimental Summary Moriond QCD 2008

    CERN Document Server

    de Roeck, Albert


    2008 was a vintage year for the QCD Moriond meeting. Plenty of new data from Tevatron, HERA, B-Factories and other experiments have been reported. Some brand new results became public just before or even during the conference. A few new hints for New Physics came up in Winter 2008, but these await further scrutiny. This paper is the write-up of the experimental summary talk given at the Moriond QCD March meeting.

  8. Experimental Study on Hysucat Vessels

    Institute of Scientific and Technical Information of China (English)

    M.S.Seif; M.Askari


    The paper contains the results of an experimental study on a planing catamaran. The aim of this study is resistance reduction with application of foils. Experiments are performed in different conditions and the results are compared with each other. The foils are used in different configurations and it is concluded that unsuitable design may result in larger resistance. But, it is also shown that, for a good design, the resistance may be reduced considerably.

  9. Experimental Research of Engine Foundations

    Directory of Open Access Journals (Sweden)

    Violeta-Elena Chiţan


    Full Text Available This paper tries a compact presentation of experimental research of engine-foundations. The dynamic phenomena are so complex, that the vibrations cannot be estimated in the design stage. The design engineer of an engine foundation must foresee through a dynamic analysis of the vibrations, those measures that lead to the avoidance or limiting of the bad effects caused by the vibrations.

  10. Photovoltaic plants: an experimental study

    Energy Technology Data Exchange (ETDEWEB)

    Cirillo, E.; Fato, I.; Lazzarin, R.

    A photovoltaic unit, designed at the University of Bari and already in operation, is described as well as the methodology followed to measure the main characteristic parameters of its operation. The experimental results, compared with those obtained by applying semi-empirical calculations, suggest that load intermittence should be taken into account by introducing a parameter (N) into the calculation, and that intervention of the solar section control device should be considered.

  11. Experimental Mathematics and Mathematical Physics

    Energy Technology Data Exchange (ETDEWEB)

    Bailey, David H.; Borwein, Jonathan M.; Broadhurst, David; Zudilin, Wadim


    One of the most effective techniques of experimental mathematics is to compute mathematical entities such as integrals, series or limits to high precision, then attempt to recognize the resulting numerical values. Recently these techniques have been applied with great success to problems in mathematical physics. Notable among these applications are the identification of some key multi-dimensional integrals that arise in Ising theory, quantum field theory and in magnetic spin theory.

  12. Experimental characteristics of vortex heaters (United States)

    Piralishvili, Sh. A.; Novikov, N. N.

    The performance of a Ranque-Hilsch vortex tube is investigated experimentally for the case where the tube operates as a heater, with the mass of the heated gas remaining constant. The results obtained indicate that energy separation zones with sufficiently high (50 percent) relative heating effects can be achieved for a gas flow ratio of unity. A nomogram is presented for calculating the relative and absolute heating effects as a function of the tube geometry.

  13. Experimental observation of fractional echoes (United States)

    Karras, G.; Hertz, E.; Billard, F.; Lavorel, B.; Siour, G.; Hartmann, J.-M.; Faucher, O.; Gershnabel, Erez; Prior, Yehiam; Averbukh, Ilya Sh.


    We report the observation of fractional echoes in a double-pulse excited nonlinear system. Unlike standard echoes, which appear periodically at delays which are integer multiples of the delay between the two exciting pulses, the fractional echoes appear at rational fractions of this delay. We discuss the mechanism leading to this phenomenon, and provide experimental demonstration of fractional echoes by measuring third harmonic generation in a thermal gas of CO2 molecules excited by a pair of femtosecond laser pulses.

  14. Experimental investigation of horizontal convection


    Muñoz Córdoba, Lucía


    Fluid circulation driven by buoyancy forces due to a thermal gradient on a horizontal boundary, known as horizontal convection, is experimentally studied. For that purpose, a methacrylate box with inner dimensions 300x150x150 mm3 (LxWxH) whose bottom is composed by a heat exchanger and a printed circuit board is lled with water. The heat exchanger provides a uniform temperature boundary condition while the printed circuit board provides a boundary condition of uniform heat ...

  15. Error bars in experimental biology



    Error bars commonly appear in figures in publications, but experimental biologists are often unsure how they should be used and interpreted. In this article we illustrate some basic features of error bars and explain how they can help communicate data and assist correct interpretation. Error bars may show confidence intervals, standard errors, standard deviations, or other quantities. Different types of error bars give quite different information, and so figure legends must make clear what er...


    Directory of Open Access Journals (Sweden)

    G. I. Netylko


    Full Text Available The experimental investigation for the purpose of modeling of knee osteonecrosis were performed in 36 rats. The chronic renal insufficiency by means of left nephrectomy and electrocoagulation in 25% cortical substance of right kidney was induced before 6 months till experiment with subsequent introduction of 0,1% adrenalin solution and methylprednisolone in paraarticular structures. The results of experiment showed the polyetiologic feature of disease.

  17. Experimental Satellite 2 Successfully Launched

    Institute of Scientific and Technical Information of China (English)



    Small satellite Experimental Satellite 2 (SY-2) was launched by LM-2C launch vehicle from Xichang Satellite Launch Center on Nov. 18, 2004. Later the satellite entered the preset sun-synchronous orbit, which is 700 kilometers above the earth. The launch was the eighthmission this year by China Aerospace Science and Technology Corporation(CASC), which aims to test the technology of the satellite, conduct survey and monitoring of the land and resources and geographical environment on a trial basis.

  18. Elements of Bayesian experimental design

    Energy Technology Data Exchange (ETDEWEB)

    Sivia, D.S. [Rutherford Appleton Lab., Oxon (United Kingdom)


    We consider some elements of the Bayesian approach that are important for optimal experimental design. While the underlying principles used are very general, and are explained in detail in a recent tutorial text, they are applied here to the specific case of characterising the inferential value of different resolution peakshapes. This particular issue was considered earlier by Silver, Sivia and Pynn (1989, 1990a, 1990b), and the following presentation confirms and extends the conclusions of their analysis.

  19. Chaotic principle an experimental test

    CERN Document Server

    Bonetto, F; Garrido, P L


    The chaotic hypothesis discussed in [GC1] is tested experimentally in a simple conduction model. Besides a confirmation of the hypothesis predictions the results suggest the validity of the hypothesis in the much wider context in which, as the forcing strength grows, the attractor ceases to be an Anosov system and becomes an Axiom A attractor. A first test of the new predictions is also attempted.

  20. Experimental Crystallization of Yamato 980459 (United States)

    Jones, John H.; Galenas, M. G.; Danielson, L. R.


    Currently, only two martian meteorites QUE 94201 (QUE) and Yamato 980459 (Y98) have been experimentally shown to me true melt compositions. Most martian meteorites are instead, cumulates or partial cumulates. We have performed experiments on a Y98 composition to assess whether QUE could be related to Y98 by some fractionation process [1]. Y98 is a basaltic shergottite from the SNC (Shergotty, Nakhla, Chassigny) meteorite group. Y98 is composed of 26% olivine, 48% pyroxene, 25% mesostasis, and no plagioclase [2]. The large size of the olivine megacrysts and absence of plagioclase suggest that the parental melt which formed this meteorite had begun cooling slowly until some mechanism, such as magma ascent, caused rapid cooling [3]. Y98 s olivines have the highest Mg content of all the shergottites suggesting that it is the most primitive [4]. Y98 has been determined to be a melt composition by comparing the composition of experimental liquidus olivines with the composition of the cores of Y98 olivines [4]. The liquidus of Y98 is predicted by MELTS [5] and by experimentation [6] to be 1450 C. Analyses of Y98 show it to be very depleted in LREEs and it has similar depleted patterns as other shergottites such as QUE [7].

  1. Highlights on experimental neutrino physics

    Energy Technology Data Exchange (ETDEWEB)

    Kemp, Ernesto [Universidade Estadual de Campinas (UNICAMP), SP (Brazil)


    Full text: In the last years a remarkable progress was achieved in a deeper understanding of neutrino sector. Nowadays we know all mixing angles and mass splits which govern the neutrino oscillation phenomena. The parameters of neutrino mixing were measured by combining results of different experimental approaches including accelerator beams, nuclear reactors, radiative decays and astrophysical neutrinos. Nevertheless, there are open questions which can be viewed as key points to consolidate our knowledge on the intrinsic properties of neutrinos such as mass hierarchy and the existence of a CP violation in leptonic sector. To answer these questions and also to improve the precision of the already known mixing parameters, a series of huge experimental efforts are being set up, even in a world-wide scale in some cases. In this presentation I will review the current knowledge of the fundamental properties of neutrinos and the experimental scenario in which we expect, in a time frame of a decade, to find missing pieces in the leptonic sector. The findings can strengthen the foundations of the Standard Model as well as open very interesting paths for new physics. (author)

  2. Experimental Chagas' disease in dogs

    Directory of Open Access Journals (Sweden)

    Marta de Lana


    Full Text Available This paper describes the development of experimental Chagas' disease in 64 out-bred young dogs. Twenty-nine animals were inoculated with the Be-62 and 35 with Be-78 Trypanosoma cruzi strains. Twenty-six were infected with blood trypomastigotes by different inoculation routes and 38 with metacyclic trypomastigotes from the vector via the conjunctival route. Twenty of the 26 dogs infected with blood trypomastigotes were autopsied during the acute phase. Eleven died spontaneously and nine were sacrificed. Six remained alive until they died suddenly (two or were autopsied (four. Twelve of the 38 dogs infected with metacyclic trypomastigotes evolved naturally to the chronic phase and remained alive for 24-48 months. The parasitemia, clinical aspects and serology (IgM and IgG as well as electrocardiogram, hemogram and heart anatomo-histopathologic patterns of acute and chronic cardiac forms of Chagas' disease as seen in human infections, were reproduced. The most important finding is the reproductibility of diffuse fibrosing chronic chagasic cardiopathy in all dogs infected with Be-78 T. cruzi strain autopsied between the 90th and 864th days of infection. Thus, the dog can be considered as a suitable experimental model to study Chagas' disease according to the requisites of the World Health Organization (1984. Futhermore the animal is easily obtained and easy to handle and maintain in experimental laboratory conditions.

  3. Experimental Trichomonas infection: Morphological aspects

    Directory of Open Access Journals (Sweden)

    E. N. Shumkova


    Full Text Available Background. Growth tendency the asymptomatic forms of an urogenital trichomoniasis, frequency of complications from reproductive organs, uncertainty of many aspects of the violations of a spermatogenesis influencing reproductive function all this proves need of search of the urogenital trichomoniasis adequate experimental model. Lack of the corresponding experimental model is limited by our opportunities for carrying out the standardized, controlled researches on studying of transmission, pathogenesis, the immune answer, therapy and development of vaccines at a triсhomonas infection.Objective is studying action of Trichomonas vaginalis on a spermatogenny epithelium the mature of individuals of guinea pigs in the conditions of sharp and chronic experience.Materials and methods. Experiments are made on the “Reproductive System (Guinea Pigs + Trichomonas vaginalis” modeling the natural course of an infection. In experiment 2 groups of animals: 1st (n = 8 – experimental, 2nd (n = 8 – control were formed. Against the background of the reduction of the immune status (hydrocortisone 125 mg/kg intramuscularly 1 time in day during 2 days the animals of the 1st group were injected intraurethral suspension containing 1 × 106 Trichomonas on 0.5 ml of culture medium, the animals of the 2nd group – 0.5 ml of medium. Under the condition of the acute experiment the animals were sacrificed on day 9 (the middle of the cycle of spermatogenesis – I experienced group and on day 30 (full spermatogenic cycle – II experimental group. The control animals were slaughtered in the same period. The material for histological study was prepared by the traditional way.Results. In an experimental model of “Reproductive system (guinea pigs + T. vaginalis”, staging and degree of disturbance of spermatogenesis, depending on the duration of trichomonas infection were shown. So, in acute experience morphological changes correspond to changes in the

  4. Oral feeding with ethinyl estradiol suppresses and treats experimental autoimmune encephalomyelitis in SJL mice and inhibits the recruitment of inflammatory cells into the central nervous system. (United States)

    Subramanian, Sandhya; Matejuk, Agata; Zamora, Alex; Vandenbark, Arthur A; Offner, Halina


    There is much interest in the possible ameliorating effects of estrogen on various autoimmune diseases. We previously established the protective effects of 17 beta-estradiol (E2) on experimental autoimmune encephalomyelitis (EAE). In the current study we investigated the effectiveness of oral treatment with ethinyl estradiol (EE) on EAE and the mechanisms involved. Ethinyl estradiol is a semisynthetic estrogen compound found in birth control pills, and its chemical structure allows this compound to retain activity when given orally. We found that oral EE, like E2, drastically suppressed EAE induced by proteolipid protein 139-151 peptide when given at initiation of EAE. However, unlike E2, EE reduced clinical severity when given after the onset of clinical signs. Treatment with EE significantly decreased the secretion of proinflammatory cytokines (IFN-gamma, TNF-alpha, and IL-6) by activated T cells as well as the expression of a key matrix metalloproteinase, disease-mediating chemokines/receptors, and IgG2a levels, but increased the expression of TGF-beta 3 in the CNS. The absence of infiltrating lymphocytes together with the suppression of cytokines, matrix metalloproteinase, and chemokines/receptors suggests that EE, like E2, protects mice from EAE by inhibiting the recruitment of T cells and macrophages into the CNS. These results suggest that oral ethinyl estradiol might be a successful candidate as therapy for multiple sclerosis.

  5. The philosophy of scientific experimentation: a review. (United States)

    Radder, Hans


    Practicing and studying automated experimentation may benefit from philosophical reflection on experimental science in general. This paper reviews the relevant literature and discusses central issues in the philosophy of scientific experimentation. The first two sections present brief accounts of the rise of experimental science and of its philosophical study. The next sections discuss three central issues of scientific experimentation: the scientific and philosophical significance of intervention and production, the relationship between experimental science and technology, and the interactions between experimental and theoretical work. The concluding section identifies three issues for further research: the role of computing and, more specifically, automating, in experimental research, the nature of experimentation in the social and human sciences, and the significance of normative, including ethical, problems in experimental science.

  6. China experimental fast reactor; Le reacteur rapide experimental chinois

    Energy Technology Data Exchange (ETDEWEB)

    Tianmin, X. [Institut d' Ingenierie Nucleaire de Pekin (China); Cunren, L. [Centre d' Etude de Surete de Pekin (China)


    The Chinese experimental fast reactor (CEFR) is a pool-type sodium-cooled fast reactor whose short term purposes are: -) the validation of computer codes, -) the check of the relevance of standards, and -) the gathering of experimental data on fast reactors. On the long term the expectations will focus on: -) gaining experience in fast reactor operations, -) the testing of nuclear fuels and materials, and -) the study of sodium compounds. The main technical features of CEFR are: -) thermal power output: 65 MW (electrical power output: 20 MW), -) size of the core: height: 45 cm, diameter: 60 cm, -) maximal linear output: 430 W/cm, -) neutron flux: 3.7*10{sup 15} n/cm{sup 2}/s, -) input/output sodium temperature: 360 / 530 Celsius degrees, -) 2 loops for the primary system and 2 loops for the secondary system. The temperature coefficient and the power coefficient are settled to stay negative for any change in the values of the core parameters. The installation of the reactor vessel will be completed by mid 2007. The first criticality of CEFR is expected during the first semester of 2010. (A.C.)

  7. The philosophy of scientific experimentation: a review


    Radder, H.


    Practicing and studying automated experimentation may benefit from philosophical reflection on experimental science in general. This paper reviews the relevant literature and discusses central issues in the philosophy of scientific experimentation. The first two sections present brief accounts of the rise of experimental science and of its philosophical study. The next sections discuss three central issues of scientific experimentation: the scientific and philosophical significance of interve...

  8. Experimental Blade Research - phase 2


    Eder, Martin Alexander; Branner, Kim; Berring, Peter; Belloni, Federico; Stensgaard Toft, Henrik; Sørensen, John Dalsgaard; Corre, Adrien; Lindby, Torben; Quispitupa, Amilcar; Petersen, Thomas Karl


    This report is a summary of the results obtained in the project: Experimental Blade Research – phase 2 (EBR2). The project was supported by the Danish Energy Authority through the 2010 Energy Technology Development and Demonstration Program (EUDP 2010-II) and has journal no. 64011-0006. The project has been running from spring 2011 to the end of 2014.Being a summary report, this report only contains a collection of the research topics and the major results. For more details, see the publicati...

  9. Experimental quantum multiparty communication protocols (United States)

    Smania, Massimiliano; Elhassan, Ashraf M.; Tavakoli, Armin; Bourennane, Mohamed


    Quantum information science breaks limitations of conventional information transfer, cryptography and computation by using quantum superpositions or entanglement as resources for information processing. Here we report on the experimental realisation of three-party quantum communication protocols using single three-level quantum system (qutrit) communication: secret-sharing, detectable Byzantine agreement and communication complexity reduction for a three-valued function. We have implemented these three schemes using the same optical fibre interferometric setup. Our realisation is easily scalable without compromising on detection efficiency or generating extremely complex many-particle entangled states.

  10. Error bars in experimental biology. (United States)

    Cumming, Geoff; Fidler, Fiona; Vaux, David L


    Error bars commonly appear in figures in publications, but experimental biologists are often unsure how they should be used and interpreted. In this article we illustrate some basic features of error bars and explain how they can help communicate data and assist correct interpretation. Error bars may show confidence intervals, standard errors, standard deviations, or other quantities. Different types of error bars give quite different information, and so figure legends must make clear what error bars represent. We suggest eight simple rules to assist with effective use and interpretation of error bars.

  11. Essay on experimental avitaminosis K


    Solano Rodríguez, Juana María; Facultad de Medicina, Universidad Nacional Mayor de San Marcos, Lima, Perú


    We have made an experimental test of avitaminosis K in order to study the hitipatológicas and radiological lesions in relation to haematological abnormalities and changes in prothrombin in the blood. The clinical picture observed in animals is similar in all respects to that described by Dam, Schonheyder, Almquist and colleagues. With respect to prothrombin time values ​​Quick, we note: a) Normal values: In the control animals, normal prothrombin time is 85% and the Quick time is 45 seconds. ...

  12. A simple Cavendish experimental apparatus (United States)

    Kossler, W. J.; Klein, Susann; Morrow, Dominick; Juliao, Andre


    A simple Cavendish apparatus is described that allows measurement of the gravitational constant G and makes observable the gravitational attraction between commonplace objects. The apparatus consists of a torsion balance constructed from readily available materials, including lead bricks and fishing weights ("sinkers"). A computer program is used to determine the gravitational field at the location of the small mass due to a nearby lead brick, which allows students to gain experience with numerical methods. Experimental results obtained are compatible with the accepted value of G.

  13. Top Quark Current Experimental Status

    CERN Document Server

    Juste, A


    Ten years after its discovery at the Tevatron collider, we still know little about the top quark. Its large mass suggests it may play a key role in the mechanism of Electroweak Symmetry Breaking (EWSB), or open a window of sensitivity to new physics related to EWSB and preferentially coupled to it. To determine whether this is the case, precision measurements of top quark properties are necessary. The high statistics samples being collected by the Tevatron experiments during Run II start to incisively probe the top quark sector. This report summarizes the experimental status of the top quark, focusing in particular on the recent measurements from the Tevatron.

  14. User Experimentation with Terminological Ontologies

    DEFF Research Database (Denmark)

    Pram Nielsen, Louise

    This paper outlines work-in-progress research suggesting that domain-specific knowledge in terminological resources can be transferred efficiently to end-users across different levels of expertise and by means of different information modes including articles (written mode) and concept diagrams...... (graph mode). An experimental approach is applied in an eye-tracking laboratory, where a natural user situation is replicated for Danish professional potential end-users of a ter-minology and knowledge bank in a chosen pilot domain (taxation)....

  15. Flexible experimental FPGA based platform

    DEFF Research Database (Denmark)

    Andersen, Karsten Holm; Nymand, Morten


    This paper presents an experimental flexible Field Programmable Gate Array (FPGA) based platform for testing and verifying digital controlled dc-dc converters. The platform supports different types of control strategies, dc-dc converter topologies and switching frequencies. The controller platform...... interface supporting configuration and reading of setup parameters, controller status and the acquisition memory in a simple way. The FPGA based platform, provides an easy way within education or research to use different digital control strategies and different converter topologies controlled by an FPGA...

  16. Experimental plasma research project summaries

    Energy Technology Data Exchange (ETDEWEB)


    This report contans descriptions of the activities supported by the Experimental Plasma Research Branch of APP. The individual project summaries were prepared by the principal investigators and include objectives and milestones for each project. The projects are arranged in six research categories: Plasma Properties; Plasma Heating; Plasma Measurements and Instrumentation; Atomic, Molecular and Nuclear Physics; Advanced Superconducting Materials; and the Fusion Plasma Research Facility (FPRF). Each category is introduced with a statement of objectives and recent progress and followed by descriptions of individual projects. An overall budget summary is provided at the beginning of the report.

  17. Experimental Plasma Research project summaries

    Energy Technology Data Exchange (ETDEWEB)



    This report contains descriptions of the activities supported by the Experimental Plasma Research Branch of APP. The individual project summaries were prepared by the principal investigators and include objectives and milestones for each project. The projects are arranged in six research categories: Plasma Properties; Plasma Heating; Plasma Diagnostics; Atomic, Molecular and Nuclear Physics; Advanced Superconducting Materials; and the Fusion Plasma Research Facility (FPRF). Each category is introduced with a statement of objectives and recent progress and followed by descriptions of individual projects. An overall budget summary is provided at the beginning of the report.

  18. Inactivation of T cell receptor peptide-specific CD4 regulatory T cells induces chronic experimental autoimmune encephalomyelitis (EAE). (United States)

    Kumar, V; Stellrecht, K; Sercarz, E


    T cell receptor (TCR)-recognizing regulatory cells, induced after vaccination with self-reactive T cells or TCR peptides, have been shown to prevent autoimmunity. We have asked whether this regulation is involved in the maintenance of peripheral tolerance to myelin basic protein (MBP) in an autoimmune disease model, experimental autoimmune encephalomyelitis (EAE). Antigen-induced EAE in (SJL x B10.PL)F1 mice is transient in that most animals recover permanently from the disease. Most of the initial encephalitogenic T cells recognize MBP Ac1-9 and predominantly use the TCR V beta 8.2 gene segment. In mice recovering from MBP-induced EAE, regulatory CD4+ T cells (Treg) specific for a single immunodominant TCR peptide B5 (76-101) from framework region 3 of the V beta 8.2 chain, become primed. We have earlier shown that cloned B5-reactive Treg can specifically downregulate responses to Ac1-9 and also protect mice from EAE. These CD4 Treg clones predominantly use the TCR V beta 14 or V beta 3 gene segments. Here we have directly tested whether deletion/blocking of the Treg from the peripheral repertoire affects the spontaneous recovery from EAE. Treatment of F1 mice with appropriate V beta-specific monoclonal antibodies resulted in an increase in the severity and duration of the disease; even relapses were seen in one-third to one-half of the Treg-deleted mice. Interestingly, chronic disease in treated mice appears to be due to the presence of Ac1-9-specific T cells. Thus, once self-tolerance to MBP is broken by immunization with the antigen in strong adjuvant, TCR peptide-specific CD4 Treg cells participate in reestablishing peripheral tolerance. Thus, a failure to generate Treg may be implicated in chronic autoimmune conditions.

  19. Project experimental house in Caceres; Proyecto vivienda experimental en Caceres

    Energy Technology Data Exchange (ETDEWEB)

    Gamero, E.; Mendez, L.


    The project envisages to develop and efficient methodology for the design and building of social housing in the region of Extremadura, with the aim to obtaining sustainable buildings, with a better energy behaviour, and the use of renewable energy sources, in addition to ensuring a substantial increase of the quality of construction. the project is based on the construction of two isolated houses which will have the same geographical orientation and equal structural system, so they both will be subject to the same climate conditions. One of the houses (pattern house) will be built following exactly the construction being used for the Special Housing Plan, whilst the second on (Experimental house) will serve as a laboratory where to test and demonstrate different sustainability measures and renewable energy sources. (Author)

  20. Experimental results on evaporation waves (United States)

    Grana Otero, Jose; Parra Fabian, Ignacio


    A liquid contained in a vertical glass tube is suddenly depressurized from a high initial pressure down to one for which the stable state is vapour, so vaporization sets off at the free surface. For large enough evaporation rates, the planar vapour-liquid interface is Darrieus-Landau unstable [1], leading to the interface surface rippling close to the instability threshold. Further increasing the initial to final pressure ratio brings about evaporation waves [2,3], in which a highly corrugated front propagates downwards into the liquid. A new experimental method is presented as well as some experimental results obtained by tracking the evolution of the front with a high speed camera. In addition, a number of new phenomena related to the dynamics of bubbles growth at the walls has been uncovered. In particular, a new mode of propagation of the evaporation front is found. In this mode the front originates from below the interface, so the propagation is upwards against gravity with a curved but smooth front.[4pt] [1] F. J. Higuera, Phys. Fluids, V. 30, 679 (1987).[0pt] [2] J.E.Shepherd and B.Sturtevant, J.Fluid Mech., V.121,379 (1982).[0pt] [3] P.Reinke and G.Yadigaroglu, Int.J.Multiph. Flow, V.27,1487 (2001).

  1. Experimental evolution in biofilm populations. (United States)

    Steenackers, Hans P; Parijs, Ilse; Foster, Kevin R; Vanderleyden, Jozef


    Biofilms are a major form of microbial life in which cells form dense surface associated communities that can persist for many generations. The long-life of biofilm communities means that they can be strongly shaped by evolutionary processes. Here, we review the experimental study of evolution in biofilm communities. We first provide an overview of the different experimental models used to study biofilm evolution and their associated advantages and disadvantages. We then illustrate the vast amount of diversification observed during biofilm evolution, and we discuss (i) potential ecological and evolutionary processes behind the observed diversification, (ii) recent insights into the genetics of adaptive diversification, (iii) the striking degree of parallelism between evolution experiments and real-life biofilms and (iv) potential consequences of diversification. In the second part, we discuss the insights provided by evolution experiments in how biofilm growth and structure can promote cooperative phenotypes. Overall, our analysis points to an important role of biofilm diversification and cooperation in bacterial survival and productivity. Deeper understanding of both processes is of key importance to design improved antimicrobial strategies and diagnostic techniques.

  2. Skill development in experimental courses

    Directory of Open Access Journals (Sweden)

    Héctor Bagán


    Full Text Available Experimental courses offer a good opportunity to work with competences, promoting the incorporation of strategies oriented towards motivating students to actively involve in the learning process, promoting reflexive learning and developing generic skills. This study presents different ways of developing and evaluating some important general skills, settle on four specific objectives: 1. To increase student motivation using samples of potential interest to students and explaining real-live application of their samples analyses; 2. To assist students’ self-regulation and learning autonomy by using the portfolio; 3. To promote group work through experiments in pairs and small-group discussions; 4. To develop communication skills through small-group discussions and oral presentations. Results show that the type of sample used and real-life application has important influence on motivation. The portfolio is a good tool to promote reflection and to evaluate both specific and generic skills in experimental courses, the dynamics of a laboratory course permit students to develop their group-work and communicative skills, and peer evaluations both improve students’ communication skills and promote metacognitive reflection. Finally, the project demonstrates that it is possible to train students in general skills using the specific course content and that the incorporation of participatory methodologies encourages students to become actively involved in the teaching-learning process.

  3. Experimental study of MWEDM technology

    Institute of Scientific and Technical Information of China (English)

    DI Shi-chun; HUANG Rui-ning; CHI Guan-xin; ZHAO Wan-sheng


    This work deals with an experimental investigation of the machining characteristics of Micro Wire Electrical Discharge Machining (MWEDM). The MWEDM process consists of only one cutting operation varying with machining conditions. Experimental results show that the peak current and pulse duration have an obvious influence on surface roughness and machining time, and they also have an optimum value for the highest cutting speed. The servo reference voltage influences the surface roughness and machining time as well. In particular,the surface characteristics of work-pieces and a micro wire electrode were analyzed in detail too. Utilizing a micro wire electrode with diameter 30μm, MWEDM can machine a micro slot 38μm wide, which proves that the discharge gap can be controlled not more than 4μm. It can also machine micro gears respectively with a module 40μm, thickness 1mm, and a module 100μm, thickness 3.5mm. All kinds of micro shaped holes and complex micro parts can be easily machined as well.

  4. Animal husbandry and experimental design. (United States)

    Nevalainen, Timo


    If the scientist needs to contact the animal facility after any study to inquire about husbandry details, this represents a lost opportunity, which can ultimately interfere with the study results and their interpretation. There is a clear tendency for authors to describe methodological procedures down to the smallest detail, but at the same time to provide minimal information on animals and their husbandry. Controlling all major variables as far as possible is the key issue when establishing an experimental design. The other common mechanism affecting study results is a change in the variation. Factors causing bias or variation changes are also detectable within husbandry. Our lives and the lives of animals are governed by cycles: the seasons, the reproductive cycle, the weekend-working days, the cage change/room sanitation cycle, and the diurnal rhythm. Some of these may be attributable to routine husbandry, and the rest are cycles, which may be affected by husbandry procedures. Other issues to be considered are consequences of in-house transport, restrictions caused by caging, randomization of cage location, the physical environment inside the cage, the acoustic environment audible to animals, olfactory environment, materials in the cage, cage complexity, feeding regimens, kinship, and humans. Laboratory animal husbandry issues are an integral but underappreciated part of investigators' experimental design, which if ignored can cause major interference with the results. All researchers should familiarize themselves with the current routine animal care of the facility serving them, including their capabilities for the monitoring of biological and physicochemical environment.

  5. Experimental evolution in biofilm populations (United States)

    Steenackers, Hans P.; Parijs, Ilse; Foster, Kevin R.; Vanderleyden, Jozef


    Biofilms are a major form of microbial life in which cells form dense surface associated communities that can persist for many generations. The long-life of biofilm communities means that they can be strongly shaped by evolutionary processes. Here, we review the experimental study of evolution in biofilm communities. We first provide an overview of the different experimental models used to study biofilm evolution and their associated advantages and disadvantages. We then illustrate the vast amount of diversification observed during biofilm evolution, and we discuss (i) potential ecological and evolutionary processes behind the observed diversification, (ii) recent insights into the genetics of adaptive diversification, (iii) the striking degree of parallelism between evolution experiments and real-life biofilms and (iv) potential consequences of diversification. In the second part, we discuss the insights provided by evolution experiments in how biofilm growth and structure can promote cooperative phenotypes. Overall, our analysis points to an important role of biofilm diversification and cooperation in bacterial survival and productivity. Deeper understanding of both processes is of key importance to design improved antimicrobial strategies and diagnostic techniques. PMID:26895713

  6. Dietary heme adversely affects experimental colitis in rats, despite heat-shock protein induction

    NARCIS (Netherlands)

    Schepens, Marloes A. A.; Vink, Carolien; Schonewille, Arjan J.; Dijkstra, Gerard; van der Meer, Roelof; Bovee-Oudenhoven, Ingeborg M. J.


    Objective: Research on dietary modulation of inflammatory bowel disease is in its infancy. Dietary heme, mimicking red meat, is cytotoxic to colonic epithelium and thus may aggravate colitis. Alternatively, heme-induced colonic stress might also result in potential protective heat-shock proteins (HS

  7. Communications satellites - The experimental years (United States)

    Edelson, B. I.


    Only eight years after the launc of Sputnik-1 by the Soviet Union, the first commercial satellite, 'Early Bird', entered service. In just twelve years commercial satellite service extended around the earth and became profitable. The reasons for the successful development of the communications satellite services in a comparatively short time are considered. These reasons are related to the presence of three ingredients, taking into account technology to create the system, communications requirements to form a market, and a management structure to implement the system. The formation of the concept of using earth orbiting satellites for telecommunications is discussed. It is pointed out that the years from 1958 to 1964 were the true 'experimental years' for satellite communications. The rapid development of technology during this crucial period is described, giving attention to passive satellites, active systems, and development satellites.

  8. Characterization of experimental equine glanders. (United States)

    Lopez, Jose; Copps, John; Wilhelmsen, Catherine; Moore, Richard; Kubay, Julie; St-Jacques, Marcel; Halayko, Stacey; Kranendonk, Christiaan; Toback, Shannon; DeShazer, David; Fritz, David L; Tom, Marina; Woods, Donald E


    Considerable advances in understanding of the disease caused by Burkholderia mallei have been made employing a combination of tools including genetic techniques and animal infection models. The development of small animal models has allowed us to assess the role of a number of putative virulence determinants in the pathogenesis of disease due to B. mallei. Due to the difficulties in performing active immunization studies in small animals, and due to the fact that the horse is the target mammalian species for glanders, we have initiated experimental studies on glanders in horses. Intratracheal deposition of B. mallei produced clinical glanders with organisms being recovered from tissues of infected horses. The model should prove to be of considerable value in our ongoing studies on the pathogenesis and vaccine development for glanders.

  9. Experimental activation of bound entanglement. (United States)

    Kaneda, Fumihiro; Shimizu, Ryosuke; Ishizaka, Satoshi; Mitsumori, Yasuyoshi; Kosaka, Hideo; Edamatsu, Keiichi


    Entanglement is one of the essential resources in quantum information and communication technology (QICT). The entanglement thus far explored and applied to QICT has been pure and distillable entanglement. Yet, there is another type of entanglement, called "bound entanglement," which is not distillable by local operations and classical communication. We demonstrate the experimental "activation" of the bound entanglement held in the four-qubit Smolin state, unleashing its immanent entanglement in distillable form, with the help of auxiliary two-qubit entanglement and local operations and classical communication. We anticipate that it opens the way to a new class of QICT applications that utilize more general classes of entanglement than ever, including bound entanglement.

  10. Experimental quantum computing without entanglement. (United States)

    Lanyon, B P; Barbieri, M; Almeida, M P; White, A G


    Deterministic quantum computation with one pure qubit (DQC1) is an efficient model of computation that uses highly mixed states. Unlike pure-state models, its power is not derived from the generation of a large amount of entanglement. Instead it has been proposed that other nonclassical correlations are responsible for the computational speedup, and that these can be captured by the quantum discord. In this Letter we implement DQC1 in an all-optical architecture, and experimentally observe the generated correlations. We find no entanglement, but large amounts of quantum discord-except in three cases where an efficient classical simulation is always possible. Our results show that even fully separable, highly mixed, states can contain intrinsically quantum mechanical correlations and that these could offer a valuable resource for quantum information technologies.

  11. Experimental investigation of cavity flows

    Energy Technology Data Exchange (ETDEWEB)

    Loeland, Tore


    This thesis uses LDV (Laser Doppler Velocimetry), PIV (Particle Image Velocimetry) and Laser Sheet flow Visualisation to study flow inside three different cavity configurations. For sloping cavities, the vortex structure inside the cavities is found to depend upon the flow direction past the cavity. The shape of the downstream corner is a key factor in destroying the boundary layer flow entering the cavity. The experimental results agree well with numerical simulations of the same geometrical configurations. The results of the investigations are used to find the influence of the cavity flow on the accuracy of the ultrasonic flowmeter. A method to compensate for the cavity velocities is suggested. It is found that the relative deviation caused by the cavity velocities depend linearly on the pipe flow. It appears that the flow inside the cavities should not be neglected as done in the draft for the ISO technical report on ultrasonic flowmeters. 58 refs., 147 figs., 2 tabs.

  12. Purinergic signalling: an experimental perspective. (United States)

    Housley, G D; Thorne, P R


    Investigation of the multiple roles of extracellular nucleotides in the cochlea has developed from analysis of ATP-activated conductances in single sensory hair cells. Molecular probes such as radiolabelled ATP analogues and radiolabelled mRNA for ATP-gated ion channel subunits (P2X receptors) rapidly revealed the extensive nature of ATP signalling in this sensory organ. This has provided a foundation for physiological investigations which put extracellular nucleotides at the centre of homeostatic regulation of the driving force for sound transduction, modulation of mechanical tuning, control of cochlear blood flow and auditory neurotransmission. The purinergic signal transduction pathways associated with these processes have several novel features of significance to the broader field of purinergic neuroscience. In turn, these studies have benefited from the recent experimental advances in the field of purinergic signalling, a significant component of which is associated with the work of Professor Geoffrey Burnstock.

  13. An experimental superconducting helical undulator

    Energy Technology Data Exchange (ETDEWEB)

    Caspi, S.; Taylor, C. [Lawrence Berkeley Lab., CA (United States)


    Improvements in the technology of superconducting magnets for high energy physics and recent advancements in SC materials with the artificial pinning centers (APC){sup 2}, have made a bifilar helical SC device an attractive candidate for a single-pass free electron laser (FEL){sup 3}. Initial studies have suggested that a 6.5 mm inner diameter helical device, with a 27 mm period, can generate a central field of 2-2.5 Tesla. Additional studies have also suggested that with a stored energy of 300 J/m, such a device can be made self-protecting in the event of a quench. However, since the most critical area associated with high current density SC magnets is connected with quenching and training, a short experimental device will have to be built and tested. In this paper we discuss technical issues relevant to the construction of such a device, including a conceptual design, fields, and forces.

  14. Pharmacology of human experimental anxiety. (United States)

    Graeff, F G; Parente, A; Del-Ben, C M; Guimarães, F S


    This review covers the effect of drugs affecting anxiety using four psychological procedures for inducing experimental anxiety applied to healthy volunteers and patients with anxiety disorders. The first is aversive conditioning of the skin conductance responses to tones. The second is simulated public speaking, which consists of speaking in front of a video camera, with anxiety being measured with psychometric scales. The third is the Stroop Color-Word test, in which words naming colors are painted in the same or in a different shade, the incongruence generating a cognitive conflict. The last test is a human version of a thoroughly studied animal model of anxiety, fear-potentiated startle, in which the eye-blink reflex to a loud noise is recorded. The evidence reviewed led to the conclusion that the aversive conditioning and potentiated startle tests are based on classical conditioning of anticipatory anxiety. Their sensitivity to benzodiazepine anxiolytics suggests that these models generate an emotional state related to generalized anxiety disorder. On the other hand, the increase in anxiety determined by simulated public speaking is resistant to benzodiazepines and sensitive to drugs affecting serotonergic neurotransmission. This pharmacological profile, together with epidemiological evidence indicating its widespread prevalence, suggests that the emotional state generated by public speaking represents a species-specific response that may be related to social phobia and panic disorder. Because of scant pharmacological data, the status of the Stroop Color-Word test remains uncertain. In spite of ethical and economic constraints, human experimental anxiety constitutes a valuable tool for the study of the pathophysiology of anxiety disorders.

  15. Pharmacology of human experimental anxiety

    Directory of Open Access Journals (Sweden)

    F.G. Graeff


    Full Text Available This review covers the effect of drugs affecting anxiety using four psychological procedures for inducing experimental anxiety applied to healthy volunteers and patients with anxiety disorders. The first is aversive conditioning of the skin conductance responses to tones. The second is simulated public speaking, which consists of speaking in front of a video camera, with anxiety being measured with psychometric scales. The third is the Stroop Color-Word test, in which words naming colors are painted in the same or in a different shade, the incongruence generating a cognitive conflict. The last test is a human version of a thoroughly studied animal model of anxiety, fear-potentiated startle, in which the eye-blink reflex to a loud noise is recorded. The evidence reviewed led to the conclusion that the aversive conditioning and potentiated startle tests are based on classical conditioning of anticipatory anxiety. Their sensitivity to benzodiazepine anxiolytics suggests that these models generate an emotional state related to generalized anxiety disorder. On the other hand, the increase in anxiety determined by simulated public speaking is resistant to benzodiazepines and sensitive to drugs affecting serotonergic neurotransmission. This pharmacological profile, together with epidemiological evidence indicating its widespread prevalence, suggests that the emotional state generated by public speaking represents a species-specific response that may be related to social phobia and panic disorder. Because of scant pharmacological data, the status of the Stroop Color-Word test remains uncertain. In spite of ethical and economic constraints, human experimental anxiety constitutes a valuable tool for the study of the pathophysiology of anxiety disorders.

  16. Design of Formulated Products: Experimental Component

    DEFF Research Database (Denmark)

    Conte, Elisa; Gani, Rafiqul; Cheng, Y. S.


    : computer-aided design (Stage 1), which generates a list of feasible candidates, experimental planning (Stage 2), which generates a list of experiments and checks the available experimental set-ups, and experimental testing (Stage 3), which measures the necessary data and verifies the desirable attributes...

  17. 27 CFR 40.232 - Experimental purposes. (United States)


    ... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Experimental purposes. 40... Products § 40.232 Experimental purposes. A manufacturer of tobacco products may use tobacco products for experimental purposes without determination and payment of tax as set forth in this section. (a) What...

  18. 47 CFR 5.73 - Experimental report. (United States)


    ... 47 Telecommunication 1 2010-10-01 2010-10-01 false Experimental report. 5.73 Section 5.73 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL EXPERIMENTAL RADIO SERVICE (OTHER THAN BROADCAST) Applications and Licenses § 5.73 Experimental report. (a) Unless specifically stated as a condition of...

  19. 50 CFR 648.12 - Experimental fishing. (United States)


    ... 50 Wildlife and Fisheries 8 2010-10-01 2010-10-01 false Experimental fishing. 648.12 Section 648... Experimental fishing. The Regional Administrator may exempt any person or vessel from the requirements of... red crab), N (tilefish), and O (skates) of this part for the conduct of experimental...

  20. 50 CFR 665.17 - Experimental fishing. (United States)


    ... 50 Wildlife and Fisheries 9 2010-10-01 2010-10-01 false Experimental fishing. 665.17 Section 665... ADMINISTRATION, DEPARTMENT OF COMMERCE (CONTINUED) FISHERIES IN THE WESTERN PACIFIC General § 665.17 Experimental... incidental harvest of MUS that would otherwise be prohibited by this part. No experimental fishing may...

  1. The '3Is' of animal experimentation. (United States)


    Animal experimentation in scientific research is a good thing: important, increasing and often irreplaceable. Careful experimental design and reporting are at least as important as attention to welfare in ensuring that the knowledge we gain justifies using live animals as experimental tools.


    Directory of Open Access Journals (Sweden)

    B. Samrajya LAKSHMI


    Full Text Available In Andhra Pradesh, India, chemical experimenting in under graduate college labs by students is neglected because most of the intermediate (10+1 and 10+2 students concentrate on writing competitive exams like EAMCET (Engineering and Medical Common Entrance Test, IIT JEE (Indian Institute of Technology Joint Entrance Test, AIEEE (All India Engineering Entrance Examination, AFMS (Armed Forces Medical Services, AIMS (All India Institute of Medical Science. The students spend most of their time in preparing for competitive exams, practicing bits, and writing many model exams. Even Parents, staff, and management are also motivated and allow the students towards preparation for competitive exams because of the increase in number of engineering seats and demand of medical seats. Ultimately, the quality and quantity of students who join the B.Sc. (Bachelor of Science has been decreasing day by day. Even after joining the B.Sc., the students are motivated towards immediate white collared job oriented courses like M.C.A (Master of Computer Applications and M.B.A (Master Business Administration and spending their time for preparing for competitive exams for those courses. Only a few students are interested to join Post graduation in chemistry and try to learn experimental skills in chemistry laboratory. However, the motivated students towards undergraduate chemistry will be demotivated towards it due to lack of fundamentals in chemistry (in 10+2 level, which are essential for better job market. Ultimately, the students are in confusion and neglect learning the skills in doing experiments in chemistry lab. The present paper focuses on the thorough quest of one such teacher who strives for his own professional development. He has developed his own method of guiding the students for their improvement of skills in doing experiments in lab. The teacher explored solutions to his problems or problems of students by sorting out the critical incidents from his own

  3. Endometriose: modelo experimental em ratas Endometriosis: experimental model in rats

    Directory of Open Access Journals (Sweden)

    Eduardo Schor


    Full Text Available Objetivo: divulgar a metodologia da indução de endometriose experimental em animais de laboratório. Método: utilizamos ratas albinas, virgens, adultas de aproximadamente três meses de idade, que foram inicialmente anestesiadas pelo éter etílico. Aberta a cavidade abdominal, identificamos os cornos uterinos e retiramos um fragmento de aproximadamente 4 cm do corno uterino direito. Esse fragmento foi mergulhado em solução fisiológica e sob lupa estereoscópica foi separado o endométrio do miométrio e feitos retângulos de aproximadamente 4 por 5 mm. Esses foram fixados por meio de fio de sutura, sobre vasos sangüíneos visíveis a olho nu, na parede lateral do abdômen, tomando-se sempre o cuidado de manter a porção do endométrio livre voltada para a luz da cavidade abdominal. Após 21 dias os animais foram novamente operados para verificarmos o tamanho dos implantes e para retirada do endométrio ectópico para análise histológica. Resultados: macroscopicamente observamos crescimento significativo dos implantes endometriais. Ao exame microscópico pudemos observar a presença de epitélio glandular e estroma semelhantes ao do endométrio tópico. Conclusões: o modelo utilizado reproduz a doença, em ratas, sendo método auxiliar de valia para estudar esta afecção, principalmente a ação de medicamentos sobre esses implantes.Purpose: to demonstrate the experimental endometriosis induction in animals. Method: we used adult female Wistar rats weighing 200 - 250 g anesthetized with ethyl ether to open the abdominal cavity. After identifying the uterine horns, we removed an approximately 4 cm fragment from the right uterine horn. This fragment was placed in physiological saline and, with the aid of a stereoscopic magnifying glass, the endometrium was separated from the myometrium and cut into rectangles of approximately 4 x 5 mm. These rectangles were fastened to the lateral abdominal wall near great blood vessels, taking care

  4. Experimental evolution meets marine phytoplankton. (United States)

    Reusch, Thorsten B H; Boyd, Philip W


    Our perspective highlights potentially important links between disparate fields-biological oceanography, climate change research, and experimental evolutionary biology. We focus on one important functional group-photoautotrophic microbes (phytoplankton), which are responsible for ∼50% of global primary productivity. Global climate change currently results in the simultaneous change of several conditions such as warming, acidification, and nutrient supply. It thus has the potential to dramatically change phytoplankton physiology, community composition, and may result in adaptive evolution. Although their large population sizes, standing genetic variation, and rapid turnover time should promote swift evolutionary change, oceanographers have focussed on describing patterns of present day physiological differentiation rather than measure potential adaptation in evolution experiments, the only direct way to address whether and at which rate phytoplankton species will adapt to environmental change. Important open questions are (1) is adaptation limited by existing genetic variation or fundamental constraints? (2) Will complex ecological settings such as gradual versus abrupt environmental change influence adaptation processes? (3) How will increasing environmental variability affect the evolution of phenotypic plasticity patterns? Because marine phytoplankton species display rapid acclimation capacity (phenotypic buffering), a systematic study of reaction norms renders them particularly interesting to the evolutionary biology research community.

  5. Experimental high-speed network (United States)

    McNeill, Kevin M.; Klein, William P.; Vercillo, Richard; Alsafadi, Yasser H.; Parra, Miguel V.; Dallas, William J.


    Many existing local area networking protocols currently applied in medical imaging were originally designed for relatively low-speed, low-volume networking. These protocols utilize small packet sizes appropriate for text based communication. Local area networks of this type typically provide raw bandwidth under 125 MHz. These older network technologies are not optimized for the low delay, high data traffic environment of a totally digital radiology department. Some current implementations use point-to-point links when greater bandwidth is required. However, the use of point-to-point communications for a total digital radiology department network presents many disadvantages. This paper describes work on an experimental multi-access local area network called XFT. The work includes the protocol specification, and the design and implementation of network interface hardware and software. The protocol specifies the Physical and Data Link layers (OSI layers 1 & 2) for a fiber-optic based token ring providing a raw bandwidth of 500 MHz. The protocol design and implementation of the XFT interface hardware includes many features to optimize image transfer and provide flexibility for additional future enhancements which include: a modular hardware design supporting easy portability to a variety of host system buses, a versatile message buffer design providing 16 MB of memory, and the capability to extend the raw bandwidth of the network to 3.0 GHz.

  6. Molecular approaches in experimental neuroimaging

    Energy Technology Data Exchange (ETDEWEB)

    Tavitian, B. [CEA Saclay, 91 - Gif sur Yvette (France)


    We quantified and compared six parameters (resolution, depth, sensitivity, portability, quantification and cost) of four molecular imaging techniques (MRI, optics, ultrasound and TEP), with the three types of electromagnetic radiation used in vivo (Frequencies (10{sup 6} to 10{sup 22} Hz), Photonic Energy (10{sup -4} to 10{sup 9} eV) and Wavelengths (10{sup -2} to 10{sup -15} m)). This form of molecular imaging demands the most sensitive technique available (Pl. 26-2 to 26-4). Four examples of experimental in vivo approaches on small animals are shown: molecular passage through the blood-brain barrier (endothelial cells, astrocytes and occludin, pharmacokinetics, studied with PET) (Pl. 2-5 to 2-11); imaging of receptors and ligands, especially peripheral benzodiazepine receptors (PBR) by PET and MRI in the rat (Pl. 2-12 to Pl. 2-15); neuro-pathology of neuro-degenerative and inflammatory diseases and stroke by PET and MRI in the rat (Pl. 2-16 to 2-17); and the study of responses to stimulation explored with in vivo imaging of calcium signals and their variations by photonic analysis, as on the scale of mitochondrial calcium (Pl.2-18 to Pl.2-22). (author)

  7. Ten Problems in Experimental Mathematics

    Energy Technology Data Exchange (ETDEWEB)

    Bailey, David H.; Borwein, Jonathan M.; Kapoor, Vishaal; Weisstein, Eric


    This article was stimulated by the recent SIAM ''100 DigitChallenge'' of Nick Trefethen, beautifully described in a recent book. Indeed, these ten numeric challenge problems are also listed in a recent book by two of present authors, where they are followed by the ten symbolic/numeric challenge problems that are discussed in this article. Our intent was to present ten problems that are characteristic of the sorts of problems that commonly arise in ''experimental mathematics''. The challenge in each case is to obtain a high precision numeric evaluation of the quantity, and then, if possible, to obtain a symbolic answer, ideally one with proof. Our goal in this article is to provide solutions to these ten problems, and in the process present a concise account of how one combines symbolic and numeric computation, which may be termed ''hybrid computation'', in the process of mathematical discovery.

  8. Ukraine experimental neutron source facility.

    Energy Technology Data Exchange (ETDEWEB)

    Gohar, Y.; Bolshinsky, I.; Nekludov, I.; Karnaukhov, I. (Nuclear Engineering Division); (INL); (Kharkov Institute of Physics and Technology)


    Kharkov Institute of Physics and Technology (KIPT) of Ukraine has a plan to construct an experimental neutron source facility. The facility has been developed for producing medical isotopes, training young nuclear professionals, supporting the Ukraine nuclear industry, providing capability for performing reactor physics, material research, and basic science experiments. Argonne National Laboratory (ANL) of USA is collaborating with KIPT on developing this facility. A driven subcritical assembly utilizing the KIPT electron accelerator with a target assembly is used to generate the neutron source. The target assembly utilizes tungsten or uranium for neutron production through photonuclear reactions with 100-KW of electron beam power. The neutron source intensity, spectrum, and spatial distribution have been studied to maximize the neutron yield and satisfy different engineering requirements. The subcritical assembly is designed to obtain the highest possible neutron flux intensity with a subcriticality of 0.98. Low enrichment uranium is used for the fuel material because it enhances the neutron source performance. Safety, reliability, and environmental considerations are included in the facility conceptual design. Horizontal neutron channels are incorporated for performing basic research including cold neutron source. This paper describes the conceptual design and summarizes some of the related analyses.

  9. Vascular Remodeling in Experimental Hypertension

    Directory of Open Access Journals (Sweden)

    Norma R. Risler


    Full Text Available The basic hemodynamic abnormality in hypertension is an increased peripheral resistance that is due mainly to a decreased vascular lumen derived from structural changes in the small arteries wall, named (as a whole vascular remodeling. The vascular wall is an active, flexible, and integrated organ made up of cellular (endothelial cells, smooth muscle cells, adventitia cells, and fibroblasts and noncellular (extracellular matrix components, which in a dynamic way change shape or number, or reorganize in response to physiological and pathological stimuli, maintaining the integrity of the vessel wall in physiological conditions or participating in the vascular changes in cardiovascular diseases such as hypertension. Research focused on new signaling pathways and molecules that can participate in the mechanisms of vascular remodeling has provided evidence showing that vascular structure is not only affected by blood pressure, but also by mechanisms that are independent of the increased pressure. This review will provide an overview of the evidence, explaining some of the pathophysiologic mechanisms participating in the development of the vascular remodeling, in experimental models of hypertension, with special reference to the findings in spontaneously hypertensive rats as a model of essential hypertension, and in fructose-fed rats as a model of secondary hypertension, in the context of the metabolic syndrome. The understanding of the mechanisms producing the vascular alterations will allow the development of novel pharmacological tools for vascular protection in hypertensive disease.

  10. Teaching experimental design to biologists. (United States)

    Zolman, J F


    The teaching of research design and data analysis to our graduate students has been a persistent problem. A course is described in which students, early in their graduate training, obtain extensive practice in designing experiments and interpreting data. Lecture-discussions on the essentials of biostatistics are given, and then these essentials are repeatedly reviewed by illustrating their applications and misapplications in numerous research design problems. Students critique these designs and prepare similar problems for peer evaluation. In most problems the treatments are confounded by extraneous variables, proper controls may be absent, or data analysis may be incorrect. For each problem, students must decide whether the researchers' conclusions are valid and, if not, must identify a fatal experimental flaw. Students learn that an experiment is a well-conceived plan for data collection, analysis, and interpretation. They enjoy the interactive evaluations of research designs and appreciate the repetitive review of common flaws in different experiments. They also benefit from their practice in scientific writing and in critically evaluating their peers' designs.

  11. Experimental investigations of plasma bullets

    Energy Technology Data Exchange (ETDEWEB)

    Mericam-Bourdet, N; Laroussi, M; Begum, A; Karakas, E, E-mail: mlarouss@odu.ed [Laser and Plasma Engineering Institute, Old Dominion University, Norfolk, VA 23529 (United States)


    Recently several investigators reported on various means of generating cold plasma jets at atmospheric pressure. More interestingly, these jets turned out to be not continuous plasmas but trains of small high velocity plasma packets/bullets. However, until now little is known of the nature of these 'bullets'. Here we present experimental insights into the physical and chemical characteristics of bullets. We show that their time of initiation, their velocity and the distance they travel are directly dependent on the value of the applied voltage. We also show that these bullets can be controlled by the application of an external electric field. Using an intensified charge coupled device camera we report on their geometrical shape, which was revealed to be 'donut' shaped, therefore giving an indication that solitary surface ionization waves may be responsible for the creation of these bullets. In addition, using emission spectroscopy, we follow the evolution of various species along the trajectory of the bullets, in this way correlating the bullet propagation with the evolution of their chemical activity.

  12. Experimental evolution of bet hedging. (United States)

    Beaumont, Hubertus J E; Gallie, Jenna; Kost, Christian; Ferguson, Gayle C; Rainey, Paul B


    Bet hedging-stochastic switching between phenotypic states-is a canonical example of an evolutionary adaptation that facilitates persistence in the face of fluctuating environmental conditions. Although bet hedging is found in organisms ranging from bacteria to humans, direct evidence for an adaptive origin of this behaviour is lacking. Here we report the de novo evolution of bet hedging in experimental bacterial populations. Bacteria were subjected to an environment that continually favoured new phenotypic states. Initially, our regime drove the successive evolution of novel phenotypes by mutation and selection; however, in two (of 12) replicates this trend was broken by the evolution of bet-hedging genotypes that persisted because of rapid stochastic phenotype switching. Genome re-sequencing of one of these switching types revealed nine mutations that distinguished it from the ancestor. The final mutation was both necessary and sufficient for rapid phenotype switching; nonetheless, the evolution of bet hedging was contingent upon earlier mutations that altered the relative fitness effect of the final mutation. These findings capture the adaptive evolution of bet hedging in the simplest of organisms, and suggest that risk-spreading strategies may have been among the earliest evolutionary solutions to life in fluctuating environments.

  13. Characterisation of some experimental silicones. (United States)

    Parker, S; Meththananda, I; Braden, M; Pearson, G J


    Release of antimicrobials/antibacterials like chlorhexidine diacetate (CHD) has proved successful in inhibiting Candidal colonisation of silicone-based biomaterials. However, their addition will increase water uptake and may compromise the mechanical integrity. Two experimental silicones (S1 and S2) differing only in the surface treatment of the filler, were investigated. Ultimate tensile strength (UTS), % elongation at break (Eb), Shore A hardness and, when doped with 1% CHD, water uptake and CHD release were measured. Elastic modulus (E) was calculated from the hardness measurements. There was no significant difference in UTS and Eb between the two materials. However S1 had a higher hardness (30.6 +/- 0.97) and thus E (0.76 MPa) than S2 (hardness = 23.8 +/- 0.48, E = 0.45 MPa). Water uptake for S2 (0.6%) was higher than for S2 (0.1) and addition of CHD dramatically increased the uptake of both (S1 = 3.1%, S2 = 4.0%). Release of CHD was higher for S2 (30%) than S1 (27%). Equating osmotic pressure within the droplets with elastic restraining force gave an extension ratio of 1.95 for S1 and 5.39 for S2. Thus, addition of a hydrophilic agent can compromise the mechanical integrity of low modulus silicones.

  14. Compendium of Experimental Cetane Numbers

    Energy Technology Data Exchange (ETDEWEB)

    Yanowitz, J.; Ratcliff, M. A.; McCormick, R. L.; Taylor, J. D.; Murphy, M. J.


    This report is an updated version of the 2004 Compendium of Experimental Cetane Number Data and presents a compilation of measured cetane numbers for pure chemical compounds. It includes all available single compound cetane number data found in the scientific literature up until March 2014 as well as a number of unpublished values, most measured over the past decade at the National Renewable Energy Laboratory. This Compendium contains cetane values for 389 pure compounds, including 189 hydrocarbons and 201 oxygenates. More than 250 individual measurements are new to this version of the Compendium. For many compounds, numerous measurements are included, often collected by different researchers using different methods. Cetane number is a relative ranking of a fuel's autoignition characteristics for use in compression ignition engines; it is based on the amount of time between fuel injection and ignition, also known as ignition delay. The cetane number is typically measured either in a single-cylinder engine or a constant volume combustion chamber. Values in the previous Compendium derived from octane numbers have been removed, and replaced with a brief analysis of the correlation between cetane numbers and octane numbers. The discussion on the accuracy and precision of the most commonly used methods for measuring cetane has been expanded and the data has been annotated extensively to provide additional information that will help the reader judge the relative reliability of individual results.

  15. Experimental studies of magnetic perovskites (United States)

    Golovanov, Vladimir Valentinovich


    The present work addresses the phenomenon of Giant Magnetoresistance (GMR) and the role of Jahn-Teller distortion in the conduction mechanism of GMR materials. For this purpose, GMR and related perovskites are studied experimentally using infrared reflection spectroscopy, synchrotron x-ray diffraction, and electrical transport measurements. Reflectivity and x-ray diffraction studies of a vacancy doped rhombohedrally distorted GMR material, La0.936Mn0.982O3, indicate the presence of dynamic Jahn-Teller distortion above the magnetic ordering temperature (Tc = 225K) and a substantial reduction of the distortion below Tc. In particular, above Tc, the optical conductivity of large single crystals of the material shows the broad peak around 10,000 cm-1, which shifts towards zero frequency as the ferromagnetic state develops. The peak is attributed to the Jahn-Teller splitting of the two-fold degenerate eg level. Powder x-ray diffraction measurements performed on the same material reveal a sharp 3% reduction of the rhombohedral distortion at the magnetic ordering temperature. This reduction reflects the decrease in the magnitude of the dynamic Jahn-Teller distortion at the magnetic ordering. The transport and magnetic measurements on non Jahn-Teller active La1-xSrxCoO3 perovskites show much lower magnetoresistance, compatible with the conventional double-exchange theory. The relatively high values of magnetoresistance for low doped (x ≤ 0.15) compounds at low temperatures are also interpreted in terms of the double-exchange model.

  16. Experimental toxoplasmosis in pregnant rabbits/ Toxoplasmose experimental em coelhas gestantes

    Directory of Open Access Journals (Sweden)

    Alvimar José da Costa


    Full Text Available The clinical, hematological, obstetrical, immunological and pathological aspects of the experimental toxoplasmosis were investigated in pregnant rabbits orally inoculated with Toxoplasma gondii oocysts. Pregnant rabbits showed to be highly sensible to the toxoplasmic infection. Abortion and death occurred in 100% of the inoculated rabbits. Fever peak was observed between 4o and 9o day pos-infection. Blood parameter showed alterations. Because the hyperacute character presented by the toxoplasmic infection, the humoral immune response was weak. The microscopic and macroscopic exams demonstrated, mainly, alterations in liver, kidney and lungs. These results suggested that pregnant rabbits, orally infected with oocysts of T. gondii are extremely susceptible to this parasite, showing severe alterations in several organs, as well as premature abortion and death.Neste ensaio foram comparados aspectos clínicos, obstétricos, imunológicos e patológicos entre coelhas gestantes inoculadas com oocistos de Toxoplasma gondii e coelhas gestantes não inoculadas. Os resultados obtidos demonstram ser a coelha gestante altamente sensível à infecção toxoplásmica. Aborto e óbito foram observados em 100% das coelhas infectadas, antes do término da gestação. Os aumentos máximos de temperatura corporal foram observados entre o quarto e o nono dia pós-inoculação (DPI. Alterações hematológicas também foram observadas. Devido ao caráter hiperagudo decorrente da infecção toxoplásmica, detectou-se resposta imune humoral nas coelhas infectadas somente no 7o DPI. Os exames anátomo-histopatológicos demonstraram, principalmente, alterações hepáticas, renais e pulmonares. Com base nos dados obtidos no estudo, comprovou-se que coelhas gestantes são extremamente sensíveis a oocistos de T. gondii, apresentando severas alterações em diversos órgãos, assim como aborto e óbito prematuro.

  17. Erythropoietin attenuates pulmonary vascular remodeling in experimental pulmonary arterial hypertension through interplay between endothelial progenitor cells and heme-oxygenase

    Directory of Open Access Journals (Sweden)

    Rosa L.E. Loon


    Full Text Available BackgroundPulmonary arterial hypertension (PAH is a pulmonary vascular disease with a high mortality, characterized by typical angio-proliferative lesions. Erythropoietin (EPO attenuates pulmonary vascular remodeling in PAH. We postulated that EPO acts through mobilization of endothelial progenitor cells (EPCs and activation of the cytoprotective enzyme heme oxygenase-1 (HO1.MethodsRats with flow-associated PAH, resembling pediatric PAH, were treated with HO-1 inducer EPO in the presence or absence of the selective HO-activity-inhibitor tin-mesoporphyrin (SnMP. HO-activity, circulating EPCs and pulmonary vascular lesions were assessed after 3 weeks.ResultsIn PAH-rats, circulating EPCs were decreased and HO-activity was increased compared to control. EPO-treatment restored circulating EPCs and improved pulmonary vascular remodeling, as shown by a reduced wall thickness and occlusion rate of the intra-acinar vessels. Inhibition of HO-activity with SnMP aggravated PAH. Moreover, SnMP treatment abrogated EPO-induced amelioration of pulmonary vascular remodeling, while surprisingly further increasing circulating EPCs as compared with EPO alone.ConclusionsIn experimental PAH, EPO treatment restored the number of circulating EPC’s to control level, improved pulmonary vascular remodeling, and showed important interplay with HO-activity. Inhibition of increased HO-activity in PAH-rats exacerbated progression of pulmonary vascular remodeling, despite the presence of restored numbers of circulating EPC’s. We suggest that both EPO-induced HO1 and EPCs are promising targets to ameliorate the pulmonary vasculature in PAH.

  18. Protective Role of Cyclooxygenase (COX)-2 in Experimental Lung Injury: Evidence of a Lipoxin A(4)-Mediated Effect.

    LENUS (Irish Health Repository)


    BACKGROUND: Polymorphoneutrophils (PMNs) are activated by inflammatory mediators following splanchnic ischemia\\/reperfusion (I\\/R), potentially injuring organs such as the lung. As a result, some patients develop respiratory failure following abdominal aortic aneurysm repair. Pulmonary cyclooxygenase (COX)-2 protects against acid aspiration and bacterial instillation via lipoxins, a family of potent anti-inflammatory lipid mediators. We explored the role of COX-2 and lipoxin A(4) in experimental I\\/R-mediated lung injury. MATERIALS AND METHODS: Sprague-Dawley rats were assigned to one of the following five groups: (1) controls; (2) aortic cross-clamping for 45 min and reperfusion for 4 h (I\\/R group); (3) I\\/R and SC236, a selective COX-2 inhibitor; (4) I\\/R and aspirin; and (5) I\\/R and iloprost, a prostacyclin (PGI(2)) analogue. Lung injury was assessed by wet\\/dry ratio, myeloperoxidase (MPO) activity, and bronchoalveolar lavage (BAL) neutrophil counts. BAL levels of thromboxane, PGE(2), 6-keto-PGF(1)alpha (a hydrolysis product of prostacyclin), lipoxin A(4), and 15-epi-lipoxin A(4) were analyzed by enzyme immunoassay (EIA). Immunostaining for COX-2 was performed. RESULTS: I\\/R significantly increased tissue MPO, the wet\\/dry lung ratio, and neutrophil counts. These measures were significantly further aggravated by SC236 and improved by iloprost. I\\/R increased COX-2 immunostaining and both PGE(2) and 6-keto-PGF(1alpha) levels in BAL. SC236 markedly reduced these prostanoids and lipoxin A(4) compared with I\\/R alone. Iloprost markedly increased lipoxin A(4) levels. The deleterious effect of SC236 and the beneficial effect of iloprost was associated with a reduction and an increase, respectively, in lipoxin A(4) levels. CONCLUSIONS: Lipoxin A(4) warrants further evaluation as a mediator of COX-2 regulated lung protection.

  19. Magnetic Launch Assist Experimental Track (United States)


    In this photograph, a futuristic spacecraft model sits atop a carrier on the Magnetic Launch Assist System, formerly known as the Magnetic Levitation (MagLev) System, experimental track at the Marshall Space Flight Center (MSFC). Engineers at MSFC have developed and tested Magnetic Launch Assist technologies that would use magnetic fields to levitate and accelerate a vehicle along a track at very high speeds. Similar to high-speed trains and roller coasters that use high-strength magnets to lift and propel a vehicle a couple of inches above a guideway, a Magnetic Launch Assist system would electromagnetically drive a space vehicle along the track. A full-scale, operational track would be about 1.5-miles long and capable of accelerating a vehicle to 600 mph in 9.5 seconds. This track is an advanced linear induction motor. Induction motors are common in fans, power drills, and sewing machines. Instead of spinning in a circular motion to turn a shaft or gears, a linear induction motor produces thrust in a straight line. Mounted on concrete pedestals, the track is 100-feet long, about 2-feet wide, and about 1.5-feet high. The major advantages of launch assist for NASA launch vehicles is that it reduces the weight of the take-off, the landing gear, the wing size, and less propellant resulting in significant cost savings. The US Navy and the British MOD (Ministry of Defense) are planning to use magnetic launch assist for their next generation aircraft carriers as the aircraft launch system. The US Army is considering using this technology for launching target drones for anti-aircraft training.

  20. Macrophage plasticity in experimental atherosclerosis.

    Directory of Open Access Journals (Sweden)

    Jamila Khallou-Laschet

    Full Text Available As in human disease, macrophages (MØ are central players in the development and progression of experimental atherosclerosis. In this study we have evaluated the phenotype of MØ associated with progression of atherosclerosis in the apolipoprotein E (ApoE knockout (KO mouse model.We found that bone marrow-derived MØ submitted to M1 and M2 polarization specifically expressed arginase (Arg II and Arg I, respectively. This distinct arginase expression was used to evaluate the frequency and distribution of M1 and M2 MØ in cross-sections of atherosclerotic plaques of ApoE KO mice. Early lesions were infiltrated by Arg I(+ (M2 MØ. This type of MØ favored the proliferation of smooth muscle cells, in vitro. Arg II(+ (M1 MØ appeared and prevailed in lesions of aged ApoE KO mice and lesion progression was correlated with the dominance of M1 over the M2 MØ phenotype. In order to address whether the M2->M1 switch could be due to a phenotypic switch of the infiltrated cells, we performed in vitro repolarization experiments. We found that fully polarized MØ retained their plasticity since they could revert their phenotype. The analysis of the distribution of Arg I- and Arg II-expressing MØ also argued against a recent recruitment of M1 MØ in the lesion. The combined data therefore suggest that the M2->M1 switch observed in vivo is due to a conversion of cells already present in the lesion. Our study suggests that interventional tools able to revert the MØ infiltrate towards the M2 phenotype may exert an atheroprotective action.

  1. Compendium of Experimental Cetane Numbers

    Energy Technology Data Exchange (ETDEWEB)

    Yanowitz, Janet [Ecoengineering, Sharonville, OH (United States); Ratcliff, Matthew A. [National Renewable Energy Lab. (NREL), Golden, CO (United States); McCormick, Robert L. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Taylor, J. D. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Murphy, M. J. [Battelle, Columbus, OH (United States)


    This report is an updated version of the 2014 Compendium of Experimental Cetane Number Data and presents a compilation of measured cetane numbers for pure chemical compounds. It includes all available single-compound cetane number data found in the scientific literature up until December 2016 as well as a number of previously unpublished values, most measured over the past decade at the National Renewable Energy Laboratory. This version of the compendium contains cetane values for 496 pure compounds, including 204 hydrocarbons and 292 oxygenates. 176 individual measurements are new to this version of the compendium, all of them collected using ASTM Method D6890, which utilizes an Ignition Quality Tester (IQT) a type of constant-volume combustion chamber. For many compounds, numerous measurements are included, often collected by different researchers using different methods. The text of this document is unchanged from the 2014 version, except for the numbers of compounds in Section 3.1, the Appendices, Table 1. Primary Cetane Number Data Sources and Table 2. Number of Measurements Included in Compendium. Cetane number is a relative ranking of a fuel's autoignition characteristics for use in compression ignition engines. It is based on the amount of time between fuel injection and ignition, also known as ignition delay. The cetane number is typically measured either in a single-cylinder engine or a constant-volume combustion chamber. Values in the previous compendium derived from octane numbers have been removed and replaced with a brief analysis of the correlation between cetane numbers and octane numbers. The discussion on the accuracy and precision of the most commonly used methods for measuring cetane number has been expanded, and the data have been annotated extensively to provide additional information that will help the reader judge the relative reliability of individual results.

  2. Epistemological Dizziness in the Psychology Laboratory: Lively Subjects, Anxious Experimenters, and Experimental Relations, 1950-1970. (United States)

    Morawski, Jill


    Since the demise of introspective techniques in the early twentieth century, experimental psychology has largely assumed an administrative arrangement between experimenters and subjects wherein subjects respond to experimenters' instructions and experimenters meticulously constrain that relationship through experimental controls. During the postwar era this standard arrangement came to be questioned, initiating reflections that resonated with Cold War anxieties about the nature of the subjects and the experimenters alike. Albeit relatively short lived, these interrogations of laboratory relationships gave rise to unconventional testimonies and critiques of experimental method and epistemology. Researchers voiced serious concerns about the honesty and normality of subjects, the politics of the laboratory, and their own experimental conduct. Their reflective commentaries record the intimacy of subject and experimenter relations and the plentiful cultural materials that constituted the experimental situation, revealing the permeable boundaries between laboratory and everyday life.

  3. Nitric oxide-releasing aspirin but not conventional aspirin improves healing of experimental colitis

    Institute of Scientific and Technical Information of China (English)

    Malgorzata Zwolinska-Wcislo; Tomasz Brzozowski; Agata Ptak-Belowska; Aneta Targosz; Katarzyna Urbanczyk; Slawomir Kwiecien; Zbigniew Sliwowski


    AIM: To determine the eff ect of non-selective cyclooxygenase (COX) inhibitors, selective COX-2 inhibitors and nitric oxide (NO)-releasing aspirin in the healing of ulcerative colitis. METHODS: Rats with 2,4,6 trinitrobenzenesulfonic acid (TNBS)-induced colitis received intragastric (ig) treatment with vehicle, aspirin (ASA) (a nonselective COX inhibitor), celecoxib (a selective COX-2 inhibitor) or NO-releasing ASA for a period of ten days. The area of colonic lesions, colonic blood flow (CBF), myeloperoxidase (MPO) activity and expression of proinflammatory markers COX-2, inducible form of nitric oxide synthase (iNOS), IL-1β and tumor necrosis factor (TNF)-α were assessed. The eff ects of glyceryl trinitrate (GTN), a NO donor, and 2-(4-carboxyphenyl)-4,5-dihydro-4,4,5,5- tetramethyl-1H-imidazolyl-1-oxy-3-oxide, onopotassium salt (carboxy-PTIO), a NO scavenger, administered without and with ASA or NO-ASA, and the involvement of capsaicin-sensitive aff erent nerves in the mechanism of healing the experimental colitis was also determined. RESULTS: Rats with colitis developed macroscopic and microscopic colonic lesions accompanied by a significant decrease in the CBF, a significant rise in colonic weight, MPO activity and plasma IL.1β and TNF-α levels. These eff ects were aggravated by ASA and 5-(4-chlorophenyl)-1-(4-methoxyphenyl)- 3-(trifluoromethyl)-1H-pyrazole (SC-560), but not celecoxib and counteracted by concurrent treatment with a synthetic prostaglandin E2 (PGE2) analog. Treatment with NO-ASA dose-dependently accelerated colonic healing followed by a rise in plasma NOx content and CBF, suppression of MPO and downregulation of COX-2, iNOS, IL-1β and TNF-α mRNAs. Treatment with GTN, the NO donor, significantly inhibited the ASA-induced colonic lesions and increased CBF, while carboxy-PTIO or capsaicin-denervation counteracted the NO-ASAinduced improvement of colonic healing and the accompanying increase in the CBF. These eff ects were restored by co

  4. Experimental generation of volcanic lightning (United States)

    Cimarelli, Corrado; Alatorre-Ibargüengoitia, Miguel; Kueppers, Ulrich; Scheu, Bettina; Dingwell, Donald B.


    the plume that emerge as the key variables in volcanic lightning generation. A proportionality between fine ash content of the jet and number of lightning strikes is also evident in our experiments. This first recorded experimental generation of volcanic lightning means that rapid progress can now be expected (under controlled laboratory conditions) in understanding electrical phenomena produced during explosive volcanic eruptions. This in turn may aid the development of lightning monitoring systems for the forecasting of volcanic ash emissions into the atmosphere. Furthermore, our experiments are significant for the investigation of self-charging mechanism of particles that are relevant for atmospheric phenomena (such as dust storms) on Earth and other planetary bodies.

  5. Experimental toxoplasmosis in broiler chicks. (United States)

    Kaneto, C N; Costa, A J; Paulillo, A C; Moraes, F R; Murakami, T O; Meireles, M V


    To evaluate chicken toxoplasmosis both as an economic and a public health subject, 84 broiler chicks of a commercial strain, 30 days old, were distributed into seven groups of 12 birds (three replications of four chicks) experimentally infected with three developing T. gondii stages of the P strain as follows: tachyzoites, intravenous (two groups: 5.0 x 10(5) and 5.0 x 10(6)), cysts, per os (two groups: 1.0 x 10(2) and 1.0 x 10(3)) and oocysts, per os (three groups: 5.0 x 10(2), 5.0 x 10(3) and 5.0 x 10(4)). Twelve chicks received only a placebo (control group). During the next 30 days the following parameters were estimated: productivity (weight gain and feed conversion), clinical signs, including rectal temperature and parasitemia (bioassay). No clinical signs suggesting toxoplasmosis were seen and no statistical differences on productivity standards were found in comparison between inoculated and control chicks. However, fowls inoculated with tachyzoites and oocysts occasionally showed hyperthermia. Some haematological changes were detected in fowls inoculated with T. gondii. Anatomo-histopathological changes were not observed. From 14 parasitemias detected, 35.7% appeared on the 5th day after inoculation and 57.1% of them resulted from oocysts inoculation. After 30-35 days all birds were slaughtered: fragments from 12 organs or tissues from each of them were subjected to artificial peptic digestion and after that injected into T. gondii antibody-free mice (IIFR). T. gondii was detected in brain (12), pancreas (five), spleen (five), retina (five), kidney (two), heart (four), proventriculus (three), liver (two), intestine (two), lung (one), and skeletal muscle (one). Similar to observations with parasitemia, from 42 T. gondii isolations, 59.5% came from chicks which had received oocysts. It can thus be inferred that the developing form, expelled by cats, is the most important for T. gondii chicken infection and that brain is the most infected organ in birds

  6. Lipid metabolism in experimental animals

    Directory of Open Access Journals (Sweden)

    Sánchez-Muñiz, Francisco J.


    Full Text Available Publications are scarce in the way in chich metabolic processes are affected by the ingestion of heated fats used to prepare food. Similarly studies measuring metabolic effects of the consumption on fried food are poorly known. The purpose of this presentation is to summarize information on frying fats and frying foods upon lipid metabolism in experimental animals. Food consumption is equivalent or even higher when oils or the fat content of frying foods are poorly alterated decreasing their acceptability when their alteration degree increase. After 4hr. experiment the digestibility and absorption coefficients of a single dosis of thermooxidized oils were significantly decreased in rats, however the digestive utilization of frying thermooxidized oils included in diets showed very little change in comparison with unused oils by feeding trials on rats. Feeding rats different frying fats induced a slight hypercholesterolemic effect being the magnitude of this effect related to the linoleic decrease in diet produced by frying. However HDL, the main rat-cholesterol carrier, also increased, thus the serum cholesterol/HDL-cholesterol ratio did not change. Results suggest that rats fed frying fats adapt their lipoprotein metabolism increasing the number of HDL particles. Deep fat frying deeply changed the fatty acid composition of foods, being possible to increase their n-9 or n-6 fatty acid and to decrease the saturated fatty acid contents by frying. When olive oil-and sunflower oil-fried sardines were used as the only protein and fat sources of rats-diets in order to prevent the dietary hypercholesterolemia it was provided that both fried-sardine diets showed a powerful check effect on the cholesterol raising effect induced by dietary cholesterol. The negative effect of feeding rats cholesterol plus bovine bile to induce hypercholesterolemia on some cell-damage markers such as lactate dehydrogenase, transaminases, alkaline phosphatase, was

  7. The Automation of the Transonic Experimental Facility (TEF) and the Aerodynamic Experimental Facility (AEF) (United States)


    ARL-TR-7506 ● OCT 2015 US Army Research Laboratory The Automation of the Transonic Experimental Facility (TEF) and the...Laboratory The Automation of the Transonic Experimental Facility (TEF) and the Aerodynamic Experimental Facility (AEF) by Charith R Ranawake Weapons...To) 05/2015–08/2015 4. TITLE AND SUBTITLE The Automation of the Transonic Experimental Facility (TEF) and the Aerodynamic Experimental Facility

  8. 2016 International Symposium on Experimental Robotics

    CERN Document Server

    Nakamura, Yoshihiko; Khatib, Oussama; Venture, Gentiane


    Experimental Robotics XV is the collection of papers presented at the International Symposium on Experimental Robotics, Roppongi, Tokyo, Japan on October 3-6, 2016. 73 scientific papers were selected and presented after peer review. The papers span a broad range of sub-fields in robotics including aerial robots, mobile robots, actuation, grasping, manipulation, planning and control and human-robot interaction, but shared cutting-edge approaches and paradigms to experimental robotics. The readers will find a breadth of new directions of experimental robotics. The International Symposium on Experimental Robotics is a series of bi-annual symposia sponsored by the International Foundation of Robotics Research, whose goal is to provide a forum dedicated to experimental robotics research. Robotics has been widening its scientific scope, deepening its methodologies and expanding its applications. However, the significance of experiments remains and will remain at the center of the discipline. The ISER gatherings are...

  9. Establishment for quality control of experimental animal

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Tae Hwan; Kim, Soo Kwan; Kim, Tae Kyoung


    Until now, because we have imported experimental animal from foreign experimental animal corporation, we could have saved money by establishing the quality control of animal in barrier system. In order to improve the quality of animal experiment and efficiency of biomedical study, it is indispensable to control many factors that effect in the experiment. Therefore, it is essential to organize the system of laboratory animal care for enhancing reliability and revivability of experimental results. The purpose of the present investigation was to establish the quality control system of experimental animals that we can provide good quality animals according to the experimental condition of each investigator although the exact quality control system to estimate the infection of bacteria and virus easily remains ill-defined yet. Accordingly, we established the useful quality control system for microbiologic monitoring and environmental monitoring to protect experimental animal from harmful bacteria and virus.

  10. 黄褐斑病因、加重因素及对生活质量影响的横断面研究%Etiology and aggravating factors of melasma and its influence on quality of life: a cross-sectional study

    Institute of Scientific and Technical Information of China (English)

    王辉; 郭丽芳; 葛一平; 吴余乐; 吴秋菊; 张孟丽; 王千秋; 林彤


    Objective To investigate the etiology,aggravating factors of melasma and its influence on quality of life in patients.Methods Demographic,behavioral and clinical data were collected from 166 female patients with melasma through a questionnaire survey.Melasma area severity index (MASI),dermatology life quality index (DLQI) and melasma quality of life scale (MELA-SQOL) were calculated.Multiple linear regression analysis was carried out to identify factors influencing melasma severity and quality of life in patients.Results Of the 166 patients,55 (33.13%) had a history of pregnancy within 1 year before the occurrence of melasma,and 8 (4.82%) had a history of sun exposure within 1 month before it.The MASI,DLQI and MELA-SQOL scores were 5.99 ± 4.01,4.34 ± 4.41 and 30.54 ± 17.91 in these patients respectively.Multiple linear regression analysis showed that the MELA-SQOL score significantly decreased with age (β =-0.220,t =2.874,P< 0.05),but increased with deepening of skin color (β =0.217,t =2.827,P< 0.05).Moreover,the MASI score significantly increased with age among premenopausal patients with melasma (β =0.244,t =3.387,P =0.001),and higher in patients with Fitzpatrick skin type Ⅳ than in those with Fitzpatrick skin type Ⅲ (β =0.322,t =4.615,P < 0.001).Conclusions The occurrence of melasma is associated with fluctuation of hormone levels and sun exposure.The darker the lesion color and the younger the age,the greater the impact on the quality of life in patients with melasma.Melasma is more severe in patients with Fitzpatrick skin type Ⅳ than in those with Fitzpatrick skin type Ⅲ,and seems to exacerbate with age among premenopausal patients.%目的 研究黄褐斑患者的病因、加重因素及对生活质量的影响.方法 通过问卷形式收集166例女性黄褐斑患者的人口学资料、行为学资料、临床资料,并计算黄褐斑面积及严重程度评分(MASI)、皮肤病生活质量评分(DLQI)、黄褐斑生活质量评

  11. Experimental investigations on dry stone masonry walls



    Brick unreinforced masonry walls have been widely studied both from experimental and numerical point of view, but scarce experimental information is available for dry stone masonry walls that constitute the material more frequently used in the construction of ancient historical constructions. Therefore, the present work aims at increasing the insight about the behavior of typical ancient masonry walls under cyclic loading. To attain such goal, different experimental approaches are consi...

  12. Experimental effects of exposure to pornography

    DEFF Research Database (Denmark)

    Hald, Gert Martin; Malamuth, Neil N


    Using a randomly selected community sample of 200 Danish young adult men and women in a randomized experimental design, the study investigated the effects of a personality trait (agreeableness), past pornography consumption, and experimental exposure to non-violent pornography on attitudes...... supporting violence against women (ASV). We found that lower levels of agreeableness and higher levels of past pornography consumption significantly predicted ASV. In addition, experimental exposure to pornography increased ASV but only among men low in agreeableness. This relationship was found...

  13. Experimental investigation of new neutron moderator materials

    Energy Technology Data Exchange (ETDEWEB)

    Mocko, Michal [Los Alamos National Laboratory; Daemen, Luke L [Los Alamos National Laboratory; Hartl, Monika [Los Alamos National Laboratory; Huegle, Thomas [Los Alamos National Laboratory; Muhrer, Guenter [Los Alamos National Laboratory


    In this study we present experimental investigation of thermal neutron energy spectra produced by lead and bismuth hydroxides (Pb(OH){sub 2}, and Bi(OH){sub 3}). The experimental energy spectra are compared with a thermal neutron energy spectrum of water measured in the same geometry. We present an MCNPX geometry model used to help with the experimental data interpretation. We demonstrate a very good reproduction of the experimental thermal neutron energy spectrum produced by the water moderator. We show a sensitivity study with the Pb(OH){sub 2}, and Bi(OH){sub 3} materials on different combinations of thermal neutron scattering kernels.

  14. Online Experimentation in Education and Training

    Directory of Open Access Journals (Sweden)

    Maria Teresa Restivo


    Full Text Available The increasing use of emergent technologies in industry, medicine, research, training and education attests to the relevance of their integration in teaching/learning approaches. Online experimentation comprises remote and virtual experimentation also supported and complemented by other online tools that incorporate necessarily the use of emergent technologies. The present work synthesizes the final outcomes of a project aiming to develop, use and disseminate Online Experimentation, funded by the Calouste Gulbenkian Foundation. Some application examples are given to illustrate the use of online experimentation on different contexts, such as secondary and higher education (STEM, lifelong learning or industrial training.

  15. Quasi experimental designs in pharmacist intervention research. (United States)

    Krass, Ines


    Background In the field of pharmacist intervention research it is often difficult to conform to the rigorous requirements of the "true experimental" models, especially the requirement of randomization. When randomization is not feasible, a practice based researcher can choose from a range of "quasi-experimental designs" i.e., non-randomised and at time non controlled. Objective The aim of this article was to provide an overview of quasi-experimental designs, discuss their strengths and weaknesses and to investigate their application in pharmacist intervention research over the previous decade. Results In the literature quasi experimental studies may be classified into five broad categories: quasi-experimental design without control groups; quasi-experimental design that use control groups with no pre-test; quasi-experimental design that use control groups and pre-tests; interrupted time series and stepped wedge designs. Quasi-experimental study design has consistently featured in the evolution of pharmacist intervention research. The most commonly applied of all quasi experimental designs in the practice based research literature are the one group pre-post-test design and the non-equivalent control group design i.e., (untreated control group with dependent pre-tests and post-tests) and have been used to test the impact of pharmacist interventions in general medications management as well as in specific disease states. Conclusion Quasi experimental studies have a role to play as proof of concept, in the pilot phases of interventions when testing different intervention components, especially in complex interventions. They serve to develop an understanding of possible intervention effects: while in isolation they yield weak evidence of clinical efficacy, taken collectively, they help build a body of evidence in support of the value of pharmacist interventions across different practice settings and countries. However, when a traditional RCT is not feasible for

  16. New model systems for experimental evolution. (United States)

    Collins, Sinéad


    Microbial experimental evolution uses a few well-characterized model systems to answer fundamental questions about how evolution works. This special section highlights novel model systems for experimental evolution, with a focus on marine model systems that can be used to understand evolutionary responses to global change in the oceans.

  17. ISABELLE. Volume 3. Experimental areas, large detectors

    Energy Technology Data Exchange (ETDEWEB)


    This section presents the papers which resulted from work in the Experimental Areas portion of the Workshop. The immediate task of the group was to address three topics. The topics were dictated by the present state of ISABELLE experimental areas construction, the possibility of a phased ISABELLE and trends in physics and detectors.

  18. Experimental results on the Pygmy Dipole Resonance

    Directory of Open Access Journals (Sweden)

    Savran Deniz


    Full Text Available The so-called Pygmy Dipole Resonance, an additional structure of low-lying electric dipole strength, has attracted strong interest in the last years. Different experimental approaches have been used in the last decade in order to investigate this new interesting nuclear excitation mode. In this contribution an overview on the available experimental data is given.

  19. The Experimental Design Ability Test (EDAT) (United States)

    Sirum, Karen; Humburg, Jennifer


    Higher education goals include helping students develop evidence based reasoning skills; therefore, scientific thinking skills such as those required to understand the design of a basic experiment are important. The Experimental Design Ability Test (EDAT) measures students' understanding of the criteria for good experimental design through their…

  20. Quasi-Experimental Designs for Causal Inference (United States)

    Kim, Yongnam; Steiner, Peter


    When randomized experiments are infeasible, quasi-experimental designs can be exploited to evaluate causal treatment effects. The strongest quasi-experimental designs for causal inference are regression discontinuity designs, instrumental variable designs, matching and propensity score designs, and comparative interrupted time series designs. This…

  1. Experimental design and priority PLS regression

    DEFF Research Database (Denmark)

    Høskuldsson, Agnar


    Rules, ideas and algorithms of the H-principle are used to analyse models that are derived from experimental design. Some of the basic ideas of experimental design are reviewed and related to the methodology of the H-principle. New methods of optimal response surfaces are developed....

  2. Valuable lessons-learned in transcriptomics experimentation. (United States)

    Bruning, Oskar; Rauwerda, Han; Dekker, Rob J; de Leeuw, Wim C; Wackers, Paul F K; Ensink, Wim A; Jonker, Martijs J; Breit, Timo M


    We have collected several valuable lessons that will help improve transcriptomics experimentation. These lessons relate to experiment design, execution, and analysis. The cautions, but also the pointers, may help biologists avoid common pitfalls in transcriptomics experimentation and achieve better results with their transcriptome studies.

  3. Nuclear symmetry energy: An experimental overview

    Indian Academy of Sciences (India)

    D V Shetty; S J Yennello


    The nuclear symmetry energy is a fundamental quantity important for studying the structure of systems as diverse as the atomic nucleus and the neutron star. Considerable efforts are being made to experimentally extract the symmetry energy and its dependence on nuclear density and temperature. In this article, the experimental studies carried out up-to-date and their current status are reviewed.

  4. Experimental Confirmation of a Modified Lorenz System

    Institute of Scientific and Technical Information of China (English)

    LIU Ling; LIU Chong-Xin; ZHANG Yan-Bin


    We experimentally demonstrate the butterfly-shaped chaotic attractor we have proposed before [Int. J. Nonlin.Sci. Numerical Simulation 7 (2006) 187]. Some basic dynamical properties and chaotic behaviour of this new butterfly attractor are studied and they are in agreement with the results of our theoretical analysis. Moreover,the proposed system is experimental demonstrated.

  5. 27 CFR 24.77 - Experimental wine. (United States)


    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Experimental wine. 24.77... OF THE TREASURY LIQUORS WINE Administrative and Miscellaneous Provisions Tax Exempt Wine § 24.77 Experimental wine. (a) General. Any scientific university, college of learning, or institution of...

  6. Cell Culture Microfluidic Biochips: Experimental Throughput Maximization

    DEFF Research Database (Denmark)

    Minhass, Wajid Hassan; Pop, Paul; Madsen, Jan


    Microfluidic biochips offer a promising alternative to a conventional biochemical laboratory, integrating all necessary functionalities on-chip in order to perform biochemical applications. Researchers have started to propose computer-aided design tools for the synthesis of such biochips. Our focus...... metaheuristic for experimental design generation for the cell culture microfluidic biochips, and we have evaluated our approach using multiple experimental setups....

  7. Mainstreaming Caenorhabditis elegans in experimental evolution. (United States)

    Gray, Jeremy C; Cutter, Asher D


    Experimental evolution provides a powerful manipulative tool for probing evolutionary process and mechanism. As this approach to hypothesis testing has taken purchase in biology, so too has the number of experimental systems that use it, each with its own unique strengths and weaknesses. The depth of biological knowledge about Caenorhabditis nematodes, combined with their laboratory tractability, positions them well for exploiting experimental evolution in animal systems to understand deep questions in evolution and ecology, as well as in molecular genetics and systems biology. To date, Caenorhabditis elegans and related species have proved themselves in experimental evolution studies of the process of mutation, host-pathogen coevolution, mating system evolution and life-history theory. Yet these organisms are not broadly recognized for their utility for evolution experiments and remain underexploited. Here, we outline this experimental evolution work undertaken so far in Caenorhabditis, detail simple methodological tricks that can be exploited and identify research areas that are ripe for future discovery.

  8. Experimental Monte Carlo Quantum Process Certification

    CERN Document Server

    Steffen, L; Fedorov, A; Baur, M; Wallraff, A


    Experimental implementations of quantum information processing have now reached a level of sophistication where quantum process tomography is impractical. The number of experimental settings as well as the computational cost of the data post-processing now translates to days of effort to characterize even experiments with as few as 8 qubits. Recently a more practical approach to determine the fidelity of an experimental quantum process has been proposed, where the experimental data is compared directly to an ideal process using Monte Carlo sampling. Here we present an experimental implementation of this scheme in a circuit quantum electrodynamics setup to determine the fidelity of two qubit gates, such as the cphase and the cnot gate, and three qubit gates, such as the Toffoli gate and two sequential cphase gates.

  9. Quantum Experimental Data in Psychology and Economics

    CERN Document Server

    Aerts, Diederik; Haven, Emmanuel


    We prove a theorem which shows that a collection of experimental data of probabilistic weights related to decisions with respect to situations and their disjunction cannot be modeled within a classical probabilistic weight structure in case the experimental data contain the effect referred to as the 'disjunction effect' in psychology. We identify different experimental situations in psychology, more specifically in concept theory and in decision theory, and in economics (namely situations where Savage's Sure-Thing Principle is violated) where the disjunction effect appears and we point out the common nature of the effect. We analyze how our theorem constitutes a no-go theorem for classical probabilistic weight structures for common experimental data when the disjunction effect is affecting the values of these data. We put forward a simple geometric criterion that reveals the non classicality of the considered probabilistic weights and we illustrate our geometrical criterion by means of experimentally measured...

  10. Experimental model updating using frequency response functions (United States)

    Hong, Yu; Liu, Xi; Dong, Xinjun; Wang, Yang; Pu, Qianhui


    In order to obtain a finite element (FE) model that can more accurately describe structural behaviors, experimental data measured from the actual structure can be used to update the FE model. The process is known as FE model updating. In this paper, a frequency response function (FRF)-based model updating approach is presented. The approach attempts to minimize the difference between analytical and experimental FRFs, while the experimental FRFs are calculated using simultaneously measured dynamic excitation and corresponding structural responses. In this study, the FRF-based model updating method is validated through laboratory experiments on a four-story shear-frame structure. To obtain the experimental FRFs, shake table tests and impact hammer tests are performed. The FRF-based model updating method is shown to successfully update the stiffness, mass and damping parameters of the four-story structure, so that the analytical and experimental FRFs match well with each other.

  11. Optimal Bayesian Experimental Design for Combustion Kinetics

    KAUST Repository

    Huan, Xun


    Experimental diagnostics play an essential role in the development and refinement of chemical kinetic models, whether for the combustion of common complex hydrocarbons or of emerging alternative fuels. Questions of experimental design—e.g., which variables or species to interrogate, at what resolution and under what conditions—are extremely important in this context, particularly when experimental resources are limited. This paper attempts to answer such questions in a rigorous and systematic way. We propose a Bayesian framework for optimal experimental design with nonlinear simulation-based models. While the framework is broadly applicable, we use it to infer rate parameters in a combustion system with detailed kinetics. The framework introduces a utility function that reflects the expected information gain from a particular experiment. Straightforward evaluation (and maximization) of this utility function requires Monte Carlo sampling, which is infeasible with computationally intensive models. Instead, we construct a polynomial surrogate for the dependence of experimental observables on model parameters and design conditions, with the help of dimension-adaptive sparse quadrature. Results demonstrate the efficiency and accuracy of the surrogate, as well as the considerable effectiveness of the experimental design framework in choosing informative experimental conditions.

  12. Considering RNAi experimental design in parasitic helminths. (United States)

    Dalzell, Johnathan J; Warnock, Neil D; McVeigh, Paul; Marks, Nikki J; Mousley, Angela; Atkinson, Louise; Maule, Aaron G


    Almost a decade has passed since the first report of RNA interference (RNAi) in a parasitic helminth. Whilst much progress has been made with RNAi informing gene function studies in disparate nematode and flatworm parasites, substantial and seemingly prohibitive difficulties have been encountered in some species, hindering progress. An appraisal of current practices, trends and ideals of RNAi experimental design in parasitic helminths is both timely and necessary for a number of reasons: firstly, the increasing availability of parasitic helminth genome/transcriptome resources means there is a growing need for gene function tools such as RNAi; secondly, fundamental differences and unique challenges exist for parasite species which do not apply to model organisms; thirdly, the inherent variation in experimental design, and reported difficulties with reproducibility undermine confidence. Ideally, RNAi studies of gene function should adopt standardised experimental design to aid reproducibility, interpretation and comparative analyses. Although the huge variations in parasite biology and experimental endpoints make RNAi experimental design standardization difficult or impractical, we must strive to validate RNAi experimentation in helminth parasites. To aid this process we identify multiple approaches to RNAi experimental validation and highlight those which we deem to be critical for gene function studies in helminth parasites.

  13. Physical and Mathematical Modeling in Experimental Papers. (United States)

    Möbius, Wolfram; Laan, Liedewij


    An increasing number of publications include modeling. Often, such studies help us to gain a deeper insight into the phenomena studied and break down barriers between experimental and theoretical communities. However, combining experimental and theoretical work is challenging for authors, reviewers, and readers. To help maximize the usefulness and impact of combined theoretical and experimental research, this Primer describes the purpose, usefulness, and different types of models and addresses the practical aspect of integrated publications by outlining characteristics of good modeling, presentation, and fruitful collaborations.

  14. Experimental realization of nonadiabatic holonomic quantum computation. (United States)

    Feng, Guanru; Xu, Guofu; Long, Guilu


    Because of its geometric nature, holonomic quantum computation is fault tolerant against certain types of control errors. Although proposed more than a decade ago, the experimental realization of holonomic quantum computation is still an open challenge. In this Letter, we report the first experimental demonstration of nonadiabatic holonomic quantum computation in a liquid NMR quantum information processor. Two noncommuting one-qubit holonomic gates, rotations about x and z axes, and the two-qubit holonomic CNOT gate are realized by evolving the work qubits and an ancillary qubit nonadiabatically. The successful realizations of these universal elementary gates in nonadiabatic holonomic quantum computation demonstrates the experimental feasibility of this quantum computing paradigm.

  15. Experimental millimeter-wave satellite communications system (United States)

    Suzuki, Yoshiaki; Shimada, Masaaki; Arimoto, Yoshinori; Shiomi, Tadashi; Kitazume, Susumu

    This paper describes an experimental system of millimeter-wave satellite communications via Japan's Engineering Test Satellite-VI (ETS-VI) and a plan of experiments. Two experimental missions are planned using ETS-VI millimeter-wave (43/38 GHz bands) transponder, considering the millimeter-wave characteristics such as large transmission capacity and possibility to construct a small earth station with a high gain antenna. They are a personal communication system and an inter-satellite communication system. Experimental system including the configuration and the fundamental functions of the onboard transponder and the outline of the experiments are presented.

  16. Reflections on experimental science Martin Perl

    CERN Document Server

    Perl, Martin Lewis


    This is a collection of important lecture and original articles and commentaries by Martin Perl, discoverer of the tau lepton and the third generation of elementary particles, and this year's Nobel Prize winner. This book contains a fascinating and realistic picture of experimental science based on the high energy physics research work carried out by him. Using reprints of his articles with his commentaries, the author presents the various aspects of experimental research in science: the pleasures and risks of experimental work; the pain and frustration with experiments that are useless or fai

  17. Solid Oxide Fuel Cell Experimental Laboratory (United States)

    Federal Laboratory Consortium — NETL’s Solid Oxide Fuel Cell Experimental Laboratory in Morgantown, WV, gives researchers access to models and simulations that predict how solid oxide fuel cells...

  18. Evapotranspiration studies for protective barriers: Experimental plans

    Energy Technology Data Exchange (ETDEWEB)

    Link, S.O.; Waugh, W.J.


    This document describes a general theory and experimental plans for predicting evapotranspiration in support of the Protective Barrier Program. Evapotranspiration is the combined loss of water from plants and soil surfaces to the atmosphere. 45 refs., 1 fig., 4 tabs.

  19. Complement activation in experimental human malaria infection.

    NARCIS (Netherlands)

    Roestenberg, M.; McCall, M.B.B.; Mollnes, T.E.; Deuren, M. van; Sprong, T.; Klasen, I.S.; Hermsen, C.C.; Sauerwein, R.W.; Ven, A.J.A.M. van der


    The objective of this study was to investigate complement activation in uncomplicated, early phases of human malaria. Fifteen healthy volunteers were experimentally infected with Plasmodium falciparum malaria. Parasitemia and complement activation products were assessed. During blood stage parasitem

  20. Learning, forecasting and optimizing: an experimental study

    NARCIS (Netherlands)

    Bao, T.; Duffy, J.; Hommes, C.


    Rational Expectations (RE) models have two crucial dimensions: (i) agents on average correctly forecast future prices given all available information, and (ii) given expectations, agents solve optimization problems and these solutions in turn determine actual price realizations. Experimental tests o

  1. Learning, forecasting and optimizing : An experimental study

    NARCIS (Netherlands)

    Bao, Te; Duffy, John; Hommes, Cars


    Rational Expectations (RE) models have two crucial dimensions: (i) agents on average correctly forecast future prices given all available information, and (ii) given expectations, agents solve optimization problems and these solutions in turn determine actual price realizations. Experimental tests o

  2. Learning, forecasting and optimizing: an experimental study

    NARCIS (Netherlands)

    Bao, T.; Duffy, J.; Hommes, C.


    Rational Expectations (RE) models have two crucial dimensions: 1) agents correctly forecast future prices given all available information, and 2) given expectations, agents solve optimization problems and these solutions in turn determine actual price realizations. Experimental testing of such model

  3. PMWS: Experimental model and co-infections

    DEFF Research Database (Denmark)

    Allan, G. M.; McNeilly, F.; Ellis, J;


    and pneumonia and typical histological lesions include lymphocytic depletion and multinucleated giant cell formation in lymph nodes, degeneration and necrosis of hepatocytes, and multifocal lymphohistocytic interstitial pneumonia. This communication will review the results of experimental infections...

  4. On Experimental Research and Its Application

    Institute of Scientific and Technical Information of China (English)

    Cao Yanqing; Yangyihui; Wangcongyi


    This paper firstly analyzes the definition, components and different types of experimental research and also discuss the characteristics of its design. Then it demonstrates its practical application on 8 concrete example. Lastly, the author concludes it with some suggestions

  5. Experimental design methods for bioengineering applications. (United States)

    Keskin Gündoğdu, Tuğba; Deniz, İrem; Çalışkan, Gülizar; Şahin, Erdem Sefa; Azbar, Nuri


    Experimental design is a form of process analysis in which certain factors are selected to obtain the desired responses of interest. It may also be used for the determination of the effects of various independent factors on a dependent factor. The bioengineering discipline includes many different areas of scientific interest, and each study area is affected and governed by many different factors. Briefly analyzing the important factors and selecting an experimental design for optimization are very effective tools for the design of any bioprocess under question. This review summarizes experimental design methods that can be used to investigate various factors relating to bioengineering processes. The experimental methods generally used in bioengineering are as follows: full factorial design, fractional factorial design, Plackett-Burman design, Taguchi design, Box-Behnken design and central composite design. These design methods are briefly introduced, and then the application of these design methods to study different bioengineering processes is analyzed.

  6. Depressed mood and smoking experimentation among preteens. (United States)

    Polen, Michael R; Curry, Susan J; Grothaus, Louis C; Bush, Terry M; Hollis, Jack F; Ludman, Evette J; McAfee, Timothy A


    The authors examined children's depressed mood, parental depressed mood, and parental smoking in relation to children's smoking susceptibility and experimentation over 20 months in a cohort of 418 preteens (ages 10-12 at baseline) and their parents. Depressed mood in preteens was strongly related to experimentation but not to susceptibility. In cross-sectional analyses parental depressed mood was related to children's experimentation, but in longitudinal analyses parental depressed mood at baseline did not differentiate children who experimented from those who did not. Although parental smoking was strongly related to experimentation, it was not related to susceptibility either cross-sectionally or longitudinally. Depressed mood among preteens and parents appeared to be more strongly related to children's smoking behaviors than to their intentions to smoke.

  7. An Introduction to Experimental Design Research

    DEFF Research Database (Denmark)

    Cash, Philip; Stanković, Tino; Štorga, Mario


    Design research brings together influences from the whole gamut of social, psychological, and more technical sciences to create a tradition of empirical study stretching back over 50 years (Horvath 2004; Cross 2007). A growing part of this empirical tradition is experimental, which has gained...... in importance as the field has matured. As in other evolving disciplines, e.g. behavioural psychology, this maturation brings with it ever-greater scientific and methodological demands (Reiser 1939; Dorst 2008). In particular, the experimental paradigm holds distinct and significant challenges for the modern...... design researcher. Thus, this book brings together leading researchers from across design research in order to provide the reader with a foundation in experimental design research; an appreciation of possible experimental perspectives; and insight into how experiments can be used to build robust...

  8. Multiparton interactions. Theory and experimental findings

    Energy Technology Data Exchange (ETDEWEB)

    Diehl, Markus


    I give an introduction to multiparton interactions in proton-proton collisions, with a focus on the perturbative regime. Recent experimental results are discussed, as well as progress and open questions in theory.

  9. Experimental design of a waste glass study

    Energy Technology Data Exchange (ETDEWEB)

    Piepel, G.F.; Redgate, P.E.; Hrma, P.


    A Composition Variation Study (CVS) is being performed to support a future high-level waste glass plant at Hanford. A total of 147 glasses, covering a broad region of compositions melting at approximately 1150{degrees}C, were tested in five statistically designed experimental phases. This paper focuses on the goals, strategies, and techniques used in designing the five phases. The overall strategy was to investigate glass compositions on the boundary and interior of an experimental region defined by single- component, multiple-component, and property constraints. Statistical optimal experimental design techniques were used to cover various subregions of the experimental region in each phase. Empirical mixture models for glass properties (as functions of glass composition) from previous phases wee used in designing subsequent CVS phases.

  10. Chemical-Based Formulation Design: Virtual Experimentation

    DEFF Research Database (Denmark)

    Conte, Elisa; Gani, Rafiqul

    This paper presents a software, the virtual Product-Process Design laboratory (virtual PPD-lab) and the virtual experimental scenarios for design/verification of consumer oriented liquid formulated products where the software can be used. For example, the software can be employed for the design...... system engineering community, it is possible now to replace, at least, some of the experimental steps with efficient and validated model-based approaches. For example, the search space can be significantly reduced through computer-aided screenings of the active ingredient (AI), the solvent mixture......, the additives and/or their mixtures (formulations). Therefore, the experimental resources can focus on a few candidate product formulations to find the best product. The virtual PPD-lab allows various options for experimentations related to design and/or verification of the product. For example, the selection...

  11. Yakima Hatchery Experimental Design : Annual Progress Report.

    Energy Technology Data Exchange (ETDEWEB)

    Busack, Craig; Knudsen, Curtis; Marshall, Anne


    This progress report details the results and status of Washington Department of Fisheries' (WDF) pre-facility monitoring, research, and evaluation efforts, through May 1991, designed to support the development of an Experimental Design Plan (EDP) for the Yakima/Klickitat Fisheries Project (YKFP), previously termed the Yakima/Klickitat Production Project (YKPP or Y/KPP). This pre- facility work has been guided by planning efforts of various research and quality control teams of the project that are annually captured as revisions to the experimental design and pre-facility work plans. The current objective are as follows: to develop genetic monitoring and evaluation approach for the Y/KPP; to evaluate stock identification monitoring tools, approaches, and opportunities available to meet specific objectives of the experimental plan; and to evaluate adult and juvenile enumeration and sampling/collection capabilities in the Y/KPP necessary to measure experimental response variables.

  12. General footage ISOLDE experimental hall HD

    CERN Multimedia


    Overview of the ISOLDE experimental hall. Equipment and experiments. Taken from the WITCH / EBIS platform: ISOLDE hall infrastructure, GHM line, LA1, LA2, LA0, central beamline, COLLAPS experiment, CRIS experiment, ISOLTRAP experiment, laser guidance from building 508 into the hall for laser spectroscopy COLLAPS and CRIS. Taken from the HIE ISOLDE shielding tunnel roof: ISOLDE hall infrastructure, WITCH experiment, VITO line, TAS experiment. General footage: High Tension room entrance and EBIS platform, staircases and passages in the experimental hall.

  13. Report on HOM experimental methods and code

    CERN Document Server

    Shinton, I R R; Flisgen, T


    Experimental methods and various codes used are reported on with the aim to understand the signals picked up from the higher order modes in the third harmonic cavities within the ACC39 module at FLASH. Both commercial computer codes have been used, and also codes written for the express purpose of understanding the sensitivity of the modal profiles to geometrical errors and other sources of experimental errors.

  14. Experimental Investigation on Caisson Breakwater Sliding

    DEFF Research Database (Denmark)

    Ruol, Piero; Martin, Paolo; Andersen, Thomas Lykke;


    weight and same geometries are tested under regular and irregular waves. It is found that, under breaking conditions, the expected inaccuracy of the prediction of the force, inherent on the variability of the breaking process, induce unacceptable errors in the prediction of the sliding. This observation...... endorses other previous experimental results. Conversely, when the actual measured input force is used as input, the analytical Shimosako formula fit quite well the experimental sliding distance....

  15. Design of Uranium Solution Critical Experimental Device

    Institute of Scientific and Technical Information of China (English)

    YI; Da-yong; GUO; Zhi-jia; YAO; Cheng-zhi; SHI; Chen-lei


    <正>In 2012, Department of reactor engineering design completes the design and mechanical analysis of Uranium solution critical experimental device. According to user’s requirements and nuclear safety regulations, design and analysis mainly involves two sets of core structure, uranium solution loop, water loop and experimental bench, etc. The core which includes a core vessel, reactor core support, safety rods, control rods, and so on, is used for containing uranium solution and fuel element and fulfilling the

  16. [Animal experimentation, computer simulation and surgical research]. (United States)

    Carpentier, Alain


    We live in a digital world In medicine, computers are providing new tools for data collection, imaging, and treatment. During research and development of complex technologies and devices such as artificial hearts, computer simulation can provide more reliable information than experimentation on large animals. In these specific settings, animal experimentation should serve more to validate computer models of complex devices than to demonstrate their reliability.

  17. Experimental Creation of Entanglement Using Separable States

    Institute of Scientific and Technical Information of China (English)

    YANG Xiao-Dong; WANG An-Min; MA Xiao-San; XU Feng; YOU Hao; NIU Wan-Qing


    @@ We experimentally demonstrate that the entanglement can be created on two distant particles using separable states. We show that two working particles can share some entanglement, while one ancilla particle always remains separable from the two working particles during the experimental evolution of the system. Our experiment can be viewed as a benchmark to illustrate the idea that no prior entanglement is necessary to create entanglement.

  18. Chemicals-Based Formulation Design: Virtual Experimentations

    DEFF Research Database (Denmark)

    Conte, Elisa; Gani, Rafiqul


    This paper presents a systematic procedure for virtual experimentations related to the design of liquid formulated products. All the experiments that need to be performed when designing a liquid formulated product (lotion), such as ingredients selection and testing, solubility tests, property mea...... on the design of an insect repellent lotion will show that the software is an essential instrument in decision making, and that it reduces time and resources since experimental efforts can be focused on one or few product alternatives....

  19. Nutrition and Experimental Dental Caries


    田村,俊吉; タムラ, シュンキチ; Shunkichi, TAMURA


    Nutrition is an effective factor for the inhibition of the development of dental caries. The constitution of diet has a strong bearing on the development of dental caries. However the theoretical background regarding the development of dental caries has not been sastifactorily established. Experimentally, we have clarified the relation of nutrition and dental caries in rats. Experimental animals used in this study were Wistar strain Albino rats (closed colony, Tamura, 1950). Young rats of 21 ...

  20. New product development using experimental design


    Zhang, Zhihai


    New product development is one of the most powerful but difficult activities in business. It is also a very important factor affecting final product quality. There are many techniques available for new product development. Experimental design is now regarded as one of the most significant techniques. In this article, we will discuss how to use the technique of experimental design in developing a new product - an extrusion press. In order to provide a better understanding of this specific proc...