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Sample records for a-interior design bv

  1. BV photometry of UX ARIETIS

    NASA Astrophysics Data System (ADS)

    Mohin, S.; Raveendran, A. V.

    1989-03-01

    Differential BV photometry of UX Ari obtained on 58 nights during 1984-1985, 1985-1986, 1986-1987, and 1987-1988 observing season is presented. It is found that (B-V) is phase dependent, with the system being reddest at the light maximum. This is interpreted as being due to the variable fractional contribution by the G5 V component to the total light at shorter wavelengths. An analysis of the available data indicates that, at larger amplitudes of the photometric wave, the brightness at maximum increases and that at minimum decreases, and both converge to DeltaV of about 1.0 mag at very low amplitudes. It implies that the low wave amplitudes are essentially due to more homogeneity in the surface distribution of spots rather than to low levels of spot activity. The variation in wave amplitude is found to be near-sinusoidal with a period around 13-14 years.

  2. BV and non-BV associated Gardnerella vaginalis establish similar synergistic interactions with other BV-associated microorganisms in dual-species biofilms.

    PubMed

    Castro, Joana; Cerca, Nuno

    2015-12-01

    Dual-species biofilm formation between Gardnerella vaginalis strains isolated from women with or without bacterial vaginosis (BV) and other 24 BV-associated microorganisms support that the key difference in virulence potential between BV-negative and BV-positive G. vaginalis strains seems not to be related with biofilm maturation. PMID:26505928

  3. Increased Capacity Cryocoolers at Thales Cryogenics BV

    NASA Astrophysics Data System (ADS)

    Willems, D.; Mullié, J.; v. d. Groep, W.; Benschop, T.

    2010-04-01

    The flexure-bearing technology of Thales Cryogenics BV is being used in an extensive range of pulse-tube and Stirling cryocoolers. Compressors based on this flexure-bearing technology have a high reliability, long lifetime, and low vibrations. They are therefore the compressors of choice for high-end cryocoolers. Recently, the range of compressors has been extended with a larger compressor, capable of delivering more than 300 W of mechanical power. Apart from the above-mentioned characteristics, this particular compressor model has a high efficiency of more than 85% at its rated performance. In this paper, the design validation of this compressor is presented. This includes the verification of the individual loss mechanisms present in linear motor driven compressors. Furthermore, the potential of this compressor is demonstrated by its application in two cryocoolers. First the performance of a large, 15 W pulse tube (LPT9710) is presented. The combination of the large compressor with a newly designed pulse tube has resulted in a cooler with an efficiency of up to 15% of Carnot. Finally, measurements on a combination of the large compressor with a 20 mm Stirling cold finger are presented to demonstrate the potential performance of a—yet to be developed—large-capacity Stirling cold finger.

  4. Macrophage activation by OM-85 BV.

    PubMed

    Mauël, J

    1992-01-01

    Peritoneal or bone-marrow-derived murine macrophages were exposed for 24 h in vitro to dilutions of the bacterial extract OM-85 BV, in the presence or absence of other added compounds [macrophage-activating factor (MAF), recombinant murine interferon-gamma (IFN-gamma)]. Various metabolic responses and functional activities were then measured. Glucose oxidation through the hexose monophosphate shunt pathway was markedly stimulated in OM-85 BV-treated macrophages compared to control macrophages. Similarly, OM-85 BV primed macrophages for superoxide production upon triggering by phorbol myristate acetate. Both effects were further enhanced by simultaneous treatment of the cells with MAF with OM-85 BV. The bacterial extract also induced macrophages to release large amounts of nitrite (a marker of the activated state). As regards functional responses, coincubation with MAF and OM-85 BV activated macrophages to destroy target cells as well as intracellular microorganisms; in the latter case, similar results were obtained when MAF was replaced by IFN-gamma. In all these tests, the possibility that the observed effects were due to contamination of the bacterial extracts by endotoxin could be excluded. The above results indicate that OM-85 BV induces metabolic and functional properties in macrophages that are characteristic of the activated state and are important for host defence. PMID:1332156

  5. Clinical efficacy of OM-85 BV in COPD and chronic bronchitis: a systematic review.

    PubMed

    Sprenkle, Mark D; Niewoehner, Dennis E; MacDonald, Roderick; Rutks, Indulis; Wilt, Timothy J

    2005-03-01

    OM-85 BV is an immunomodulatory agent used for prevention of exacerbations in persons with chronic lung disease. We conducted a systematic review of OM-85 BV to evaluate its efficacy and safety. A systematic search for relevant articles was performed. Studies were included if they involved persons with chronic obstructive pulmonary disease or chronic bronchitis and were randomized to OM-85 BV or placebo. Investigators extracted data on study design, participant characteristics, and clinical outcomes. Thirteen trials involving 2066 individuals met inclusion criteria. Three trials enrolled an older, more homogenous population with chronic obstructive pulmonary disease. Utilizing quantitative pooled analysis in these studies, with one or more acute exacerbations as the endpoint, we found a non-statistically significant trend in favor of OM-85 BV [relative risk 0.83, 95% confidence interval 0.65-1.05]. Ten trials enrolled a heterogeneous population with chronic bronchitis. In these trials, exacerbation rates were less with OM-85 BV in 4 of 9 trials reporting this outcome. Varied results in the outcomes of hospitalization, symptom scores, and antibiotic or steroid use were found across studies. Withdrawals and adverse events were similar between OM-85 BV and placebo. While OM-85 BV is used to prevent exacerbations in persons with chronic lung disease, consistent evidence across multiple important outcomes does not exist to clearly demonstrate clinical benefit. Further randomized controlled trials enrolling large numbers of persons with well-defined COPD are necessary to confirm the effectiveness of this agent. PMID:17136978

  6. How Do Health Care Providers Diagnose Bacterial Vaginosis (BV)?

    MedlinePlus

    ... Information Clinical Trials Resources and Publications How do health care providers diagnose bacterial vaginosis (BV)? Skip sharing on ... BV requires a vaginal exam by a qualified health care provider and the laboratory testing of fluid collected ...

  7. Parrot Bornavirus (PaBV)-2 isolate causes different disease patterns in cockatiels than PaBV-4.

    PubMed

    Piepenbring, Anne K; Enderlein, Dirk; Herzog, Sibylle; Al-Ibadi, Basim; Heffels-Redmann, Ursula; Heckmann, Julia; Lange-Herbst, Hildburg; Herden, Christiane; Lierz, Michael

    2016-01-01

    Psittaciform 1 bornavirus (PaBV) has already been shown to be the aetiologic agent of proventricular dilatation disease, a significant disease of birds. However, the pathogenesis of PaBV infection has not yet been resolved and valid data regarding the pathogenicity of different PaBV species are lacking. Thus, the present study was aimed to characterize the influence of two different PaBV species on the course of disease. Eighteen cockatiels were inoculated intracerebrally (i.c.) or intravenously (i.v.) with a PaBV-2 isolate under the same conditions as in a previous study using PaBV-4. Birds were surveyed and sampled for 33 weeks to analyse the course of infection and disease in comparison to that of PaBV-4. Similar to PaBV-4, PaBV-2 induced a persistent infection with seroconversion (from day 6 p.i. onwards) and shedding of viral RNA (from day 27 p.i. onwards). However, in contrast to PaBV-4, more birds displayed clinical signs and disease progression was more severe. After PaBV-2 infection, 12 birds exhibited clinical signs and 10 birds revealed a dilated proventriculus in necropsy. After PaBV-4 infection only four birds revealed clinical signs and seven birds showed a dilatation of the proventriculus. Clinically, different courses of disease were observed after PaBV-2 infection, mainly affecting the gastrointestinal tract. This had not been detected after PaBV-4 infection where more neurological signs were noted. The results provide evidence for different disease patterns according to different PaBV species, allowing the comparison between the infection with two PaBV species, and thus underlining the role of viral and individual host factors for disease outcome. PMID:27100150

  8. Nociceptive sensitization by the secretory protein Bv8

    PubMed Central

    Negri, Lucia; Lattanzi, Roberta; Giannini, Elisa; Metere, Alessio; Colucci, Mariantonella; Barra, Donatella; Kreil, Günther; Melchiorri, Pietro

    2002-01-01

    The small protein Bv8, isolated from amphibian skin, belongs to a novel family of secretory proteins (Bv8-Prokineticin family, SWISS-PROT: Q9PW66) whose orthologues have been conserved throughout evolution, from invertebrates to humans. When injected intravenously or subcutaneously (from 0.06 to 500 pmol kg−1) or intrathecally (from 6 fmol to 250 pmol) in rats, Bv8 produced an intense systemic nociceptive sensitization to mechanical and thermal stimuli applied to the tail and paws. Topically delivered into one rat paw, 50 fmol of Bv8 decreased by 50% the nociceptive threshold to pressure in the injected paw without affecting the threshold in the contralateral paw. The two G-protein coupled prokineticin receptors, PK-R1 and PK-R2, were expressed in rat dorsal root ganglia (DRG) and in dorsal quadrants of spinal cord (DSC) and bound Bv8 and the mammalian orthologue, EG-VEGF, with high affinity. In DSC, PK-R1 was more abundant than PK-R2, whereas both receptors were equally expressed in DRG. IC50 of Bv8 and EG-VEGF to inhibit [125I]-Bv8 binding to rat DRG and DSC were 4.1±0.4 nM Bv8 and 76.4±7.6 nM EG-VEGF, in DRG; 7.3±0.9 nM Bv8 and 330±41 nM EG-VEGF, in DSC. In the small diameter neurons (<30 μm) of rat DRG cultures, Bv8 concentrations, ranging from 0.2 to 10 nM, raised [Ca2+]i in a dose-dependent manner. These data suggest that Bv8, through binding to PK receptors of DSC and primary sensitive neurons, results in intense sensitization of peripheral nociceptors to thermal and mechanical stimuli. PMID:12466223

  9. OM-85 BV: primary versus secondary prevention.

    PubMed

    Collet, J P; Boissel, J P

    1994-01-01

    Recurrent upper respiratory tract infections in children have an important socioeconomic impact, with consequences on both the quality of life of the children, the possible medical sequelae and the inherent direct and indirect costs. The possibility to prevent these infections is limited in the absence of specific vaccines against microorganisms responsible for most of the respiratory tract infections (i.e. respiratory syncitial virus, adenovirus, rhinovirus). Immunoactive bacterial extracts that stimulate the nonspecific component of the immune system may protect against a large variety of microorganisms that enter the body by the oral and respiratory pathway; they may, therefore, play an important role with regard to this preventive action. OM-85 BV is an IBE that has been used in children who suffer from repeated infections to prevent the occurrence of new episodes (secondary prevention). In this condition, the drug has been shown to be effective in protecting children against recurrent airway infections. Its use as a primary preventive agent to prevent the development of repeated infections in children attending day-care centers (a very high-risk environment for repeated infections), however, did not show a similar efficacy. The risk of having > or = 4 episodes of upper respiratory tract infections over a period of 7.5 months was 26.7% in the verum group and 33.8% in the placebo group (relative risk 0.79, confidence interval 0.59-1.06]. In an exploratory analysis concentrating on the 3-month treatment period, however, a 48% reduction of the risk of presenting > or = 3 episodes was observed. Furthermore, this exploratory analysis showed a strong correlation between drug efficacy and age of the children.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7800967

  10. 33. FUEL HANDLING BUILDING (LOCATION A), INTERIOR LOOKING NORTH FROM ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    33. FUEL HANDLING BUILDING (LOCATION A), INTERIOR LOOKING NORTH FROM ABOVE CLEAN ROOM - Shippingport Atomic Power Station, On Ohio River, 25 miles Northwest of Pittsburgh, Shippingport, Beaver County, PA

  11. Magnetopause orientation: Comparison between generic residue analysis and BV method

    NASA Astrophysics Data System (ADS)

    Dorville, Nicolas; Haaland, Stein; Anekallu, Chandrasekhar; Belmont, Gérard; Rezeau, Laurence

    2015-05-01

    Determining the direction normal to the magnetopause layer is a key step for any study of this boundary. Various techniques have been developed for this purpose. We focus here on generic residue analysis (GRA) methods, which are based on conservation laws, and the new iterative BV method, where B represents the magnetic field and V refers to the ion velocity. This method relies on a fit of the magnetic field hodogram against a modeled geometrical shape and on the way this hodogram is described in time. These two methods have different underlying model assumptions and validity ranges. We compare here magnetopause normals predicted by BV and GRA methods to better understand the sensitivity of each method on small departures from its own physical hypotheses. This comparison is carried out first on artificial data with magnetopause-like noise. Then a statistical study is carried out using a list of 149 flank and dayside magnetopause crossings from Cluster data where the BV method is applicable, i.e., where the magnetopause involves a single-layer current sheet, with a crudely C-shaped magnetic hodogram. These two comparisons validate the quality of the BV method for all these cases where it is applicable. The method provides quite reliable normal directions in all these cases, even when the boundary is moving with a varying velocity, which distorts noticeably the results of most of the other methods.

  12. Photometric Studies of the Contact Binary BV Draconis

    NASA Astrophysics Data System (ADS)

    Lee, Jae Woo Lee; Han, Wonyong; Kim, Chun-Hwey

    1999-12-01

    We performed CCD photometric observations of W UMa type contact binary BV Dra during eight nights from May 1996 to June 1999 using 61cm telescope at Sobaeksan Optical Astronomy Observatory, and completed BVR light curves of the system. From our observations, we derived nine new times of minimum lights (five timings for primary eclipse, four for secondary) and determined new light elements with the times of minima observed since 1999. Our BVR light curves and Batten & Lu (1986)'s radial-velocity ones were simultaneously analyzed with contact mode (Mode 3) of Wilson-Devinney's binary model, and the photometric and spectroscopic solutions for BV Dra were solved. In the analysis, we derived the solutions of 1999 light curves with and without spots, respectively. As the results, asymmetry of light curves may be interpreted as produced by the existence of two spots; hot spot on the secondary and cool on the primary. Combining solutions of light curves and radial-velocity ones, absolute dimensions of BV Dra are M1=0.40M , M2=1.01M ,R1=0.72R , R2=0.40R . In mass-radius diagram, the less massive and hotter primary component of BV Dra is near TAMS and the secondary is near ZAMS, which is very similar to the other W-type W UMa binaries.

  13. Functionally charged nanosize particles differentially activate BV2 microglia.

    EPA Science Inventory

    The effect of particle surface charge on the biological activation of immortalized mouse microglia (BV2) was examined. Nanosize (860-950 nm) spherical polystyrene microparticles (SPM) were coated with carboxyl (COOH-) or dimethyl amino (CH3)2-N- groups to give a net negative or p...

  14. The endocrine-gland-derived VEGF homologue Bv8 promotes angiogenesis in the testis: Localization of Bv8 receptors to endothelial cells

    PubMed Central

    LeCouter, Jennifer; Lin, Rui; Tejada, Max; Frantz, Gretchen; Peale, Franklin; Hillan, Kenneth J.; Ferrara, Napoleone

    2003-01-01

    We recently identified an angiogenic mitogen, endocrine-gland-derived vascular endothelial growth factor (EG-VEGF), with selective activity for endothelial cells of endocrine tissues. Here we describe the characterization of a highly related molecule, Bv8, also known as prokineticin-2. Human Bv8 shares 60% identity and 75% similarity with EG-VEGF. The human and mouse Bv8 genes share a common structure. Like EG-VEGF, Bv8 is able to induce proliferation, survival and migration of adrenal cortical capillary endothelial cells. Bv8 gene expression is induced by hypoxic stress. Bv8 expression occurs predominantly in the testis and is largely restricted to primary spermatocytes. Adenoviral delivery of Bv8 or EG-VEGF to the mouse testis resulted in a potent angiogenic response. We have localized the expression of the Bv8/EG-VEGF receptors within the testis to vascular endothelial cells. The testis exhibits relatively high turnover of endothelial cells. Therefore, Bv8 and EG-VEGF, along with other factors such as VEGF-A, may maintain the integrity and also regulate proliferation of the blood vessels in the testis. PMID:12604792

  15. Benfotiamine Attenuates Inflammatory Response in LPS Stimulated BV-2 Microglia

    PubMed Central

    Bozic, Iva; Savic, Danijela; Laketa, Danijela; Bjelobaba, Ivana; Milenkovic, Ivan; Pekovic, Sanja; Nedeljkovic, Nadezda; Lavrnja, Irena

    2015-01-01

    Microglial cells are resident immune cells of the central nervous system (CNS), recognized as key elements in the regulation of neural homeostasis and the response to injury and repair. As excessive activation of microglia may lead to neurodegeneration, therapeutic strategies targeting its inhibition were shown to improve treatment of most neurodegenerative diseases. Benfotiamine is a synthetic vitamin B1 (thiamine) derivate exerting potentially anti-inflammatory effects. Despite the encouraging results regarding benfotiamine potential to alleviate diabetic microangiopathy, neuropathy and other oxidative stress-induced pathological conditions, its activities and cellular mechanisms during microglial activation have yet to be elucidated. In the present study, the anti-inflammatory effects of benfotiamine were investigated in lipopolysaccharide (LPS)-stimulated murine BV-2 microglia. We determined that benfotiamine remodels activated microglia to acquire the shape that is characteristic of non-stimulated BV-2 cells. In addition, benfotiamine significantly decreased production of pro-inflammatory mediators such as inducible form of nitric oxide synthase (iNOS) and NO; cyclooxygenase-2 (COX-2), heat-shock protein 70 (Hsp70), tumor necrosis factor alpha α (TNF-α), interleukin-6 (IL-6), whereas it increased anti-inflammatory interleukin-10 (IL-10) production in LPS stimulated BV-2 microglia. Moreover, benfotiamine suppressed the phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2), c-Jun N-terminal kinases (JNK) and protein kinase B Akt/PKB. Treatment with specific inhibitors revealed that benfotiamine-mediated suppression of NO production was via JNK1/2 and Akt pathway, while the cytokine suppression includes ERK1/2, JNK1/2 and Akt pathways. Finally, the potentially protective effect is mediated by the suppression of translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in the nucleus. Therefore, benfotiamine may

  16. IMM-H004, a novel coumarin derivative compound, attenuates the production of inflammatory mediatory mediators in lipopolysaccharide-activated BV2 microglia.

    PubMed

    Song, Xiu-Yun; Hu, Jin-Feng; Sun, Ming-Na; Li, Zhi-Peng; Zhu, Zhi-Xiang; Song, Lian-Kun; Yuan, Yu-He; Liu, Gang; Chen, Nai-Hong

    2014-07-01

    Therapeutic strategies designed to inhibit the activation of microglia may lead to significant advancement in the treatment of most neurodegenerative diseases. 7-hydroxy-5-methoxy-4-methyl-3-(4-methylpiperazin-1-yl)-coumarin (IMM-H004) is a novel compound and has been reported exerting potent neuroprotective effects which may be related to anti-inflammation. In the present study, the anti-inflammatory effects of IMM-H004 were investigated in lipopolysaccharide (LPS)-treated BV2 microglia. Our observations indicated that treatment with IMM-H004 significantly inhibited BV2 microglia activation, protected PC12 cells and primary neurons against indirect toxicity mediated by exposure to conditioned medium (CM) from LPS-treated BV2 cells. Additionally, IMM-H004 significantly suppressed the release of TNF-α, IL-1β and NO, and suppressed the expression of pro-inflammatory mediators and cytokines such as iNOS, COX-2, and IL-6 in LPS-stimulated BV2 microglia. The nuclear translocation of NF-κB and the phosphorylation level of JNK and p38 MAPK pathways were also inhibited by IMM-H004 in LPS-treated BV2 microglia. Moreover, IMM-H004 also was a strong selective OH scavenger whose effect was similar with vitamin C. Overall, our findings suggested that IMM-H004 might be a promising therapeutic agent for alleviating the progress of neurodegenerative diseases associated with microglia activation. PMID:24878446

  17. BV supersolutions to equations of 1-Laplace and minimal surface type

    NASA Astrophysics Data System (ADS)

    Scheven, Christoph; Schmidt, Thomas

    2016-08-01

    We propose notions of BV supersolutions to (the Dirichlet problem for) the 1-Laplace equation, the minimal surface equation, and equations of similar type. We then establish some related compactness and consistency results. Our main technical tool is a generalized product of L∞ divergence-measure fields and gradient measures of BV functions. This product crucially depends on the choice of a representative of the BV function, and the proofs of its basic properties involve results on one-sided approximation and fine (semi)continuity in the BV context.

  18. Vaccinium bracteatum Thunb. Exerts Anti-Inflammatory Activity by Inhibiting NF-κB Activation in BV-2 Microglial Cells

    PubMed Central

    Kwon, Seung-Hwan; Ma, Shi-Xun; Ko, Yong-Hyun; Seo, Jee-Yeon; Lee, Bo-Ram; Lee, Taek Hwan; Kim, Sun Yeou; Lee, Seok-Yong; Jang, Choon-Gon

    2016-01-01

    This study was designed to evaluate the pharmacological effects of Vaccinium bracteatum Thunb. methanol extract (VBME) on microglial activation and to identify the underlying mechanisms of action of these effects. The anti-inflammatory properties of VBME were studied using lipopolysaccharide (LPS)-stimulated BV-2 microglial cells. We measured the production of nitric oxide (NO), inducible NO synthase (iNOS), cyclooxygenase (COX)-2, prostaglandin E2 (PGE2), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6) as inflammatory parameters. We also examined the effect of VBME on intracellular reactive oxygen species (ROS) production and the activity of nuclear factor-kappa B p65 (NF-κB p65). VBME significantly inhibited LPS-induced production of NO and PGE2 and LPS-mediated upregulation of iNOS and COX-2 expression in a dose-dependent manner; importantly, VBME was not cytotoxic. VBME also significantly reduced the generation of the pro-inflammatory cytokines TNF-α, IL-1β, and IL-6. In addition, VBME significantly dampened intracellular ROS production and suppressed NF-κB p65 translocation by blocking IκB-α phosphorylation and degradation in LPS-stimulated BV2 cells. Our findings indicate that VBME inhibits the production of inflammatory mediators in BV-2 microglial cells by suppressing NF-κB signaling. Thus, VBME may be useful in the treatment of neurodegenerative diseases due to its ability to inhibit inflammatory mediator production in activated BV-2 microglial cells. PMID:27169820

  19. Anti-Neuroinflammatory Effects of Uncaria sinensis in LPS-Stimulated BV2 Microglia Cells and Focal Cerebral Ischemic Mice.

    PubMed

    Kang, Bo Kyung; Kim, Mi Kyoung; Kim, So Young; Lee, Seung Jin; Choi, Young Whan; Choi, Byung Tae; Shin, Hwa Kyoung

    2015-01-01

    Uncaria sinensis (US) has long been used as a traditional Korean medicine to treat cardiovascular and central nervous system diseases, including hypertension and cerebral ischemia. Several recent studies have indicated that US has neuroprotective and cerebrovascular protective effects in ischemic brain injury; however, little is known about the anti-inflammatory effects of US. Therefore, the present study was designed to validate the anti-inflammatory effects of US. The anti-neuroinflammatory properties of US on pro-inflammatory mediators were investigated in lipopolysaccharide (LPS)-stimulated murine BV2 microglia and injured brains induced by photothrombotic cortical ischemia. Hexane extracts of US (HEUS) significantly suppressed the production of nitric oxide (NO) and prostaglandin E2 (PGE2) in LPS-stimulated BV2 microglia and inhibited LPS-induced expression of iNOS and COX-2 in a dose-dependent manner without causing cytotoxicity in BV2 cells. In addition, HEUS significantly reduced the generation of pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6. Moreover, HEUS treatment inhibited the transcriptional activity and nuclear translocation of NF-κB in LPS-stimulated BV2 cells. In an in vivo study, treatment of HEUS resulted in significantly reduced infarct volume and improved neurological function 48 h after ischemic brain injury, possibly through the inhibition of the production of pro-inflammatory cytokines. HEUS inhibits LPS-stimulated production of pro-inflammatory mediators and prevents cerebral ischemic damage, suggesting that US may have therapeutic potential for the prevention and treatment of ischemic stroke accompanied by microglia activation. PMID:26364663

  20. Bundle-forming pilus locus of Aeromonas veronii bv. Sobria.

    PubMed

    Hadi, Nahal; Yang, Qin; Barnett, Timothy C; Tabei, S Mohammed B; Kirov, Sylvia M; Shaw, Jonathan G

    2012-04-01

    Little is known about the colonization mechanisms of Aeromonas spp. Previous work has suggested that the type IV bundle-forming pilus (Bfp) is an aeromonad intestinal colonization factor. This study provides the first genetic characterization of this structure. To define the role of Bfp in Aeromonas veronii bv. Sobria adherence, a 22-kb locus encoding the bundle-forming pilus was isolated; this contained 17 pilus-related genes similar to the mannose-sensitive hemagglutinin (MSHA) of Vibrio cholerae. Reverse transcriptase PCR (RT-PCR) demonstrated that the locus had two major transcriptional units, mshI to mshF and mshB to mshQ. Transcriptional fusion experiments demonstrated the presence of two strong promoters upstream of mshI and mshB. The locus encoded four putative prepilin proteins, one of which (MshA) corresponded to the N-terminal sequence of the previously isolated major pilin protein. All the pilin genes were inactivated, mutation of each minor or major pilin gene greatly reduced the bacterium's ability to adhere and form biofilms, and complementation of each mutant in trans rescued this phenotype. Mutation of the major pilin MshA and MshB, a minor pilin, resulted in their loss. The position of the mshH gene is conserved within a number of bacteria, and we have shown it is not transcriptionally linked to the other msh genes; moreover, its mutation did not have a dramatic effect on either adhesion or biofilm formation. We conclude that the bundle-forming pilus is required for A. veronii bv. Sobria adherence and biofilm formation; furthermore, both the major and minor pilin proteins are essential for this process. PMID:22311923

  1. Bundle-Forming Pilus Locus of Aeromonas veronii bv. Sobria

    PubMed Central

    Hadi, Nahal; Yang, Qin; Barnett, Timothy C.; Tabei, S. Mohammed B.; Kirov, Sylvia M.

    2012-01-01

    Little is known about the colonization mechanisms of Aeromonas spp. Previous work has suggested that the type IV bundle-forming pilus (Bfp) is an aeromonad intestinal colonization factor. This study provides the first genetic characterization of this structure. To define the role of Bfp in Aeromonas veronii bv. Sobria adherence, a 22-kb locus encoding the bundle-forming pilus was isolated; this contained 17 pilus-related genes similar to the mannose-sensitive hemagglutinin (MSHA) of Vibrio cholerae. Reverse transcriptase PCR (RT-PCR) demonstrated that the locus had two major transcriptional units, mshI to mshF and mshB to mshQ. Transcriptional fusion experiments demonstrated the presence of two strong promoters upstream of mshI and mshB. The locus encoded four putative prepilin proteins, one of which (MshA) corresponded to the N-terminal sequence of the previously isolated major pilin protein. All the pilin genes were inactivated, mutation of each minor or major pilin gene greatly reduced the bacterium's ability to adhere and form biofilms, and complementation of each mutant in trans rescued this phenotype. Mutation of the major pilin MshA and MshB, a minor pilin, resulted in their loss. The position of the mshH gene is conserved within a number of bacteria, and we have shown it is not transcriptionally linked to the other msh genes; moreover, its mutation did not have a dramatic effect on either adhesion or biofilm formation. We conclude that the bundle-forming pilus is required for A. veronii bv. Sobria adherence and biofilm formation; furthermore, both the major and minor pilin proteins are essential for this process. PMID:22311923

  2. Vaccination with BV8S2 protein amplifies TCR-specific regulation and protection against experimental autoimmune encephalomyelitis in TCR BV8S2 transgenic mice.

    PubMed

    Offner, H; Adlard, K; Bebo, B F; Schuster, J; Burrows, G G; Buenafe, A C; Vandenbark, A A

    1998-09-01

    TCR determinants overexpressed by autopathogenic Th1 cells can naturally induce a second set of TCR-specific regulatory T cells. We addressed the question of whether immune regulation could be induced naturally in a genetically restricted model in which a major portion of TCR-specific regulatory T cells expressed the same target TCR BV8S2 chain as the pathogenic T cells specific for myelin basic protein (MBP). We found vigorous T cell responses to BV8S2 determinants in naive mice that could be further potentiated by vaccination with heterologous BV8S2 proteins, resulting in the selective inhibition of MBP-specific Th1 cells and protection against experimental encephalomyelitis. Moreover, coculture with BV8S2-specific T cells or their supernatants reduced proliferation, IFN-gamma secretion, and encephalitogenic activity of MBP-specific T cells. These results suggest that immune regulation occurs through a nondeletional cytokine-driven suppressive mechanism. PMID:9725209

  3. The bacterial extract OM-85 BV protects mice against influenza and Salmonella infection.

    PubMed

    Bessler, Wolfgang G; Vor dem Esche, Ulrich; Masihi, Noel

    2010-09-01

    The bacterial extract OM-85 BV has been shown to provide protection against recurrent respiratory infections. We here investigated its efficacy against viral and bacterial infections in murine models. We first evaluated the role of OM-85 BV protecting from an A/PR/8/34 (H1N1) influenza virus infection. In a group treated with 1.75 mg/mouse OM-85 BV all animals survived, compared to 70% in the untreated control group and a group treated with a lower dosage. In addition, the appearance of clinical signs was delayed, their intensity was decreased, and they disappeared faster; also a marked increase in the influenza hemagglutination inhibition antibody level was observed. Since bacterial infections often superimpose viral lung infections, we also investigated on the protection of mice from a Salmonella typhimurium infection after the oral administration of OM-85 BV. Here, 100% of the OM-85 BV treated animals survived compared to 58% of the untreated control group. The mechanism of protection was further investigated: OM-85 BV acts, on the one hand, as an immunogen: the repeated administration of OM-85 BV induced a marked increase in serum antibody levels recognizing pathogenic bacterial strains. On the other hand, the extract acts as a stimulator of the nonspecific macrophage, monocyte, dendritic cell, and granulocyte response. Our findings demonstrate the antimicrobial activity of OM-85 BV against infections, as also has been shown in clinical studies. PMID:20601184

  4. 78 FR 9884 - Approval of Subzone Status; Zimmer Manufacturing BV; Ponce, Puerto Rico

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-12

    ... Foreign-Trade Zones Board Approval of Subzone Status; Zimmer Manufacturing BV; Ponce, Puerto Rico Pursuant... application to the Board for the establishment of a subzone at the facility of Zimmer Manufacturing BV located... comment has been given in the Federal Register (77 FR 68102, 11/15/2012) and the application has...

  5. Pharmacological activity of a Bv8 analogue modified in position 24

    PubMed Central

    Lattanzi, R; Sacerdote, P; Franchi, S; Canestrelli, M; Miele, R; Barra, D; Visentin, S; DeNuccio, C; Porreca, F; De Felice, M; Guida, F; Luongo, L; de Novellis, V; Maione, S; Negri, L

    2012-01-01

    BACKGROUND AND PURPOSE The amphibian peptide Bv8 induces potent nociceptive sensitization in rodents. Its mammalian homologue, prokineticin 2 (PROK2), is strongly up-regulated in inflamed tissues and is a major determinant in triggering inflammatory pain. Bv8 and PROK2 activate two closely related GPCRs, PK1 and PK2, in a relatively non-selective fashion. To characterize better the roles of the two receptors in hyperalgesia and to obtain ligands whose binding affinity and efficacy differed for the two receptors, we modified the Bv8 molecule in regions essential for receptor recognition and activation. EXPERIMENTAL APPROACH We modified the Bv8 molecule by substituting Trp in position 24 with Ala (A-24) and compared it with Bv8 for binding and activating PK1 and PK2 receptors in cell preparations and in affecting nociceptive thresholds in rodents. KEY RESULTS A-24 preferentially bound to PK2 receptors and activated them with a lower potency (5-fold) than Bv8. When systemically injected, A-24 induced Bv8-like hyperalgesia in rats and in mice, at doses 100 times higher than Bv8. Locally and systemically injected at inactive doses, A-24 antagonized Bv8-induced hyperalgesia. In rat and mouse models of inflammatory and post-surgical pain, A-24 showed potent and long-lasting anti-hyperalgesic activity. Unlike Bv8, A-24 increased β-endorphin levels in mouse brain. CONCLUSIONS AND IMPLICATIONS A-24 induced its anti-hyperalgesic effect in rodents by directly blocking nociceptor PK1 receptors and by activating the central opioid system and the descending pain control pathway through brain PK2 receptors. PMID:22122547

  6. Benfotiamine upregulates antioxidative system in activated BV-2 microglia cells

    PubMed Central

    Bozic, Iva; Savic, Danijela; Stevanovic, Ivana; Pekovic, Sanja; Nedeljkovic, Nadezda; Lavrnja, Irena

    2015-01-01

    Chronic microglial activation and resulting sustained neuroinflammatory reaction are generally associated with neurodegeneration. Activated microglia acquires proinflammatory cellular profile that generates oxidative burst. Their persistent activation exacerbates inflammation, which damages healthy neurons via cytotoxic mediators, such as superoxide radical anion and nitric oxide. In our recent study, we have shown that benfotiamine (S-benzoylthiamine O-monophosphate) possesses anti-inflammatory effects. Here, the effects of benfotiamine on the pro-oxidative component of activity of LPS-stimulated BV-2 cells were investigated. The activation of microglia was accompanied by upregulation of intracellular antioxidative defense, which was further promoted in the presence of benfotiamine. Namely, activated microglia exposed to non-cytotoxic doses of benfotiamine showed increased levels and activities of hydrogen peroxide- and superoxide-removing enzymes—catalase and glutathione system, and superoxide dismutase. In addition, benfotiamine showed the capacity to directly scavenge superoxide radical anion. As a consequence, benfotiamine suppressed the activation of microglia and provoked a decrease in NO and ·O−2 production and lipid peroxidation. In conclusion, benfotiamine might silence pro-oxidative activity of microglia to alleviate/prevent oxidative damage of neighboring CNS cells. PMID:26388737

  7. Role of Bv8 in neutrophil-dependent angiogenesis in a transgenic model of cancer progression

    PubMed Central

    Shojaei, Farbod; Singh, Mallika; Thompson, Jennifer D.; Ferrara, Napoleone

    2008-01-01

    The secreted Bv8 protein has been recently characterized as a regulator of myeloid cell mobilization and a neutrophil-derived mediator of tumor angiogenesis in several xenografts, but its role in tumor progression in an endogenous setting was unknown. The rat insulin promoter (RIP)–T-antigen (Tag) is a well characterized transgenic mouse model of multistage pancreatic β-cell tumorigenesis. Also, the role of neutrophils in RIP-Tag angiogenic switching, as assessed by systemic ablation using anti-Gr1 antibodies at different stages of tumor progression, has been recently described. Here, we show that early treatment of RIP-Tag mice with anti-Bv8 antibodies resulted in a significant reduction in the number of angiogenic islets relative to control antibody-treated mice, implicating Bv8 in the angiogenic switch during neoplasia. Histological analysis showed a significant reduction in vascular surface areas in hyperplastic and angiogenic lesions in pancreatic islets from anti-Bv8-treated mice. Anti-Bv8 treatment also inhibited the mobilization and homing of CD11b+Gr1+ cells to the peripheral blood and the emerging neoplastic lesions. However, anti-Bv8 treatment had no effect on tumor vascularization or burden when initiated at later stages of tumor progression. The stage-dependent efficacy of anti-Bv8 treatment appears remarkably similar to that reported after neutrophil ablation, suggesting that Bv8 is an important mediator of neutrophil-dependent angiogenesis in this transgenic model. In summary, our studies verify a role for Bv8 in the mobilization and recruitment of myeloid cells and in the induction of tumor angiogenesis in the early stages of neoplastic progression. PMID:18268320

  8. Activation of natural killer cells and cytokine production in humans by bacterial extracts (OM-85 BV).

    PubMed

    Wybran, J; Libin, M; Schandene, L

    1990-01-01

    The influence of Broncho-Vaxom (BV) on different immune parameters was investigated in vitro on human peripheral blood mononuclear cells (PBMC). It was found that BV enhances the natural killer (NK) activity of PBMC and increases their spontaneous and phytohemagglutin (PHA)-induced production of tumor-necrosis factor--alpha and interleukin-2 as well as the PHA-stimulated production of interferon-gamma. These immunostimulating actions of BV on NK activity and cytokine production can contribute to the understanding of the enhancement of the body's defense mechanisms against respiratory tract infections. PMID:2117183

  9. The intrinsic values and color excesses of (B-V) for 115 F-K supergiants

    NASA Technical Reports Server (NTRS)

    Kelsall, T.

    1972-01-01

    Color excesses in B-V are determined indirectly from a study of Stromgren's b-y color for a sample of F0 - K5 supergiants. The resulting E(B-V)'s are estimated to have an expected precision of + or - 0.05. With the calculated color excesses and the observed values of B-V given in various catalogs, the run of B-V with spectral type is obtained. This B-V/(spectral type) relationship is compared with those found previously by other investigators.

  10. Self-assembling of impurity clusters in AlN:(Ga, BV, CV), (BV, CV = P, As; P, Sb; As, Sb)

    NASA Astrophysics Data System (ADS)

    Elyukhin, V. A.

    2015-11-01

    The self-assembling conditions of arrays of tetrahedral impurity clusters of two types in zinc blende AlN:(Ga, BV, CV), (BV, CV = P, As; P, Sb; As, Sb) are represented. Doping with one cation and two anion isoelectronic impurities transforms AlN into AlN-rich GaxAl1-xBVyCVzN1-y-z alloy of GaBV, GaCV, GaN, AlBV, AlCV and AlN. The cause of self-assembling is the preference of GaBV, GaCV and AlN bonding over that of GaN, AlBV, AlCV. The conditions are considered from 0 °C to 1000 °C in the dilute and ultra dilute limits for the cation and anion impurities, correspondingly. The temperature ranges between the cluster occurrence and self-assembling completion when the same anion impurities are in clusters are very small. 1P4Ga and 1As4Ga cluster occurrence temperatures are equal, correspondingly, to 797 °C and 736 °C at Ga content 2% and P and As contents 0.01%. 1P4Ga and 1Sb4Ga cluster occurrence temperatures are equal, correspondingly, to 976 °C and 736 °C at the same impurity contents. The cluster densities in AlN:(Ga, As, Sb) are close to those in AlN:(Ga, P, Sb). The results demonstrate that studied semiconductors are promising materials to produce arrays of identical ∼1 nm low band gap objects of two types embedded in the wide band gap matrix.

  11. Clinical experience with OM-85 BV in upper and lower respiratory tract infections.

    PubMed

    Derenne, J P; Delclaux, B

    1992-01-01

    The preventive effect of OM-85 BV on recurrent ENT and respiratory tract infections has been documented in a series of clinical trials. This article reviews the more significant controlled clinical trials investigating the efficacy and safety of OM-85 BV in airway infections. The literature reviewed covers all age groups. In summary, the administration of OM-85 BV was associated with a decrease in the number of acute exacerbations, with an increase in the number of patients remaining free from infections and with a decrease in antibiotic consumption. These results indicate the efficacy of oral immunostimulation with the bacterial extract OM-85 BV in all age groups and demonstrate its protective effect against recurrent airway infections. PMID:1439237

  12. The behavioural variant frontotemporal dementia (bvFTD) syndrome in psychiatry

    PubMed Central

    Lanata, Serggio C; Miller, Bruce L

    2016-01-01

    The primary goal of this article is to critically discuss the syndromic overlap that exists between early behavioural variant frontotemporal dementia (bvFTD)—the most common clinical syndrome associated with frontotemporal lobar degeneration (FTLD)—and several primary psychiatric disorders. We begin by summarising the current state of knowledge regarding FTLD, including the recent discovery of FTLD-causative genetic mutations. Clinicopathological correlations in FTLD are subsequently discussed, while emphasising that clinical syndromes of FTD are dictated by the distribution of FTLD pathology in the brain. We then review a large number of cases with suspected and confirmed bvFTD that had previously been diagnosed with a primary psychiatric disorder. The clinical and neuroscientific implications of this overlap are discussed, focusing on the importance of early diagnosis for clinical and therapeutic reasons. We propose that largely due to the paucity of biomarkers for primary psychiatric disorders, and the limited use of FTLD-related biomarkers by psychiatrists at present, it is very difficult to separate patients with early bvFTD from those with primary psychiatric disorders based on clinical grounds. Furthermore, specific limitations of the Diagnostic and Statistical Manual of Mental Disorders (DSM) 5 criteria for bvFTD may inadvertently discourage recognition of bvFTD in mental health settings. Clinically, more research is needed to develop tools that allow early differentiation of bvFTD from primary psychiatric disease, as bvFTD therapies will likely be most effective in the earliest stages of disease. From a neuroscience perspective, we argue that bvFTD provides an excellent paradigm for investigating the neural basis of psychiatric disorders. PMID:26216940

  13. The behavioural variant frontotemporal dementia (bvFTD) syndrome in psychiatry.

    PubMed

    Lanata, Serggio C; Miller, Bruce L

    2016-05-01

    The primary goal of this article is to critically discuss the syndromic overlap that exists between early behavioural variant frontotemporal dementia (bvFTD)-the most common clinical syndrome associated with frontotemporal lobar degeneration (FTLD)-and several primary psychiatric disorders. We begin by summarising the current state of knowledge regarding FTLD, including the recent discovery of FTLD-causative genetic mutations. Clinicopathological correlations in FTLD are subsequently discussed, while emphasising that clinical syndromes of FTD are dictated by the distribution of FTLD pathology in the brain. We then review a large number of cases with suspected and confirmed bvFTD that had previously been diagnosed with a primary psychiatric disorder. The clinical and neuroscientific implications of this overlap are discussed, focusing on the importance of early diagnosis for clinical and therapeutic reasons. We propose that largely due to the paucity of biomarkers for primary psychiatric disorders, and the limited use of FTLD-related biomarkers by psychiatrists at present, it is very difficult to separate patients with early bvFTD from those with primary psychiatric disorders based on clinical grounds. Furthermore, specific limitations of the Diagnostic and Statistical Manual of Mental Disorders (DSM) 5 criteria for bvFTD may inadvertently discourage recognition of bvFTD in mental health settings. Clinically, more research is needed to develop tools that allow early differentiation of bvFTD from primary psychiatric disease, as bvFTD therapies will likely be most effective in the earliest stages of disease. From a neuroscience perspective, we argue that bvFTD provides an excellent paradigm for investigating the neural basis of psychiatric disorders. PMID:26216940

  14. Characterization of a novel gene encoding ankyrin repeat domain from Cotesia vestalis polydnavirus (CvBV)

    SciTech Connect

    Shi Min; Chen Yafeng; Huang Fang; Liu Pengcheng; Zhou Xueping; Chen Xuexin

    2008-06-05

    Cotesia vestalis (Haliday) is an endoparasitoid of Plutella xylostella (L.) larvae and injects a polydnavirus (CvBV) into its host during oviposition. In this report we describe the characterization of a gene (CvBV805) and its products. CvBV805 is located on the segment S8 of CvBV genome; it has a size of 909 bp and encodes a predicted protein of 125 amino acids. This protein contains an ankyrin repeat domain with a high degree of similarity with I{kappa}B-like genes. Gene transcripts were detected in extracts of the host as early as 2 h post-parasitization (p.p.) and continued to be detected through 24 h. Tissue-specific expression patterns showed that CvBV805 might be involved in early host immunosuppression. CvBV805 was detected in parasitized hosts at 12 h p.p. and in rBac-eGFP-CvBV805-infected Tn-5B1-4 cells at 72 h.p.i. by using western blots analysis. The size of the protein expressed in the host hemocytes and infected Tn-5B1-4 cells was 17 kDa and 56 kDa (including eGFP), respectively, which nearly corresponded with the predicted molecular weight (14.31 kDa) of CvBV805, suggesting that the protein did not undergo extensive post-translational modification. The protein was confirmed to be present within the nuclear region in hemocytes of the parasitized P. xylostella larvae at 48 h p.p. using confocal laser scanning microscopy.

  15. The Phenotype of the C9ORF72 Expansion Carriers According to Revised Criteria for bvFTD

    PubMed Central

    Solje, Eino; Aaltokallio, Heidi; Koivumaa-Honkanen, Heli; Suhonen, Noora M.; Moilanen, Virpi; Kiviharju, Anna; Traynor, Bryan; Tienari, Pentti J.; Hartikainen, Päivi; Remes, Anne M.

    2015-01-01

    Background The C9ORF72 expansion is one of the most common genetic etiologies observed with behavioural variant frontotemporal dementia (bvFTD). Revised diagnostic criteria for bvFTD (FTDC) were recently introduced but only a few studies have evaluated the accuracy of these criteria. Objective The objective of the study was to evaluate the applicability of the FTDC criteria and assess the psychiatric history of these patients. Methods The study examined 36 patients carrying the C9ORF72 expansion and suffering from bvFTD (N = 32) or from bvFTD with motor neuron disease (bvFTD-MND, N = 4). Neuropsychological, neuropsychiatric, structural brain imaging and PET/SPECT data were evaluated. Results We found 0.75 sensitivity (SD 0.44, 95%CI 0.57–0.87) for possible bvFTD and 0.64 (SD 0.44, 95%CI 0.57–0.87) for probable bvFTD. The sensitivity was even higher in bvFTD patients without MND, i.e., 0.81 for possible bvFTD and 0.69 for probable bvFTD. PET/SPECT was normal in 17.6% of scanned patients with bvFTD. A history of psychiatric symptoms (psychotic and/or mood symptoms) was detected in 61% of cases. Conclusions The FTDC possible and probable bvFTD criteria seem to identify the majority of the C9ORF72 expansion carriers with bvFTD, even though they exhibit only a limited number of behavioral criteria but a significant amount of psychiatric symptoms. The presence of a normal PET/SPECT does not exclude the possibility the C9ORF72 associated bvFTD. PMID:26146826

  16. Facility 5A, interior oblique view from the west end. View ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Facility 5A, interior oblique view from the west end. View facing east-northeast - U.S. Naval Base, Pearl Harbor, Forge Shop & Galvanizing Shop, Sixth Street between Avenues D & E, Pearl City, Honolulu County, HI

  17. Facility 5A, interior oblique view from the east end. View ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Facility 5A, interior oblique view from the east end. View facing west-northwest - U.S. Naval Base, Pearl Harbor, Forge Shop & Galvanizing Shop, Sixth Street between Avenues D & E, Pearl City, Honolulu County, HI

  18. UNIT 578A INTERIOR VIEW OF THE LIVING ROOM THROUGH THE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    UNIT 578A INTERIOR VIEW OF THE LIVING ROOM THROUGH THE DINING ROOM DOORWAY. NOTE THE TELEPHONE NICHE IN THE DINING ROOM AT RIGHT. VIEW FACING WEST. - Hickam Field, NCO Housing Type 5, 206 Tenth Street, Honolulu, Honolulu County, HI

  19. Immunotherapy with an oral bacterial extract (OM-85 BV) for upper respiratory infections.

    PubMed

    Paupe, J

    1991-01-01

    The efficacy of Broncho-Vaxom/Imocur (OM-85 BV), an orally administered lyophilized bacterial extract, for recurrent respiratory and ear, nose and throat (ENT) infections was evaluated in 116 children aged 6 months to 19 years by comparing its activity in 61 children with that of a placebo in 55 children. The study was randomized, double-blind, and comprised a 90-day treatment period followed by a 90-day follow-up period without test drugs. Over the 180 days, 39.5% of patients taking OM-85 BV remained free from infection compared with 16.5% on placebo (p less than 0.01). 44% on OM-85 BV did not need antibiotics compared with 23.5% on placebo (p less than 0.05). These differences were even greater in the subgroup of children aged 6 years and less (34 vs. 3.5% for the absence of infections, p less than 0.01 and 37 vs. 10% for the need of antibiotics, p less than 0.05). Tolerance to OM-85 BV was excellent, and laboratory investigations showed no abnormalities attributable to this product. This work confirms that the immunomodulator OM-85 BV is an effective immunotherapy for recurrent respiratory and ENT infections in children. PMID:1745846

  20. TLR4 Signaling in MPP+-Induced Activation of BV-2 Cells

    PubMed Central

    Zhou, Peng; Weng, Ruihui; Chen, Zhaoyu; Wang, Rui; Zou, Jing; Liu, Xu; Liao, Jinchi; Wang, Yanping; Xia, Ying; Wang, Qing

    2016-01-01

    Aims. This work was conducted to establish an in vitro Parkinson's disease (PD) model by exposing BV-2 cells to 1-methyl-4-phenylpyridinium (MPP+) and exploring the roles of TLR2/TLR4/TLR9 in inflammatory responses to MPP+. Methods/Results. MTT assay showed that cell viability of BV-2 cells was 84.78 ± 0.86% and 81.18 ± 0.99% of the control after incubation with 0.1 mM MPP+ for 12 hours and 24 hours, respectively. Viability was not significantly different from the control group. With immunofluorescence technique, we found that MPP+ incubation at 0.1 mM for 12 hours was the best condition to activate BV-2 cells. In this condition, the levels of TNF-α, IL-1β, and iNOS protein were statistically increased compared to the control according to ELISA tests. Real time RT-PCR and western blot measurements showed that TLR4 was statistically increased after 0.1 mM MPP+ incubation for 12 hours. Furthermore, after siRNA interference of TLR4 mRNA, NF-κB activation and the levels of TNF-α, IL-1β, and iNOS were all statistically decreased in this cell model. Conclusion. MPP+ incubation at the concentration of 0.1 mM for 12 hours is the best condition to activate BV-2 cells for mimicking PD inflammation in BV-2 cells. TLR4 signalling plays a critical role in the activation of BV-2 cells and the induction of inflammation in this cell model. PMID:26881113

  1. Complete genome sequence of Mesorhizobium ciceri bv. biserrulae type strain (WSM1271T)

    SciTech Connect

    Nandesena, Kemanthi; Yates, Ron; Tiwari, Ravi; O'Hara, Graham; Howieson, John; Ninawi, Mohamed; Chertkov, Olga; Detter, J. Chris; Tapia, Roxanne; Han, Cliff; Woyke, Tanja; Pitluck, Sam; Nolan, Matt; Land, Miriam L; Liolios, Konstantinos; Pati, Amrita; Copeland, A; Kyrpides, Nikos C; Ivanova, N; Goodwin, Lynne A.; Meenakshi, Uma; Reeve, Wayne

    2013-01-01

    Mesorhizobium ciceri bv. biserrulae strain WSM1271T was isolated from root nodules of the pasture legume Biserrula pelecinus growing in the Mediterranean basin. Previous studies have shown this aerobic, motile, Gram negative, non-spore-forming rod preferably nodulates B. pelecinus a legume with many beneficial agronomic attributes for sustainable agriculture in Australia. We describe the genome of Mesorhizobium ciceri bv. biserrulae strain WSM1271T consisting of a 6,264,489 bp chro-mosome and a 425,539 bp plasmid that together encode 6,470 protein-coding genes and 61 RNA-only encoding genes.

  2. Distinct effects of Broncho-Vaxom (OM-85 BV) on gp130 binding cytokines

    PubMed Central

    Roth, M; Block, L

    2000-01-01

    BACKGROUND—Broncho-Vaxom (OM-85 BV) is known to support respiratory tract resistance to bacterial infections. In vivo and in vitro studies in animals and humans have shown that the action of the drug is based on the modulation of the host immune response, and it has been found to upregulate interferon γ (IFN-γ) and interleukin (IL)-2, IL-6, and IL-8. These immunomodulatory effects of the compound may explain its stimulation on T helper cells and natural killer cells. Following earlier findings that OM-85 BV induces the synthesis of IL-6, a study was undertaken to investigate its possible effect on other gp130 binding cytokines including IL-11, IL-12, leukaemia inhibitory factor (LIF), oncostatin M (OSM), and ciliary neutrophil factor (CNTF). Its modulation of the corresponding receptors of the above mentioned cytokines and of the signal transducer gp130 in human pulmonary fibroblasts and peripheral blood lymphocytes was also studied.
METHODS—Transcription of cytokines was assessed by Northern blot analysis. Secretion of cytokines was analysed using commercially available enzyme linked immunosorbent assay kits. Cytokine receptors and gp130 proteins were determined by Western blot analysis.
RESULTS—OM-85 BV increased the expression of IL-11 in human lung fibroblasts, but not in lymphocytes, in a dose and time dependent manner by maximal fivefold within 20 hours. The compound inhibited serum induced IL-12 expression in peripheral blood lymphocytes but did not induce OSM, LIF, or CNTF at any concentration. In lung fibroblasts the expression of the IL-6 receptor was enhanced fourfold at a concentration of 10 µg/ml OM-85 BV while that of the IL-11 receptor was not altered. In peripheral blood lymphocytes LIF receptor α expression was downregulated in the presence of 10 µg/ml OM-85 BV. At a concentration of 10 µg/ml OM-85 BV enhanced gp130 gene transcription fivefold and increased gp130 protein accumulation in cell membranes by 2.5times

  3. BV RI CCD photometry of 361,281 objects in the field of M 31

    NASA Technical Reports Server (NTRS)

    Magnier, E. A.; Lewin, W. H. G.; Van Paradijs, J.; Hasinger, G.; Jain, A.; Pietsch, W.; Truemper, J.

    1992-01-01

    Deep BV RI CCD photometry was performed on a 1 sq deg region of M 31. A catalog of photometry and astrometry of a total of 361,281 stars is presented, with typical completion limits of BV RI = (22.3, 22.2, 22.2, 20.9). Photometric accuracy is about 2 percent at V = 19. This catalog allows detailed studies of stellar populations and reddening. The data are currently being used to assist in finding the optical counterparts of Einstein and ROSAT X-ray sources.

  4. BV-Regularity of the Boltzmann Equation in Non-Convex Domains

    NASA Astrophysics Data System (ADS)

    Guo, Y.; Kim, C.; Tonon, D.; Trescases, A.

    2016-06-01

    We consider the Boltzmann equation in a general non-convex domain with the diffuse boundary condition. We establish optimal BV estimates for such solutions. Our method consists of a new W 1,1-trace estimate for the diffuse boundary condition and a delicate construction of an {\\varepsilon}-tubular neighborhood of the singular set.

  5. 77 FR 48473 - Airworthiness Directives; Fokker Services B.V. Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-14

    ... February 21, 2012 (77 FR 9871). That earlier NPRM proposed to supersede AD 2004-15-08, Amendment 39-13742 (69 FR 44586, July 27, 2004), to require actions intended to address the unsafe condition for the products listed above. Since that NPRM (77 FR 9871, February 21, 2012) was issued, Fokker Services B.V....

  6. Bacterial extract OM-85 BV protects mice against experimental chronic rhinosinusitis

    PubMed Central

    Tao, Yanli; Yuan, Tiejun; Li, Xuechang; Yang, Shuqin; Zhang, Fanping; Shi, Li

    2015-01-01

    Objectives: To investigate the therapeutic effects of OM-85 BV as an adjunctive treatment on experimental chronic rhinosinusitis (CRS) in mice. Methodology: Female BALB/c mice aged 8-12 weeks were sensitized and administrated by intranasal Aspergillus fumigatis (AF) three times per week for 1 week, 3 weeks, 2 months and 3 months (n = 10 each time point). The mice were randomly and equally assigned to four groups: normal control group, model group, OM-85-BV plus amoxicillin group, and isolated amoxicillin group. Inflammatory changes were determined by hematoxylin-eosin (HE) staining. The expression levels of suppressor of cytokine signaling (SOCS) 1, SOCS3, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ in samples were assessed by using real-time PCR (RT-PCR) and Western blotting. Results: There were significantly inflammatory and structural changes between the model and other groups. Compared to the model group, the mRNA expression levels of SOCS1, SOCS3, TNF-α, and IFN-γ were significantly decreased in OM-85-BV plus amoxicillin group and isolated amoxicillin group, along with the protein levels. Conclusion: The bacterial extract OM-85 BV is a low-cost alternatively adjunctive drug to treat CRS with simple oral administration, good safety, and few side effects. PMID:26261565

  7. 77 FR 9871 - Airworthiness Directives; Fokker Services B.V. Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-21

    ... FR 14661, March 19, 2008). (c) Applicability This AD applies to Fokker Services B.V. Model F.28 Mark.... Discussion On July 9, 2004, we issued AD 2004-15-08, Amendment 39-13742 (69 FR 44586, July 27, 2004). This AD... 2004-15-08, Amendment 39-13742 (69 FR 44586, July 27, 2004): The European Aviation Safety Agency...

  8. 77 FR 68063 - Airworthiness Directives; Fokker Services B.V. Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-15

    ... (69 FR 44586, July 27, 2004), and adding the following new AD: 2012-22-15 Fokker Services B.V..., Amendment 39-15432 (73 FR 14661, March 19, 2008). (c) Applicability (1) This AD applies to Fokker Services B... reference of certain other publications listed in this AD as of August 31, 2004 (69 FR 44586, July 27,...

  9. 76 FR 20501 - Airworthiness Directives; Fokker Services B.V. Model F.27 Mark 050 Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-13

    ... and Maintenance and Inspection Requirements'' (66 FR 23086, May 7, 2001). In addition to new... Procedures (44 FR 11034, February 26, 1979); and 3. Will not have a significant economic impact, positive or... Services B.V. Model F.27 Mark 050 Airplanes AGENCY: Federal Aviation Administration (FAA), Department...

  10. Functionally Charged Polystyrene Particles Activate Immortalized Mouse Microglia (BV2): Cellular and Genomic Response

    EPA Science Inventory

    The effect of particle surface charge on the biological activation of immortalized mouse microglia (BV2) was examined. Same size (~850-950 nm) spherical polystyrene microparticles (SPM) with net negative (carboxyl, COOH-) or positive (dimethyl amino, CH3)2

  11. Trimethyltin-Induced Microglial Activation via NADPH Oxidase and MAPKs Pathway in BV-2 Microglial Cells

    PubMed Central

    Kim, Da Jung; Kim, Yong Sik

    2015-01-01

    Trimethyltin (TMT) is known as a potent neurotoxicant that causes neuronal cell death and neuroinflammation, particularly in the hippocampus. Microglial activation is one of the prominent pathological features of TMT neurotoxicity. Nevertheless, it remains unclear how microglial activation occurs in TMT intoxication. In this study, we aimed to investigate the signaling pathways in TMT-induced microglial activation using BV-2 murine microglial cells. Our results revealed that TMT generates reactive oxygen species (ROS) and increases the expression of CD11b and nuclear factor-κB- (NF-κB-) mediated nitric oxide (NO) and tumor necrosis factor- (TNF-) α in BV-2 cells. We also observed that NF-κB activation was controlled by p38 and JNK phosphorylation. Moreover, TMT-induced ROS generation occurred via nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in BV-2 cells. Interestingly, treatment with the NADPH oxidase inhibitor apocynin significantly suppressed p38 and JNK phosphorylation and NF-κB activation and ultimately the production of proinflammatory mediators upon TMT exposure. These findings indicate that NADPH oxidase-dependent ROS generation activated p38 and JNK mitogen-activated protein kinases (MAPKs), which then stimulated NF-κB to release proinflammatory mediators in the TMT-treated BV-2 cells. PMID:26221064

  12. 76 FR 49533 - Spyker Automobielen B.V.; Receipt of Application for Temporary Exemption from FMVSS No. 126

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-10

    ... NV plans to sell Spyker Automobielen B.V. to CPP Global Holdings, a private holding company in the... Automobile AG, and, in light of the plans to sell Spyker Automobielen B.V. to CPP Global Holdings, NHTSA will...: August 5, 2011. Christopher J. Bonanti, Associate Administrator for Rulemaking. BILLING CODE 4910-59-P...

  13. BUILDING NO. 9957A. INTERIOR DETAIL OF OFFICE AND BATHROOM DOORS, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    BUILDING NO. 9957-A. INTERIOR DETAIL OF OFFICE AND BATHROOM DOORS, HALLWAY, TILES, SINK, ETC. ROOM IS THIRD FROM RIGHT AS YOU ENTER BUILDING FROM RAMP NO. 4. - Madigan Hospital, Standard & Combination Wards, Bounded by Wilson & McKinley Avenues & Garfield & Lincoln Streets, Tacoma, Pierce County, WA

  14. Facility S17A, interior view of underground room showing bypass valves ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Facility S17A, interior view of underground room showing by-pass valves standing in a row along edge of wall, view facing southeast - U.S. Naval Base, Pearl Harbor, Dry Dock No. 1, Pumpwell, By-Pass Valve & Saltwater Pumphouse, North end of Fifth Street, between Dry Dock No. 1 & Facility GD2 , Pearl City, Honolulu County, HI

  15. UNIT 578A INTERIOR VIEW OF THE KITCHEN. SHOWING THE SINGLESTORY ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    UNIT 578A INTERIOR VIEW OF THE KITCHEN. SHOWING THE SINGLE-STORY LIGHT OVER THREE-PANEL DOOR TO THE SERVICE PORCH AND THE BUILT-IN SPICE RACK. VIEW FACING WEST. - Hickam Field, NCO Housing Type 5, 206 Tenth Street, Honolulu, Honolulu County, HI

  16. Titanium dioxide (P25) produces reactive oxygen species in immortalized brain microglia (BV2): implications for nanoparticle neurotoxicity.

    PubMed

    Long, Thomas C; Saleh, Navid; Tilton, Robert D; Lowry, Gregory V; Veronesi, Bellina

    2006-07-15

    Concerns with the environmental and health risk of widely distributed, commonly used nanoparticles are increasing. Nanosize titanium dioxide (TiO2) is used in air and water remediation and in numerous products designed for direct human use and consumption. Its effectiveness in deactivating pollutants and killing microorganisms relates to photoactivation and the resulting free radical activity. This property, coupled with its multiple potential exposure routes, indicates that nanosize TiO2 could pose a risk to biological targets that are sensitive to oxidative stress damage (e.g., brain). In this study, brain microglia (BV2) were exposed to a physicochemically characterized (i.e., dispersion stability, particle size distribution, and zeta potential) nanomaterial, Degussa P25, and cellular expressions of reactive oxygen species were measured with fluorescent probes. P25's zeta potentials, measured in cell culture media and physiological buffer were -11.6 +/- 1.2 mV and -9.25 +/- 0.73 mV, respectively. P25 aggregation was rapid in both media and buffer with the hydrodynamic diameter of stable P25 aggregates ranging from 826 nm to 2368 nm depending on the concentration. The biological response of BV2 microglia to noncytotoxic (2.5-120 ppm) concentrations of P25 was a rapid (<5 min) and sustained (120 min) release of reactive oxygen species. The time course of this release suggested that P25 not only stimulated the immediate "oxidative burst" response in microglia but also interfered with mitochondrial energy production. Transmission electron microscopy indicated that small groups of nanosized particles and micron-sized aggregates were engulfed bythe microglia and sequestered as intracytoplasmic aggregates after 6 and 18 h exposure to P25 (2.5 ppm). Cell viability was maintained at all test concentrations (2.5-120 ppm) over the 18 h exposure period. These data indicate that mouse microglia respond to Degussa P25 with cellular and morphological expressions of free

  17. VizieR Online Data Catalog: HR 7355 differential BV light curves (Mikulasek+, 2010)

    NASA Astrophysics Data System (ADS)

    Mikulasek, Z.; Krticka, J.; Henry, G. W.; de Villiers, S. N.; Paunzen, E.; Zejda, M.

    2010-02-01

    Differential BV photometry of the He strong CP star HR 5153=HD 182180 versus the comparison star HD 179520. Most of data was acquired by G.W.Henry (GWH) with the T3 0.4-m automatic photoelectric telescope (APT) at Fairborn Observatory in southern Arizona during 2008 May and June. The T3 APT uses a temperature-stabilised EMI 9924B photomultiplier tube to measure photon count rates sequentially through B and V filters. We acquired there 43 B and 38 V measurements. We also obtained 7 continuous hours of BV photometry with a photoelectric photometer attached to a 0.28-m reflector on the night of 2009 July 26 UT at the private observatory of S.N. de Villiers (SNV) in Cape Town, South Africa. We acquired 16 and 17 measurements in B and V. (1 data file).

  18. Four years of immunization with OM-85 BV to prevent respiratory infections in HIV+ patients.

    PubMed

    Capetti, Amedeo; Cossu, Maria Vittoria; Carenzi, Laura; Rizzardini, Giuliano

    2013-09-01

    We report an interventional, non-randomized experience of OM-85 BV immunization in a group of 104 HIV-infected subjects presenting recurrent seasonal respiratory bacterial infections. We compared the number of respiratory events, the use of antibiotics and the cost related to antibiotics before (2005-2006) and after (2008-2011) the introduction of such intervention. The year 2007 was excluded from the analysis since half of the patients were immunized in that year in an exploratory approach. Respiratory infections dropped in all groups but in subjects with recurrent otitis, leading to a reduction in the use of antibiotics. This is the first report of the effect of OM-85 BV in vivo in HIV-infected subjects. PMID:23792443

  19. Genome sequence of the clover-nodulating Rhizobium leguminosarum bv. trifolii strain TA1

    PubMed Central

    Reeve, Wayne; Tian, Rui; De Meyer, Sofie; Melino, Vanessa; Terpolilli, Jason; Ardley, Julie; Tiwari, Ravi; Howieson, John; Yates, Ronald; O’Hara, Graham; Ninawi, Mohamed; Teshima, Hazuki; Bruce, David; Detter, Chris; Tapia, Roxanne; Han, Cliff; Wei, Chia-Lin; Huntemann, Marcel; Han, James; Chen, I-Min; Mavromatis, Konstantinos; Markowitz, Victor; Ivanova, Natalia; Ovchinnikova, Galina; Pagani, Ioanna; Pati, Amrita; Goodwin, Lynne; Pitluck, Sam; Woyke, Tanja; Kyrpides, Nikos

    2013-01-01

    Rhizobium leguminosarum bv. trifolii strain TA1 is an aerobic, motile, Gram-negative, non-spore-forming rod that is an effective nitrogen fixing microsymbiont on the perennial clovers originating from Europe and the Mediterranean basin. TA1 however is ineffective with many annual and perennial clovers originating from Africa and America. Here we describe the features of R. leguminosarum bv. trifolii strain TA1, together with genome sequence information and annotation. The 8,618,824 bp high-quality-draft genome is arranged in a 6 scaffold of 32 contigs, contains 8,493 protein-coding genes and 83 RNA-only encoding genes, and is one of 20 rhizobial genomes sequenced as part of the DOE Joint Genome Institute 2010 Community Sequencing Program. PMID:24976881

  20. Four years of immunization with OM-85 BV to prevent respiratory infections in HIV+ patients

    PubMed Central

    Capetti, Amedeo; Cossu, Maria Vittoria; Carenzi, Laura; Rizzardini, Giuliano

    2013-01-01

    We report an interventional, non-randomized experience of OM-85 BV immunization in a group of 104 HIV-infected subjects presenting recurrent seasonal respiratory bacterial infections. We compared the number of respiratory events, the use of antibiotics and the cost related to antibiotics before (2005–2006) and after (2008–2011) the introduction of such intervention. The year 2007 was excluded from the analysis since half of the patients were immunized in that year in an exploratory approach. Respiratory infections dropped in all groups but in subjects with recurrent otitis, leading to a reduction in the use of antibiotics. This is the first report of the effect of OM-85 BV in vivo in HIV-infected subjects. PMID:23792443

  1. Th1-orientated immunological properties of the bacterial extract OM-85-BV.

    PubMed

    Huber, M; Mossmann, H; Bessler, W G

    2005-05-20

    The bacterial extract OM-85-BV prepared from 21 pathogenic bacterial strains is administered orally to adults and children for the treatment and prevention of recurrent infections of the respiratory tract. We analyzed in vitro and in vivo the immunomodulatory effects of the extract. The lysate acted as a non specific macrophage activator, inducing NO production as well as the translocation of transcription factor NF-kappaB into the nucleus in murine bone marrow-derived macrophages. Besides stimulating unspecifically the immune system, a bacteria-specific humoral immune response was revealed. After oral application, a trend to increase bacteria-specific IgG and IgA in serum was observed. Also a marked increase of bacteria specific IgA in saliva as well as in supernatants of Peyer's patches and mesenteric lymph nodes-derived cell cultures was found. The immunomodulatory properties of the extract were also investigated with respect to shifting the Th1/Th2 bias in an in vivo allergy model. BALB/c mice were orally immunized with OM-85-BV and subsequently sensitized intraperitoneally with the allergen ovalbumin. The group pretreated with OM-85-BV showed a decrease of both total and ovalbumin specific IgE. Accordingly, in spleen cell supernatants the Th1-associated cytokine IFN-gamma was increased, and the Th2-associated cytokine IL-4 was downregulated. Our findings suggest that the immunoprotective effects of OM-85-BV observed in human beings may be correlated to its Th1 augmenting properties. PMID:15946922

  2. Benzyl isothiocyanate inhibits inflammasome activation in E. coli LPS-stimulated BV2 cells.

    PubMed

    Lee, Chang-Min; Lee, Dae-Sung; Jung, Won-Kyo; Yoo, Jong Su; Yim, Mi-Jin; Choi, Yung Hyun; Park, Saegwang; Seo, Su-Kil; Choi, Jung Sik; Lee, Young-Min; Park, Won Sun; Choi, Il-Whan

    2016-09-01

    Inflammasomes are multi-protein complexes that play a crucial role in innate immune responses. Benzyl isothiocyanate (BITC) is a naturally occurring compound found in cruciferous vegetables, and BITC exhibits potential as a chemopreventive agent. However, whether BITC exerts inflammasome-mediated regulatory effects on neuroinflammation is unknown. In this study, we examined the effects of BITC on inflammasome-mediated interleukin-1β (IL-1β) production in E. coli lipopolysaccharide (LPS)-stimulated BV2 microglial cells. IL-1β production is tightly regulated at the post-translational level through the inflammasoume. We measured the levels of IL-1β produced from the LPS-exposed BV2 microglial cells using enzyme-linked immunosorbent assays (ELISAs). The BITC regulatory mechanisms in inflammasome-mediated cellular signaling pathways were examined by RT-PCR, western blot analysis and electrophoretic mobility shift assays. BITC inhibited the secretion of IL-1β induced by LPS in the BV2 microglial cells. BITC inhibited inflammasome activation and NLR family, pyrin domain containing 3 (NLRP3)-mediated caspase-1 activation, and decreased the levels of inflammasome activation pro-inflammatory mediators, including mitochondrial reactive oxygen species (ROS) and adenosine triphosphate (ATP) secretion in the LPS-stimulated BV2 microglial cells. Furthermore, we demonstrated that nuclear factor-κB (NF-κB) activation induced by LPS was inhibited by BITC, which may contribute to the attenuated secretion of IL-1β. These BITC-mediated inhibitory effects on IL-1β expression may thus regulate neuroinflammation through the inflammasome-mediated signaling pathway. PMID:27430883

  3. Draft Genome Sequence of Lactococcus lactis subsp. lactis bv. diacetylactis CRL264, a Citrate-Fermenting Strain

    PubMed Central

    Zuljan, Federico; Espariz, Martín; Blancato, Victor S.; Esteban, Luis; Alarcón, Sergio

    2016-01-01

    We report the draft genome sequence of Lactococcus lactis subsp. lactis bv. diacetylactis CRL264, a natural strain isolated from artisanal cheese from northwest Argentina. L. lactis subsp. lactis bv. diacetylactis is one of the most important microorganisms used as starter culture around the world. The CRL264 strain constitutes a model microorganism in the studies on the generation of aroma compounds (diacetyl, acetoin, and 2,3-butanediol) by lactic acid bacteria. Our genome analysis shows similar genetic organization to other available genomes of L. lactis bv. diacetylactis strains. PMID:26847906

  4. Draft Genome Sequence of Lactococcus lactis subsp. lactis bv. diacetylactis CRL264, a Citrate-Fermenting Strain.

    PubMed

    Zuljan, Federico; Espariz, Martín; Blancato, Victor S; Esteban, Luis; Alarcón, Sergio; Magni, Christian

    2016-01-01

    We report the draft genome sequence of Lactococcus lactis subsp. lactis bv. diacetylactis CRL264, a natural strain isolated from artisanal cheese from northwest Argentina. L. lactis subsp. lactis bv. diacetylactis is one of the most important microorganisms used as starter culture around the world. The CRL264 strain constitutes a model microorganism in the studies on the generation of aroma compounds (diacetyl, acetoin, and 2,3-butanediol) by lactic acid bacteria. Our genome analysis shows similar genetic organization to other available genomes of L. lactis bv. diacetylactis strains. PMID:26847906

  5. Use of OM-85 BV for the prevention of acute respiratory tract infections in occupational medicine.

    PubMed

    Carmona-Ramírez, M A; Alvárez-Gómez, V; Berber, A

    2002-01-01

    This study evaluated the safety and efficacy of the immunostimulatory agent OM-85 BV in 112 male car-factory workers who were highly susceptible to acute respiratory tract infections (ARTIs), each having experienced > or = 4 ARTIs during 1999. From January to March 2000, each worker received one capsule of OM-85 BV (7 mg) per day for 10 consecutive days each month. The patients were followed for a further 9 months. Mean number of ARTIs decreased from 8.2 +/- 2.1 per worker in 1999 to 5.3 +/- 2.9 in 2000; i.e. a difference of -2.9 (95% confidence intervals, -3.5 to -2.4). Similar effects were observed in men who had different job roles, and no adverse events were reported during drug administration. We concluded that OM-85 BV appears to be safe and effective in reducing the incidence of ARTIs in susceptible workers, although further double-blind, placebo-controlled clinical trials are required. PMID:12166352

  6. Anti-inflammatory effects of cordycepin via suppression of inflammatory mediators in BV2 microglial cells.

    PubMed

    Jeong, Jin-Woo; Jin, Cheng-Yun; Kim, Gi-Young; Lee, Jae-Dong; Park, Cheol; Kim, Gun-Do; Kim, Wun-Jae; Jung, Won-Kyo; Seo, Su Kil; Choi, Il-Whan; Choi, Yung Hyun

    2010-12-01

    Cordyceps militaris, a traditional medicinal mushroom, produces the bioactive compound cordycepin (3'-deoxyadenosine). Although cordycepin has been shown to have pharmacological, immunological stimulating, anti-cancer, and anti-inflammatory activities, its activities and cellular mechanisms during microglial activation have yet to be elucidated. Thus, we evaluated the anti-inflammatory effect of cordycepin on the production of inflammatory mediators in lipopolysaccharide (LPS)-stimulated murine BV2 microglia. We also investigated the effects of cordycepin on LPS-induced nuclear factor-kappaB (NF-κB) activation and on phosphorylation of mitogen-activated protein kinases (MAPKs). After LPS stimulation, nitric oxide (NO), prostaglandin E₂ (PGE₂), and pro-inflammatory cytokine production was detected in BV2 microglia. However, we found that cordycepin significantly inhibited the excessive production of NO, PGE₂, and pro-inflammatory cytokines in a concentration-dependent manner without causing cytotoxicity. In addition, cordycepin suppressed NF-κB translocation by blocking IkappaB-α (IκB-α) degradation and inhibited the phosphorylation of Akt, ERK-1/2, JNK, and p38 kinase. Our results indicate that the inhibitory effect of cordycepin on LPS-stimulated inflammatory mediator production in BV2 microglia is associated with the suppression of the NF-κB, Akt, and MAPK signaling pathways. Therefore, cordycepin may be useful in treating neurodegenerative diseases by inhibiting inflammatory mediator production in activated microglia. PMID:20937401

  7. Safflower Yellow regulates microglial polarization and inhibits inflammatory response in LPS-stimulated Bv2 cells.

    PubMed

    Yang, Xing-Wang; Li, Yan-Hua; Zhang, Hui; Zhao, Yong-Fei; Ding, Zhi-Bin; Yu, Jie-Zhong; Liu, Chun-Yun; Liu, Jian-Chun; Jiang, Wei-Jia; Feng, Qian-Jin; Xiao, Bao-Guo; Ma, Cun-Gen

    2016-03-01

    Activated microglia, especially polarized M1 cells, produce pro-inflammatory cytokines and free radicals, thereby contributing directly to neuroinflammation and various brain disorders. Given that excessive or chronic neuroinflammation within the central nervous system (CNS) exacerbates neuronal damage, molecules that modulate neuroinflammation are candidates as neuroprotective agents. In this study, we provide evidence that Safflor yellow (SY), the main active component in the traditional Chinese medicine safflower, modulates inflammatory responses by acting directly on BV2 microglia. LPS stimulated BV2 cells to upregulate expression of TLR4-Myd88 and MAPK-NF-κB signaling pathways and to release IL-1β, IL-6, TNF-α, and COX-2. However, SY treatment inhibited expression of TLR4-Myd88 and p-38/p-JNK-NF-κB, downregulated expression of iNOS, CD16/32, and IL-12, and upregulated CD206 and IL-10. In conclusion, our results demonstrate that SY exerts an anti-inflammatory effect on BV2 microglia, possibly through TLR-4/p-38/p-JNK/NF-κB signaling pathways and the conversion of microglia from inflammatory M1 to an anti-inflammatory M2 phenotype. PMID:26634402

  8. A tetramethoxychalcone from Chloranthus henryi suppresses lipopolysaccharide-induced inflammatory responses in BV2 microglia.

    PubMed

    Luo, Xiao-Ling; Liu, Si-Yu; Wang, Li-Jun; Zhang, Qiu-Yan; Xu, Peng; Pan, Li-Long; Hu, Jin-Feng

    2016-03-01

    Neuroinflammation underlies the pathogenesis and progression of neurodegenerative diseases. 2׳-hydroxy-4,3׳,4׳,6׳-tetramethoxychalcone (HTMC) is a known chalcone derivative isolated from Chloranthus henryi with anti-inflammatory activities in BV2 macrophages. However, its pharmacological effects on microglial cells have not been demonstrated. To this end, we examined the effects of HTMC on lipopolysaccharide (LPS)-induced inflammatory responses in BV2 microglial cells. HTMC concentration-dependently inhibited LPS-induced expression of inflammatory enzymes including inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), nitric oxide (NO) production, and the secretion of inflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6. In addition, HTMC inhibited reactive oxygen species (ROS) production by reducing NADPH oxidase (Nox) 2 and Nox4 expression. In addition, HTMC interfered LPS-induced c-Jun N-terminal kinase 1/2 (JNK) phosphorylation in a time- and concentration-dependent manner. By inhibiting phosphorylation and nuclear translocation of Jun, HTMC suppressed LPS-induced activator protein-1 (AP-1) activation. Taken together, our data indicate that HTMC suppresses inflammatory responses in LPS-stimulated BV2 microglial cells by modulating JNK-AP-1 and NADPH oxidases-ROS pathways. HTMC represents a promising therapeutic agent for neurodegenerative and related aging-associated diseases. PMID:26852953

  9. OM-85 BV upregulates the expression of adhesion molecules on phagocytes through a CD 14-independent pathway.

    PubMed

    Marchant, A; Goldman, M

    1996-04-01

    OM-85 BV is a preparation of bacterial extracts which proved to be of some efficacy in the prevention of respiratory tract infections. However, the mechanisms of action of this drug remain unclear. As we recently observed that OM-85 BV upregulates the expression of adhesion molecules on phagocytes, we took advantage of this property to determine whether the activating effects of OM-85 BV on monocytes and granulocytes depend on its interaction with CD14 molecules. Indeed, CD14 represents the major cell surface receptor for lipopolysaccharide and other bacterial products at the surface of leucocytes. First, we found that the upregulation of Mac-1 (CD11b/CD18) induced in vitro by OM-85 BV on monocytes was not blocked by an anti-CD14 monoclonal antibody (mAb) which inhibits monocyte responses to lipopolysaccharide. Similarly, the anti-CD14 mAb inhibited upregulation of Mac-1 on granulocytes when it was induced by lipopolysaccharide but not by OM-85 BV. To confirm that the effects of OM-85 on the expression of Mac-1 is CD14-independent, we analysed the responses of a patient with paroxysmal nocturnal haemoglobinuria, a disease associated with a defect of CD14 expression at the membrane of phagocytes. We found that monocytes and granulocytes of this patient displayed an impairment in Mac-1 upregulation in response to lipopolysaccharide whereas they responded normally to OM-85 BV. We conclude that OM-85 BV activates phagocytes through a CD14-independent pathway. The characterisation of the cell surface receptors of monocytes and granulocytes involved in the interactions with OM-85 BV might provide a molecular clue to the mode of action of this preparation of bacterial extracts. PMID:8894805

  10. Genome Sequence of Corynebacterium pseudotuberculosis MB20 bv. equi Isolated from a Pectoral Abscess of an Oldenburg Horse in California

    PubMed Central

    Guimarães, Luís C.; Veras, Adonney A. O.; de Sá, Pablo H. C. G.; Graças, Diego A.; Pinheiro, Kenny C.; Silva, Andreia S. S.; Folador, Edson L.; Benevides, Leandro J.; Viana, Marcus V. C.; Carneiro, Adriana R.; Schneider, Maria P. C.; Spier, Sharon J.; Edman, Judy M.; Ramos, Rommel T. J.; Azevedo, Vasco; Silva, Artur

    2014-01-01

    The genome of Corynebacterium pseudotuberculosis MB20 bv. equi was sequenced using the Ion Personal Genome Machine (PGM) platform, and showed a size of 2,363,089 bp, with 2,365 coding sequences and a GC content of 52.1%. These results will serve as a basis for further studies on the pathogenicity of C. pseudotuberculosis bv. equi. PMID:25395628

  11. Anti-Inflammatory Effects of Progesterone in Lipopolysaccharide-Stimulated BV-2 Microglia

    PubMed Central

    Lei, Beilei; Mace, Brian; Dawson, Hana N.; Warner, David S.; Laskowitz, Daniel T.; James, Michael L.

    2014-01-01

    Female sex is associated with improved outcome in experimental brain injury models, such as traumatic brain injury, ischemic stroke, and intracerebral hemorrhage. This implies female gonadal steroids may be neuroprotective. A mechanism for this may involve modulation of post-injury neuroinflammation. As the resident immunomodulatory cells in central nervous system, microglia are activated during acute brain injury and produce inflammatory mediators which contribute to secondary injury including proinflammatory cytokines, and nitric oxide (NO) and prostaglandin E2 (PGE2), mediated by inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2), respectively. We hypothesized that female gonadal steroids reduce microglia mediated neuroinflammation. In this study, the progesterone’s effects on tumor necrosis factor alpha (TNF-α), iNOS, and COX-2 expression were investigated in lipopolysaccharide (LPS)-stimulated BV-2 microglia. Further, investigation included nuclear factor kappa B (NF-κB) and mitogen activated protein kinase (MAPK) pathways. LPS (30 ng/ml) upregulated TNF-α, iNOS, and COX-2 protein expression in BV-2 cells. Progesterone pretreatment attenuated LPS-stimulated TNF-α, iNOS, and COX-2 expression in a dose-dependent fashion. Progesterone suppressed LPS-induced NF-κB activation by decreasing inhibitory κBα and NF-κB p65 phosphorylation and p65 nuclear translocation. Progesterone decreased LPS-mediated phosphorylation of p38, c-Jun N-terminal kinase and extracellular regulated kinase MAPKs. These progesterone effects were inhibited by its antagonist mifepristone. In conclusion, progesterone exhibits pleiotropic anti-inflammatory effects in LPS-stimulated BV-2 microglia by down-regulating proinflammatory mediators corresponding to suppression of NF-κB and MAPK activation. This suggests progesterone may be used as a potential neurotherapeutic to treat inflammatory components of acute brain injury. PMID:25080336

  12. Microglial cells (BV-2) internalize titanium dioxide (TiO2) nanoparticles: toxicity and cellular responses.

    PubMed

    Rihane, Naima; Nury, Thomas; M'rad, Imen; El Mir, Lassaad; Sakly, Mohsen; Amara, Salem; Lizard, Gérard

    2016-05-01

    Because of their whitening and photocatalytic effects, titanium dioxide nanoparticles (TiO2-NPs) are widely used in daily life. These NPs can be found in paints, plastics, papers, sunscreens, foods, medicines (pills), toothpastes, and cosmetics. However, the biological effect of TiO2-NPs on the human body, especially on the central nervous system, is still unclear. Many studies have demonstrated that the brain is one of the target organs in acute or chronic TiO2-NPs toxicity. The present study aimed to investigate the effect of TiO2-NPs at different concentrations (0.1 to 200 μg/mL) on murine microglial cells (BV-2) to assess their activity on cell growth and viability, as well as their neurotoxicity. Different parameters were measured: cell viability, cell proliferation and DNA content (SubG1 peak), mitochondrial depolarization, overproduction of reactive oxygen species (especially superoxide anions), and ultrastructural changes. Results showed that TiO2-NPs induced some cytotoxic effects with a slight inhibition of cell growth. Thus, at high concentrations, TiO2-NPs were not only able to inhibit cell adhesion but also enhanced cytoplasmic membrane permeability to propidium iodide associated with a loss of mitochondrial transmembrane potential and an overproduction of superoxide anions. No induction of apoptosis based on the presence of a SubG1 peak was detected. The microscopic observations also indicated that small groups of nanosized particles and micron-sized aggregates were engulfed by the BV-2 cells and sequestered as intracytoplasmic aggregates after 24-h exposure to TiO2-NPs. Altogether, our data show that the accumulation TiO2-NPs in microglial BV-2 cells favors mitochondrial dysfunctions and oxidative stress. PMID:26846246

  13. Identification of protein secretion systems and novel secreted proteins in Rhizobium leguminosarum bv. viciae

    PubMed Central

    Krehenbrink, Martin; Downie, J Allan

    2008-01-01

    Background Proteins secreted by bacteria play an important role in infection of eukaryotic hosts. Rhizobia infect the roots of leguminous plants and establish a mutually beneficial symbiosis. Proteins secreted during the infection process by some rhizobial strains can influence infection and modify the plant defence signalling pathways. The aim of this study was to systematically analyse protein secretion in the recently sequenced strain Rhizobium leguminosarum bv. viciae 3841. Results Similarity searches using defined protein secretion systems from other Gram-negative bacteria as query sequences revealed that R. l. bv. viciae 3841 has ten putative protein secretion systems. These are the general export pathway (GEP), a twin-arginine translocase (TAT) secretion system, four separate Type I systems, one putative Type IV system and three Type V autotransporters. Mutations in genes encoding each of these (except the GEP) were generated, but only mutations affecting the PrsDE (Type I) and TAT systems were observed to affect the growth phenotype and the profile of proteins in the culture supernatant. Bioinformatic analysis and mass fingerprinting of tryptic fragments of culture supernatant proteins identified 14 putative Type I substrates, 12 of which are secreted via the PrsDE, secretion system. The TAT mutant was defective for the symbiosis, forming nodules incapable of nitrogen fixation. Conclusion None of the R. l. bv. viciae 3841 protein secretion systems putatively involved in the secretion of proteins to the extracellular space (Type I, Type IV, Type V) is required for establishing the symbiosis with legumes. The PrsDE (Type I) system was shown to be the major route of protein secretion in non-symbiotic cells and to secrete proteins of widely varied size and predicted function. This is in contrast to many Type I systems from other bacteria, which typically secrete specific substrates encoded by genes often localised in close proximity to the genes encoding the

  14. Effect of CCL2 on BV2 microglial cell migration: Involvement of probable signaling pathways.

    PubMed

    Bose, Shambhunath; Kim, Sunyoung; Oh, Yeonsoo; Moniruzzaman, Md; Lee, Gyeongjun; Cho, Jungsook

    2016-05-01

    Microglia, the resident macrophages of the central nervous system, play a vital role in the regulation of innate immune function and neuronal homeostasis of the brain. Currently, much interest is being generated regarding the investigation of the microglial migration that results in their accumulation at focal sites of injury. Chemokines including CCL2 are known to cause the potential induction of migration of microglial cells, although the underlying mechanisms are not well understood. In the present study, using murine neonatal BV2 microglial cells as a model, we investigate the impact of CCL2 on the migration of microglial cells and address the probable molecular events within the cellular signaling cascades mediating CCL2-induced cell migration. Our results demonstrate concentration- and time-dependent induction of BV2 cell migration by CCL2 and reveal complex mechanisms involving the activation of MEK, ERK1/2, and Akt, and their cross-talk. In addition, we demonstrate that the MEK/ERK pathway activated by CCL2 treatment mediate p90RSK activation in BV2 cells. Moreover, our findings indicate that Akt, ERK1/2, and p90RSK are the downstream effectors of PI3K in the CCL2-induced signaling. Finally, phosphorylation of the transcription factors c-jun and ATF-1 is found to be a further downstream signaling cascade in the CCL2-mediated action. Our results suggest that CCL2-induced activation of c-jun and ATF-1 is likely to be linked to the MEK/ERK and PI3K signaling pathways, respectively. Taken together, these findings contribute to a better understanding of CCL2-induced microglial migration and the probable signaling pathways involved. PMID:26878647

  15. Effects of microgravity on the binding of acetylsalicylic acid by Rhizobium leguminosarum bv. trifolii

    NASA Astrophysics Data System (ADS)

    Urban, James E.; Gerren, Richard; Zoelle, Jeffery

    1995-07-01

    Bacteroids can be induced in vitro by treating growing Rhizobium leguminosarum bv. trifolii with succinic acid or succinic acid structural analogs like acetylsalicylic acid. Quantitating bacteroid induction by measuring acetylsalicylic binding under normal (1 g) conditions showed two forms of binding to occur. In one form of binding cells immediately bound comparatively high levels of acetylsalicylic acid, but the binding was quickly reversed. The second form of binding increased with time by first-order kinetics, and reached saturation in 40 s. Similar experiments performed in the microgravity environment aboard the NASA 930 aircraft showed only one form of binding and total acetylsalicylic acid bound was 32% higher than at 1 g.

  16. U BV RI PHOTOMETRIC STANDARD STARS AROUND THE SKY AT +50 deg DECLINATION

    SciTech Connect

    Landolt, Arlo U.

    2013-11-01

    U BV RI photoelectric observations have been made of 335 stars around the sky, and centered approximately at +50 deg declination. The majority of the stars fall in the magnitude range 9 < V < 16, and in the color range –0.3 < (B – V) < +1.8. Those 243 stars best suited as new broadband photometric standard stars average 12.5 measures each from data taken on 98 different nights over a period of 17 years at the Kitt Peak National and Lowell Observatories.

  17. E(BV) Determinations of O and B Stars Using Artificial Neural Networks

    NASA Astrophysics Data System (ADS)

    Gulati, R.; Gupta, R.; Singh, H.

    1997-07-01

    We propose a new method to determine E(B-V) from low dispersion ultraviolet spectra by using artificial neural networks. This method has been applied to O and B stars in the IUE low dispersion catalog. A comparison of the ANN based determinations with the classical method of comparing observed (B-V) with intrinsic color (B-V)o is performed to assess the reliability and limitation of the new method. We have been able to determine E(B-V) to an accuracy of 0.08 magnitudes and also been able to single out a star which follows an anomalous interstellar extinction law. (SECTION: Computing and Data Analysis)

  18. Global gene expression changes in BV2 microglial cell line during rabies virus infection.

    PubMed

    Zhao, Pingsen; Yang, Yujiao; Feng, Hao; Zhao, Lili; Qin, Junling; Zhang, Tao; Wang, Hualei; Yang, Songtao; Xia, Xianzhu

    2013-12-01

    Microglia plays a crucial role during virus pathogenesis in the central nervous system (CNS). Infection by rabies virus (RABV) causes a fatal infection in the CNS of all warm-blooded animals. However, the microglial responses to RABV infection have been scarcely reported. To better understand microglia-RABV interactions at the transcriptional level, a genome wide gene expression profile in mouse microglial cells line BV2 was performed using microarray analysis. The global messenger RNA changes in murine microglial cell line BV2 after 12, 24 and 48 h of infection with rabies virus CVS-11 strain were investigated using DNA Microarray and quantitative real-time PCR. Infection of CVS-11 at different time points induced different gene expression signatures in BV2 cells. The expression patterns of differentially expressed genes are shown by K-means clustering in four clusters in RABV- or mock-infected microglia at 12, 24 and 48h post infection (hpi). Gene ontology and network analysis of the differentially expressed genes in responses to RABV were performed by the Ingenuity Pathway Analysis system (IPA, Ingenuity® Systems, http://www.ingenuity.com). The results revealed that 28 genes were significantly up-regulated (P<0.01) and 1 gene was significantly down-regulated (P<0.01) in microglial cells at 12hpi, 72 genes were significantly up-regulated (P<0.01) and 24 genes were significantly down-regulated (P<0.01) at 24hpi, and 671 genes were significantly up-regulated (P<0.01) and 190 genes were significantly down-regulated (P<0.01) at 48hpi. Genes in BV2 were significantly regulated (P<0.01) in response to RABV infection and they were found to be interferon stimulated genes (Isg15, Isg20, Oasl1, Oasl2, Ifit2, Irf7 and Ifi203), chemokine genes (Ccl5, Cxcl10 and Ccrl2) and the proinflammatory factor gene (Interleukin 6). The results indicated that the differentially expressed genes from microglial cells after RABV infection were mainly involved in innate immune responses

  19. Anti-inflammatory effects of thymoquinone in activated BV-2 microglial cells.

    PubMed

    Taka, Equar; Mazzio, Elizabeth A; Goodman, Carl B; Redmon, Natalie; Flores-Rozas, Hernan; Reams, Renee; Darling-Reed, Selina; Soliman, Karam F A

    2015-09-15

    Thymoquinone (TQ), the main pharmacological active ingredient within the black cumin seed (Nigella sativa) is believed to be responsible for the therapeutic effects on chronic inflammatory conditions such as arthritis, asthma and neurodegeneration. In this study, we evaluated the potential anti-inflammatory role of TQ in lipopolysaccharide (LPS)-stimulated BV-2 murine microglia cells. The results obtained indicate that TQ was effective in reducing NO2(-) with an IC50 of 5.04μM, relative to selective iNOS inhibitor LNIL-l-N6-(1-iminoethyl)lysine (IC50 4.09μM). TQ mediated reduction in NO2(-) was found to parallel the decline of iNOS protein expression as confirmed by immunocytochemistry. In addition, we evaluated the anti-inflammatory effects of TQ on ninety-six (96) cytokines using a RayBio AAM-CYT-3 and 4 cytokine antibody protein array. Data obtained establish a baseline protein expression profile characteristic of resting BV-2 cells in the order of osteopontin>MIP-1alpha>MIP-1g>IGF-1 and MCP-I. In the presence of LPS [1ug/ml], activated BV-2 cells produced a sharp rise in specific pro-inflammatory cytokines/chemokine's IL-6, IL-12p40/70, CCL12 /MCP-5, CCL2/MCP-1, and G-CSF which were attenuated by the addition of TQ (10μM). The TQ mediated attenuation of MCP-5, MCP-1 and IL-6 protein in supernatants from activated BV-2 cells were corroborated by independent ELISA. Moreover, the data obtained from the RT(2) PCR demonstrated a similar pattern where the LPS mediated elevation of mRNA for IL-6, CCL12/MCP-5, CCL2/MCP-1 were significantly attenuated by TQ (10μM). Also, in this study, consistent data were obtained for both protein antibody array densitometry and ELISA assays. In addition, TQ was found to reduce LPS mediated elevation in gene expression of Cxcl10 and a number of other cytokines in the panel. These findings demonstrate the significant anti-inflammatory properties of TQ in LPS activated microglial cells. Therefore, the obtained results might indicate

  20. Stimulation of immunoprotective mechanisms by OM-85 BV. A review of results from in vivo and in vitro studies.

    PubMed

    Mauël, J

    1994-01-01

    OM-85 BV, an immunomodulating preparation containing extracts from eight commonly pathogenic bacterial species, has been used with success as an oral adjuvant in the prevention of respiratory tract infections. Results from in vitro and in vivo experiments suggest various mechanisms that can underlie this beneficial effect. Thus, exposure of murine macrophages in vitro to OM-85 BV led to stimulation of biochemical and functional parameters associated with the disposal of microorganisms and tumor cells. Similarly, blood-derived human phagocytes were stimulated to express adhesion molecules (LFA-1, MAC-1, p150,95, ICAM-1), to synthesize TNF-alpha and IL-2, and to develop a natural killer activity. These in vitro functions are reflected in the activation of immunological processes in vivo following administration of OM-85 BV per os. Oral treatment of mice and rabbits increased the capacity of the animals to clear bacteria from the blood, an effect that could be ascribed to enhanced functional activity of polymorphonuclear leukocytes. Administration of OM-85 BV per os also led to enhanced salivary IgA levels in man, and in gut and lung secretions in animals. Stimulation of migration and the beneficial effects of OM-85 BV correlated with phagocytosis-induced superoxide production in human bronchoalveolar lavage cells from orally treated individuals. Finally, injection of OM-85 BV was shown to enhance recovery from irradiation in animals, presumably by improving hemopoietic recovery. These findings indicate that OM-85 BV is capable of stimulating both cellular and humoral components of the immune response.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7800969

  1. Prenylated Flavonoids from Cudrania tricuspidata Suppress Lipopolysaccharide-Induced Neuroinflammatory Activities in BV2 Microglial Cells

    PubMed Central

    Kim, Dong-Cheol; Yoon, Chi-Su; Quang, Tran Hong; Ko, Wonmin; Kim, Jong-Su; Oh, Hyuncheol; Kim, Youn-Chul

    2016-01-01

    In Korea and China, Cudrania tricuspidata Bureau (Moraceae) is an important traditional medicinal plant used to treat lumbago, hemoptysis, and contusions. The C. tricuspidata methanol extract suppressed both production of NO and PGE2 in BV2 microglial cells. Cudraflavanone D (1), isolated from this extract, remarkably suppressed the protein expression of inducible NO synthase and cyclooxygenase-2, and decreased the levels of NO and PGE2 in BV2 microglial cells exposed to lipopolysaccharide. Cudraflavanone D (1) also decreased IL-6, TNF-α, IL-12, and IL-1β production, blocked nuclear translocation of NF-κB heterodimers (p50 and p65) by interrupting the degradation and phosphorylation of inhibitor of IκB-α, and inhibited NF-κB binding. In addition, cudraflavanone D (1) suppressed the phosphorylation of c-Jun N-terminal kinase (JNK) and p38 MAPK pathways. This study indicated that cudraflavanone D (1) can be a potential drug candidate for the cure of neuroinflammation. PMID:26907256

  2. Suppression of LPS-induced inflammatory responses by inflexanin B in BV2 microglial cells.

    PubMed

    Lim, Ji-Youn; Sul, Donggeun; Hwang, Bang Yeon; Hwang, Kwang Woo; Yoo, Ki-Yeol; Park, So-Young

    2013-02-01

    Microglia are a type of resident macrophage that functions as an inflammation modulator in the central nervous system. Over-activation of microglia by a range of stimuli disrupts the physiological homeostasis of the brain, and induces inflammatory response and degenerative processes, such as those implicated in neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. Therefore, we investigated the possible anti-inflammatory mechanisms of inflexanin B in murine microglial BV2 cells. Lipopolysaccharide (LPS) activated BV2 cells and induced the production of pro-inflammatory mediators such as nitric oxide (NO), prostaglandin E2 (PGE2), and cytokines (interleukins-1β and -6, and tumour necrosis factor α). The LPS-induced production of pro-inflammatory mediators was associated with the enhancement of nuclear factor-kappaB (NF-κB) nuclear translocation and the activation of mitogen-activated protein kinase (MAPK) including ERK1/2 and JNK. Conversely, pretreatment of cells with inflexanin B (10 and 20 μg/mL) significantly reduced the production of pro-inflammatory mediators. This was accompanied with the reduced nuclear translocation of NF-κB and reduced activation of MAPKs. These results suggest that inflexanin B attenuated the LPS-induced inflammatory process by inhibiting the activation of NF-κB and MAPKs. PMID:23458198

  3. Novel organization of the common nodulation genes in Rhizobium leguminosarum bv. phaseoli strains.

    PubMed Central

    Vázquez, M; Dávalos, A; de las Peñas, A; Sánchez, F; Quinto, C

    1991-01-01

    Nodulation by Rhizobium, Bradyrhizobium, and Azorhizobium species in the roots of legumes and nonlegumes requires the proper expression of plant genes and of both common and specific bacterial nodulation genes. The common nodABC genes form an operon or are physically mapped together in all species studied thus far. Rhizobium leguminosarum bv. phaseoli strains are classified in two groups. The type I group has reiterated nifHDK genes and a narrow host range of nodulation. The type II group has a single copy of the nifHDK genes and a wide host range of nodulation. We have found by genetic and nucleotide sequence analysis that in type I strain CE-3, the functional common nodA gene is separated from the nodBC genes by 20 kb and thus is transcriptionally separated from the latter genes. This novel organization could be the result of a complex rearrangement, as we found zones of identity between the two separated nodA and nodBC regions. Moreover, this novel organization of the common nodABC genes seems to be a general characteristic of R. leguminosarum bv. phaseoli type I strains. Despite the separation, the coordination of the expression of these genes seems not to be altered. PMID:1991718

  4. Inhibition of Nitric Oxide Production in BV2 Microglial Cells by Triterpenes from Tetrapanax papyriferus.

    PubMed

    Cho, Namki; Moon, Eun Hye; Kim, Hyun Woo; Hong, Jaewoo; Beutler, John A; Sung, Sang Hyun

    2016-01-01

    It is well known that activated microglia produce nitric oxide (NO), which has an important role in the pathophysiology of several neurodegenerative diseases such as Alzheimer's disease. In the course of searching for novel therapeutic agents from medicinal plants against neuroinflammatory diseases, the methanolic extract of Tetrapanax papyriferus was found to have significant NO inhibitory activity in lipopolysaccharide (LPS)-stimulated BV2 microglia cells. Nine oleanane-type triterpenes, including two new compounds, epipapyriogenin C-3-O-β-d-glucopyranoside (6) and 11-O-butylpapyrioside LIIc (9), were isolated from the leaves and stems of Tetrapanax papyriferus. The structures of these compounds were elucidated with 1D- and 2D-NMR and MS data. Among these Δ(11,13) oleanane-type triterpenes, compound 3 showed significant NO inhibitory activity in BV-2 cells, reducing the LPS-induced expression of COX-2 and pro-inflammatory cytokines such as TNF-α and IL-6. Compounds 7 and 9 also showed NO inhibitory activities among the Δ(12) oleanane-type triterpene saponins. These results show that oleanane-type triterpenes isolated from T. papyriferus could be a potential natural resource of NO inhibitors used in the treatment of neurodegenerative disorders. PMID:27070561

  5. Prenylated Flavonoids from Cudrania tricuspidata Suppress Lipopolysaccharide-Induced Neuroinflammatory Activities in BV2 Microglial Cells.

    PubMed

    Kim, Dong-Cheol; Yoon, Chi-Su; Quang, Tran Hong; Ko, Wonmin; Kim, Jong-Su; Oh, Hyuncheol; Kim, Youn-Chul

    2016-01-01

    In Korea and China, Cudrania tricuspidata Bureau (Moraceae) is an important traditional medicinal plant used to treat lumbago, hemoptysis, and contusions. The C. tricuspidata methanol extract suppressed both production of NO and PGE₂ in BV2 microglial cells. Cudraflavanone D (1), isolated from this extract, remarkably suppressed the protein expression of inducible NO synthase and cyclooxygenase-2, and decreased the levels of NO and PGE₂ in BV2 microglial cells exposed to lipopolysaccharide. Cudraflavanone D (1) also decreased IL-6, TNF-α, IL-12, and IL-1β production, blocked nuclear translocation of NF-κB heterodimers (p50 and p65) by interrupting the degradation and phosphorylation of inhibitor of IκB-α, and inhibited NF-κB binding. In addition, cudraflavanone D (1) suppressed the phosphorylation of c-Jun N-terminal kinase (JNK) and p38 MAPK pathways. This study indicated that cudraflavanone D (1) can be a potential drug candidate for the cure of neuroinflammation. PMID:26907256

  6. Effects of aspirin on expression of iron transport and storage proteins in BV-2 microglial cells.

    PubMed

    Xu, Yan Xin; Du, Fang; Jiang, Li Rong; Gong, Jing; Zhou, Yu-Fu; Luo, Qian Qian; Qian, Zhong Ming; Ke, Ya

    2015-12-01

    In the light of recent studies, we hypothesized that aspirin might have the functions to regulate the expression of iron transport proteins and then affect cellular iron levels. To test this hypothesis, we investigated the effects of aspirin on expression of iron uptake protein transferrin receptor 1 (TfR1), iron release protein ferroportin 1 (Fpn1) and iron storage protein ferritin using Western blot analysis and on tumor necrosis factor (TNF)-αlpha, interleukin (IL)-6, interleukin (IL)-10 and hepcidin using quantitative real-time PCR in BV-2 microglial cells treated with lipopolysaccharides (LPS). We found that aspirin significantly down-regulated TfR1, while also up-regulated Fpn1 and ferritin expressions in BV-2 microglial cells in vitro. We also showed that TfR1 and Fpn1 expressions were significantly higher, while ferritin contents, IL-6, TNF-alpha and hepcidin mRNA levels were lower in cells treated with aspirin plus LPS than those in cells treated with LPS only. We concluded that aspirin has a negative effect on cell iron contents under 'normal' conditions and could partly reverse LPS-induced-disruption in cell iron balance under in vitro inflammatory conditions. Our findings also suggested that hepcidin might play a dominant role in the control of TfR1 expression by aspirin in the cells treated with LPS. PMID:26522688

  7. Anti-inflammatory effect of ginsenoside Rg5 in lipopolysaccharide-stimulated BV2 microglial cells.

    PubMed

    Lee, Yu Young; Park, Jin-Sun; Jung, Ji-Sun; Kim, Dong-Hyun; Kim, Hee-Sun

    2013-01-01

    Microglia are resident immune cells in the central nervous system. They play a role in normal brain development and neuronal recovery. However, overactivation of microglia causes neuronal death, which is associated with neurodegenerative diseases, such as Parkinson's disease and Alzheimer's disease. Therefore, controlling microglial activation has been suggested as an important target for treatment of neurodegenerative diseases. In the present study, we investigated the anti-inflammatory effect of ginsenoside Rg5 in lipopolysaccharide (LPS)-stimulated BV2 microglial cells and rat primary microglia. The data showed that Rg5 suppressed LPS-induced nitric oxide (NO) production and proinflammatory TNF-α secretion. In addition, Rg5 inhibited the mRNA expressions of iNOS, TNF-α, IL-1b, COX-2 and MMP-9 induced by LPS. Further mechanistic studies revealed that Rg5 inhibited the phophorylations of PI3K/Akt and MAPKs and the DNA binding activities of NF-kB and AP-1, which are upstream molecules controlling inflammatory reactions. Moreover, Rg5 suppressed ROS production with upregulation of hemeoxygenase-1 (HO-1) expression in LPS-stimulated BV2 cells. Overall, microglial inactivation by ginsenoside Rg5 may provide a therapeutic potential for various neuroinflammatory disorders. PMID:23698769

  8. Effects of OM-85 BV in patients with chronic obstructive pulmonary disease: A systematic review and meta-analysis.

    PubMed

    Pan, Lei; Jiang, Xue-Ge; Guo, Jun; Tian, Yuan; Liu, Chang-Ting

    2015-10-01

    This study aimed to identify the effects of OM-85 BV in patients with chronic obstructive pulmonary disease (COPD). PubMed, Embase, CINAHL, and ClinicalTrials.gov were searched for eligible randomized controlled trials (RCTs). The major end point was exacerbation rate, and the minor end points included duration of hospitalization, severity of acute exacerbation, incidence rate of patients using antibiotics, and adverse events. All data were derived with relative risks (RRs) and weighted mean differences. Five RCTs with 1190 patients were enrolled in the meta-analysis. OM-85 BV was associated with 20% and 39% reductions in exacerbation rate (RR, 0.80; 95% confidence interval [CIs], 0.65-0.97; P = .03) and incidence rate of patients using antibiotics (RR, 0.61; 95%CI, 0.48-0.77; P < .0001) compared with the placebo. However, OM-85 BV was not significantly associated with duration of hospitalization, severity of acute exacerbation, and total adverse events. Current evidence supporting the benefits of OM-85 BV to COPD patients is inadequate. Further larger-scale trials must be conducted to validate our findings and the efficacy of OM-85 BV in COPD patients. PMID:25903441

  9. Interactions between Lactobacillus crispatus and bacterial vaginosis (BV)-associated bacterial species in initial attachment and biofilm formation.

    PubMed

    Machado, António; Jefferson, Kimberly Kay; Cerca, Nuno

    2013-01-01

    Certain anaerobic bacterial species tend to predominate the vaginal flora during bacterial vaginosis (BV), with Gardnerella vaginalis being the most common. However, the exact role of G. vaginalis in BV has not yet been determined. The main goal of this study was to test the hypothesis that G. vaginalis is an early colonizer, paving the way for intermediate (e.g., Fusobacterium nucleatum) and late colonizers (e.g., Prevotella bivia). Theoretically, in order to function as an early colonizer, species would need to be able to adhere to vaginal epithelium, even in the presence of vaginal lactobacilli. Therefore, we quantified adherence of G. vaginalis and other BV-associated bacteria to an inert surface pre-coated with Lactobacillus crispatus using a new Peptide Nucleic Acid (PNA) Fluorescence In Situ Hybridization (FISH) methodology. We found that G. vaginalis had the greatest capacity to adhere in the presence of L. crispatus. Theoretically, an early colonizer would contribute to the adherence and/or growth of additional species, so we next quantified the effect of G. vaginalis biofilms on the adherence and growth of other BV-associated species by quantitative Polymerase Chain Reaction (qPCR) technique. Interestingly, G. vaginalis derived a growth benefit from the addition of a second species, regardless of the species. Conversely, G. vaginalis biofilms enhanced the growth of P. bivia, and to a minor extent of F. nucleatum. These results contribute to our understanding of BV biofilm formation and the progression of the disorder. PMID:23739678

  10. VizieR Online Data Catalog: Proper motions and BV photometry in NGC 1513 (Frolov+, 2002)

    NASA Astrophysics Data System (ADS)

    Frolov, V. N.; Jilinski, E. G.; Ananjevskaja, J. K.; Poljakov, E. V.; Bronnikova, N. M.; Gorshanov, D. L.

    2002-10-01

    The results of astrometric and photometric investigations of the poorly studied open cluster NGC 1513 are presented. The proper motions of 333 stars with a root-mean-square error of 1.9mas/yr were obtained by means of the automated measuring complex "Fantasy". Eight astrometric plates covering the time interval of 101 years were measured and a total of 141 astrometric cluster members identified. BV CCD-photometry was obtained for stars in an area 17'x17' centered on the cluster. Altogether 33 stars with high reliability were considered to be cluster members by two criteria. The estimated age of NGC 1513 is 2.54E+08 years. (2 data files).

  11. NEW BV(RI){sub C} PHOTOMETRY FOR PRAESEPE: FURTHER TESTS OF BROADBAND PHOTOMETRIC CONSISTENCY

    SciTech Connect

    Joner, Michael D.; Taylor, Benjamin J.; Laney, C. David; Van Wyk, Francois

    2011-11-15

    New BV(RI){sub C} measurements of Praesepe made at the South African Astronomical Observatory (SAAO) are presented. When those measurements are combined with those reported in previous papers in this series, it is found that they support previously determined V zero points for Praesepe, M67, and the Hyades. Support is also found for joint (V - R){sub C} and (R - I){sub C} zero points established previously for Praesepe and NGC 752. For the SAAO system of standard stars, a B - V correction to the Johnson system of about -9 mmag appears to be reasonably well established. The preferred (though not definitive) V correction is about +7 mmag. For the Landolt V system, zero-point identity with the Johnson system at a 2{sigma} level of 4.8 mmag is found, and no color term as large as 4 mmag (mag){sup -1} is detected. Updated CDS data files for Praesepe are briefly described.

  12. The origin of hyper-ferroelectricity in Li BO3 (B=V, Nb, Ta, Os)

    NASA Astrophysics Data System (ADS)

    He, Lixin; Li, Pengfei; Ren, Xinguo; Guo, G.-C.

    The electronic and structural properties of Li BO3 (B=V, Nb, Ta, Os) are investigated via first-principles methods. We show that Li BO3 are belong to the recently proposed hyperferroelectrics, i.e., they all have unstable longitudinal optical phonon modes. Especially, the ferroelectric-like instability in the metal LiOsO3 is a limiting case of a hyperferroelectrics, whose optical dielectric constant goes to infinity. We further show via an effective Hamiltonian that in contrast to normal proper ferroelectricity, in which the ferroelectric instability usually comes from long range coulomb interactions, the hyperferroelectric instability is due to the structure instability driven by the short range interactions. This could happen in systems with large ion size mismatches, which therefore provides a useful guidance in searching for novel hyperferroelectrics.

  13. Examination of Taxonomic Uncertainties Surrounding Brucella abortus bv. 7 by Phenotypic and Molecular Approaches

    PubMed Central

    Garin-Bastuji, Bruno; Le Carrou, Gilles; Allix, Sebastien; Perrett, Lorraine L.; Dawson, Claire E.; Groussaud, Pauline; Stubberfield, Emma J.; Koylass, Mark; Whatmore, Adrian M.

    2014-01-01

    Brucella taxonomy is perpetually being reshuffled, at both the species and intraspecies levels. Biovar 7 of Brucella abortus was suspended from the Approved Lists of Bacterial Names Brucella classification in 1988, because of unpublished evidence that the reference strain 63/75 was a mixture of B. abortus biovars 3 and 5. To formally clarify the situation, all isolates previously identified as B. abortus bv. 7 in the AHVLA and ANSES strain collections were characterized by classical microbiological and multiple molecular approaches. Among the 14 investigated strains, including strain 63/75, only four strains, isolated in Kenya, Turkey, and Mongolia, were pure and showed a phenotypic profile in agreement with the former biovar 7, particularly agglutination with both anti-A/anti-M monospecific sera. These results were strengthened by molecular strategies. Indeed, genus- and species-specific methods allowed confirmation that the four pure strains belonged to the B. abortus species. The combination of most approaches excluded their affiliation with the recognized biovars (biovars 1 to 6 and 9), while some suggested that they were close to biovar 3.These assays were complemented by phylogenetic and/or epidemiological methods, such as multilocus sequence analysis (MLSA) and variable-number tandem repeat (VNTR) analysis. The results of this polyphasic investigation allow us to propose the reintroduction of biovar 7 into the Brucella classification, with at least three representative strains. Interestingly, the Kenyan strain, sharing the same biovar 7 phenotype, was genetically divergent from other three isolates. These discrepancies illustrate the complexity of Brucella taxonomy. This study suggests that worldwide collections could include strains misidentified as B. abortus bv. 7, and it highlights the need to verify their real taxonomic position. PMID:24362435

  14. 75 FR 35605 - Airworthiness Directives; Fokker Services B.V. Model F.28 Mark 0070 and 0100 Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-23

    ... was published in the Federal Register on March 9, 2010 (75 FR 10696). That NPRM proposed to correct an... Regulatory Policies and Procedures (44 FR 11034, February 26, 1979); and 3. Will not have a significant...-16342; AD 2010-13-11] RIN 2120-AA64 Airworthiness Directives; Fokker Services B.V. Model F.28 Mark...

  15. 75 FR 64963 - Airworthiness Directives; Fokker Services B.V. Model F.28 Mark 0070 and 0100 Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-21

    ... Policies and Procedures (44 FR 11034, February 26, 1979); and 3. Will not have a significant economic.... Model F.28 Mark 0070 and 0100 Airplanes AGENCY: Federal Aviation Administration (FAA), DOT. ACTION... Fokker Services B.V. Model F.28 Mark 0070 and 0100 airplanes, certificated in any category, equipped...

  16. 77 FR 68102 - Foreign-Trade Zone 163-Ponce, PR; Application for Subzone; Zimmer Manufacturing BV; Ponce, PR

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-15

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF COMMERCE Foreign-Trade Zones Board Foreign-Trade Zone 163--Ponce, PR; Application for Subzone; Zimmer Manufacturing... Manufacturing BV located in Ponce, Puerto Rico. The application was submitted pursuant to the provisions of...

  17. 75 FR 27668 - Airworthiness Directives; Fokker Services B.V. Model F.28 Mark 0070 and 0100 Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-18

    ... rule'' under the DOT Regulatory Policies and Procedures (44 FR 11034, February 26, 1979); and 3. Will... Services B.V. Model F.28 Mark 0070 and 0100 Airplanes AGENCY: Federal Aviation Administration (FAA), DOT... cause of the MLG extension problem was the (partially) blocked hydraulic return line from the...

  18. 75 FR 2055 - Airworthiness Directives; Fokker Services B.V. Model F.28 Mark 0070 and 0100 Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-14

    ... products. That NPRM was published in the Federal Register on September 1, 2009 (74 FR 45139). That NPRM... ``significant rule'' under the DOT Regulatory Policies and Procedures (44 FR 11034, February 26, 1979); and 3...-16170; AD 2010-01-11] RIN 2120-AA64 Airworthiness Directives; Fokker Services B.V. Model F.28 Mark...

  19. Caspase-1 inhibition attenuates activation of BV2 microglia induced by LPS-treated RAW264.7 macrophages

    PubMed Central

    Pan, Yang; Shen, Bo; Gao, Qin; Zhu, Jun; Dong, Jingde; Zhang, Li; Zhang, Yingdong

    2016-01-01

    Abstract Neuroinflammation has been recognized as a factor in the pathogenesis of neurodegenerative diseases. Emerging evidence suggests that peripheral inflammation, besides neuroinflammation, functions as a modulator of disease progression and neuropathology in several neurodegenerative diseases. However, detailed correlations among peripheral inflammation, neuroinflammation and neurodegeneration remain unknown. In the present study, we prepared a peripheral inflammation model with lipopolysaccharides (LPS)-stimulated RAW264.7 macrophages to explore its activation on BV2 microglia. We found that LPS induced the production of IL-1β, IL-6 and TNF-α in the culture medium of RAW264.7 macrophages. We further showed that LPS plus ATP activated inflammasome, evidenced by the upregulation of caspase-1 and IL-1β, which was suppressed by ZYVAD, a caspase-1 inhibitor. Furthermore, the conditioned medium obtained from LPS-treated RAW264.7 macrophages activated BV2 microglia, stimulating the release of IL-1β, IL-6 and TNF-α from BV2 cells. ZYVAD pretreatment markedly suppressed BV2 microglia activation induced by RAW264.7 cells conditioned medium. Taken together, our study indicates that macrophage-mediated peripheral inflammation subsequently evokes neuroinflammation and may aggravate neural damage. Inflammasome and caspase-1 may be potential targets for modulating systemic inflammatory responses in neurodegenerative diseases.

  20. 75 FR 35624 - Airworthiness Directives; Fokker Services B.V. Model F.27 Mark 500 and 600 Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-23

    ... Procedures (44 FR 11034, February 26, 1979); and 3. Will not have a significant economic impact, positive or.... Model F.27 Mark 500 and 600 Airplanes AGENCY: Federal Aviation Administration (FAA), Department of.... Applicability (c) This AD applies to Fokker Services B.V. Model F.27 Mark 500 and 600 airplanes; certified...

  1. 75 FR 10696 - Airworthiness Directives; Fokker Services B.V. Model F.28 Mark 0070 and 0100 Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-09

    ... rule'' under the DOT Regulatory Policies and Procedures (44 FR 11034, February 26, 1979); and 3. Will.... Model F.28 Mark 0070 and 0100 Airplanes AGENCY: Federal Aviation Administration (FAA), DOT. ACTION...) None. Applicability (c) This AD applies to Fokker Services B.V. Model F.28 Mark 0070 and Mark...

  2. Resveratrol induces the expression of interleukin-10 and brain-derived neurotrophic factor in BV2 microglia under hypoxia.

    PubMed

    Song, Juhyun; Cheon, So Yeong; Jung, Wonsug; Lee, Won Taek; Lee, Jong Eun

    2014-01-01

    Microglia are the resident macrophages of the central nervous system (CNS) and play an important role in neuronal recovery by scavenging damaged neurons. However, overactivation of microglia leads to neuronal death that is associated with CNS disorders. Therefore, regulation of microglial activation has been suggested to be an important target for treatment of CNS diseases. In the present study, we investigated the beneficial effect of resveratrol, a natural phenol with antioxidant effects, in the microglial cell line, BV2, in a model of hypoxia injury. Resveratrol suppressed the mRNA expression of the pro-inflammatory molecule, tumor necrosis factor-α, and promoted the mRNA expression of the anti-inflammatory molecule, interleukin-10, in BV2 microglia under hypoxic conditions. In addition, resveratrol inhibited the activation of the transcription factor, nuclear factor kappa-light-chain enhancer of activated B cells (NF-κB), which is upstream in the control of inflammatory reactions in hypoxia-injured BV2 microglia. Moreover, resveratrol promoted the expression of brain-derived neurotrophic factor (BDNF) in BV2 microglia under hypoxic stress. Overall, resveratrol may promote the beneficial function of microglia in ischemic brain injury. PMID:25184950

  3. 75 FR 69606 - Airworthiness Directives; Fokker Services B.V. Model F.28 Mark 0070 and 0100 Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-15

    ... rule'' under the DOT Regulatory Policies and Procedures (44 FR 11034, February 26, 1979); and 3. Will... information (MCAI) originated by an aviation authority of another country to identify and correct an unsafe... information identified in this proposed AD, contact Fokker Services B.V., Technical Services Dept., P.O....

  4. Are Frontal Cognitive and Atrophy Patterns Different in PSP and bvFTD? A Comparative Neuropsychological and VBM Study

    PubMed Central

    Lagarde, Julien; Valabrègue, Romain; Corvol, Jean-Christophe; Pineau, Fanny; Le Ber, Isabelle; Vidailhet, Marie; Dubois, Bruno; Levy, Richard

    2013-01-01

    Progressive supranuclear palsy (PSP) and frontotemporal lobar degeneration (FTD) are two clinicohistological entities that share a severe prefrontal syndrome. To what extent do the cognitive syndrome and the location of the underlying brain atrophy unify or segregate these entities? Here, we examined the clinical and radiological patterns of frontal involvement and the neural bases of the cognitive dysfunctions observed in the Richardson form of PSP and the behavioral variant of FTD (bvFTD). The cognitive profile and grey and white matter volume of PSP (n = 19) and bvFTD (n = 16) patients and control participants (n = 18) were compared using a standard battery of neuropsychological tests and voxel-based morphometry (VBM), respectively. Analyses of correlations between neuropsychological and morphometric data were additionally performed. The severity and qualitative pattern of cognitive dysfunction was globally similar between the two patient groups. Grey matter volume was decreased in widespread frontal areas and in the temporal uncus in bvFTD, while it was decreased in the frontal and temporal lobes as well as in the thalamus in PSP. We also found an unexpected involvement of the frontal rectal gyrus in PSP patients compared to controls. Correlation analyses yielded different results in the two groups, with no area showing significant correlations in PSP patients, while several frontal and some temporal areas did so in bvFTD patients. In spite of minor neuropsychological and morphological differences, this study shows that the patterns of cognitive dysfunction and atrophy are very similar in PSP and bvFTD. However, executive dysfunction in these diseases may stem from partially divergent cortical and subcortical neural circuits. PMID:24278277

  5. Phenomenological study of the Bc→BP, BV decays with perturbative QCD approach

    NASA Astrophysics Data System (ADS)

    Sun, Junfeng; Yang, Yueling; Chang, Qin; Lu, Gongru

    2014-06-01

    Inspired by the recent LHCb measurements and forthcoming great potential on Bc meson, we study the exclusive Bc→BqP, BqV decays with the perturbative QCD approach, where q =u, d, s and P and V denote the lightest pseudoscalar and vector SU(3) nonet meson, respectively. By retaining the quark transverse momentum, employing the Sudakov factors, and choosing the typical scale as the maximum virtualities of the internal particles, we calculate the Bc→B transition from factors, and our results show that about 90% of the contribution to form factors comes from the αs/π <0.3 region. The contributions of penguin and annihilation to branching ratios are very small due to the serious suppression by the CKM factors. There are some hierarchy relations among the Bc→BP, BV decays. The branching ratios for Bc→Bd ,sπ, Bd ,sρ, BsK are large and could be measured by the running LHCb.

  6. Evidence of immunomodulatory effects of a novel probiotic, Bifidobacterium longum bv. infantis CCUG 52486.

    PubMed

    You, Jialu; Yaqoob, Parveen

    2012-12-01

    Bifidobacterium longum bv. infantis CCUG 52486 was originally isolated from healthy elderly subjects and demonstrated to have particular ecological fitness and anti-pathogenic effects. Bifidobacteria are commonly associated with immuno-modulatory properties, especially in older people, but this strain has not been investigated for effects on immune function. This study aimed to explore the immunomodulatory effects of this novel probiotic, compared with three commercial strains, B. longum SP 07/3, Lactobacillus rhamnosus GG (L.GG) and Lactobacillus casei Shirota (LcS). Human peripheral blood mononuclear cells (PBMCs) were isolated from fasting blood of young or older volunteers and exposed to probiotic strains or Con A. NK activity and activation, and cytokine release was enhanced by all probiotics with strain specificities. The effect of B. infantis on NK activity was influenced by ageing. Except for L.GG, probiotics increased IFN-γ production to a much greater degree in young subjects and increased IL-6 production to a much greater degree in older subjects. Based on IL-10/IL-12 ratios, B. infantis resulted in the most anti-inflammatory profile of all of the probiotics. These results suggest that B. infantis CCUG 52486 has strong immunomodulatory potential compared with well-known commercial strains and that the immune response to probiotics may be influenced by ageing. PMID:22882710

  7. Genome sequence of the clover symbiont Rhizobium leguminosarum bv. trifolii strain CC275e.

    PubMed

    Delestre, Clément; Laugraud, Aurélie; Ridgway, Hayley; Ronson, Clive; O'Callaghan, Maureen; Barrett, Brent; Ballard, Ross; Griffiths, Andrew; Young, Sandra; Blond, Celine; Gerard, Emily; Wakelin, Steve

    2015-01-01

    Rhizobium leguminosarum bv. trifolii strain CC275e is a highly effective, N2-fixing microsymbiont of white clover (Trifolium repens L.). The bacterium has been widely used in both Australia and New Zealand as a clover seed inoculant and, as such, has delivered the equivalent of millions of dollars of nitrogen into these pastoral systems. R. leguminosarum strain CC275e is a rod-shaped, motile, Gram-negative, non-spore forming bacterium. The genome was sequenced on an Illumina MiSeq instrument using a 2 × 150 bp paired end library and assembled into 29 scaffolds. The genome size is 7,077,367 nucleotides, with a GC content of 60.9 %. The final, high-quality draft genome contains 6693 protein coding genes, close to 85 % of which were assigned to COG categories. This Whole Genome Shotgun project has been deposited at DDBJ/EMBL/GenBank under the accession JRXL00000000. The sequencing of this genome will enable identification of genetic traits associated with host compatibility and high N2 fixation characteristics in Rhizobium leguminosarum. The sequence will also be useful for development of strain-specific markers to assess factors associated with environmental fitness, competiveness for host nodule occupancy, and survival on legume seeds (New Zealand Ministry of Business, Innovation and Employment program, 'Improving forage legume-rhizobia performance' contract C10X1308 and DairyNZ Ltd.). PMID:26649149

  8. (-)-Epigallocatechin-3-gallate inhibits voltage-gated proton currents in BV2 microglial cells.

    PubMed

    Jin, Sanghee; Park, Mijung; Song, Jin-Ho

    2013-01-01

    (-)-Epigallocatechin-3-gallate (EGCG), the principal constituent of green tea, protects neurons from toxic insults by suppressing the microglial secretion of neurotoxic inflammatory mediators. Voltage-gated proton channels are expressed in microglia, and are required for NADPH oxidase-dependent reactive oxygen species generation. Brain damage after ischemic stroke is dependent on proton channel activity. Accordingly, we examined whether EGCG could inhibit proton channel function in the murine microglial BV2 cells. EGCG potently inhibited proton currents with an IC(50) of 3.7 μM. Other tea catechins, (-)-epigallocatechin, (-)-epicatechin and (-)-epicatechin-3-gallate, were far less potent than EGCG. EGCG did not change the kinetics of proton currents such as the activation and the deactivation time constants, the reversal potential and the activation voltage, suggesting that the gating process of proton channels were not altered by EGCG. EGCG is known to disturb lipid rafts by sequestering cholesterol. However, neither extraction of cholesterol with methyl-β-cyclodextrin or cholesterol supplementation could reverse the EGCG inhibition of proton currents. In addition, the EGCG effect was preserved in the presence of the cytoskeletal stabilizers paclitaxel and phalloidin, phosphatase inhibitors, the antioxidant Trolox, superoxide dismutase or catalase. The proton channel inhibition can be a substantial mechanism for EGCG to suppress microglial activation and subsequent neurotoxic events. PMID:23201067

  9. Bv8/prokineticin 2 is involved in Aβ-induced neurotoxicity

    PubMed Central

    Severini, Cinzia; Lattanzi, Roberta; Maftei, Daniela; Marconi, Veronica; Ciotti, Maria Teresa; Petrocchi Passeri, Pamela; Florenzano, Fulvio; Del Duca, Ester; Caioli, Silvia; Zona, Cristina; Balboni, Gianfranco; Salvadori, Severo; Nisticò, Robert; Negri, Lucia

    2015-01-01

    Bv8/Prokineticin 2 (PROK2) is a bioactive peptide initially discovered as a regulator of gastrointestinal motility. Among multiple biological roles demonstrated for PROK2, it was recently established that PROK2 is an insult-inducible endangering mediator for cerebral damage. Aim of the present study was to evaluate the PROK2 and its receptors’ potential involvement in amyloid beta (Aβ) neurotoxicity, a hallmark of Alzheimer’s disease (AD) and various forms of traumatic brain injury (TBI). Analyzing primary cortical cultures (CNs) and cortex and hippocampus from Aβ treated rats, we found that PROK2 and its receptors PKR1 and PKR2 mRNA are up-regulated by Aβ, suggesting their potential involvement in AD. Hence we evaluated if impairing the prokineticin system activation might have protective effect against neuronal death induced by Aβ. We found that a PKR antagonist concentration-dependently protects CNs against Aβ1–42-induced neurotoxicity, by reducing the Aβ-induced PROK2 neuronal up-regulation. Moreover, the antagonist completely rescued LTP impairment in hippocampal slices from 6 month-old Tg2576 AD mice without affecting basal synaptic transmission and paired pulse-facilitation paradigms. These results indicate that PROK2 plays a role in cerebral amyloidosis and that PROK2 antagonists may represent a new approach for ameliorating the defining pathology of AD. PMID:26477583

  10. VizieR Online Data Catalog: DD Mon BV light curves (Qian+ 1997)

    NASA Astrophysics Data System (ADS)

    Qian, S.; Liu, Q.; Yang, Y.; Gu, S.; Huang, Z.

    1997-04-01

    New BV light curves of the short-period eclipsing binary system DD Mon have been obtained. Light-curve variability is seen in both B and V bands as compared with the light curves obtained in 1986 by Yamasaki et al. (1990AJ.....99.1218Y). The light curves are analyzed by using Wilson-Devinney's synthetic light-curve program, and the present photometric solution reveals that DD Mon is a near-contact binary with the secondary component filling the Roche lobe. Combined with Yamasaki et al.'s (1990AJ.....99.1218Y) spectroscopic results, absolute quantities of DD Mon are derived: mass of the primary M1=1.05+/-0.08M⊙, mass of the secondary M2=0.47+/-0.04M⊙, radius of the primary R1=1.36+/-0.04R⊙, radius of the secondary R2=1.03+/-0.03R⊙. These results show that the components of DD Mon have evolved away from the ZAMS and through a mass-transfer process to the present semi-detached state. The variation in shape of the light curve may be caused by the evolution of the system and the activity of dark spots. (2 data files).

  11. Thioxanthenes, chlorprothixene and flupentixol inhibit proton currents in BV2 microglial cells.

    PubMed

    Kim, Jiwon; Song, Jin-Ho

    2016-05-15

    The thioxanthene antipsychotic drugs chlorprothixene and flupentixol have anti-inflammatory and antioxidant properties. The reactive oxygen species produced by NADPH oxidase during microglia-mediated inflammatory responses cause neuronal damage, thereby contributing to various neurodegenerative diseases. Voltage-gated proton channels sustain the NADPH oxidase activity, and inhibition of the channels' activity reduces the production of reactive oxygen species. Herein, the effects of chlorprothixene and flupentixol on proton currents were investigated in BV2 microglial cells using the whole-cell patch-clamp method. Both drugs inhibited the proton currents in a concentration-dependent manner (IC50=1.7μM and 6.6μM, respectively). Chlorprothixene at 3μM slightly shifted the activation voltage toward depolarization. Both the activation and the deactivation kinetics of the proton currents were slowed by chlorprothixene 1.2- and 3.5-fold, respectively. Thus, the inhibition of proton currents may be partly responsible for the antioxidant effects of thioxanthene antipsychotic drugs. PMID:26945819

  12. In vivo study on the immunomodulating effects of OM-85 BV on survival, inflammatory cell recruitment and bacterial clearance in Klebsiella pneumonia.

    PubMed

    Broug-Holub, E; Kraal, G

    1997-01-01

    Oral administration of the bacterial extract OM-85 BV has been shown to prime alveolar macrophages (AM) in such a way that they secrete significantly more nitric oxide, tumor necrosis factor-alpha and interleukin-1beta upon in vitro stimulation with lipopolysaccharide (LPS). As increased cytokine secretion by AM may account for the therapeutic effect of OM-85 BV in respiratory tract infections, we studied the effect of orally administered OM-85 BV on the outcome of Klebsiella pneumoniae-induced pneumonia. Mice received a daily oral dose of OM-85 BV (350 mg/kg body weight) for 5 days and were intratracheally infected with 333, 1000 or 3333 CFU K. pneumoniae on day 8. It was shown that OM-85 BV pretreatment of mice has no effect on bacterial clearance, neutrophil recruitment and survival in this acute respiratory tract infection. Also, OM-85 BV treatment had no protective effect in a recurrent infection with K. pneumoniae. It is concluded that AM activation by oral treatment with OM-85 BV is not sufficient to play a protective role in respiratory tract infection with K. pneumoniae. PMID:9637354

  13. Root colonization of different plants by plant-growth-promoting Rhizobium leguminosarum bv. trifolii R39 studied with monospecific polyclonal antisera.

    PubMed Central

    Schloter, M; Wiehe, W; Assmus, B; Steindl, H; Becke, H; Höflich, G; Hartmann, A

    1997-01-01

    Monospecific polyclonal antisera raised against Rhizobium leguminosarum bv. trifolii R39, a bacterium which was isolated originally from red clover nodules, were used to study the colonization of roots of leguminous and nonleguminous plants (Pisum sativum, Lupinus albus, Triticúm aestivum, and Zea mays) after inoculation. Eight weeks after inoculation of soil-grown plants, between 0.1 and 1% of the total bacterial population in the rhizospheres of all inoculated plants were identified as R. leguminosarum bv. trifolii R39. To characterize the associative colonization of the nonleguminous plants by R.leguminosarum bv. trifolii R39 in more detail, a time course study was performed with inoculated roots of Z. mays. R. leguminosarum bv. trifolii R39 was found almost exclusively in the rhizosphere soil and on the rhizoplane 4 weeks after inoculation. Colonization of inner root tissues was detected only occasionally at this time. During the process of attachment of R. leguminosarum bv. trifolii R39 to the rhizoplane, bacterial lipopolysaccharides were overexpressed, and this may be important for plant-microbe interaction. Fourteen weeks after inoculation, microcolonies of R. leguminosarum bv. trifolii R39 were detected in lysed cells of the root cortex as well as in intracellular space of central root cylinder cells. At the beginning of flowering (18 weeks after inoculation), the number of R. leguminosarum bv. trifolii R39 organisms decreased in the rhizosphere soil, rhizoplane, and inner root tissue. PMID:9143133

  14. Over-expression of BvMTSH, a fusion gene for maltooligosyltrehalose synthase and maltooligosyltrehalose trehalohydrolase, enhances drought tolerance in transgenic rice.

    PubMed

    Joo, Joungsu; Choi, Hae Jong; Lee, Youn Hab; Lee, Sarah; Lee, Choong Hwan; Kim, Chung Ho; Cheong, Jong-Joo; Choi, Yang Do; Song, Sang Ik

    2014-01-01

    Plant abiotic stress tolerance has been modulated by engineering the trehalose synthesis pathway. However, many stress-tolerant plants that have been genetically engineered for the trehalose synthesis pathway also show abnormal development. The metabolic intermediate trehalose 6-phosphate has the potential to cause aberrations in growth. To avoid growth inhibition by trehalose 6-phosphate, we used a gene that encodes a bifunctional in-frame fusion (BvMTSH) of maltooligosyltrehalose synthase (BvMTS) and maltooligosyltrehalose trehalohydrolase (BvMTH) from the nonpathogenic bacterium Brevibacterium helvolum. BvMTS converts maltooligosaccharides into maltooligosyltrehalose and BvMTH releases trehalose. Transgenic rice plants that over-express BvMTSH under the control of the constitutive rice cytochrome c promoter (101MTSH) or the ABA-inducible Ai promoter (105MTSH) show enhanced drought tolerance without growth inhibition. Moreover, 101MTSH and 105MTSH showed an ABA-hyposensitive phenotype in the roots. Our results suggest that over-expression of BvMTSH enhances drought-stress tolerance without any abnormal growth and showes ABA hyposensitive phenotype in the roots. PMID:24209631

  15. Influence of OM-85 BV on different humoral and cellular immune defense mechanisms of the respiratory tract.

    PubMed

    Emmerich, B; Pachmann, K; Milatovic, D; Emslander, H P

    1992-01-01

    To clarify the mode of action of an oral bacterial extract (OM-85 BV) on local airway immunity pre- and posttherapeutic washings from bronchoalveolar lavage (BAL) fluid of 28 adult patients with nonobstructive chronic bronchitis were analysed. In comparison to healthy controls, an elevation of total cell count due to an increased number of PMN leukocytes, and an impaired activity of the alveolar macrophages measured by the chemiluminescence response to opsonized zymosan was observed in patients with chronic bronchitis. After treatment with OM-85 BV, the BAL CD4+/CD8+ lymphocyte ratio and BAL interferon-gamma levels were increased. The alveolar macrophage activity was normalized and the BAL IgA was regulated from a reduced or hyperelevated to a moderately increased level. PMID:1439235

  16. Toll-Interleukin 1 Receptor domain-containing adaptor protein positively regulates BV2 cell M1 polarization.

    PubMed

    Gong, Leilei; Wang, Hanxiang; Sun, Xiaolei; Liu, Chun; Duan, Chengwei; Cai, Rixin; Gu, Xingxing; Zhu, Shunxing

    2016-06-01

    Microglial activation, including classical (M1) and alternative (M2) activation, plays important roles in the development of several central nervous system disorders and promotes tissue reconstruction. Toll-like receptor (TLR)4 is important for microglial polarization. TIR domain-containing adaptor protein (TIRAP) is an intracellular adaptor protein, which is responsible for the early phase of TLR4 activation. The role of TIRAP in BV2 cell M1 polarization is still unknown. In this study, we showed that TIRAP expression is greatly elevated in lipopolysaccharide (LPS)/interferon (IFN)-γ-treated microglia. TIRAP overexpression promoted BV2 microglial M1 polarization by increasing M1-related marker production (inducible nitric oxide synthase, CD86, interleukin-6, interleukin-1β and tumour necrosis factor-α). In contrast, TIRAP knockdown prevented M1-related marker production. Mechanistically, TIRAP could interact with TNF Receptor-Associated Factor 6 (TRAF6) to increase M1-related marker production in TIRAP overexpressed and LPS/IFN-γ-treated BV2 cells. In addition, silencing of TIRAP effectively inhibited the activation of the Transforming Growth Factor-Beta-Activated Kinase 1/I-Kappa-B Kinase /Nuclear Factor of Kappa Light Polypeptide Gene Enhancer in B-Cells (TAK1/IKK/NF-κB) signalling pathway and the phosphorylation of Akt and mitogen-activated protein kinases, which were activated by LPS/IFN-γ stimulation. Thus, our results suggest that TIRAP positively regulated BV2 microglial M1 polarization through TLR4-mediated TAK1/IKK/NF-κB, mitogen-activated protein kinases and Akt signalling pathways. PMID:27061018

  17. Mesenchymal stem cells inhibit lipopolysaccharide-induced inflammatory responses of BV2 microglial cells through TSG-6

    PubMed Central

    2014-01-01

    Microglia are the primary immunocompetent cells in brain tissue and microglia-mediated inflammation is associated with the pathogenesis of various neuronal disorders. Recently, many studies have shown that mesenchymal stem cells (MSCs) display a remarkable ability to modulate inflammatory and immune responses through the release of a variety of bioactive molecules, thereby protecting the central nervous system. Previously, we reported that MSCs have the ability to modulate inflammatory responses in a traumatic brain injury model and that the potential mechanisms may be partially attributed to upregulated TNF-α stimulated gene/protein 6 (TSG-6) expression. However, whether TSG-6 exerts an anti-inflammatory effect by affecting microglia is not fully understood. In this study, we investigated the anti-inflammatory effects of MSCs and TSG-6 in an in vitro lipopolysaccharide (LPS)-induced BV2 microglial activation model. We found that MSCs and TSG-6 significantly inhibited the expression of pro-inflammatory mediators in activated microglia. However, MSC effects on microglia were attenuated when TSG-6 expression was silenced. In addition, we found that the activation of nuclear factor (NF)-κB and mitogen-activated protein kinase (MAPK) pathways in LPS-stimulated BV2 microglial cells was significantly inhibited by TSG-6. Furthermore, we found that the presence of CD44 in BV2 microglial cells was essential for MSC- and TSG-6-mediated inhibition of pro-inflammatory gene expression and of NF-κB and MAPK activation in BV2 microglial cells. The results of this study suggest that MSCs can modulate microglia activation through TSG-6 and that TSG-6 attenuates the inflammatory cascade in activated microglia. Our study indicates that novel mechanisms are responsible for the immunomodulatory effect of MSCs on microglia and that MSCs, as well as TSG-6, might be promising therapeutic agents for the treatment of neurotraumatic injuries or neuroinflammatory diseases associated with

  18. A combinational effect of acetaminophen and oriental herbs on the regulation of inflammatory mediators in microglia cell line, BV2.

    PubMed

    Kim, Hyemin; Bae, Seyeon; Kwon, Kil-Young; Hwang, Young-Il; Kang, Jae Seung; Lee, Wang Jae

    2015-12-01

    The mechanism of Western medicine that is commonly used for pain relief is well-known. However, very little is known for oriental herbs, and even less is known for mixture of the two. We investigated the combinational effect of 3 kinds of oriental herbs, usually used for the control of headache, and acetaminophen to relieve headache in microglia cell line, BV2. Lipopolysaccharide (LPS) stimulation induced to produce nitrite and increased the expression of inflammation-related factors like inducible nitric oxide synthase and cyclooxygenase-2 (COX-2) in murine microglia cell line, BV2. Oriental herbs such as Angelica tenuissima, Angelica dahurica, and Scutellaria baicalensis reduced the production of nitric oxide and the expression of COX-2. Moreover, a treatment of acetaminophen combined with oriental herbs was more decreased the COX-2 expression, and its product, prostaglandin E2 production in BV2 cells. Therefore, a combined treatment of oriental herbs such as A. tenuissima, A. dahurica, and S. baicalensis and Western medicine like acetaminophen has a synergistic effect on the decrease of LPS-induced inflammation in microglia. PMID:26770874

  19. Characterization of pathogenic Aeromonas veronii bv. veronii associated with ulcerative syndrome from chinese longsnout catfish (Leiocassis longirostris Günther)

    PubMed Central

    Cai, Shuang-Hu; Wu, Zao-He; Jian, Ji-Chang; Lu, Yi-Shan; Tang, Ju-Feng

    2012-01-01

    273 bacterial strains were isolated from 20 Chinese longsnout catfish samples. The biochemical characteristics of all strains conformed to the species description of Aeromonas veronii bv. veronii on the basis of Vitek GNI+ card. Furthermore, 16S rDNA, gyrB and rpoD sequences of the representative strain PY50 were sequenced and showed high similarity with A. veronii bv. veronii in Genbank. Antibiotic-resistance of the representative strain PY50 was assessed by the Kirby-Bauer disk diffusion method, and the results showed it was susceptible and moderately susceptible to 13 and 4 of the 21 antimicrobial agents tested. Extracellular products of strain PY50 contained gelatinase, lecithinase, elastase, most of lipase and lipopolysaccharide. Virulence of strain PY50 and extracellular products to Chinese longsnout catfish were also tested, and LD50 were about 3.47×104 CFU per fish and 11.22 μg per fish in intraperitoneal injection respectively. This is the first report that A. veronii bv. veronii was the pathogenic agent of ulcerative syndrome in Chinese longsnout catfish. PMID:24031843

  20. Sequential distribution of pTDP-43 pathology in behavioral variant frontotemporal dementia (bvFTD).

    PubMed

    Brettschneider, Johannes; Del Tredici, Kelly; Irwin, David J; Grossman, Murray; Robinson, John L; Toledo, Jon B; Lee, Edward B; Fang, Lubin; Van Deerlin, Vivianna M; Ludolph, Albert C; Lee, Virginia M-Y; Braak, Heiko; Trojanowski, John Q

    2014-03-01

    We examined regional distribution patterns of phosphorylated 43-kDa TAR DNA-binding protein (pTDP-43) intraneuronal inclusions in frontotemporal lobar degeneration (FTLD). Immunohistochemistry was performed on 70 μm sections from FTLD-TDP autopsy cases (n = 39) presenting with behavioral variant frontotemporal dementia. Two main types of cortical pTDP-43 pathology emerged, characterized by either predominantly perikaryal pTDP-43 inclusions (cytoplasmic type, cFTLD) or long aggregates in dendrites (neuritic type, nFTLD). Cortical involvement in nFTLD was extensive and frequently reached occipital areas, whereas cases with cFTLD often involved bulbar somatomotor neurons and the spinal cord. We observed four patterns indicative of potentially sequential dissemination of pTDP-43: cases with the lowest burden of pathology (pattern I) were characterized by widespread pTDP-43 lesions in the orbital gyri, gyrus rectus, and amygdala. With increasing burden of pathology (pattern II) pTDP-43 lesions emerged in the middle frontal and anterior cingulate gyrus as well as in anteromedial temporal lobe areas, the superior and medial temporal gyri, striatum, red nucleus, thalamus, and precerebellar nuclei. More advanced cases showed a third pattern (III) with involvement of the motor cortex, bulbar somatomotor neurons, and the spinal cord anterior horn, whereas cases with the highest burden of pathology (pattern IV) were characterized by pTDP-43 lesions in the visual cortex. We interpret the four neuropathological patterns in bvFTD to be consistent with the hypothesis that pTDP-43 pathology can spread sequentially and may propagate along axonal pathways. PMID:24407427

  1. Differential diagnosis of behavioral variant of fronto-temporal dementia (bvFTD)

    PubMed Central

    Pąchalska, Maria; Bidzan, Leszek; Łukowicz, Małgorzata; Bidzan, Mariola; Markiewicz, Katarzyna; Jastrzębowska, Grażyna; Talar, Jan

    2011-01-01

    Summary Background The aim of the paper is the differential diagnosis of various types of Fronto-Temporal Dementia (FTD), with the focus on its behavioural variant (bvFTD). Material/Method Material and Method. Screening was done in order to assess the depth of dementia with the short version of MMSE, while evaluation of various variants of FTD was performed with the use of such neuropsychological tests as Newcomb and Chicago Fluency Tests, Wechsler Memory Scale - III (WMS-III), Western Aphasia Battery (WAB-R), and the Boston Naming Test (BNT). Behaviour was evaluated with a Polish version of the Frontal Behavioral Inventory (FBInv). The inventory consists of 24 questions which enable an evaluation of social behaviour disorders. The study included 112 patients - 68 men and 46 women treated in the Reintegrative -Training Centre of the Foundation for Persons with Brain Dysfunctions in Kraków and in the Clinic for Developmental Psychiatry, Psychotic Disorders and Old Age Psychiatry, of the Medical University at Gdańsk, who were suffering from various types of dementia. Results It was found that FTD patients scored the highest, while the VAD patients scored somewhat lower in the FBInv. At the same time the scores obtained by PPA patients were higher in comparison to the control groups, but not as high as in the case of patients with FTD. In the process of the neurotherapy of FTD patients we found a reduction of the behavioral disturbances, despite the progression of the illness. Conclusions The results obtained in the present study confirmed the diagnostic value of FBInv in the differential diagnosis of various types of FTD and in the evaluation of neurotherapy efficacy. PMID:21629185

  2. Sequential distribution of pTDP-43 pathology in behavioral variant frontotemporal dementia (bvFTD)

    PubMed Central

    Grossman, Murray; Robinson, John L.; Toledo, Jon B.; Fang, Lubin; Van Deerlin, Vivianna M.; Ludolph, Albert C.; Lee, Virginia M.-Y.; Braak, Heiko; Trojanowski, John Q.

    2014-01-01

    We examined regional distribution patterns of phosphorylated 43-kDa TAr DNA-binding protein (pTDP-43) intraneuronal inclusions in frontotemporal lobar degeneration (FTLD). Immunohistochemistry was performed on 70 μm sections from FTLD-TDP autopsy cases (n = 39) presenting with behavioral variant frontotemporal dementia. Two main types of cortical pTDP-43 pathology emerged, characterized by either predominantly perikaryal pTDP-43 inclusions (cytoplasmic type, cFTLD) or long aggregates in dendrites (neuritic type, nFTLD). Cortical involvement in nFTLD was extensive and frequently reached occipital areas, whereas cases with cFTLD often involved bulbar somatomotor neurons and the spinal cord. We observed four patterns indicative of potentially sequential dissemination of pTDP-43: cases with the lowest burden of pathology (pattern I) were characterized by widespread pTDP-43 lesions in the orbital gyri, gyrus rectus, and amygdala. With increasing burden of pathology (pattern II) pTDP-43 lesions emerged in the middle frontal and anterior cingulate gyrus as well as in anteromedial temporal lobe areas, the superior and medial temporal gyri, striatum, red nucleus, thalamus, and precerebellar nuclei. More advanced cases showed a third pattern (III) with involvement of the motor cortex, bulbar somatomotor neurons, and the spinal cord anterior horn, whereas cases with the highest burden of pathology (pattern IV) were characterized by pTDP-43 lesions in the visual cortex. We interpret the four neuropathological patterns in bvFTD to be consistent with the hypothesis that pTDP-43 pathology can spread sequentially and may propagate along axonal pathways. PMID:24407427

  3. VizieR Online Data Catalog: V444 Cyg BV differential light curves (Eris+, 2011)

    NASA Astrophysics Data System (ADS)

    Eris, F. Z.; Ekmekci, F.

    2015-04-01

    Photometric and spectroscopic characteristics of the WN5+O6 binary system, V444 Cyg, were studied. The Wilson-Devinney (WD) analysis, using new BV observations carried out at the Ankara University Observatory, revealed the masses, radii, and temperatures of the components of the system as MWR=10.64M⊙, MO=24.68M⊙, RWR=7.19R⊙, RO=6.85R⊙, TWR=31000K, and TO=40000K, respectively. It was found that both components had a full spherical geometry, whereas the circumstellar envelope of the WR component had an asymmetric structure. The O-C analysis of the system revealed a period lengthening of 0.139+/-0.018s/yr, implying a mass loss rate of (6.76+/-0.39)x10-6M_⊙/yr for the WR component. Moreover, 106 IUE-NEWSIPS spectra were obtained from NASA's IUE archive for line identification and determination of line profile variability with phase, wind velocities and variability in continuum fluxes. The integrated continuum flux level (between 1200-2000Å) showed a mild and regular increase from orbital phase 0.00 up to 0.50 and then a decrease in the same way back to phase 0.00. This is evaluated as the O component making a constant and regular contribution to the system's UV light as the dominant source. The CIV line, originating in the circumstellar envelope, had the highest velocity while N IV line, originating in deeper layers of the envelope, had the lowest velocity. The average radial velocity calculated by using the CIV line (wind velocity) was found as 2326km/s. (4 data files).

  4. The Regulatory Protein RosR Affects Rhizobium leguminosarum bv. trifolii Protein Profiles, Cell Surface Properties, and Symbiosis with Clover.

    PubMed

    Rachwał, Kamila; Boguszewska, Aleksandra; Kopcińska, Joanna; Karaś, Magdalena; Tchórzewski, Marek; Janczarek, Monika

    2016-01-01

    Rhizobium leguminosarum bv. trifolii is capable of establishing a symbiotic relationship with plants from the genus Trifolium. Previously, a regulatory protein encoded by rosR was identified and characterized in this bacterium. RosR possesses a Cys2-His2-type zinc finger motif and belongs to Ros/MucR family of rhizobial transcriptional regulators. Transcriptome profiling of the rosR mutant revealed a role of this protein in several cellular processes, including the synthesis of cell-surface components and polysaccharides, motility, and bacterial metabolism. Here, we show that a mutation in rosR resulted in considerable changes in R. leguminosarum bv. trifolii protein profiles. Extracellular, membrane, and periplasmic protein profiles of R. leguminosarum bv. trifolii wild type and the rosR mutant were examined, and proteins with substantially different abundances between these strains were identified. Compared with the wild type, extracellular fraction of the rosR mutant contained greater amounts of several proteins, including Ca(2+)-binding cadherin-like proteins, a RTX-like protein, autoaggregation protein RapA1, and flagellins FlaA and FlaB. In contrast, several proteins involved in the uptake of various substrates were less abundant in the mutant strain (DppA, BraC, and SfuA). In addition, differences were observed in membrane proteins of the mutant and wild-type strains, which mainly concerned various transport system components. Using atomic force microscopy (AFM) imaging, we characterized the topography and surface properties of the rosR mutant and wild-type cells. We found that the mutation in rosR gene also affected surface properties of R. leguminosarum bv. trifolii. The mutant cells were significantly more hydrophobic than the wild-type cells, and their outer membrane was three times more permeable to the hydrophobic dye N-phenyl-1-naphthylamine. The mutation of rosR also caused defects in bacterial symbiotic interaction with clover plants. Compared with

  5. The Regulatory Protein RosR Affects Rhizobium leguminosarum bv. trifolii Protein Profiles, Cell Surface Properties, and Symbiosis with Clover

    PubMed Central

    Rachwał, Kamila; Boguszewska, Aleksandra; Kopcińska, Joanna; Karaś, Magdalena; Tchórzewski, Marek; Janczarek, Monika

    2016-01-01

    Rhizobium leguminosarum bv. trifolii is capable of establishing a symbiotic relationship with plants from the genus Trifolium. Previously, a regulatory protein encoded by rosR was identified and characterized in this bacterium. RosR possesses a Cys2-His2-type zinc finger motif and belongs to Ros/MucR family of rhizobial transcriptional regulators. Transcriptome profiling of the rosR mutant revealed a role of this protein in several cellular processes, including the synthesis of cell-surface components and polysaccharides, motility, and bacterial metabolism. Here, we show that a mutation in rosR resulted in considerable changes in R. leguminosarum bv. trifolii protein profiles. Extracellular, membrane, and periplasmic protein profiles of R. leguminosarum bv. trifolii wild type and the rosR mutant were examined, and proteins with substantially different abundances between these strains were identified. Compared with the wild type, extracellular fraction of the rosR mutant contained greater amounts of several proteins, including Ca2+-binding cadherin-like proteins, a RTX-like protein, autoaggregation protein RapA1, and flagellins FlaA and FlaB. In contrast, several proteins involved in the uptake of various substrates were less abundant in the mutant strain (DppA, BraC, and SfuA). In addition, differences were observed in membrane proteins of the mutant and wild-type strains, which mainly concerned various transport system components. Using atomic force microscopy (AFM) imaging, we characterized the topography and surface properties of the rosR mutant and wild-type cells. We found that the mutation in rosR gene also affected surface properties of R. leguminosarum bv. trifolii. The mutant cells were significantly more hydrophobic than the wild-type cells, and their outer membrane was three times more permeable to the hydrophobic dye N-phenyl-1-naphthylamine. The mutation of rosR also caused defects in bacterial symbiotic interaction with clover plants. Compared with

  6. Effects of BV-Associated Bacteria and Sexual Intercourse on Vaginal Colonization with the Probiotic Lactobacillus crispatus CTV-05

    PubMed Central

    Ngugi, Benjamin M.; Hemmerling, Anke; Bukusi, Elizabeth A.; Kikuvi, Gideon; Gikunju, Joseph; Shiboski, Stephen; Fredricks, David N.; Cohen, Craig R.

    2011-01-01

    Objective Several fastidious bacteria have been associated with bacterial vaginosis (BV), but their role in lactobacilli recolonization failure is unknown. We studied the effect of seven BV-associated bacterial species and two Lactobacillus species on vaginal colonization with L. crispatus CTV-05 (LACTIN-V). Methods Twenty four women with BV were given a 5-day course of metronidazole vaginal gel and then randomized 3:1 to receive either LACTIN-V or placebo applied vaginally once daily for 5 initial consecutive days, followed by a weekly application over 2 weeks. Vaginal swabs for L. crispatus CTV-05 culture and 9-bacterium specific 16S rRNA gene quantitative PCR assays were analyzed on several study visits for the 18 women receiving LACTIN-V. Results Vaginal colonization with CTV-05 was achieved in 61% of the participants receiving LACTIN-V at either the day 10 or the 28 visit and 44% at day 28. Participants not colonized with CTV-05 had generally higher median concentrations of BV-associated bacteria compared to those who colonized. Between enrollment and day 28, the median concentration of Gardnerella vaginalis minimally reduced from 104.5 to 104.3 16S rRNA gene copies per swab in women who colonized with CTV-05 but increased from 105.7 to 107.3 in those who failed to colonize (p=0.19). Similarly, the median concentration of Atopobium spp. reduced from 102.7 16S rRNA gene copies per swab to below limit of detection in women who colonized with CTV-05 but increased from 102.7 to 106.6 in those who failed to colonize (p=0.04). The presence of endogenous L. crispatus at enrollment was found to be significantly associated with a reduced odds of colonization with CTV-05 on day 28 (p=0.003) and vaginal intercourse during the study significantly impaired successful CTV-05 colonization (p=0.018). Conclusion Vaginal concentration of certain BV-associated bacteria, vaginal intercourse during treatment and presence of endogenous L. crispatus at enrollment predict

  7. Expression of BvGLP-1 encoding a germin-like protein from sugar beet in Arabidopsis thaliana leads to resistance against phytopathogenic fungi.

    PubMed

    Knecht, Katrin; Seyffarth, Monique; Desel, Christine; Thurau, Tim; Sherameti, Irena; Lou, Binggan; Oelmüller, Ralf; Cai, Daguang

    2010-04-01

    Nematode (Heterodera schachtii) resistance in sugar beet (Beta vulgaris) is controlled by a single dominant resistance gene, Hs1(pro-1). BvGLP-1 was cloned from resistant sugar beet. The BvGLP-1 messenger (m)RNA is highly upregulated in the resistant plants after nematode infection, suggesting its role in the Hs1(pro-1) mediated resistance. BvGLP-1 exhibits sequence homology to a set of plant germin-like proteins (GLP), from which several have proved to be functional in plant basal or defense resistance against fungal pathogens. To test whether BvGLP-1 is also involved in the plant-fungus interaction, we transferred BvGLP-1 into Arabidopsis and challenged the transgenic plants with the pathogenic fungi Verticillium longisporum and Rhizoctonia solani as well as with the beneficial endophytic fungus Piriformospora indica. The expression of BvGLP-1 in Arabidopsis elevated the H(2)O(2) content and conferred significant resistance to V. longisporum and R. solani but did not affect the beneficial interaction with P. indica in seedlings. Microscopic observations revealed a dramatic reduction in the amount of hyphae of the pathogenic fungi on the root surface as well as of fungal mycelium developed inside the roots of transgenic Arabidopsis compared with wild-type plants. Molecular analysis demonstrated that the BvGLP-1 expression in Arabidopsis constitutively activates the expression of a subset of plant defense-related proteins such as PR-1 to PR-4 and PDF1.2 but not PDF2.1 and PDF2.3. In contrast, the PDF2.1 mRNA level was downregulated. These data suggest an important role of BvGLP-1 in establishment of plant defense responses, which follow specific signaling routes that diverge from those induced by the beneficial fungus. PMID:20192832

  8. 78 FR 48832 - Airworthiness Directives; Fokker Services B.V. Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-12

    ... System Design Review, Flammability Reduction and Maintenance and Inspection Requirements'' (66 FR 23086... items and critical design configuration control limitations. We are proposing this AD to prevent an... Limitation Items (ALI) and Critical Design Configuration Control Limitations (CDCCL ) [and revising...

  9. Induction of interleukin 6 and interleukin 8 expression by Broncho-Vaxom (OM-85 BV) via C-Fos/serum responsive element.

    PubMed Central

    Keul, R.; Roth, M.; Papakonstantinou, E.; Nauck, M.; Perruchoud, A. P.; Block, L. H.

    1996-01-01

    BACKGROUND: Broncho-Vaxom (OM-85 BV) increases the resistance of the respiratory tract to bacterial infections by modulating host immune responses. The compound increases serum IgG levels but decreases IgE levels in patients suffering from chronic bronchitis or chronic obstructive pulmonary disease. It increases concentrations of gamma-interferon (IFN-gamma), IgA, and interleukin (IL)-2 in bronchoalveolar lavage fluid of patients with bronchitis. Treatment with OM-85 BV increases the number of T helper and natural killer cells. In this study the effects of OM-85 BV on transcription of cytokines is investigated in human lung fibroblasts. METHODS: Transcription and synthesis of IL-6 and IL-8 were assessed in cultured primary human lung fibroblasts using standard methods of Northern blot analysis for the level of mRNAs and enzyme linked immunosorbent assay for proteins. RESULTS: Broncho-Vaxom (OM-85 BV) at different concentrations induced transcription of IL-6 and IL-8. The effect of the drug on transcription of IL-6 and IL-8 genes correlated with secretion of the proteins into cell supernatants. OM-85 BV-dependent expression of the interleukin genes involved C-Fos/serum responsive element (C-Fos/SRE). CONCLUSIONS: The data suggest that the various immunopharmacological activities of OM-85 BV that have been described in clinical studies may be explained by its ability to induce expression of IL-6 and IL-8. Images PMID:8711646

  10. Dual RNA Sequencing Reveals the Expression of Unique Transcriptomic Signatures in Lipopolysaccharide-Induced BV-2 Microglial Cells

    PubMed Central

    Kim, Sun Hwa; Park, Kyoung Sun; Lee, Young Seek; Jung, Kyoung Hwa; Chai, Young Gyu

    2015-01-01

    Microglial cells become rapidly activated through interactions with pathogens, and the persistent activation of these cells is associated with various neurodegenerative diseases. Previous studies have investigated the transcriptomic signatures in microglia or macrophages using microarray technologies. However, this method has numerous restrictions, such as spatial biases, uneven probe properties, low sensitivity, and dependency on the probes spotted. To overcome this limitation and identify novel transcribed genes in response to LPS, we used RNA Sequencing (RNA-Seq) to determine the novel transcriptomic signatures in BV-2 microglial cells. Sequencing assessment and quality evaluation showed that approximately 263 and 319 genes (≥ 1.5 log2-fold), such as cytokines and chemokines, were strongly induced after 2 and 4 h, respectively, and the induction of several genes with unknown immunological functions was also observed. Importantly, we observed that previously unidentified transcription factors (TFs) (irf1, irf7, and irf9), histone demethylases (kdm4a) and DNA methyltransferases (dnmt3l) were significantly and selectively expressed in BV-2 microglial cells. The gene expression levels, transcription start sites (TSS), isoforms, and differential promoter usage revealed a complex pattern of transcriptional and post-transcriptional gene regulation upon infection with LPS. In addition, gene ontology, molecular networks and pathway analyses identified the top significantly regulated functional classification, canonical pathways and network functions at each activation status. Moreover, we further analyzed differentially expressed genes to identify transcription factor (TF) motifs (−950 to +50 bp of the 5’ upstream promoters) and epigenetic mechanisms. Furthermore, we confirmed that the expressions of key inflammatory genes as well as pro-inflammatory mediators in the supernatants were significantly induced in LPS treated primary microglial cells. This

  11. Intrinsic B-V color for galactic cepheids and some comments on the Sandage-Tammann relationship

    NASA Technical Reports Server (NTRS)

    Kelsall, T.

    1972-01-01

    Transformations are found for converting the b-y color excesses for Cepheids given by Williams (1966) and Kelsall (1971) into B-V excesses. The combination of these results with the E(B-V)'s determined by Sandage and Tammann (1971) gives precise data for eighty-eight galactic Cepheids. The period-color and period-color-(amplitude defect) relationships, that are germane to the LogP intervals 0.4 to 1.4 and 0.4 to 1.3, respectively, are found.

  12. Relative Entropy and the Stability of Shocks and Contact Discontinuities for Systems of Conservation Laws with non- BV Perturbations

    NASA Astrophysics Data System (ADS)

    Leger, Nicholas; Vasseur, Alexis

    2011-07-01

    We develop a theory based on relative entropy to show the uniqueness and L 2 stability (up to a translation) of extremal entropic Rankine-Hugoniot discontinuities for systems of conservation laws (typically 1-shocks, n-shocks, 1-contact discontinuities and n-contact discontinuities of large amplitude) among bounded entropic weak solutions having an additional trace property. The existence of a convex entropy is needed. No BV estimate is needed on the weak solutions considered. The theory holds without smallness conditions. The assumptions are quite general. For instance, strict hyperbolicity is not needed globally. For fluid mechanics, the theory handles solutions with vacuums.

  13. Anti-neuroinflammatory effect of aurantiamide acetate from the marine fungus Aspergillus sp. SF-5921: inhibition of NF-κB and MAPK pathways in lipopolysaccharide-induced mouse BV2 microglial cells.

    PubMed

    Yoon, Chi-Su; Kim, Dong-Cheol; Lee, Dong-Sung; Kim, Kyoung-Su; Ko, Wonmin; Sohn, Jae Hak; Yim, Joung Han; Kim, Youn-Chul; Oh, Hyuncheol

    2014-12-01

    In the course of a search for anti-neuroinflammatory metabolites from marine fungi, aurantiamide acetate (1) was isolated from marine-derived Aspergillus sp. as an anti-neuroinflammatory component. Compound 1 dose-dependently inhibited the production of nitric oxide (NO) and prostaglandin E2 (PGE2) in BV2 microglial cells. It also attenuated inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), and other pro-inflammatory cytokines, such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). In a further study designed to elucidate the mechanism of its anti-neuroinflammatory effect, compound 1 was shown to block the activation of nuclear factor-kappa B (NF-κB) in lipopolysaccharide (LPS)-induced BV2 microglial cells by inhibiting the phosphorylation of the inhibitor kappa B-α (IκB)-α. In addition, compound 1 decreased the phosphorylation levels of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinases (MAPKs). These results suggest that compound 1 has an anti-neuroinflammatory effect on LPS stimulation through its inhibition of the NF-κB, JNK and p38 pathways. PMID:25448500

  14. 78 FR 46303 - Airworthiness Directives; Fokker Services B.V. Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-31

    ... fuel system; and revising the airplane maintenance program by incorporating critical design... switch and subsequently, the implementation of the associated Critical Design Configuration Control...'' (66 FR 23086, May 7, 2001). In addition to new airworthiness standards for transport airplanes and...

  15. [Safety and efficacy of OM-85-BV plus amoxicillin/clavulanate in the treatment of subacute sinusitis and the prevention of recurrent infections in children].

    PubMed

    Gómez Barreto, D; De la Torre, C; Alvarez, A; Faure, A; Berber, A

    1998-01-01

    A 6-month double-blind, prospective, randomized, placebo-controlled trial was conducted to establish the safety and efficacy of OM-85-BV in the treatment of subacute sinusitis and in the following prevention of the respiratory tract infections in 56 children from 18 months to 9 years of age. In the subacute phase of the sinusitis the patients were given one OM-85-BV capsule (3.5 mg of bacterial extracts) (n = 26) or placebo (n = 30), daily for ten days; additionally both groups took amoxicillin/clavulanate 40/10 mg/kg daily in three divided doses for 21 days. For the following two months the patients took one OM-85-BV capsule or placebo, ten days a month. In the subacute phase the OM-85-BV group of patients improved sooner (5.56 +/- 4.98 vs 10 +/- 8.49 days) and had a shorter convalescence (15.38 +/- 8.91 vs 20.28 +/- 7.17 days). During the six month follow-up the patients in the OM-85-BV group had a lower number of infections (1.56 +/- 0.3 vs 2.22 +/- 0.43) and required a lower number of drug treatments (1.47 +/- 0.32 vs 1.94 +/- 0.42). One patient treated with OM-85-BV presented a mild rash which disappeared three days after the drug discontinuation. We conclude that OM-85-BV is safe at pediatric ages, as well as accelerates the cure and improvement of subacute sinusitis while it lowers the incidence of respiratory infections. PMID:9585823

  16. SMAC Mimetic BV6 Enables Sensitization of Resistant Tumor Cells but also Affects Cytokine-Induced Killer (CIK) Cells: A Potential Challenge for Combination Therapy

    PubMed Central

    Rettinger, Eva; Glatthaar, Andreas; Abhari, Behnaz Ahangarian; Oelsner, Sarah; Pfirrmann, Verena; Huenecke, Sabine; Kuçi, Selim; Kreyenberg, Hermann; Willasch, Andre M.; Klingebiel, Thomas; Fulda, Simone; Bader, Peter

    2014-01-01

    Allogeneic hematopoietic stem cell transplantation (HSCT) is an established treatment option for high-risk hematological malignancies, and may also be offered to patients with solid malignancies refractory to conventional therapies. In case of patients’ relapse, refractory tumor cells may then be targeted by cellular therapy-based combination strategies. Here, we investigated the potential of small molecule IAP (SMAC mimetic) BV6 in increasing cytokine-induced killer (CIK) cell-mediated cytotoxicity against different tumor targets. Four-hour pre-incubation with 2.5 μMol BV6 moderately enhanced CIK cell-mediated lysis of hematological (H9, THP-1, and Tanoue) and solid malignancies (RH1, RH30, and TE671). However, BV6 also increased apoptosis of non-malignant cells like peripheral blood mononuclear cells and most notably had an inhibitory effect on immune cells potentially limiting their cytotoxic potential. Hence, cytotoxicity increased in a dose-dependent manner when BV6 was removed before CIK cells were added to tumor targets. However, cytotoxic potential was not further increasable by extending BV6 pre-incubation period of target cells from 4 to 12 h. Molecular studies revealed that BV6 sensitization of target cells involved activation of caspases. Here, we provide evidence that SMAC mimetic may sensitize targets cells for CIK cell-induced cell death. However, BV6 also increased apoptosis of non-malignant cells like CIK cells and peripheral mononuclear cells. These findings may therefore be important for cell- and small molecule IAP-based combination therapies of resistant cancers after allogeneic HSCT. PMID:25101252

  17. Low-Dose Ribavirin Treatments Attenuate Neuroinflammatory Activation of BV-2 Cells by Interfering with Inducible Nitric Oxide Synthase

    PubMed Central

    Bozic, Iva; Savic, Danijela; Jovanovic, Marija; Bjelobaba, Ivana; Laketa, Danijela; Nedeljkovic, Nadezda; Stojiljkovic, Mirjana; Pekovic, Sanja; Lavrnja, Irena

    2015-01-01

    Microglia play a key role in defending central nervous system from various internal and external threats. However, their excessive and/or chronic activation is associated with deleterious effects in a variety of neurodegenerative diseases. Previously, we have shown that ribavirin when applied in clinically relevant dosage (10 μM) modulates activated microglia in complex fashion inducing both anti- and proinflammatory effects, simultaneously causing cytotoxicity. Here, we examined potential of low-dose ribavirin (0.1 and 1 μM) to modulate activated BV-2 microglia. Morphological and functional activation of BV-2 cells was achieved with lipopolysaccharide (LPS) stimulation. Our results demonstrated that low-dose ribavirin did not induce cell death, while 10 μM ribavirin promoted LPS induced apoptosis. We determined that 1 μM ribavirin was equally efficient in deactivation of LPS induced morphological changes as 10 μM ribavirin treatment. Ribavirin showed halfway success in reducing markers of functional activation of microglia. Namely, none of the doses had effect on LPS triggered production of proinflammatory cytokine tumor necrosis factor alpha. On the other hand, low-dose ribavirin proved its effectiveness in reduction of another inflammatory mediator, nitric oxide, by inhibiting inducible form of nitric oxide synthase. Our results imply that low-dose ribavirin may alleviate nitrosative stress during neuroinflammation. PMID:26413464

  18. Population Genomics Analysis of Legume Host Preference for Specific Rhizobial Genotypes in the Rhizobium leguminosarum bv. viciae Symbioses.

    PubMed

    Jorrin, Beatriz; Imperial, Juan

    2015-03-01

    Rhizobium leguminosarum bv. viciae establishes root nodule symbioses with several legume genera. Although most isolates are equally effective in establishing symbioses with all host genera, previous evidence suggests that hosts select specific rhizobial genotypes among those present in the soil. We have used population genomics to further investigate this observation. Pisum sativum, Lens culinaris, Vicia sativa, and V. faba plants were used to trap rhizobia from a well-characterized soil, and pooled genomic DNA from 100 isolates from each plant were sequenced. Sequence reads were aligned to the R. leguminosarum bv. viciae 3841 reference genome. High overall conservation of sequences was observed in all subpopulations, although several multigenic regions were absent from the soil population. A large fraction (16 to 22%) of sequence reads could not be recruited to the reference genome, suggesting that they represent sequences specific to that particular soil population. Although highly conserved, the 16S to 23S ribosomal RNA gene region presented single nucleotide polymorphisms (SNP) regarding the reference genome, but no striking differences could be found among plant-selected subpopulations. Plant-specific SNP patterns were, however, clearly observed within the nod gene cluster, supporting the existence of a plant preference for specific rhizobial genotypes. This was also shown after genome-wide analysis of SNP patterns. PMID:25514682

  19. Third Harmonic Generation microscopy as a diagnostic tool for the investigation of microglia BV-2 and breast cancer cells activation

    NASA Astrophysics Data System (ADS)

    Gavgiotaki, E.; Filippidis, G.; Psilodimitrakopoulos, S.; Markomanolaki, H.; Kalognomou, M.; Agelaki, S.; Georgoulias, V.; Athanassakis, I.

    2015-07-01

    Nonlinear optical imaging techniques have created new opportunities of research in the biomedical field. Specifically, Third Harmonic Generation (THG) seems to be a suitable noninvasive imaging tool for the delineation and quantification of biological structures at the microscopic level. The aim of this study was to extract information as to the activation state of different cell types by using the THG imaging microscopy as a diagnostic tool. BV-2 microglia cell line was used as a representative biological model enabling the study of resting and activated state of the cells linked to various pathological conditions. Third Harmonic Generation (THG) and Two Photon Excitation Fluorescence (TPEF) measurements were simultaneously collected from stained breast cancer cells, by employing a single homemade experimental apparatus and it was shown that high THG signals mostly arise from lipid bodies. Continuously, BV-2 microglia cells were examined with or without activation by lipopolysaccharide (LPS) in order to discriminate between control and activated cells based on the quantification of THG signals. Statistically quantification was accomplished in both mean area and mean intensity values of THG. The values for mean total area and mean THG intensity values have been increased in activated versus the non-activated cells. Similar studies of quantification are underway in breast cancer cells for the exact discrimination on different cell lines. Furthermore, laser polarization dependence of SHG and THG signal in unstained biological samples is investigated.

  20. Autographa californica multiple nucleopolyhedrovirus ac142, a core gene that is essential for BV production and ODV envelopment

    SciTech Connect

    McCarthy, Christina B.; Da, Xiaojiang; Donly, Cam; Theilmann, David A.

    2008-03-15

    Autographa californica multiple nucleopolyhedrovirus (AcMNPV) ac142 is a baculovirus core gene and encodes a protein previously shown to associate with occlusion-derived virus (ODV). To determine its role in the baculovirus life cycle, we used the AcMNPV bacmid system to generate an ac142 deletion virus (AcBAC{sup ac142KO-PH-GFP}). Fluorescence and light microscopy revealed that AcBAC{sup ac142KO-PH-GFP} exhibits a single-cell infection phenotype. Titration assays and Western blot confirmed that AcBAC{sup ac142KO-PH-GFP} is unable to produce budded virus (BV). However, viral DNA replication is unaffected and the development of occlusion bodies in AcBAC{sup ac142KO-PH-GFP}-transfected cells evidenced progression to very late phases of the viral infection. Western blot analysis showed that AC142 is expressed in the cytoplasm and nucleus throughout infection and that it is a structural component of BV and ODV which localizes to nucleocapsids. Electron microscopy indicates that ac142 is required for nucleocapsid envelopment to form ODV and their subsequent occlusion, a fundamental process to all baculoviruses.

  1. Genetic diversity of a natural population of Rhizobium leguminosarum bv. viciae nodulating plants of Vicia faba in the Vesuvian area.

    PubMed

    Ventorino, Valeria; Chiurazzi, Mario; Aponte, Maria; Pepe, Olimpia; Moschetti, Giancarlo

    2007-12-01

    A total of 98 rhizobial strains, isolated during the winter of the years 2003 (35 isolates), 2004 (33 isolates), and 2005 (30 isolates) were analyzed to determine the genetic diversity of the natural population nodulating Vicia faba plants and to identify dominant genotypes. All isolates were identified as Rhizobium leguminosarum bv. viciae by biovar-specific polymerase chain reaction amplification of the nodC gene. Intraspecific DNA polymorphism was evaluated through the restriction endonucleases analysis combined with pulsed-field gel electrophoresis. Four genotypes characterized 53% of the isolates, showing a high occurrence; moreover, they were recovered over the 3 years, thus showing a lasting persistence in the soil, which could mean a high degree of saprophytic competitiveness. The richness, diversity, and dominance indexes of genotypes were calculated to monitor the evolution of the rhizobial population during the 3 years. The genetic diversity of the analyzed strains decreased along the 3 years. In fact, the biodiversity index H' decreased from 2.6 in the first and second year to 1.9 in the third year; probably, as a result of bean monocropping, specific genotypes of Rh. leguminosarum bv. viciae were naturally selected. PMID:17899266

  2. Effectiveness of photochemical and sonochemical processes in degradation of Basic Violet 16 (BV16) dye from aqueous solutions

    PubMed Central

    2012-01-01

    In this study, degradation of Basic Violet 16 (BV16) by ultraviolet radiation (UV), ultrasonic irradiation (US), UV/H2O2 and US/H2O2 processes was investigated in a laboratory-scale batch photoreactor equipped with a 55W immersed-type low-pressure mercury vapor lamp and a sonoreactor with high frequency (130kHz) plate type transducer at 100W of acoustic power. The effects of initial dye concentration, concentration of H2O2 and solution pH and presence of Na2SO4 was studied on the sonochemical and photochemical destruction of BV16 in aqueous phase. The results indicated that in the UV/H2O2 and US/H2O2 systems, a sufficient amount of H2O2 was necessary, but a very high H2O2 concentration would inhibit the reaction rate. The optimum H2O2 concentration was achieved in the range of 17 mmol/L at dye concentration of 30 mg/L. A degradation of 99% was obtained with UV/H2O2 within 8 minutes while decolorization efficiency by using UV (23%), US (<6%) and US/H2O2(<15%) processes were negligible for this kind of dye. Pseudo-first order kinetics with respect to dyestuffs concentrations was found to fit all the experimental data. PMID:23369268

  3. Impact of a mixed bacterial lysate (OM-85 BV) on the immunogenicity, safety and tolerability of inactivated influenza vaccine in children with recurrent respiratory tract infection.

    PubMed

    Esposito, Susanna; Marchisio, Paola; Prada, Elisabetta; Daleno, Cristina; Porretti, Laura; Carsetti, Rita; Bosco, Annalisa; Ierardi, Valentina; Scala, Alessia; Principi, Nicola

    2014-05-01

    It is known that the immunogenicity and efficacy of conventional inactivated influenza vaccines (IIVs) are not completely satisfactory in children. The aim of this prospective, randomised, single-blind study was to compare the immune response to, and the effectiveness and safety of, an IIV (Fluarix, GlaxoSmithKline Biologicals, Rixensart, Belgium) administered to 68 children aged 36-59 months affected by recurrent respiratory tract infections (RRTIs) who were vaccinated with (n=33) or without (n=35) the mixed bacterial lysate OM-85 BV (Broncho-vaxom, Vifor Pharma, Geneva, Switzerland). OM-85 BV had no effect on seroconversion or seroprotection rates, geometric mean titres, or dendritic cells, which were not significantly different between the two groups. Moreover, OM-85 BV did not significantly increase the pool of the memory B cells that produce IgG and IgM antibodies against the influenza antigens. However, respiratory morbidity was significantly lower in the children treated with OM-85 BV (p<0.05), thus confirming its positive effect on the incidence of RRTIs. There was no difference in the incidence of adverse events between the two groups. These findings show that the immune response of children to influenza vaccine is not significantly influenced by the administration of OM-85 BV. However, the use of OM-85 before and at the same time as IIV seems to reduce respiratory morbidity, and seems to be safe and well tolerated. PMID:24681270

  4. RE-186 labeled 16.88 IgM and 88BV59 IgG human antibody studies to assess potential for radioimmunotherapy

    SciTech Connect

    Breitz, H.; Seiler, C.; Weiden, P. ||

    1994-05-01

    Two studies with Re-186-MAG{sub 2}GABA labeled human antibodies were carried out to assess feasibility for radioimmunotherapy. Antibodies 16.88 and 88BV59 react with different epitopes of CTA 16.88, a tumor associated antigen of colorectal carcinoma. In a phase I dose escalation study, 14 patients received 60 mg/m{sup 2} 16.88 IgM MoAb. The dose of Re-186 ranged from 25 mCi/m{sup 2} to 210 mCi/m{sup 2} divided into 3 weekly infusions. In a pilot study with 88BV59, a human IgG3k MoAb, 20 mg antibody was labeled with 25 mCi/m{sup 2} Re-186 and administered to 4 patients with colon carcinoma. Tumor targeting was seen in 12 of 14 patients with 16.88 and all 4 patients with 88BV59. Retention of antibody at the tumor was longer with 88BV59. One patient developed a rash. No other acute or delayed toxicities were observed. Human anti-human antibody did not develop in any patient. The slower metabolism of the 88BV59 IgG suggests that this form of immunoconjugate merits further investigation for use in radioimmunotherapy.

  5. PCR-based identification of eight Lactobacillus species and 18 hr-HPV genotypes in fixed cervical samples of South African women at risk of HIV and BV.

    PubMed

    Dols, Joke A M; Reid, Gregor; Kort, Remco; Schuren, Frank H J; Tempelman, Hugo; Bontekoe, Tj Romke; Korporaal, Hans; Van der Veer, E M; Smit, Pieter W; Boon, Mathilde E

    2012-06-01

    Vaginal lactobacilli assessed by PCR-based microarray and PCR-based genotyping of HPV in South African women at risk for HIV and BV. Vaginal lactobacilli can be defined by microarray techniques in fixed cervical samples of South African women. Cervical brush samples suspended in the coagulant fixative BoonFix of one hundred women attending a health centre for HIV testing in South Africa were available for this study. In the Ndlovu Medical Centre in Elandsdoorn, South Africa, identification of 18 hr-HPV genotypes was done using the INNO-LiPA method. An inventory of lactobacilli organisms was performed using microarray technology. On the basis of the Lactobacillus and Lactobacillus biofilm scoring, the cases were identified as Leiden bacterial vaginosis (BV) negative (BV-; n = 41), Leiden BV intermediate (BV±; n = 25), and Leiden BV positive (BV+; n = 34). Fifty-one women were HIV positive and 49 HIV negative. Out of the 51 HIV positive women, 35 were HPV infected. These 51 HIV positive women were frequently infected with HPV16 and HPV18. In addition, HPV35, HPV52, HPV33, and HPV66 were often detected in these samples. Lactobacillus salivarius and Lactobacillus iners were the most prevalent lactobacilli as established by the microarray technique. In women with HPV infection, the prevalence of Lactobacillus crispatus was significantly reduced. In both HIV and HPV infection, a similar (but not identical) shift in the composition of the lactobacillus flora was observed. We conclude that there is a shift in the composition of vaginal lactobacilli in HIV-infected women. Because of the prominence of HPV35, HPV52, HPV33, and HPV66, vaccination for exclusively HPV16 and HPV18 might be insufficient in South African HIV+ women. PMID:22021225

  6. Inhibitory constituents from the aerial parts of Polygala tenuifolia on LPS-induced NO production in BV2 microglia cells.

    PubMed

    Shi, Tian-Xing; Wang, Shu; Zeng, Ke-Wu; Tu, Peng-Fei; Jiang, Yong

    2013-11-01

    Five new phenolic glycosides, tenuisides A-E (1-5), and a new megastigmane glycoside, tenuiside F (6), along with seventeen known compounds (7-23) were isolated from the aerial parts of Polygala tenuifolia Willd. Their structures were established by detailed analysis of NMR and HRESIMS spectroscopic data, and the absolute configurations of compounds 5 and 6 were determined by CD spectra and in-NMR-tube Mosher's method. The inhibitory effects of these compounds were evaluated on NO production in LPS-activated BV-2 microglia cells. Compound 17 showed the strongest activity, with an IC50 value of 7.4μM, while compounds 1, 8, 14, and 18 showed the moderate activities, with IC50 values of 16.2-38.5μM. And their primary structure-activity relationships (SARs) of NO inhibitory effects were also briefly discussed. PMID:24042007

  7. Ethanol downregulates N-acyl phosphatidylethanolamine-phospholipase D expression in BV2 microglial cells via epigenetic mechanisms.

    PubMed

    Correa, Fernando; De Laurentiis, Andrea; Franchi, Ana María

    2016-09-01

    Excessive ethanol drinking has deleterious effects on the brain. However, the effects of alcohol on microglia, the main mediator of the brain's innate immune response remain poorly understood. On the other hand, the endocannabinoid system plays a fundamental role in regulating microglial reactivity and function. Here we studied the effects of acute ethanol exposure to murine BV2 microglial cells on N-acyl phosphatidylethanolamine-phospholipase D (NAPE-PLD), a major synthesizing enzyme of anandamide and other N-acylethanolamines. We found that ethanol downregulated microglial NAPE-PLD expression by activating cAMP/PKA and ERK1/2. These signaling pathways converged on increased phosphorylation of CREB. Moreover, ethanol induced and increase in histone acetyltransferase activity which led to higher levels of acetylation of histone H3. Taken together, our results suggest that ethanol actions on microglial NAPE-PLD expression might involve epigenetic mechanisms. PMID:27266665

  8. The effect of temperature instability on the threshold sensitivity of photodetectors based on AIII-BV photodiodes

    NASA Astrophysics Data System (ADS)

    Aleksandrov, S. E.; Gavrilov, G. A.; Kapralov, A. A.; Sotnikova, G. Yu.

    2016-03-01

    The dependence of the sensitivity of photodetectors based on AIII-BV photodiodes on accidental variations of the temperature of its elements is analyzed. It is shown that the temperature drift of the bias level in input circuits of op-amps strongly contributes to the resulting photodetector noise up to frequencies on the order of 1 MHz. To reach the limiting sensitivities of the sensors, it is necessary to stabilize the temperature of not only the photodiode chip, but also the integrated circuit of the first amplifier stage. For most of applications, the required stabilization accuracy does not exceed ±0.1°C. As a result of the analysis, prototype high-sensitivity medium-wavelength (2-5 μm) sensors were developed that operate without forced cooling and have a detection threshold of tens of nanowatts at a detection bandwidth of 0-1 MHz.

  9. Steroidal Glucosides from the Rhizomes of Tacca chantrieri and Their Inhibitory Activities of NO Production in BV2 Cells.

    PubMed

    Yen, Pham Hai; Chi, Vu Thi Quynh; Kim, Dong-Cheol; Ko, Wonmin; Oh, Hyuncheol; Kim, Youn-Chul; Dung, Duong Thi; Thanh, Nguyen Thi Viet; Quang, Tran Hong; Ngan, Nguyen Thi Thanh; Nhiema, Nguyen Xuan; Anh, Hoang Le Tuan; Minh, Chan Van; Kiem, Phan Van

    2016-01-01

    Two new steroidal glucosides, chantriolides D and E (1 and 2), along with four known compounds, chantriolide A (3), chantriolide B (4), chantriolide C (5), and (25S)-spirost-5-en-3-ol 3-O-α-L-rhamnopyranosyl-(1-->2)-O-[α-L-rhamnopyranosyl-(1-->3)]-β-D-glucopyranoside (6) were isolated from the rhizomes of Tacca chantrieri. Their structures were determined by 1D and 2D NMR spectroscopic and HR-ESI-MS data, as well as by comparison with reported data. Compounds 1 and 2 were found to show strong inhibitory NO effect in BV2 cells, with IC₅₀ values of 12.45 and 59.03 µM, respectively. PMID:26996017

  10. Inhibition of phagocytosis and lysosomal acidification suppresses neurotoxic prion peptide-induced NALP3 inflammasome activation in BV2 microglia.

    PubMed

    Shi, Fushan; Yang, Yang; Kouadir, Mohammed; Fu, Yongyao; Yang, Lifeng; Zhou, Xiangmei; Yin, Xiaomin; Zhao, Deming

    2013-07-15

    Prion diseases are neurodegenerative disorders characterized by the accumulation of misfolded prion protein. In a previous study, we showed that neurotoxic prion peptide (PrP106-126) induced NALP3 inflammasome activation in mouse primary and immortalized microglia. In the present work, we examined the relevance of phagocytosis and lysosomal acidification to the activation of the NALP3 inflammasome in PrP106-126-stimulated microglia. Our results showed that the inhibition of phagocytosis or lysosomal acidification significantly reduced IL-1β and IL-18 production, downregulated NALP3 and ASC expression, and decreased the expression of proinflammatory factors. We concluded that phagocytosis and lysosomal acidification are necessary for PrP106-126-induced NALP3 activation in BV2 cells. PMID:23680490

  11. Inhibitory effects of diallyl disulfide on the production of inflammatory mediators and cytokines in lipopolysaccharide-activated BV2 microglia

    SciTech Connect

    Park, Hye Young; Kim, Nam Deuk; Kim, Gi-Young; Hwang, Hye Jin; Kim, Byung-Woo; Kim, Wun Jae; Choi, Yung Hyun

    2012-07-15

    Diallyl disulfide (DADS), a main organosulfur component responsible for the diverse biological effects of garlic, displays a wide variety of internal biological activities. However, the cellular and molecular mechanisms underlying DADS' anti-inflammatory activity remain poorly understood. In this study, therefore, the anti-inflammatory effects of DADS were studied to investigate its potential therapeutic effects in lipopolysaccharide (LPS)-stimulated BV2 microglia. We found that pretreatment with DADS prior to treatment with LPS significantly inhibited excessive production of nitric oxide (NO) and prostaglandin E{sub 2} (PGE{sub 2}) in a dose-dependent manner. The inhibition was associated with down-regulation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression. DADS also attenuated the production of pro-inflammatory cytokines and chemokines, including interleukin-1β (IL-1β), tumor necrosis factor (TNF)-α, and monocyte chemoattractant protein-1 (MCP-1) by suppressing the expression of mRNAs for these proteins. The mechanism underlying this protective effect might be related to the inhibition of nuclear factor-kappaB, Akt and mitogen-activated protein kinase signaling pathway activation in LPS-stimulated microglial cells. These findings indicated that DADS is potentially a novel therapeutic candidate for the treatment of various neurodegenerative diseases. -- Highlights: ► DADS attenuates production of NO and PGE2 in LPS-activated BV2 microglia. ► DADS downregulates levels of iNOS and COX-2. ► DADS inhibits production and expression of inflammatory cytokines and chemokine. ► DADS exhibits these effects by suppression of NF-κB, PI3K/Akt and MAPKs pathways.

  12. Genotypic and Phenotypic Comparisons of Chromosomal Types within an Indigenous Soil Population of Rhizobium leguminosarum bv. trifolii †

    PubMed Central

    Leung, Kamtin; Strain, Steven R.; de Bruijn, Frans J.; Bottomley, Peter J.

    1994-01-01

    The relative genetic similarities of 200 isolates of Rhizobium leguminosarum bv. trifolii recovered from an Oregon soil were determined at 13 enzyme loci by multilocus enzyme electrophoresis (MLEE). These isolates represented 13 antigenically distinct serotypes recovered from nodules formed on various clover species. The MLEE-derived levels of relatedness among isolates of R. leguminosarum bv. trifolii were found to be in good agreement with the levels of relatedness established by using repetitive (repetitive extragenic palindromic and enterobacterial repetitive intergeneric consensus) sequences and the PCR technique and with levels of relatedness from previously published DNA reassociation studies. BIOLOG substrate utilization patterns showed that isolates within an electrophoretic type (ET) were phenotypically more similar to each other than to isolates of other ETs. The soil isolates were represented by 53 ETs which could be clustered into seven groups (groups B, E, G, H1, H2, I, and J). Evidence for multilocus structure within the population was obtained, and group B was identified as the primary creator of the disequilibrium. Of 75 isolates belonging to the nodule-dominant serotype AS6 complex, 72 were found in group B. Isolates WS2-01 and WS2-02 representing nodule-dominant serotypes recovered from subclover grown at another Oregon site were also found in group B. Isolates representing the most numerous ETs in group B (ETs 2 and 3) were either suboptimally effective or completely ineffective at fixing nitrogen on six different clover species. Another four groups of isolates (groups A, C, D, and F) were identified when 32 strains of diverse origins were analyzed by MLEE and incorporated into the cluster analysis. Group A was most dissimilar in comparisons with other groups and contained strain USDA 2124 (T24), which produces trifolitoxin and has unique symbiotic characteristics. PMID:16349171

  13. 76 FR 20493 - Airworthiness Directives; Fokker Services B.V. Model F.27 Mark 050 Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-13

    ... 20142 were erroneously omitted in the original Fokker Service Bulletins (SB) and consequently the AD did not apply to those aeroplanes. The two SB's (some typographical errors in part numbers were also found... Fokker 50 and Fokker 60 type design, in response to these regulations, revealed that the...

  14. Complete Genome Sequence of Mesorhizobium ciceri bv. biserrulae Strain WSM1284, an Efficient Nitrogen-Fixing Microsymbiont of the Pasture Legume Biserrula pelecinus.

    PubMed

    Haskett, Timothy; Wang, Penghao; Ramsay, Joshua; O'Hara, Graham; Reeve, Wayne; Howieson, John; Terpolilli, Jason

    2016-01-01

    We report the complete genome sequence of Mesorhizobium ciceri bv. biserrulae strain WSM1284, a nitrogen-fixing microsymbiont of the pasture legume Biserrula pelecinus The genome consists of 6.88 Mb distributed between a single chromosome (6.33 Mb) and a single plasmid (0.55 Mb). PMID:27284134

  15. Clonality of Campylobacter sputorum bv. paraureolyticus determined by macrorestriction profiling and biotyping, and evidence for long-term persistent infection in cattle.

    PubMed

    On, S L; Atabay, H I; Corry, J E

    1999-02-01

    Eighteen strains of Campylobacter sputorum bv. paraureolyticus (isolated over a 12-month period from seven dairy cows contained in a single herd) were examined by resistotyping, and macrorestriction profiling using pulsed field gel electrophoresis (PFGE). The resistotypes of these strains were identical, although repeat testing indicated resistance to metronidazole was not a reliable trait for typing purposes. Five SmaI-derived genotypes were identified among the 18 strains. In 5 of 7 cows, isolates obtained from the same animal, but from different time periods, were genotypically indistinguishable, indicating persistence of infection. Macrorestriction profiles of 5 strains representing the 5 SmaI genotypes and 8 other strains of C. sputorum from various sources, were prepared using 4 endonucleases (SmaI, SalI, BamHI and KpnI). The only other strain of C. sputorum bv. paraureolyticus examined (a Canadian isolate from human faeces), was found to have a SmaI macrorestriction profile identical with one of the five clones isolated from the cattle. Moreover, SalI and BamHI profiles of all bv. paraureolyticus strains were similar, while digestion with KpnI was not observed. By contrast, the seven strains of C. sputorum bv. sputorum yielded various macrorestriction profiles with all the enzymes used, and features distinguishing the two biovars studied could be identified. This study indicates that C. sputorum can persist in cattle for at least 12 months and exhibits a clonal population genetic structure. PMID:10098802

  16. [Preventive effect of an immunomodulator, OM-85 BV, on acute exacerbations of chronic bronchitis in elderly patients. Preliminary results at six months in 291 patients].

    PubMed

    Orcel, B; Delclaux, B; Baud, M; Derenne, J P

    1993-01-01

    Three hundred fifty six patients aged 65 years or more (mean age 81.8 years) who were suffering from chronic bronchitis were included in a double-blind trial against placebo to assess the preventative effect of OM-85 BV against acute exacerbations of chronic bronchitis. OM-85 BV is an immunostimulant composed of lyophilised factions of 8 bacteria which are most frequently encountered during the course of respiratory tract infections. 291 patients completed the study. In the group treated by OM-85 BV, a significant increase in the number of patients with no episode of acute bronchitis was noted (96 versus 71, p = 0.006). There was a 38.8% reduction in the absolute numbers of episodes of acute bronchitis and a 33% reduction in the number of prescriptions for antibiotics, however there was no difference in the number of pneumonias and bronchopneumonias. These results show the protective effect of OM-85 BV against bronchial superinfections in a large population of elderly patients suffering from chronic bronchitis. PMID:8451491

  17. Complete Genome Sequence of Mesorhizobium ciceri bv. biserrulae Strain WSM1284, an Efficient Nitrogen-Fixing Microsymbiont of the Pasture Legume Biserrula pelecinus

    PubMed Central

    Haskett, Timothy; Wang, Penghao; Ramsay, Joshua; O’Hara, Graham; Reeve, Wayne; Howieson, John

    2016-01-01

    We report the complete genome sequence of Mesorhizobium ciceri bv. biserrulae strain WSM1284, a nitrogen-fixing microsymbiont of the pasture legume Biserrula pelecinus. The genome consists of 6.88 Mb distributed between a single chromosome (6.33 Mb) and a single plasmid (0.55 Mb). PMID:27284134

  18. Draft Genome Sequence of a Salmonella enterica subsp. enterica Serovar Gallinarum bv. Gallinarum Isolate Associated with Fowl Typhoid Outbreaks in Brazil

    PubMed Central

    De Carli, Silvia; Gräf, Tiago; Mayer, Fabiana Q.; Cibulski, Samuel; Lehmann, Fernanda K. M.; Fonseca, André S. K.; Ikuta, Nilo

    2016-01-01

    Salmonella enterica subsp. enterica serovar Gallinarum bv. Gallinarum strains are bird pathogens causing fowl typhoid (FT). Isolate BR_RS12 was obtained from a poultry flock with FT in 2014. The sequencing of this genome will enable to track the origin of the recent outbreaks in Brazil. PMID:26950322

  19. Gardenia jasminoides extracts and gallic acid inhibit lipopolysaccharide-induced inflammation by suppression of JNK2/1 signaling pathways in BV-2 cells

    PubMed Central

    Lin, Wen-Hung; Kuo, Heng-Hung; Ho, Li-Hsing; Tseng, Ming-Lang; Siao, An-Ci; Hung, Chang-Tsen; Jeng, Kee-Ching; Hou, Chien-Wei

    2015-01-01

    Objective(s): Gardenia jasminoides Ellis (GJ, Cape Jasmine Fruit, Zhi Zi) has been traditionally used for the treatment of infectious hepatitis, aphthous ulcer, and trauma; however, the direct evidence is lacking. Materials and Methods: We investigated the effect of the GJ extract (GJ) and gallic acid (GA) on lipopolysaccharide (LPS) induced inflammation of BV-2 microglial cells and acute liver injury in Sprague-Dawley (SD) rats. Results: Our results showed that the GJ extract and GA reduced LPS-induced nitric oxide (NO), interleukin (IL)-1, IL-6, reactive oxygen species (ROS), and prostaglandin (PGE2) production in BV-2 cells. The GJ extract and GA significantly decreased serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in LPS-treated rats. Furthermore, the water extract, but not the ethanol extract, of the GJ dose-dependently inhibited LPS-induced JNK2/1 and slightly p38 mitogen-activated protein kinases (MAPK), and cyclooxygenase-2 (COX-2) expression in BV-2 cells. Conclusion: Taken together, these results indicate that the protective mechanism of the GJ extract involves an antioxidant effect and inhibition of JNK2/1 MAP kinase and COX-2 expressions in LPS-induced inflammation of BV-2 cells. PMID:26221479

  20. Draft Genome Sequence of the Moderately Heat-Tolerant Lactococcus lactis subsp. lactis bv. diacetylactis Strain GL2 from Algerian Dromedary Milk

    PubMed Central

    Gabed, Noujoud; Yang, Manli; Bey Baba Hamed, Mohamed; Drici, Habiba; Gross, Roy; Dandekar, Thomas

    2015-01-01

    Lactococcus lactis subsp. lactis bv. diacetylactis GL2 is a moderately thermotolerant lactic acid bacterium isolated from dromedary raw milk. Here, we present the draft genome sequence of this potential new dairy starter strain, which combines thermotolerance and the capacity to metabolize lactose, casein, and citrate. PMID:26586883

  1. Anthocyanin-rich acai (Euterpe oleracea mart.) fruit pulp fractions attenuate inflammatory stress signaling in mouse brain BV-2 microglial cells

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Age-related increases in oxidative stress and inflammation are associated with loss of cognitive and motor functions. Previous research has shown that supplementation with berry fruits can modulate signaling in primary hippocampal neurons or BV-2 mouse microglial cells. Because of the high polypheno...

  2. EcoTILLING in Beta vulgaris reveals polymorphisms in the FLC-like gene BvFL1 that are associated with annuality and winter hardiness

    PubMed Central

    2013-01-01

    Background Sugar beet (Beta vulgaris ssp. vulgaris L.) is an important crop for sugar and biomass production in temperate climate regions. Currently sugar beets are sown in spring and harvested in autumn. Autumn-sown sugar beets that are grown for a full year have been regarded as a cropping system to increase the productivity of sugar beet cultivation. However, for the development of these “winter beets” sufficient winter hardiness and a system for bolting control is needed. Both require a thorough understanding of the underlying genetics and its natural variation. Results We screened a diversity panel of 268 B. vulgaris accessions for three flowering time genes via EcoTILLING. This panel had been tested in the field for bolting behaviour and winter hardiness. EcoTILLING identified 20 silent SNPs and one non-synonymous SNP within the genes BTC1, BvFL1 and BvFT1, resulting in 55 haplotypes. Further, we detected associations of nucleotide polymorphisms in BvFL1 with bolting before winter as well as winter hardiness. Conclusions These data provide the first genetic indication for the function of the FLC homolog BvFL1 in beet. Further, it demonstrates for the first time that EcoTILLING is a powerful method for exploring genetic diversity and allele mining in B. vulgaris. PMID:23531083

  3. Flavonoids isolated from Lespedeza cuneata G. Don and their inhibitory effects on nitric oxide production in lipopolysaccharide-stimulated BV-2 microglia cells

    PubMed Central

    Yoo, Guijae; Park, Seon Ju; Lee, Taek Hwan; Yang, Heejung; Baek, Yoon-su; Kim, Nanyoung; Kim, Yoon Jae; Kim, Seung Hyun

    2015-01-01

    Background: Lespedeza cuneata (Dum. Cours.) G. Don, a perennial legume native to Eastern Asia, has been used therapeutically in traditional Asian medicine to protect the function of liver, kidneys and lungs. However, its effect on inflammatory nitric oxide (NO) production and the active constituents have not yet been explored. Objective: In this study, we investigated the phytochemical constituents of L. cuneata and evaluated their effect on NO production using lipopolysaccharide (LPS)-stimulated BV2 cells. Materials and Methods: The 80% methanol extract of the aerial part of L. cuneata were used for the isolation of flavonoids. The isolated compounds were elucidated by various spectroscopic methods including nuclear magnetic resonance and mass spectrometry spectrometry. To evaluate the effect on inflammatory NO production, LPS-stimulated murine microglia BV-2 cells were used as a screening system. Results: Nine flavonoids were isolated from the aerial parts of L. cuneata. Among the isolated flavonoids, compounds 4, 5, 7 and 9 are reported from the genus Lespedeza for the first time. Moreover, compounds 1 and 6 showed significant inhibitory effects on NO production in LPS-stimulated BV2 cells without cell toxicity. Conclusion: In this study, nine flavonoids were isolated from L. cuneata. Among the compounds, only 1 and 6, which have free hydroxyl groups at both C3 and C7 showed significant inhibitory activity on NO production in LPS-stimulated BV2 cells. These results suggested L. cuneata and its flavonoid constituents as possible candidate for the treatment of various inflammatory diseases. PMID:26246745

  4. EG-VEGF, BV8, and their receptor expression in human bronchi and their modification in cystic fibrosis: Impact of CFTR mutation (delF508).

    PubMed

    Chauvet, Sylvain; Traboulsi, Wael; Thevenon, Laura; Kouadri, Amal; Feige, Jean-Jacques; Camara, Boubou; Alfaidy, Nadia; Benharouga, Mohamed

    2015-08-01

    Enhanced lung angiogenesis has been reported in cystic fibrosis (CF). Recently, two highly homologous ligands, endocrine gland vascular endothelial growth factor (EG-VEGF) and mammalian Bv8, have been described as new angiogenic factors. Both ligands bind and activate two closely related G protein-coupled receptors, the prokineticin receptor (PROKR) 1 and 2. Yet, the expression, regulation, and potential role of EG-VEGF, BV8, and their receptors in normal and CF lung are still unknown. The expression of the receptors and their ligands was examined using molecular, biochemical, and immunocytochemistry analyses in lungs obtained from CF patients vs. control and in normal and CF bronchial epithelial cells. Cystic fibrosis transmembrane conductance regulator (CFTR) activity was evaluated in relation to both ligands, and concentrations of EG-VEGF were measured by ELISA. At the mRNA level, EG-VEGF, BV8, and PROKR2 gene expression was, respectively, approximately five, four, and two times higher in CF lungs compared with the controls. At the cellular level, both the ligands and their receptors showed elevated expressions in the CF condition. Similar results were observed at the protein level. The EG-VEGF secretion was apical and was approximately two times higher in CF compared with the normal epithelial cells. This secretion was increased following the inhibition of CFTR chloride channel activity. More importantly, EG-VEGF and BV8 increased the intracellular concentration of Ca(2+) and cAMP and stimulated CFTR-chloride channel activity. Altogether, these data suggest local roles for epithelial BV8 and EG-VEGF in the CF airway peribronchial vascular remodeling and highlighted the role of CFTR activity in both ligand biosynthesis and secretion. PMID:26047640

  5. Involvement of PKA and HO-1 signaling in anti-inflammatory effects of surfactin in BV-2 microglial cells

    SciTech Connect

    Park, Sun Young; Kim, Ji-Hee; Lee, Sang Joon; Kim, YoungHee

    2013-04-01

    Surfactin, one of the most powerful biosurfactants, is a bacterial cyclic lipopeptide. Here, we investigated the anti-neuroinflammatory properties of surfactin in lipoteichoic acid (LTA)-stimulated BV-2 microglial cells. Surfactin significantly inhibited excessive production of the pro-inflammatory mediators TNF-α, IL-1β, IL-6, monocyte chemoattractant protein-1 (MCP-1), prostaglandin E{sub 2} (PGE{sub 2}), nitric oxide (NO) and reactive oxygen species (ROS), and suppressed the expression of matrix metalloproteinase-9 (MMP-9), inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2). Subsequent mechanistic studies revealed that surfactin inhibited LTA-induced nuclear factor-kappaB (NF-κB) and signal transducer and activator of transcription-1 (STAT-1) activation. However, surfactin increases the phosphorylation of the STAT-3, a component of the homeostatic mechanism causing anti-inflammatory events. We also demonstrated that surfactin induces heme oxygenase-1 (HO-1) expression and nuclear factor-regulated factor-2 (Nrf-2) activation, and that the anti-inflammatory effects of surfactin are abrogated by small interfering RNA-mediated knock-down of HO-1 or Nrf-2. Interestingly, we found that surfactin increased the level of cAMP and induced phosphorylation of cAMP responsive element binding protein (CREB) in microglial cells. Furthermore, treatment with the protein kinase A (PKA) inhibitor, H-89, blocked HO-1 induction by surfactin and abolished surfactin's suppressive effects on ROS and NO production. These results indicate that HO-1 and its upstream effector, PKA, play a pivotal role in the anti-neuroinflammatory response of surfactin in LTA-stimulated microglia. Therefore, surfactin might have therapeutic potential for neuroprotective agents to treat inflammatory and neurodegenerative diseases. - Highlights: ► Surfactin inhibits proinflammatory mediator synthesis in LTA-activated BV-2 cells. ► Surfactin suppresses NF-κB and STAT-1, but potentiates

  6. Complete genome sequence of Rhizobium leguminosarum bv. trifolii strain WSM1325, an effective microsymbiont of annual Mediterranean clovers.

    SciTech Connect

    Reeve, Wayne; O'Hara, Graham; Chain, Patrick S. G.; Ardley, Julie; Brau, Lambert; Nandesena, Kemanthi; Tiwari, Ravi; Copeland, A; Nolan, Matt; Han, Cliff; Brettin, Thomas S; Land, Miriam L; Ovchinnikova, Galina; Ivanova, N; Mavromatis, K; Markowitz, Victor; Kyrpides, Nikos C; Melino, Vanessa; Denton, Matthew; Yates, Ron; Howieson, John

    2010-01-01

    Rhizobium leguminosarum bv trifolii is a soil-inhabiting bacterium that that has the capacity to be an effective nitrogen fixing microsymbiont of a diverse range of annual Trifolium (clover) species. Strain WSM1325 is an aerobic, motile, non-spore forming, Gram-negative rod isolated from root nodules collected in 1993 from the Greek Island of Serifos. WSM1325 is manufactured commercially in Australia as an inoculant for a broad range of annual clovers of Mediterranean origin due to its superior attributes of saprophytic competence, nitrogen fixation and acid-tolerance. Here we describe the basic features of this organism, together with the complete genome sequence, and annotation. This is the first completed genome sequence for a microsymbiont of annual clovers. We reveal that its genome size is 7,418,122 bp encoding 7,232 protein-coding genes and 61 RNA-only encoding genes. This multipartite genome contains 6 distinct replicons; a chromosome of size 4,767,043 bp and 5 plasmids of size 828,924, 660,973, 516,088, 350,312 and 294,782 bp.

  7. Post-irradiation effect of Broncho-Vaxom, OM-85 BV, and its relationship to anti-oxidant activities.

    PubMed

    Saada, H N; Azab, K S; Zahran, A M

    2001-08-01

    This study was conducted to test the efficacy of Broncho-Vaxom (OM-85 BV) in rats after exposure to radiation-induced oxidative stress. Daily administration of Broncho-Vaxom (2.5 mg/kg/day) to rats for a period of 28 days produced a progressive significant increase in the activities of superoxide dismutase (SOD) and catalase in lungs and erythrocytes. No changes were recorded in reduced glutathione (GSH) content in lungs, while an increase was recorded in erythrocytes. Significant increase was also observed in serum gamma-globulin content. Intraperitoneal administration of Broncho-Vaxom to rats for 11 days before gamma-irradiation and daily during the period of irradiation, delivered as 1 Gy every other day to reach 9 Gy, significantly reduced radiation-induced lipid peroxidation (LPO) measured as thiobarbituric acid-reactive substances (TBARS) in the lungs and erythrocytes. Treatment with Broncho-Vaxom modified the radiation-induced decrease of serum gamma-globulins contents. It is postulated that Broncho-Vaxom, by enhancing the antioxidant system and increasing serum gamma-globulin content, could play an important role in modifying radiation-induced oxidative stress. PMID:11534345

  8. Characterisation of SalRAB a Salicylic Acid Inducible Positively Regulated Efflux System of Rhizobium leguminosarum bv viciae 3841

    PubMed Central

    Tett, Adrian J.; Karunakaran, Ramakrishnan; Poole, Philip S.

    2014-01-01

    Salicylic acid is an important signalling molecule in plant-microbe defence and symbiosis. We analysed the transcriptional responses of the nitrogen fixing plant symbiont, Rhizobium leguminosarum bv viciae 3841 to salicylic acid. Two MFS-type multicomponent efflux systems were induced in response to salicylic acid, rmrAB and the hitherto undescribed system salRAB. Based on sequence similarity salA and salB encode a membrane fusion and inner membrane protein respectively. salAB are positively regulated by the LysR regulator SalR. Disruption of salA significantly increased the sensitivity of the mutant to salicylic acid, while disruption of rmrA did not. A salA/rmrA double mutation did not have increased sensitivity relative to the salA mutant. Pea plants nodulated by salA or rmrA strains did not have altered nodule number or nitrogen fixation rates, consistent with weak expression of salA in the rhizosphere and in nodule bacteria. However, BLAST analysis revealed seventeen putative efflux systems in Rlv3841 and several of these were highly differentially expressed during rhizosphere colonisation, host infection and bacteroid differentiation. This suggests they have an integral role in symbiosis with host plants. PMID:25133394

  9. Single crystal structure and SHG of defect pyrochlores CsBVMoO6 (BV=Nb,Ta)

    NASA Astrophysics Data System (ADS)

    Fukina, D. G.; Suleimanov, E. V.; Yavetskiy, R. P.; Fukin, G. K.; Boryakov, A. V.; Borisov, E. N.; Borisov, E. V.; Surodin, S. I.; Saharov, N. V.

    2016-09-01

    The crystal structure and non-linear optical properties of CsNbMoO6 and CsTaMoO6 defect pyrochlores have been studied. The single crystals of these compounds grown by the flux method possess an octahedral faceting and reach up to 50 μm in size. The crystal structures of CsBVMoO6 (BV=Nb, Ta) were investigated by X-ray diffraction method. Both compounds crystallize in the cubic symmetry with noncentrosymmetric space group F-43m. The second harmonic generation of CsNbMoO6 and CsTaMoO6was found to be 1.6×10-2 and 8.5×10-4 of lithium niobate, correspondingly. It has been determined that distortions of [MO6] polyhedra (M=Nb, Ta, Mo) as well as polarizability and covalency of Nb-O and Ta-O bonds have a great effect on the second harmonic generation.

  10. [Comparison of the adaptive potential for Rhizobium leguminosarum bv. viceae nodule bacterial populations isolated in natural ecosystems and agrocenoses].

    PubMed

    Kurchak, O N; Provorov, N A; Simarov, B V

    2011-04-01

    Polymorphism analysis was performed in Rhizobium leguminosarum bv. viceae populations isolated from geographically distant regions of Ukraine and Middle Asia. Examination of cultural, biochemical, and symbiotic traits revealed interpopulation differences, which were attributed to the difference in conditions between natural ecosystems and agrocenoses. Vetch has high species diversity and is not cultivated in Middle Asia, and the corresponding rhizobial population displayed higher genetic diversity and higher polymorphism of adaptive traits ensuring saprophytic development in soil and the rhizosphere, including melanin synthesis (35%) and active exopolysaccharide production (90%). Strains of the Ukrainian population had a lower exopolysaccharide production (10%), did not produce melanin, had higher herbicide resistance, and utilized glucose and succinate (main components of plant root exudation) as carbon sources. Strains capable of efficient symbiosis with Vicia villosa Roth. had a higher frequency in the Middle Asian than in the Ukrainian population, especially among strains isolated from soil (80 and 35%, respectively). In addition, strains of the Middle Asian population better competed for nodulation. It was assumed that the formation of rhizobial populations in vetch cultivation regions (Ukraine) is aimed at adaptation to ectosymbiotic (rhizospheric) interactions with plants and anthropogenic stress factors, while strains of the vetch original center (Middle Asia) are mostly adapted to the endosymbiotic interaction and to natural edaphic stress factors. PMID:21675237

  11. Rotational/compressional nature of the magnetopause: Application of the BV technique on a magnetopause case study

    NASA Astrophysics Data System (ADS)

    Dorville, Nicolas; Belmont, Gérard; Rezeau, Laurence; Grappin, Roland; Retinò, Alessandro

    2014-03-01

    The magnetopause boundary implies two main kinds of variations: a density/temperature gradient and a magnetic field rotation. Other variations are associated with these two, concerning in particular the flow velocity, the electric field, and the plasma composition. Compressional and rotational variations are always observed in a close vicinity of each other, if not inseparably mixed. We present a case study from the Cluster data where the two are clearly separated and investigate the natures of both layers, using the new "BV" method for discontinuity analysis. We evidence that the first one is a slow shock while the second is a rotational discontinuity. The interaction between these two kinds of discontinuities is then studied with the help of 1.5-D magnetohydrodynamics simulations. The comparison with the data is quite positive and, associated with general theoretical arguments, leads to think that most of the generic properties of the magnetopause may be interpreted in this sense. Our results suggest that a "shaken" magnetopause is made of the sum of several discontinuities: slow shocks and rotational discontinuities. A statistical study on a larger set of data will be necessary to check this conjecture.

  12. Nucleotide sequence and characterization of four additional genes of the hydrogenase structural operon from Rhizobium leguminosarum bv. viciae.

    PubMed Central

    Hidalgo, E; Palacios, J M; Murillo, J; Ruiz-Argüeso, T

    1992-01-01

    The nucleotide sequence of a 2.5-kbp region following the hydrogenase structural genes (hupSL) in the H2 uptake gene cluster from Rhizobium leguminosarum bv. viciae UPM791 was determined. Four closely linked genes encoding peptides of 27.9 (hupC), 22.1 (hupD), 19.0 (hupE), and 10.4 (hupF) kDa were identified immediately downstream of hupL. Proteins with comparable apparent molecular weights were detected by heterologous expression of these genes in Escherichia coli. The six genes, hupS to hupF, are arranged as an operon, and by mutant complementation analysis, it was shown that genes hupSLCD are cotranscribed. A transcription start site preceded by the -12 to -24 consensus sequence characteristic of NtrA-dependent promoters was identified upstream of hupS. On the basis of the lack of oxygen-dependent H2 uptake activity of a hupC::Tn5 mutant and on structural characteristics of the protein, we postulate that HupC is a b-type cytochrome involved in electron transfer from hydrogenase to oxygen. The product from hupE, which is needed for full hydrogenase activity, exhibited characteristics typical of a membrane protein. The features of HupC and HupE suggest that they form, together with the hydrogenase itself, a membrane-bound protein complex involved in hydrogen oxidation. Images PMID:1597428

  13. SENP1 inhibits the IH-induced apoptosis and nitric oxide production in BV2 microglial cells.

    PubMed

    Liu, Song; Wang, Zhong-hua; Xu, Bo; Chen, Kui; Sun, Jin-yuan; Ren, Lian-ping

    2015-11-27

    To reveal SUMOylation and the roles of Sentrin-specific proteases (SENP)s in microglial cells under Intermittent hypoxia (IH) condition would provide more intensive view of understanding the mechanisms of IH-induced central nervous system (CNS) damage. Hence, in the present study, we detected the expression levels of SENPs in microglial cells under IH and normoxia conditions via RT-PCR assay. We found that SENP1 was significantly down-regulated in cells exposure to IH. Subsequently, the effect of IH for the activation of microglia and the potential roles of SENP1 in the SENP1-overexpressing cell lines were investigated via Western blotting, RT-PCR and Griess assay. The present study demonstrated the apoptosis-inducing and activating role of IH on microglia. In addition, we revealed that the effect of IH on BV-2 including apoptosis, nitric oxide synthase (iNOS) expression and nitric oxide (NO) induction can be attenuated by SENP1 overexpression. The results of the present study are of both theoretical and therapeutic significance to explore the potential roles of SENP1 under IH condition and elucidated the mechanisms underlying microglial survival and activation. PMID:26499079

  14. A highly conserved baculovirus gene p48 (ac103) is essential for BV production and ODV envelopment

    SciTech Connect

    Yuan Meijin; Wu Wenbi; Liu Chao; Wang Yanjie; Hu Zhaoyang; Yang Kai Pang Yi

    2008-09-15

    Autographa californica multiple nucleopolyhedrovirus (AcMNPV) p48 (ac103) is a highly conserved baculovirus gene of unknown function. In the present study, we generated a knockout of the p48 gene in an AcMNPV bacmid and investigated the role of P48 in baculovirus life cycle. The p48-null Bacmid vAc{sup P48-KO-PH-GFP} was unable to propagate in cell culture, while a 'repair' Bacmid vAc{sup P48-REP-PH-GFP} was able to replicate in a manner similar to a wild-type Bacmid vAc{sup PH-GFP}. Titration assays and Western blotting confirmed that vAc{sup P48-KO-PH-GFP} was unable to produce budded viruses (BVs). qPCR analysis showed that p48 deletion did not affect viral DNA replication. Electron microscopy indicated that P48 was required for nucleocapsid envelopment to form occlusion-derived viruses (ODVs) and their subsequent occlusion. Confocal analysis showed that P48 prominently condensed in the centre of the nucleus. Our results demonstrate that P48 plays an essential role in BV production and ODV envelopment in the AcMNPV life cycle.

  15. Genetic Characterization of a Novel Rhizobial Plasmid Conjugation System in Rhizobium leguminosarum bv. viciae Strain VF39SM

    PubMed Central

    Ding, Hao; Yip, Cynthia B.

    2013-01-01

    Rhizobium leguminosarum strain VF39SM contains two plasmids that have previously been shown to be self-transmissible by conjugation. One of these plasmids, pRleVF39b, is shown in this study to carry a set of plasmid transfer genes that differs significantly from conjugation systems previously studied in the rhizobia but is similar to an uncharacterized set of genes found in R. leguminosarum bv. trifolii strain WSM2304. The entire sequence of the transfer region on pRleVF39b was determined as part of a genome sequencing project, and the roles of the various genes were examined by mutagenesis. The transfer region contains a complete set of mating pair formation (Mpf) genes, a traG gene, and a relaxase gene, traA, all of which appear to be necessary for plasmid transfer. Experimental evidence suggested the presence of two putative origins of transfer within the gene cluster. A regulatory gene, trbR, was identified in the region between traA and traG and was mutated. TrbR was shown to function as a repressor of both trb gene expression and plasmid transfer. PMID:23144250

  16. Complete genome sequence of Rhizobium leguminosarum bv. trifolii strain WSM1325, an effective microsymbiont of annual Mediterranean clovers.

    PubMed Central

    Reeve, Wayne; O’Hara, Graham; Chain, Patrick; Ardley, Julie; Bräu, Lambert; Nandesena, Kemanthi; Tiwari, Ravi; Copeland, Alex; Nolan, Matt; Han, Cliff; Brettin, Thomas; Land, Miriam; Ovchinikova, Galina; Ivanova, Natalia; Mavromatis, Konstantinos; Markowitz, Victor; Kyrpides, Nikos; Melino, Vanessa; Denton, Matthew; Yates, Ron; Howieson, John

    2010-01-01

    Rhizobium leguminosarum bv trifolii is a soil-inhabiting bacterium that has the capacity to be an effective nitrogen fixing microsymbiont of a diverse range of annual Trifolium (clover) species. Strain WSM1325 is an aerobic, motile, non-spore forming, Gram-negative rod isolated from root nodules collected in 1993 from the Greek Island of Serifos. WSM1325 is produced commercially in Australia as an inoculant for a broad range of annual clovers of Mediterranean origin due to its superior attributes of saprophytic competence, nitrogen fixation and acid-tolerance. Here we describe the basic features of this organism, together with the complete genome sequence, and annotation. This is the first completed genome sequence for a microsymbiont of annual clovers. We reveal that its genome size is 7,418,122 bp encoding 7,232 protein-coding genes and 61 RNA-only encoding genes. This multipartite genome contains 6 distinct replicons; a chromosome of size 4,767,043 bp and 5 plasmids of size 828,924 bp, 660,973 bp, 516,088 bp, 350,312 bp and 294,782 bp. PMID:21304718

  17. Design

    ERIC Educational Resources Information Center

    Buchanan, Richard; Cross, Nigel; Durling, David; Nelson, Harold; Owen, Charles; Valtonen, Anna; Boling, Elizabeth; Gibbons, Andrew; Visscher-Voerman, Irene

    2013-01-01

    Scholars representing the field of design were asked to identify what they considered to be the most exciting and imaginative work currently being done in their field, as well as how that work might change our understanding. The scholars included Richard Buchanan, Nigel Cross, David Durling, Harold Nelson, Charles Owen, and Anna Valtonen. Scholars…

  18. Human monoclonal antibody 99mTc-88BV59: detection of colorectal cancer, recurrent or metastatic disease and immunogenicity assessment.

    PubMed

    Krause, B J; Baum, R P; Staib-Sebler, E; Lorenz, M; Niesen, A; Hör, G

    1997-01-01

    This study presents immunoscintigraphic results in 24 patients suffering from primary colorectal cancer, recurrent or metastatic disease after the injection of 1197-1351 MBq technetium-99m labelled totally human monoclonal antibody 88BV59. Labelling efficacy of 99mTc-88BV59 ranged from 97% to 99%. Immunoscintigraphy was performed 18-20 h after injection. Scintigraphic findings were compared with those of computed tomography (CT). Patients underwent surgery in order to evaluate immunoscintigraphic findings histologically. Sera of the patients (before injection and 1 and 3 months post infusion) were analysed for the presence of human anti-human antibodies (HAHA). None of the patients showed a HAHA response as assessed by a solid-phase ELISA assay. The antibody scan detected about 25% more lesions than CT. In the detection of extrahepatic disease, the sensitivity of the antibody scan proved to be 68%, whereas the sensitivity of CT was 41%. PMID:9044881

  19. Armeniacae semen extract suppresses lipopolysaccharide-induced expressions of cyclooxygenase [correction of cycloosygenase]-2 and inducible nitric oxide synthase in mouse BV2 microglial cells.

    PubMed

    Chang, Hyun-Kyung; Yang, Hye-Young; Lee, Taeck-Hyun; Shin, Min-Chul; Lee, Myoung-Hwa; Shin, Mal-Soon; Kim, Chang-Ju; Kim, Ok-Jin; Hong, Seon-Pyo; Cho, Sonhae

    2005-03-01

    Armeniacae semen is the seed of Prunus armeniaca L. var. ansu MAXIM which is classified into Rosaceae. In traditional oriental medicine, Armeniacae semen has been used for the treatment of pain and inflammatory diseases. In this study, the effect of Armeniacae semen extract on lipopolysaccharide-induced inflammation was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, reverse transcription-polymerase chain reaction (RT-PCR), Western blot, prostaglandin E2 immunoassay, and nitric oxide detection on mouse BV2 microglial cells. In the present results, Armeniacae semen extract suppressed prostaglandin E2 synthesis and nitric oxide production by inhibiting the lipopolysaccharide-stimulated enhancement of cyclooxygenase-2 and inducible nitric oxide synthase mRNA expression in BV2 cells. These results show that Armeniacae semen exerts anti-inflammatory and analgesic effects probably by suppression of cyclooxygenase-2 and inducible nitric oxide synthase expressions. PMID:15744067

  20. Molecular Investigation into a Malaria Outbreak in Cusco, Peru: Plasmodium falciparum BV1 Lineage is Linked to a Second Outbreak in Recent Times.

    PubMed

    Okoth, Sheila Akinyi; Chenet, Stella M; Arrospide, Nancy; Gutierrez, Sonia; Cabezas, Cesar; Matta, Jose Antonio; Udhayakumar, Venkatachalam

    2016-01-01

    In November 2013, a Plasmodium falciparum malaria outbreak of 11 cases occurred in Cusco, southern Peru, where falciparum malaria had not been reported since 1946. Although initial microscopic diagnosis reported only Plasmodium vivax infection in each of the specimens, subsequent examination by the national reference laboratory confirmed P. falciparum infection in all samples. Molecular typing of four available isolates revealed identity as the B-variant (BV1) strain that was responsible for a malaria outbreak in Tumbes, northern Peru, between 2010 and 2012. The P. falciparum BV1 strain is multidrug resistant, can escape detection by PfHRP2-based rapid diagnostic tests, and has contributed to two malaria outbreaks in Peru. This investigation highlights the importance of accurate species diagnosis given the potential for P. falciparum to be reintroduced to regions where it may have been absent. Similar molecular epidemiological investigations can track the probable source(s) of outbreak parasite strains for malaria surveillance and control purposes. PMID:26483121

  1. High-quality permanent draft genome sequence of Rhizobium leguminosarum bv. viciae strain GB30; an effective microsymbiont of Pisum sativum growing in Poland

    SciTech Connect

    Mazur, Andrzej; De Meyer, Sofie E.; Tian, Rui; Wielbo, Jerzy; Zebracki, Kamil; Seshadri, Rekha; Reddy, T. B.K.; Markowitz, Victor; Ivanova, Natalia N.; Pati, Amrita; Woyke, Tanja; Kyrpides, Nikos C.; Reeve, Wayne

    2015-07-16

    We report that Rhizobium leguminosarum bv. viciae GB30 is an aerobic, motile, Gram-negative, non-spore-forming rod that can exist as a soil saprophyte or as a legume microsymbiont of Pisum sativum. GB30 was isolated in Poland from a nodule recovered from the roots of Pisum sativum growing at Janow. GB30 is also an effective microsymbiont of the annual forage legumes vetch and pea. Here we describe the features of R. leguminosarum bv. viciae strain GB30, together with sequence and annotation. The 7,468,464 bp high-quality permanent draft genome is arranged in 78 scaffolds of 78 contigs containing 7,227 protein-coding genes and 75 RNA-only encoding genes, and is part of the GEBA-RNB project proposal.

  2. High-quality permanent draft genome sequence of Rhizobium leguminosarum bv. viciae strain GB30; an effective microsymbiont of Pisum sativum growing in Poland

    DOE PAGESBeta

    Mazur, Andrzej; De Meyer, Sofie E.; Tian, Rui; Wielbo, Jerzy; Zebracki, Kamil; Seshadri, Rekha; Reddy, T. B.K.; Markowitz, Victor; Ivanova, Natalia N.; Pati, Amrita; et al

    2015-07-16

    We report that Rhizobium leguminosarum bv. viciae GB30 is an aerobic, motile, Gram-negative, non-spore-forming rod that can exist as a soil saprophyte or as a legume microsymbiont of Pisum sativum. GB30 was isolated in Poland from a nodule recovered from the roots of Pisum sativum growing at Janow. GB30 is also an effective microsymbiont of the annual forage legumes vetch and pea. Here we describe the features of R. leguminosarum bv. viciae strain GB30, together with sequence and annotation. The 7,468,464 bp high-quality permanent draft genome is arranged in 78 scaffolds of 78 contigs containing 7,227 protein-coding genes and 75more » RNA-only encoding genes, and is part of the GEBA-RNB project proposal.« less

  3. Preventive treatment of chronic bronchitis: a meta-analysis of clinical trials with a bacterial extract (OM-85 BV) and a cost-effectiveness analysis.

    PubMed

    Bergemann, R; Brandt, A; Zoellner, U; Donner, C F

    1994-09-01

    Chronic bronchitis is a lifelong disease with significant effects on the patient and on the costs to health insurance institutions. Acute exacerbations in chronic bronchitic patients may have a negative impact on patients' quality of life and on the progression of the disease, particularly in more severe patients. The clinical efficacy of the immunoactive bacterial extract OM-85 BV has been shown in several clinical trials, a cost-effectiveness evaluation (CEA) of its use in chronic bronchitic patients has not been fulfilled so far. In this study a meta-analysis on the preventive treatment of acute exacerbations with OM-85 BV and a CEA, focusing on direct costs only, was performed. The meta-analysis showed a mean value of 0.6 prevented acute exacerbations per 6 months per patient, and a reduction of 9 days in antibiotic treatment per 6 months per patient. CEA evaluated the different cost elements. The mean direct cost (consultations, antibiotics, etc.) for the treatment of 1 acute exacerbation in chronic bronchitic patients was calculated as 143, 459 Lira. Thus for 0.6 prevented acute exacerbations per 6 months per patient a reduction in cost of 86,075 Lira (0.6-143,459) could be expected. The additional costs for the preventive treatment with OM-85 BV, based on prices for Italy, are 34,980 Lira per patient per 6 months. In conclusion, the effective cost savings per patient per 6 months are 51, 095 Lira. The sensitivity analysis revealed only one critical parameter, i.e. the clinical effectiveness of OM-85 BV. Even assuming 0.3 prevented exacerbations per 6 months per patient, the preventive treatment still proved to be cost effective. PMID:8000415

  4. Inhibition of neuroinflammation in BV2 microglia by the biflavonoid kolaviron is dependent on the Nrf2/ARE antioxidant protective mechanism.

    PubMed

    Onasanwo, Samuel A; Velagapudi, Ravikanth; El-Bakoush, Abdelmeneim; Olajide, Olumayokun A

    2016-03-01

    Kolaviron is a mixture of biflavonoids found in the nut of the West African edible seed Garcinia kola, and it has been reported to exhibit a wide range of pharmacological activities. In this study, we investigated the effects of kolaviron in neuroinflammation. The effects of kolaviron on the expression of nitric oxide/inducible nitric oxide synthase (iNOS), prostaglandin E2 (PGE2)/cyclooxygenase-2, cellular reactive oxygen species (ROS) and the pro-inflammatory cytokines were examined in lipopolysaccharide (LPS)-stimulated BV2 microglial cells. Molecular mechanisms of the effects of kolaviron on NF-κB and Nrf2/ARE signalling pathways were analysed by immunoblotting, binding assays and reporter assays. RNA interference was used to investigate the role of Nrf2 in the anti-inflammatory effect of kolaviron. Neuroprotective effect of kolaviron was assessed in a BV2 microglia/HT22 hippocampal neuron co-culture. Kolaviron inhibited the protein levels of NO/iNOS, PGE2/COX-2, cellular ROS and the pro-inflammatory cytokines (TNFα and IL-6) in LPS-stimulated microglia. Further mechanistic studies showed that kolaviron inhibited neuroinflammation by inhibiting IκB/NF-κB signalling pathway in LPS-activated BV2 microglia. Kolaviron produced antioxidant effect in BV2 microglia by increasing HO-1 via the Nrf2/antioxidant response element pathway. RNAi experiments revealed that Nrf2 is needed for the anti-inflammatory effects of kolaviron. Kolaviron protected HT22 neurons from neuroinflammation-induced toxicity. Kolaviron inhibits neuroinflammation through Nrf2-dependent mechanisms. This compound may therefore be beneficial in neuroinflammation-related neurodegenerative disorders. PMID:26838169

  5. Withania somnifera and Its Withanolides Attenuate Oxidative and Inflammatory Responses and Up-Regulate Antioxidant Responses in BV-2 Microglial Cells.

    PubMed

    Sun, Grace Y; Li, Runting; Cui, Jiankun; Hannink, Mark; Gu, Zezong; Fritsche, Kevin L; Lubahn, Dennis B; Simonyi, Agnes

    2016-09-01

    Withania somnifera (L.) Dunal, commonly known as Ashwagandha, has been used in Ayurvedic medicine for promoting health and quality of life. Recent clinical trials together with experimental studies indicated significant neuroprotective effects of Ashwagandha and its constituents. This study is aimed to investigate anti-inflammatory and anti-oxidative properties of this botanical and its two withanolide constituents, namely, Withaferin A and Withanolide A, using the murine immortalized BV-2 microglial cells. Ashwagandha extracts not only effectively inhibited lipopolysaccharide (LPS)-induced nitric oxide (NO) and reactive oxygen species (ROS) production in BV-2 cells, but also stimulates the Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway, leading to induction of heme oxygenase-1 (HO-1), both in the presence and absence of LPS. Although the withanolides were also capable of inhibiting LPS-induced NO production and stimulating Nrf2/HO-1 pathway, Withaferin A was tenfold more effective than Withanolide A. In serum-free culture, LPS can also induce production of long thin processes (filopodia) between 4 and 8 h in BV-2 cells. This morphological change was significantly suppressed by Ashwagandha and both withanolides at concentrations for suppressing LPS-induced NO production. Taken together, these results suggest an immunomodulatory role for Ashwagandha and its withanolides, and their ability to suppress oxidative and inflammatory responses in microglial cells by simultaneously down-regulating the NF-kB and upregulating the Nrf2 pathways. PMID:27209361

  6. KCHO-1, a Novel Antineuroinflammatory Agent, Inhibits Lipopolysaccharide-Induced Neuroinflammatory Responses through Nrf2-Mediated Heme Oxygenase-1 Expression in Mouse BV2 Microglia Cells

    PubMed Central

    Lee, Dong-Sung; Ko, Wonmin; Yoon, Chi-Su; Kim, Dong-Cheol; Yun, Jinju; Lee, Jun-Kyung; Jun, Ki-Young; Son, Ilhong; Kim, Dong-Woung; Song, Bong-Keun; Choi, Seulah; Jang, Jun-Hyeog; Oh, Hyuncheol; Kim, Sungchul; Kim, Youn-Chul

    2014-01-01

    The brain is vulnerable to oxidative stress and inflammation that can occur as a result of aging or neurodegenerative diseases. Our work has sought to identify natural products that regulate heme oxygenase (HO)-1 and to determine their mechanism of action in neurodegenerative diseases. KCHO-1 is a novel herbal therapeutic containing 30% ethanol (EtOH) extracts from nine plants. In this study, we investigated the antineuroinflammatory effects of KCHO-1 in lipopolysaccharide- (LPS-) treated mouse BV2 microglia. KCHO-1 inhibited the protein expression of inducible nitric oxide synthase (iNOS), iNOS-derived nitric oxide (NO), cyclooxygenase- (COX-) 2, and COX-2-derived prostaglandin E2 (PGE2) in LPS-stimulated BV2 microglia. It also reduced tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 production. This effect was correlated with the suppression of inhibitor of nuclear factor kappa B-α (IκB-α) phosphorylation and degradation and nuclear factor kappa B (NF-κB) translocation and DNA binding. Additionally, KCHO-1 upregulated HO-1 expression by promoting nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) in mouse BV2 microglia. Tin protoporphyrin (SnPP), an HO activity inhibitor, was used to verify the inhibitory effects of KCHO-1 on proinflammatory mediators and proteins associated with HO-1 expression. Our data suggest that KCHO-1 has therapeutic potential in neurodegenerative diseases caused by neuroinflammation. PMID:25580149

  7. Cynandione A from Cynanchum wilfordii attenuates the production of inflammatory mediators in LPS-induced BV-2 microglial cells via NF-κB inactivation.

    PubMed

    Yang, Seung Bo; Lee, Sang Min; Park, Ji-Hae; Lee, Tae Hoon; Baek, Nam-In; Park, Hi-Joon; Lee, Hyejung; Kim, Jiyoung

    2014-01-01

    Cynanchum wilfordii is one of most widely used medicinal plants in Oriental medicine for the treatment of various conditions. In the present study, we isolated cynandione A (CA) from an extract of Cynanchum wilfordii roots (CWE) and investigated the effects of CA on the expression of inducible nitric oxide synthase (iNOS) and pro-inflammatory cytokines in lipopolysaccharide (LPS)-induced BV-2 microglial cells. CWE and CA significantly decreased LPS-induced nitric oxide production and the expression of iNOS in a concentration-dependent manner, while they (CWE up to 500 µg/mL and CA up to 80 µM) did not exhibit cytotoxic activity. Results from reverse transcription-polymerase chain reaction (RT-PCR) analysis and enzyme-linked immunosorbent assay (ELISA) showed that CA significantly attenuated the expression of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-1β in LPS-stimulated BV-2 cells. Furthermore, CA inhibited the phosphorylation of inhibitor kappa B-alpha (IκB-α) and translocation of nuclear factor-kappa B (NF-κB) to the BV-2 cell nucleus, indicating that CWE and CA may have effective anti-inflammatory activities via NF-κB inactivation in stimulated microglial cells. PMID:25087960

  8. Biological activities of Schottenol and Spinasterol, two natural phytosterols present in argan oil and in cactus pear seed oil, on murine miroglial BV2 cells

    SciTech Connect

    El Kharrassi, Youssef; Samadi, Mohammad; Lopez, Tatiana; Nury, Thomas; El Kebbaj, Riad; Andreoletti, Pierre; El Hajj, Hammam I.; Vamecq, Joseph; Moustaid, Khadija; Latruffe, Norbert; El Kebbaj, M’Hammed Saïd; Masson, David; and others

    2014-04-11

    Highlights: • Sterol composition in argan oil and in cactus seed oil. • Chemical synthesis of two sterols: Schottenol and Spinasterol. • Sterols from argan oil or from cactus seed oil show no toxicity on BV2 cells. • Schottenol and Spinasterol modulate the activation and the expression of two nuclear receptors, LXRα and LXRβ. - Abstract: The objective of this study was to evaluate the biological activities of the major phytosterols present in argan oil (AO) and in cactus seed oil (CSO) in BV2 microglial cells. Accordingly, we first determined the sterol composition of AO and CSO, showing the presence of Schottenol and Spinasterol as major sterols in AO. While in CSO, in addition to these two sterols, we found mainly another sterol, the Sitosterol. The chemical synthesis of Schottenol and Spinasterol was performed. Our results showed that these two phytosterols, as well as sterol extracts from AO or CSO, are not toxic to microglial BV2 cells. However, treatments by these phytosterols impact the mitochondrial membrane potential. Furthermore, both Schottenol and Spinasterol can modulate the gene expression of two nuclear receptors, liver X receptor (LXR)-α and LXRβ, their target genes ABCA1 and ABCG1. Nonetheless, only Schottenol exhibited a differential activation vis-à-vis the nuclear receptor LXRβ. Thus Schottenol and Spinasterol can be considered as new LXR agonists, which may play protective roles by the modulation of cholesterol metabolism.

  9. Anti-inflammatory effects of sargachromenol-rich ethanolic extract of Myagropsis myagroides on lipopolysaccharide-stimulated BV-2 cells

    PubMed Central

    2014-01-01

    Background Excessive pro-inflammatory cytokine production from activated microglia contributes to neurodegenerative diseases, thus, microglial inactivation may delay the progress of neurodegeneration by attenuating the neuroinflammation. Among 5 selected brown algae, we found the highest antioxidant and anti-neuroinflammatory activities from Myagropsis myagroides ethanolic extract (MME) in lipopolysaccharide (LPS)-stimulated BV-2 cells. Methods The levels of nitric oxide (NO), prostaglandin E2 (PGE2), and pro-inflammatory cytokines were measured by Griess assay and enzyme linked immunesorbent assay. The levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), mitogen-activated protein kinases (MAPKs), and Akt were measured using Western blot. Nuclear translocation and transcriptional activation of nuclear factor-κB (NF-κB) were determined by immunefluorescence and reporter gene assay, respectively. Results MME inhibited the expression of iNOS and COX-2 at mRNA and protein levels, resulting in reduction of NO and PGE2 production. As a result, pro-inflammatory cytokines were reduced by MME. MME also inhibited the activation and translocation of NF-κB by preventing inhibitor κB-α (IκB-α) degradation. Moreover, MME inhibited the phosphorylation of extracellular signal regulated kinases (ERKs) and c-Jun N-terminal kinases (JNKs). Main anti-inflammatory compound in MME was identified as sargachromenol by NMR spectroscopy. Conclusions These results indicate that the anti-inflammatory effect of sargachromenol-rich MME on LPS-stimulated microglia is mainly regulated by the inhibition of IκB-α/NF-κB and ERK/JNK pathways. PMID:25005778

  10. Bacterial Vaginosis (BV)

    MedlinePlus

    ... with questions about grants, contracts & research areas Training, Education & Career Development Support for Training at Universities & Other Institutions Extramural training, fellowships & career development opportunities Training at ...

  11. Differential transcriptional profiles mediated by exposure to the cannabinoids cannabidiol and Δ9-tetrahydrocannabinol in BV-2 microglial cells

    PubMed Central

    Juknat, Ana; Pietr, Maciej; Kozela, Ewa; Rimmerman, Neta; Levy, Rivka; Coppola, Giovanni; Geschwind, Daniel; Vogel, Zvi

    2012-01-01

    BACKGROUND AND PURPOSE Apart from their effects on mood and reward, cannabinoids exert beneficial actions such as neuroprotection and attenuation of inflammation. The immunosuppressive activity of cannabinoids has been well established. However, the underlying mechanisms are largely unknown. We previously showed that the psychoactive cannabinoid Δ9-tetrahydrocannabinol (THC) and the non-psychoactive cannabidiol (CBD) differ in their anti-inflammatory signalling pathways. EXPERIMENTAL APPROACH To characterize the transcriptional effects of CBD and THC, we treated BV-2 microglial cells with these compounds and performed comparative microarray analysis using the Illumina MouseRef-8 BeadChip platform. Ingenuity Pathway Analysis was performed to identify functional subsets of genes and networks regulated by CBD and/or THC. KEY RESULTS Overall, CBD altered the expression of many more genes; from the 1298 transcripts found to be differentially regulated by the treatments, 680 gene probe sets were up-regulated by CBD and 58 by THC, and 524 gene products were down-regulated by CBD and only 36 by THC. CBD-specific gene expression profile showed changes associated with oxidative stress and glutathione depletion, normally occurring under nutrient limiting conditions or proteasome inhibition and involving the GCN2/eIF2α/p8/ATF4/CHOP-TRIB3 pathway. Furthermore, CBD-stimulated genes were shown to be controlled by nuclear factors known to be involved in the regulation of stress response and inflammation, mainly via the (EpRE/ARE)-Nrf2/ATF4 system and the Nrf2/Hmox1 axis. CONCLUSIONS AND IMPLICATIONS These observations indicated that CBD, but much less than THC, induced a cellular stress response in microglial cells and suggested that this effect could underlie its anti-inflammatory activity. LINKED ARTICLES This article is part of a themed section on Cannabinoids in Biology and Medicine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012

  12. Anti-Inflammatory Activity of Bee Venom in BV2 Microglial Cells: Mediation of MyD88-Dependent NF-κB Signaling Pathway

    PubMed Central

    Kim, Su Jung; Hong, Seung Bok; Park, Jin-Kyu

    2016-01-01

    Bee venom has long been used as a traditional folk medicine in Korea. It has been reportedly used for the treatment of arthritis, cancer, and inflammation. Although its anti-inflammatory activity in lipopolysaccharide- (LPS-) stimulated inflammatory cells has been reported, the exact mechanism of its anti-inflammatory action has not been fully elucidated. Therefore, the aim of this study was to investigate the anti-inflammatory mechanism of bee venom in BV2 microglial cells. We first investigated whether NO production in LPS-activated BV2 cells was inhibited by bee venom, and further iNOS mRNA and protein expressions were determined. The mRNA and protein levels of proinflammatory cytokines were examined using semiquantitative RT-PCR and immunoblotting, respectively. Moreover, modulation of the transcription factor NF-κB by bee venom was also investigated using a luciferase assay. LPS-induced NO production in BV2 microglial cells was significantly inhibited in a concentration-dependent manner upon pretreatment with bee venom. Bee venom markedly reduced the mRNA expression of COX-2, TNF-α, IL-1β, and IL-6 and suppressed LPS-induced activation of MyD88 and IRAK1 and phosphorylation of TAK1. Moreover, NF-κB translocation by IKKα/β phosphorylation and subsequent IκB-α degradation were also attenuated. Thus, collectively, these results indicate that bee venom exerts its anti-inflammatory activity via the IRAK1/TAK1/NF-κB signaling pathway. PMID:27563334

  13. Anti-Inflammatory Activity of Bee Venom in BV2 Microglial Cells: Mediation of MyD88-Dependent NF-κB Signaling Pathway.

    PubMed

    Im, Eun Ju; Kim, Su Jung; Hong, Seung Bok; Park, Jin-Kyu; Rhee, Man Hee

    2016-01-01

    Bee venom has long been used as a traditional folk medicine in Korea. It has been reportedly used for the treatment of arthritis, cancer, and inflammation. Although its anti-inflammatory activity in lipopolysaccharide- (LPS-) stimulated inflammatory cells has been reported, the exact mechanism of its anti-inflammatory action has not been fully elucidated. Therefore, the aim of this study was to investigate the anti-inflammatory mechanism of bee venom in BV2 microglial cells. We first investigated whether NO production in LPS-activated BV2 cells was inhibited by bee venom, and further iNOS mRNA and protein expressions were determined. The mRNA and protein levels of proinflammatory cytokines were examined using semiquantitative RT-PCR and immunoblotting, respectively. Moreover, modulation of the transcription factor NF-κB by bee venom was also investigated using a luciferase assay. LPS-induced NO production in BV2 microglial cells was significantly inhibited in a concentration-dependent manner upon pretreatment with bee venom. Bee venom markedly reduced the mRNA expression of COX-2, TNF-α, IL-1β, and IL-6 and suppressed LPS-induced activation of MyD88 and IRAK1 and phosphorylation of TAK1. Moreover, NF-κB translocation by IKKα/β phosphorylation and subsequent IκB-α degradation were also attenuated. Thus, collectively, these results indicate that bee venom exerts its anti-inflammatory activity via the IRAK1/TAK1/NF-κB signaling pathway. PMID:27563334

  14. Radioimmunoscintigraphy of colorectal carcinoma using technetium-99m-labeled, totally human monoclonal antibody 88BV59H21-2.

    PubMed

    Gulec, S A; Serafini, A N; Moffat, F L; Vargas-Cuba, R D; Sfakianakis, G N; Franceschi, D; Crichton, V Z; Subramanian, R; Klein, J L; De Jager, R L

    1995-12-01

    Radioimmunoscintigraphy (RIS) using human monoclonal antibodies offers the important clinical advantage of repeated imaging over murine monoclonal antibodies by eliminating the cross-species antibody response. This article reports a Phase I-II clinical trial with Tc-99m-labeled, totally human monoclonal antibody 88BV59H21-2 in patients with colorectal carcinoma. The study population consisted of 34 patients with colorectal cancer (20 men and 14 women; age range, 44-81 years). Patients were administered 5-10 mg antibody labeled with 21-41 mCi Tc-99m by the i.v. route and imaged at 3-10 and 16-24 h after infusion using planar and single-photon emission computed tomographic (CT) techniques. Pathological confirmation was obtained in 25 patients who underwent surgery. Human antihuman antibody (HAHA) titers were checked prior to and 1 and 3 months after the infusion. RIS with Tc-99m-labeled 88BV59H21-2 revealed a better detection rate in the abdomen-pelvis region compared with axial CT. The combined use of both modalities increased the sensitivity in both the liver and abdomen-pelvis regions. Ten patients developed mild adverse reactions (chills and fever). No HAHA response was detected in this series. Tc-99m-labeled human monoclonal antibody 88BV59H21-2 RIS shows promise as a useful diagnostic modality in patients with colorectal cancer. RIS alone or in combination with CT is more sensitive than CT in detecting tumor within the abdomen and pelvis. Repeated RIS studies may be possible, due to the lack of a HAHA response. PMID:7493345

  15. Anti-inflammatory effects of saponins derived from the roots of Platycodon grandiflorus in lipopolysaccharide‑stimulated BV2 microglial cells.

    PubMed

    Jang, Kyung-Jun; Kim, Hong Ki; Han, Min Ho; Oh, You Na; Yoon, Hyun-Min; Chung, Yoon Ho; Kim, Gi Young; Hwang, Hye Jin; Kim, Byung Woo; Choi, Yung Hyun

    2013-06-01

    Radix platycodi is the root of Platycodon grandiflorus A. DC, which has been widely used as a food material and for the treatment of a number of chronic inflammatory diseases in traditional oriental medicine. In this study, the anti‑inflammatory effects of the saponins isolated from radix platycodi (PGS) on the production of inflammatory mediators and cytokines in lipopolysaccharide (LPS)-stimulated BV2 murine microglial cells were examined. We also investigated the effects of PGS on LPS‑induced nuclear factor‑κB (NF-κB) activation and phosphoinositide 3-kinase (PI3K)/AKT and mitogen-activated protein kinase (MAPK) signaling pathways. Following stimulation with LPS, elevated nitric oxide (NO), prostaglandin E2 (PGE2) and pro-inflammatory cytokine production was detected in the BV2 microglial cells. However, PGS significantly inhibited the excessive production of NO, PGE2 and pro‑inflammatory cytokines, including interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in a concentration-dependent manner without causing any cytotoxic effects. In addition, PGS suppressed NF-κB translocation and inhibited the LPS-induced phosphorylation of AKT and MAPKs. Our results indicate that the inhibitory effect of PGS on LPS-stimulated inflammatory response in BV2 microglial cells is associated with the suppression of NF-κB activation and the PI3K/AKT and MAPK signaling pathways. Therefore, these findings suggest that PGS may be useful in the treatment of neurodegenerative diseases by inhibiting inflammatory responses in activated microglial cells. PMID:23563392

  16. Lonicera japonica THUNB. Extract Inhibits Lipopolysaccharide-Stimulated Inflammatory Responses by Suppressing NF-κB Signaling in BV-2 Microglial Cells.

    PubMed

    Kwon, Seung-Hwan; Ma, Shi-Xun; Hong, Sa-Ik; Lee, Seok-Yong; Jang, Choon-Gon

    2015-07-01

    In the current study, we evaluated the anti-inflammatory effects of Lonicera japonica THUNB. (LJ) and its underlying molecular mechanism in lipopolysaccharide (LPS)-stimulated BV-2 microglial cells. Our results indicated that LJ significantly inhibits LPS-stimulated production of nitric oxide (NO) and prostaglandin E2 (PGE2). In addition, LJ inhibited inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at both the protein and mRNA levels. In LPS-stimulated BV-2 microglial cells, LJ inhibited proinflammatory cytokines and chemokines, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), monocyte chemoattractant protein-1 (MCP-1), matrix metalloproteinase-9 (MMP-9) enzymatic activities, and/or mRNA expression, as well as reactive oxygen species (ROS) production. LJ significantly suppressed activation of nuclear factor-κB (NF-κB) and its translocation from the cytosol to the nucleus and suppressed the DNA-binding activity of NF-κB. Furthermore, LJ significantly inhibited phosphorylation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase 1/2 (ERK 1/2), p38 mitogen-activated protein kinases (MAPKs), phosphatidylinositol 3-kinases (PI3K)/Akt, and Janus kinase 1 (JAK1)/signal transducer and activator of transcription (STAT)1/3. Collectively, our findings indicated that the antineuroinflammatory properties of LJ in LPS-induced BV-2 microglial cells is due to downregulation of proinflammatory cytokines and chemokines downstream of inhibition of NF-κB activation. PMID:25897683

  17. Characterization and functional analysis of seven flagellin genes in Rhizobium leguminosarum bv. viciae. Characterization of R. leguminosarum flagellins

    PubMed Central

    2010-01-01

    Background Rhizobium leguminosarum bv. viciae establishes symbiotic nitrogen fixing partnerships with plant species belonging to the Tribe Vicieae, which includes the genera Vicia, Lathyrus, Pisum and Lens. Motility and chemotaxis are important in the ecology of R. leguminosarum to provide a competitive advantage during the early steps of nodulation, but the mechanisms of motility and flagellar assembly remain poorly studied. This paper addresses the role of the seven flagellin genes in producing a functional flagellum. Results R. leguminosarum strains 3841 and VF39SM have seven flagellin genes (flaA, flaB, flaC, flaD, flaE, flaH, and flaG), which are transcribed separately. The predicted flagellins of 3841 are highly similar or identical to the corresponding flagellins in VF39SM. flaA, flaB, flaC, and flaD are in tandem array and are located in the main flagellar gene cluster. flaH and flaG are located outside of the flagellar/motility region while flaE is plasmid-borne. Five flagellin subunits (FlaA, FlaB, FlaC, FlaE, and FlaG) are highly similar to each other, whereas FlaD and FlaH are more distantly related. All flagellins exhibit conserved amino acid residues at the N- and C-terminal ends and are variable in the central regions. Strain 3841 has 1-3 plain subpolar flagella while strain VF39SM exhibits 4-7 plain peritrichous flagella. Three flagellins (FlaA/B/C) and five flagellins (FlaA/B/C/E/G) were detected by mass spectrometry in the flagellar filaments of strains 3841 and VF39SM, respectively. Mutation of flaA resulted in non-motile VF39SM and extremely reduced motility in 3841. Individual mutations of flaB and flaC resulted in shorter flagellar filaments and consequently reduced swimming and swarming motility for both strains. Mutant VF39SM strains carrying individual mutations in flaD, flaE, flaH, and flaG were not significantly affected in motility and filament morphology. The flagellar filament and the motility of 3841 strains with mutations in flaD and

  18. (7R,8S)-Dehydrodiconiferyl Alcohol Suppresses Lipopolysaccharide-Induced Inflammatory Responses in BV2 Microglia by Inhibiting MAPK Signaling.

    PubMed

    Liu, Si-Yu; Xu, Peng; Luo, Xiao-Ling; Hu, Jin-Feng; Liu, Xin-Hua

    2016-07-01

    (7R,8S)-Dehydrodiconiferyl alcohol (DDA), a lignan isolated from the dried stems of Clematis armandii, has been found to exert potential anti-inflammatory activity in vitro. In the present study, we investigated the effects and possible mechanisms of DDA on lipopolysaccharide (LPS)-mediated inflammatory response in murine BV2 microglia. Our results revealed that non-toxic concentrations (6.25-25 μM) of DDA markedly suppressed LPS-induced production of nitric oxide, expression of inducible nitric oxide synthase and cyclooxygenase-2, and release of inflammatory factors, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 in a concentration dependent manner. In addition, DDA time- and concentration-dependently attenuated LPS-induced phosphorylation of c-Jun N-terminal kinase 1/2 (JNK), but not protein kinase B, p38, or extracellular signal-regulated kinase 1/2. Moreover, DDA significantly suppress LPS-mediated nuclear factor-κB (NF-κB) activation by inhibiting phosphorylation and nuclear translocation of NF-κB p65. Collectively, our results demonstrated that DDA inhibited LPS-stimulated inflammatory response in BV2 cell, at least in part, through inhibition of NF-κB activation and modulation of JNK signaling. PMID:26961887

  19. Amyloid β25-35 induced ROS-burst through NADPH oxidase is sensitive to iron chelation in microglial Bv2 cells.

    PubMed

    Part, Kristin; Künnis-Beres, Kai; Poska, Helen; Land, Tiit; Shimmo, Ruth; Zetterström Fernaeus, Sandra

    2015-12-10

    Iron chelation therapy and inhibition of glial nicotinamide adenine dinucleotide phosphate (NADPH) oxidase can both represent possible routes for Alzheimer's disease modifying therapies. The metal hypothesis is largely focused on direct binding of metals to the N-terminal hydrophilic 1-16 domain peptides of Amyloid beta (Aβ) and how they jointly give rise to reactive oxygen species (ROS) production. The cytotoxic effects of Aβ through ROS and metals are mainly studied in neuronal cells using full-length Aβ1-40/42 peptides. Here we study cellularly-derived ROS during 2-60min in response to non-metal associated mid domain Aβ25-35 in microglial Bv2 cells by fluorescence based spectroscopy. We analyze if Aβ25-35 induce ROS production through NADPH oxidase and if the production is sensitive to iron chelation. NADPH oxidase inhibitor diphenyliodonium (DPI) is used to confirm the production of ROS through NADPH oxidase. We modulate cellular iron homeostasis by applying cell permeable iron chelators desferrioxamine (DFO) and deferiprone (DFP). NADPH oxidase subunit gp91-phox level was analyzed by Western blotting. Our results show that Aβ25-35 induces strong ROS production through NADPH oxidase in Bv2 microglial cells. Intracellular iron depletion resulted in restrained Aβ25-35 induced ROS. PMID:26505916

  20. Chemical constituents of Polygala tenuifolia roots and their inhibitory activity on lipopolysaccharide-induced nitric oxide production in BV2 microglia.

    PubMed

    Cho, Namki; Huh, Jungmoo; Yang, Heejung; Jeong, Eun Ju; Kim, Young Choong; Kim, Jinwoong; Sung, Sang Hyun

    2012-02-01

    A methanolic extract of the roots of Polygala tenuifolia (Polygalaceae) significantly attenuated nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated BV2 microglia cells. Five xanthones, 1-hydroxy-7-methoxyxanthone (1), 3,6-dihydroxy-1,2,7-trimethoxyxanthone (2), 1,3,6-trihydroxy-2,7-dimethoxyxanthone (3), 1,7-dihydroxy-2,3-dimethoxyxanthone (4) and 1,7-dihydroxy-3-methoxyxanthone (5), and five phenylpropanoids, 4-hydroxy-3-methoxypropiophenone (6), methyl 4-hydroxy-3-methoxycinnamic acid (7), 3,4,5-trimethoxycinnamic acid (8), 4-methoxycinnamic acid (9) and β-d-(3-O-sinapoyl) fructofuranosyl-α-d-(6-O-sinapoyl)glucopyranoside (10), were isolated from CHCl(3) fraction using bioactivity-guided fractionation. Among these compounds, compounds 1, 2, 4, 5 and 7 showed significant inhibitory effects on LPS-induced NO production in BV2 microglia cells at the concentration ranging from 10.0 to 100.0 μM. PMID:21740104

  1. Biological activities of Schottenol and Spinasterol, two natural phytosterols present in argan oil and in cactus pear seed oil, on murine miroglial BV2 cells.

    PubMed

    El Kharrassi, Youssef; Samadi, Mohammad; Lopez, Tatiana; Nury, Thomas; El Kebbaj, Riad; Andreoletti, Pierre; El Hajj, Hammam I; Vamecq, Joseph; Moustaid, Khadija; Latruffe, Norbert; El Kebbaj, M'Hammed Saïd; Masson, David; Lizard, Gérard; Nasser, Boubker; Cherkaoui-Malki, Mustapha

    2014-04-11

    The objective of this study was to evaluate the biological activities of the major phytosterols present in argan oil (AO) and in cactus seed oil (CSO) in BV2 microglial cells. Accordingly, we first determined the sterol composition of AO and CSO, showing the presence of Schottenol and Spinasterol as major sterols in AO. While in CSO, in addition to these two sterols, we found mainly another sterol, the Sitosterol. The chemical synthesis of Schottenol and Spinasterol was performed. Our results showed that these two phytosterols, as well as sterol extracts from AO or CSO, are not toxic to microglial BV2 cells. However, treatments by these phytosterols impact the mitochondrial membrane potential. Furthermore, both Schottenol and Spinasterol can modulate the gene expression of two nuclear receptors, liver X receptor (LXR)-α and LXRβ, their target genes ABCA1 and ABCG1. Nonetheless, only Schottenol exhibited a differential activation vis-à-vis the nuclear receptor LXRβ. Thus Schottenol and Spinasterol can be considered as new LXR agonists, which may play protective roles by the modulation of cholesterol metabolism. PMID:24582563

  2. Down-regulation of BNIP3 by olomoucine, a CDK inhibitor, reduces LPS- and NO-induced cell death in BV2 microglial cells.

    PubMed

    Tsou, Yu-Chi; Wang, Hsiao-Hsien; Hsieh, Chii-Cheng; Sun, Kuang-Hui; Sun, Guang-Huan; Jhou, Ren-Shiang; Lin, Tz-I; Lu, Shou-Yun; Liu, Huan-Yun; Tang, Shye-Jye

    2016-08-15

    Proinflammatory responses eliciting the microglial production of cytokines and nitric oxide (NO) have been reported to play a crucial role in the acute and chronic pathogenic effects of neurodegeneration. Chemical inhibitors of cyclin-dependent kinases (CDKs) may prevent the progression of neurodegeneration by both limiting cell proliferation and reducing cell death. However, the mechanism underlying the protective effect of CDK inhibitors on microglia remains unexplored. In this study, we found that olomoucine, a CDK inhibitor, alleviated lipopolysaccharide (LPS)-induced BV2 microglial cell death by reducing the generation of NO and inhibiting the gene expression of proinflammatory cytokines. In addition, olomoucine reduced inducible NO synthase promoter activity and alleviated NF-κB- and E2F-mediated transcriptional activation. NO-induced cell death involved mitochondrial disruptions such as cytochrome c release and loss of mitochondrial membrane potential, and pretreatment with olomoucine prior to NO exposure reduced these disruptions. Microarray analysis revealed that olomoucine treatment induced prominent down-regulation of Bcl2/adenovirus E1B 19-kDa-interacting protein 3 (BNIP3), a pro-apoptotic Bcl-2 family protein that is involved in mitochondrial disruption. As BNIP3 knock-down significantly increased the viability of LPS- and NO-treated BV2 cells, we conclude that olomoucine may protect cells by limiting proinflammatory responses, thereby reducing NO generation. Simultaneously, down-regulation of BNIP3 prevents NO stimulation from inducing mitochondrial disruption. PMID:27345388

  3. Anti-neuroinflammatory activities of indole alkaloids from kanjang (Korean fermented soy source) in lipopolysaccharide-induced BV2 microglial cells.

    PubMed

    Kim, Dong-Cheol; Quang, Tran Hong; Yoon, Chi-Su; Ngan, Nguyen Thi Thanh; Lim, Seong-Il; Lee, So-Young; Kim, Youn-Chul; Oh, Hyuncheol

    2016-12-15

    Kanjang (Korean soy sauce) is a byproduct of the production of the Korean fermented soybean. In the present study, seven indole alkaloid derivatives were isolated from methanol extract of kanjang. Their structures were identified as 1-propyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid (1), 1-methyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid (2), 1-methyl-1,2,3,4-tetrahydro-β-carboline-1-carboxylic acid (3), 3-indoleacetic acid (4), Nb-acetyltryptamine (5), 1-methyl-3,4-dihydro-β-carboline (6), and flazine (7) by NMR and MS analyses. Preliminary screening for anti-neuroinflammatory effects of isolated indole alkaloids in lipopolysaccharide (LPS)-stimulated BV2 cells revealed that these compounds inhibited the production of nitric oxide and prostaglandin E2. For the subsequent investigation of anti-neuroinflammatory action of these metabolites, compounds 4 and 7 were selected, and the results revealed that these inhibitory effects correlated with the suppressive effect of 4 and 7 on inducible nitric oxide synthase and cyclooxygenase-2 expression in LPS-stimulated BV2 cells. In regards to the mechanism of the anti-inflammatory effect, 4 and 7 significantly inhibited the nuclear factor-kappa B pathway. PMID:27451156

  4. Forsythiaside A Exhibits Anti-inflammatory Effects in LPS-Stimulated BV2 Microglia Cells Through Activation of Nrf2/HO-1 Signaling Pathway.

    PubMed

    Wang, Yue; Zhao, Hongfei; Lin, Chuangxin; Ren, Jie; Zhang, Shizhong

    2016-04-01

    Inflammation and oxidative stress have been reported to play critical roles in the pathogenesis of neurodegenerative disease. Forsythiaside A, a phenylethanoside product isolated from air-dried fruits of Forsythia suspensa, has been reported to have anti-inflammatory and antioxidant effects. In this study, the anti-inflammatory effects of forsythiaside A on LPS-stimulated BV2 microglia cells and primary microglia cells were investigated. The production of inflammatory mediators TNF-α, IL-1β, NO and PGE2 were detected in this study. NF-κB, nuclear factor-erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) expression were detected by western blot analysis. Our results showed that forsythiaside A significantly inhibited LPS-induced inflammatory mediators TNF-α, IL-1β, NO and PGE2 production. LPS-induced NF-κB activation was suppressed by forsythiaside A. Furthermore, forsythiaside A was found to up-regulate the expression of Nrf2 and HO-1. In conclusion, this study demonstrates that forsythiaside A inhibits LPS-induced inflammatory responses in BV2 microglia cells and primary microglia cells through inhibition of NF-κB activation and activation of Nrf2/HO-1 signaling pathway. PMID:26498935

  5. Involvement of mitogen-activated protein kinase and NF-κB signaling pathways in perfluorooctane sulfonic acid-induced inflammatory reaction in BV2 microglial cells.

    PubMed

    Zhu, Jingying; Qian, Wenyi; Wang, Yixin; Gao, Rong; Wang, Jun; Xiao, Hang

    2015-12-01

    Microglial activation is closely related to the pathogenesis of neurodegenerative diseases by producing proinflammatory cytokines. Perfluorooctane sulfonic acid (PFOS), known as an emerging persistent organic pollutant, is reported to disturb human immune homeostasis; however, whether it affects cytokine production or the immune response in the central nervous system remains unclear. The present study was aimed to explore whether PFOS contributed to inflammatory action and to investigate the corresponding mechanisms in BV2 microglia. PFOS-mediated morphologic changes, cytokine responses and signaling events were examined by light microscopy, real-time polymerase chain reaction, enzyme-linked immunosorbent assay and Western blot assays. Our results indicated that PFOS increased BV2 cells activation and simultaneously increased tumor necrosis factor alpha and interleukin-6 expression. In addition, the c-Jun N-terminal protein kinase inhibitor (SP600125), as well as ERK1/2 blocker (PD98059), transcriptionally at least, displayed anti-inflammatory properties on PFOS-elicited cytokine responses. Moreover, the inflammatory transcription factor NF-κB was specifically activated by PFOS as well. These results, taken together, suggested that PFOS exerts its functional effects on the response of microglial cell activation via, in part, the c-Jun N-terminal protein kinase, ERK and NF-κB signaling pathways with its subsequent influence on proinflammatory action. PMID:25677194

  6. OM85-BV Induced the Productions of IL-1β, IL-6, and TNF-α via TLR4- and TLR2-Mediated ERK1/2/NF-κB Pathway in RAW264.7 Cells

    PubMed Central

    Luan, Hong; Zhang, Qian; Wang, Le; Wang, Chuanxiao; Zhang, Miao; Xu, Xiaoli; Zhou, Huan; Li, Xing'ai; Xu, Qing; He, Fan

    2014-01-01

    Broncho-Vaxom (OM85-BV) is an extract mixture from 8 strains of Gram+ and Gram− bacteria and plays an important role in anti-infection immune response by regulating macrophage activity and cytokine productions. However, the mechanism by which OM85-BV enhances the cytokine expression is still obscure. In this study, we evaluated the effects of OM85-BV on the productions of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) in RAW264.7 murine macrophages. Exposure of RAW264.7 cells to 100 μg/mL OM85-BV upregulated the expression of IL-1β, IL-6, and TNF-α at the mRNA and protein levels in a time- and dose-dependent manner. In addition, OM85-BV induced extracellular signal-regulated kinase (ERK) 1/2 and nuclear factor-kappa B (NF-κB) phosphorylation. Pretreatment with U0126 or Bay11-7082, respectively, could decrease IL-1β, IL-6, and TNF-α productions induced by OM85-BV. Application of Toll-like receptor (TLR) 4 or TLR2 small-interfering RNA (siRNA) into RAW264.7 cells could inhibit the productions of cytokines and ERK1/2 and NF-κB phosphorylation induced by OM85-BV. Consistent with this, downregulating either myeloid differentiation factor 88 (MyD88) or TRIF-related adaptor molecule (TRAM) gene with MyD88-siRNA or TRAM-siRNA separately could reduce the productions of cytokines and ERK1/2 and NF-κB phosphorylation induced by OM85-BV. Our study demonstrated that the productions of IL-1β, IL-6, and TNF-α induced by OM85-BV in RAW264.7 cells were through TLR4 and TLR2 signaling pathway-mediated activation of ERK1/2 and NF-κB. PMID:24605772

  7. Prospective, randomized comparison of OM-85 BV and a prophylactic antibiotic in children with recurrent infections and immunoglobulin A and/or G subclass deficiency☆

    PubMed Central

    Genel, Ferah; Kutukculer, Necil

    2003-01-01

    Background Patients with immunoglobulin (Ig)A and/or IgG subclass deficiency may be asymptomatic or may have recurrent, mainly respiratory infections. Objective This study compared the clinical efficacy and tolerability of prophylactic therapy with either the oral immunomodulator bacterial extract OM-85 BV or benzathine penicillin G (BPG) in the prevention of recurrent infections in symptomatic patients. Methods In this 26-month, prospective, randomized study conducted at the Department of Pediatric Immunology, Ege University (Izmir, Turkey), children aged 1 to 12 years with recurrent infections and IgA and/or IgG subclass deficiency were enrolled. After an initial 12-month control period, patients were randomized to receive OM-85 BV or BPG. OM-85 BV (3.5-mg capsule) was given once daily for the first 10 days of each month for the first 3 months of the study. IM injections of BPG were given at a dose of 1.2 million units (for patients with body weight > 27 kg) or at a half-dose (for patients with body weight ≤27 kg) every 3 weeks for 12 months. In nonresponders (ie, those who continued to have recurrent infections at 12-month follow-up), IV immunoglobulin (IVIG) replacement therapy at 400 mg/kg body weight was given every 4 weeks for an additional 12 months. The results of IVIG therapy were assessed by the authors using clinical observation. Adverse effects and adverse drug reactions were documented by the authors for each vaccine, prophylactic therapy, and IVIG. Results A total of 91 children (56 boys, 35 girls; mean [SD] age at the start of the control period, 46.4 [31.0] months) were enrolled. Of these, 44 were randomized to the OM-85 BV group and 47 to the BPG group. The year before prophylactic therapy, the mean (SD) number of reported infections was 10.7 (3.6) and the mean (SD) number of antibiotic courses was 9.7 (3.6) (OM-85 BV group: mean [SD] number of reported infections, 10.5 [3.3]; mean (SD) number of antibiotic courses, 9.3 [3.3]; BPG group: mean

  8. First Azospirillum genome from aquatic environments: Whole-genome sequence of Azospirillum thiophilum BV-S(T), a novel diazotroph harboring a capacity of sulfur-chemolithotrophy from a sulfide spring.

    PubMed

    Kwak, Yunyoung; Shin, Jae-Ho

    2016-02-01

    Azospirillum thiophilum BV-S(T), isolated from a sulfide spring, is a novel nitrogen-fixing bacterium harboring sulfur-lithotrophy. In order to identify genetic characteristics with habitat- and metabolic features contrasting to those from terrestrial Azospirillum species, we present here the genome sequence of a novel species A. thiophilum BV-S(T), with a significance of first genome report in the aquatic Azospirillum species. The genome of strain BV-S(T) is comprised of 7.6Mb chromosome with a GC content of 68.2%. This information will contribute to expand understandings of sulfur-oxidizer microbes that preserve inherencies as a diazotroph, and further it will provide insights into genome plasticity of the genus Azospirillum for niche specific adaptations. PMID:26545806

  9. O-GlcNAcylation and p50/p105 binding of c-Rel are dynamically regulated by LPS and glucosamine in BV2 microglia cells

    PubMed Central

    Hwang, So-Young; Hwang, Ji-Sun; Kim, Song-Yi; Han, Inn-Oc

    2013-01-01

    Background and Purpose Previously, we demonstrated that glucosamine (GlcN) exerts a suppressive effect on LPS-induced inducible NOS (iNOS) through the inhibition of NF-κB activation in BV2 mouse microglial cells. The purpose of the present study was to examine the mechanisms by which GlcN inhibits NF-κB activation. Experimental Approach BV2 cells were stimulated with LPS with or without GlcN. NF-κB/c-Rel activities were studied by EMSA, nuclear translocation, reporter assay or chromatin immunoprecipitation. Wheat germ agglutinin precipitation or galactosyltransferase assay were used to measure O-linked N-acetylglucosamine (O-GlcNAc) modification (O-GlcNAcylation) of c-Rel. Protein-protein interactions were examined by co-immunoprecipitation. Key Results LPS stimulated the activation of c-Rel, increased the O-GlcNAcylation of c-Rel and enhanced the binding of c-Rel to the NF-κB site in the iNOS promoter; GlcN attenuated these effects of LPS. O-GlcNAcylation of both nuclear and cytosolic forms of c-Rel was increased by LPS and reduced by GlcN. LPS increased the interaction of c-Rel with O-GlcNAc transferase (OGT) and p50/p105, and GlcN suppressed these interactions. Knockdown of OGT reduced the c-Rel O-GlcNAcylation and c-Rel–p50 interaction in response to LPS, but did not affect either the binding of c-Rel to the iNOS promoter or the transcriptional activity of c-Rel. Conclusions and Implications In BV2 microglial cells, the anti-inflammatory effect of GlcN is mediated by prevention of the prolonged activation of transcription factors, c-Rel and NF-κB. Further clarification of the mechanism by which GlcN exerts this effect will facilitate the development of pharmacological strategies for preventing excessive NO formation when targeting inflammatory diseases of the periphery or CNS. PMID:23646894

  10. Protective effects of naringin against gp120-induced injury mediated by P2X7 receptors in BV2 microglial cells.

    PubMed

    Chen, Q; Hu, J; Qin, S S; Liu, C L; Wu, H; Wang, J R; Lu, X M; Wang, J; Chen, G Q; Liu, Y; Liu, B Y; Xu, C S; Liang, S D

    2016-01-01

    This study was aimed at exploring the effects of P2X7 receptors on gp120-induced injury and naringin's protective effects against gp120-induced injury in BV2 microglia. BV2 microglia injury model was established by gp120 treatment and MTS assay was used to verify whether naringin has a cell-protective effect against gp120-induced injury. Changes in P2X7 receptor expression were assayed using RT-PCR, qPCR, and western blot. Results showed that the ODs of the Ctrl, gp120, gp120+naringin, and gp120+BBG groups were 0.91 ± 0.10, 0.71 ± 0.09, 0.83 ± 0.10, and 0.83 ± 0.10, respectively. Compared to the control group, the gp120 group showed a significantly decreased cell survival rate. Cell survival rates of the gp120+naringin group increased significantly compared to those of the gp120 group, while no difference was observed when compared to the gp120+BBG group. The relative P2X7 mRNA expression levels in the Ctrl, gp120, gp120+naringin, and gp120+BBG groups were 0.73 ± 0.06, 1.05 ± 0.06, 0.78 ± 0.05, and 0.81 ± 0.04, respectively. The corresponding P2X7 protein expression levels were 0.46 ± 0.04, 0.79 ± 0.04, 0.38 ± 0.07, and 0.42 ± 0.06. P2X7 mRNA and protein expression in the gp120 group increased significantly compared to those in the control group, and declined in the gp120+naringin group compared to those in the gp120 group. Therefore, P2X7 receptors might be involved in gp120-induced injury in BV2 microglia, and naringin might play a protective role by inhibiting the up-regulated expression of P2X7 receptors. PMID:27323041

  11. Method development to quantify Bv8 expression in circulating CD11b+ cells in patients with neovascular age-related macular degeneration (nvAMD) exhibiting Anti-VEGF refractoriness.

    PubMed

    Catchpole, Timothy; Daniels, Tad; Perkins, Jill; Csaky, Karl G

    2016-07-01

    A subset of neovascular age-related macular degeneration (nvAMD) subjects appears to be refractory to the effects of anti-VEGF treatment and require frequent intravitreal injections. Prokineticin-2 (Bv8) expression in CD11b(+) cells has been linked to anti-VEGF response. We have developed a reproducible method to quantify gene expression in circulating CD11b + cells. Utilizing this method we tested the hypothesis that high Bv8 expression in circulating CD11b(+) cells is associated with anti-VEGF refractoriness in nvAMD patients. Two groups of nvAMD subjects undergoing treatment with anti-VEGF agents were recruited and classified as refractory or non-refractory to anti-VEGF treatment (n = 33 for each group). Two blood draws were obtained from each subject 1-9 months apart. Peripheral blood mononuclear cells (PBMCs) were isolated and CD11b(+) cells were purified via magnetic bead separation. RNA was purified, and relative expression of Bv8 among the subjects was compared via quantitative PCR analysis. Utilizing this approach no significant difference was detected in the mean LogRQ values between the first and second blood draws (t-test, p = 0.826) indicating low intra-patient variability and demonstrating good reproducibility of the assay. There was no significant difference in Bv8 expression between nvAMD subjects classified as refractory versus non-refractory. We were unable to find a correlation between Bv8 expression in CD11b + cells and anti-VEGF refractoriness in human nvAMD subjects. Relatively high expression in Bv8 in these subjects did not correlate with clinical treatment history, as measured by the frequency of injections. Utilizing this well characterized technique, studies are underway to examine alternative gene expression profiles in various circulating cell populations that may contribute to anti-VEGF refractoriness. PMID:27256991

  12. Could Intrathymic Injection of Myelin Basic Protein Suppress Inflammatory Response After Co-culture of T Lymphocytes and BV-2 Microglia Cells?

    PubMed Central

    Cui, Zhan-Qun; Liu, Bao-Long; Wu, Qiao-Li; Cai, Ying; Fan, Wei-Jia; Zhang, Ming-Chao; Ding, Wei-Liang; Zhang, Bo; Kang, Jian-Min; Yan, Hua

    2016-01-01

    Background: The interaction between activated microglia and T lymphocytes can yield abundant pro-inflammatory cytokines. Our previous study proved that thymus immune tolerance could alleviate the inflammatory response. This study aimed to investigate whether intrathymic injection of myelin basic protein (MBP) in mice could suppress the inflammatory response after co-culture of T lymphocytes and BV-2 microglia cells. Methods: Totally, 72 male C57BL/6 mice were randomly assigned to three groups (n = 24 in each): Group A: intrathymic injection of 100 μl MBP (1 mg/ml); Group B: intrathymic injection of 100 μl phosphate-buffered saline (PBS); and Group C: sham operation group. Every eight mice in each group were sacrificed to obtain the spleen at postoperative days 3, 7, and 14, respectively. T lymphocytes those were extracted and purified from the spleens were then co-cultured with activated BV-2 microglia cells at a proportion of 1:2 in the medium containing MBP for 3 days. After identified the T lymphocytes by CD3, surface antigens of T lymphocytes (CD4, CD8, CD152, and CD154) and BV-2 microglia cells (CD45 and CD54) were detected by flow cytometry. The expressions of pro-inflammatory factors of BV-2 microglia cells (interleukin [IL]-1β, tumor necrosis factor-α [TNF-α], and inducible nitric oxide synthase [iNOS]) were detected by quantitative real-time polymerase chain reaction (PCR). One-way analysis of variance (ANOVA) and the least significant difference test were used for data analysis. Results: The levels of CD152 in Group A showed an upward trend from the 3rd to 7th day, with a downward trend from the 7th to 14th day (20.12 ± 0.71%, 30.71 ± 1.14%, 13.50 ± 0.71% at postoperative days 3, 7, and 14, respectively, P < 0.05). The levels of CD154 in Group A showed a downward trend from the 3rd to 7th day, with an upward trend from the 7th to 14th day (10.00 ± 0.23%, 5.28 ± 0.69%, 14.67 ± 2.71% at postoperative days 3, 7, and 14, respectively, P < 0

  13. [Secretion of Phenolic Compounds into Root Exudates of Pea Seedlings upon Inoculation with Rhizobium leguminosarum bv. viceae or Pseudomonas siringae pv. Pisi].

    PubMed

    Makarova, L E; Dudareva, L V; Petrova, I G; Vasil'eva, G G

    2016-01-01

    The content of apigenin, naringenin, pisatin, dibutyl-ortho-phthalate, and N-phenyl-2-naphthyl-amine were assayed in root exudates of pea (Pisum sativum L.) seedlings one day after their inoculation with Rhizobium leguminosarum, bv. viceae or Pseudomonas siringae pv. pisi, which represent, respectively, mutualistic and antagonistic strategies of interaction with a host plant. After inoculation with either bacteria, the concentrations of apigenin and pisatin in the root exudates were equal, whereas the concentrations of naringenin and N-phenyl-2-naphthylamine were different and those of dibutyl-o-phthalate were unchanged. A certain role is suggested for the phenolic compounds in an accomplishment of symbiotic relations of bacteria with a host plant. PMID:27266251

  14. Antigenic changes in lipopolysaccharide I of Rhizobium leguminosarum bv. viciae in root nodules of Vicia sativa subsp. nigra occur during release from infection threads.

    PubMed Central

    Goosen-de Roo, L; de Maagd, R A; Lugtenberg, B J

    1991-01-01

    Three different monoclonal antibodies raised against the O antigen-containing lipopolysaccharide (LPS I) of free-living cells were used in an immunocytochemical study to follow the fate of LPS I on the outer membrane of Rhizobium leguminosarum bv. viciae 248 during the nodulation of Vicia sativa subsp. nigra. After immunogold labeling, the LPS I epitopes were detected on the outer membrane of bacteria present in infection threads throughout the nodule. Epitopes were not detectable on bacteria released from the infection thread. The data show that the LPS I epitopes present on rhizobia in infection droplets disappear shortly before or during endocytosis of the bacteria into the host plant cell cytoplasm. The abruptness of the change suggests an active degradation or modification of LPS I epitopes rather than only a repression of their synthesis. Images PMID:1708764

  15. An investigation into the accuracy of Acuros(TM) BV in heterogeneous phantoms for a (192)Ir HDR source using LiF TLDs.

    PubMed

    Manning, Siobhan; Nyathi, Thulani

    2014-09-01

    The aim of this study was to evaluate the accuracy of the new Acuros(TM) BV algorithm using well characterized LiF:Mg,Ti TLD 100 in heterogeneous phantoms. TLDs were calibrated using an (192)Ir source and the AAPM TG-43 calculated dose. The Tölli and Johansson Large Cavity principle and Modified Bragg Gray principle methods confirm the dose calculated by TG-43 at a distance of 5 cm from the source to within 4 %. These calibrated TLDs were used to measure the dose in heterogeneous phantoms containing air, stainless steel, bone and titanium. The TLD results were compared with the AAPM TG-43 calculated dose and the Acuros calculated dose. Previous studies by other authors have shown a change in TLD response with depth when irradiated with an (192)Ir source. This TLD depth dependence was assessed by performing measurements at different depths in a water phantom with an (192)Ir source. The variation in the TLD response with depth in a water phantom was not found to be statistically significant for the distances investigated. The TLDs agreed with Acuros(TM) BV within 1.4 % in the air phantom, 3.2 % in the stainless steel phantom, 3 % in the bone phantom and 5.1 % in the titanium phantom. The TLDs showed a larger discrepancy when compared to TG-43 with a maximum deviation of 9.3 % in the air phantom, -11.1 % in the stainless steel phantom, -14.6 % in the bone phantom and -24.6 % in the titanium phantom. The results have shown that Acuros accounts for the heterogeneities investigated with a maximum deviation of -5.1 %. The uncertainty associated with the TLDs calibrated in the PMMA phantom is ±8.2 % (2SD). PMID:24866931

  16. The Anti-Inflammatory Activity of Eucommia ulmoides Oliv. Bark. Involves NF-κB Suppression and Nrf2-Dependent HO-1 Induction in BV-2 Microglial Cells.

    PubMed

    Kwon, Seung-Hwan; Ma, Shi-Xun; Hwang, Ji-Young; Ko, Yong-Hyun; Seo, Ji-Yeon; Lee, Bo-Ram; Lee, Seok-Yong; Jang, Choon-Gon

    2016-05-01

    In the present study, we investigated the anti-inflammatory properties of Eucommia ulmoides Oliv. Bark. (EUE) in lipopolysaccharide (LPS)-stimulated microglial BV-2 cells and found that EUE inhibited LPS-mediated up-regulation of pro-inflammatory response factors. In addition, EUE inhibited the elevated production of pro-inflammatory cytokines, mediators, and reactive oxygen species (ROS) in LPS-stimulated BV-2 microglial cells. Subsequent mechanistic studies revealed that EUE suppressed LPS-induced phosphorylation of mitogen-activated protein kinases (MAPKs), phosphoinositide-3-kinase (PI3K)/Akt, glycogen synthase kinase-3β (GSK-3β), and their downstream transcription factor, nuclear factor-kappa B (NF-κB). EUE also blocked the nuclear translocation of NF-κB and inhibited its binding to DNA. We next demonstrated that EUE induced the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and upregulated heme oxygenase-1 (HO-1) expression. We determined that the significant up-regulation of HO-1 expression by EUE was a consequence of Nrf2 nuclear translocation; furthermore, EUE increased the DNA binding of Nrf2. In contrast, zinc protoporphyrin (ZnPP), a specific HO-1 inhibitor, blocked the ability of EUE to inhibit NO and PGE₂ production, indicating the vital role of HO-1. Overall, our results indicate that EUE inhibits pro-inflammatory responses by modulating MAPKs, PI3K/Akt, and GSK-3β, consequently suppressing NF-κB activation and inducing Nrf2-dependent HO-1 activation. PMID:27068259

  17. Quantitative Analysis of Psoralea corylifolia Linne and its Neuroprotective and Anti-Neuroinflammatory Effects in HT22 Hippocampal Cells and BV-2 Microglia.

    PubMed

    Kim, Yu Jin; Lim, Hye-Sun; Lee, Jun; Jeong, Soo-Jin

    2016-01-01

    The seeds of Psoralea corylifolia L. (P. corylifolia), also known as "Bo-Gol-Zhee" in Korea, are used in a traditional herbal medicine for treating various skin diseases. In the present study, we performed quantitative analyses of the seven standard components of P. corylifolia: psoralen, angelicin, neobavaisoflavone, psoralidin, isobavachalcone, bavachinin, and bakuchiol, using high-performance liquid chromatography. We also investigated the neuroprotective and anti-neuroinflammation effects of P. corylifolia and its standard components in the hippocampal cell line HT22 and microglia cell line BV-2. A 70% ethanol extract of P. corylifolia was prepared and the seven standard components were separated using C-18 analytical columns by gradient solvents with acetonitrile and water, and ultraviolet detection at 215, 225 and 275 nm. The analytical method showed high linearity, with a correlation coefficient of ≥0.9999. The amounts of the standard components ranged from 0.74 to 11.71 mg/g. Among the components, bakuchiol (11.71 mg/g) was the most potent phytochemical component of P. corylifolia. Furthermore, we analyzed the inhibitory effects of the components from P. corylifolia to determine the bioactive compound needed to regulate neuronal cell changes. Angelicin, isobavachalcone, and bakuchiol suppressed lipopolysaccharide (LPS)-stimulated nitric oxide production in LPS-treated BV-2 microglia more significantly than did the other components. In HT22 hippocampal cells, neobavaisoflavone and bakuchiol had more potent inhibitory activity against hydrogen peroxide-induced cell death. Taken together of the quantification and efficacy analyses, bakuchiol appeared to be the most potent bioactive phytochemical component of P. corylifolia for the potential treatment of neurodegenerative diseases. PMID:27548120

  18. Anti-inflammatory mechanism of α-viniferin regulates lipopolysaccharide-induced release of proinflammatory mediators in BV2 microglial cells.

    PubMed

    Dilshara, Matharage Gayani; Lee, Kyoung-Tae; Kim, Hee Ju; Lee, Hak-Ju; Choi, Yung Hyun; Lee, Chang-Min; Kim, Lark Kyun; Kim, Gi-Young

    2014-07-01

    α-Viniferin is an oligostilbene of trimeric resveratrol and has anticancer activity; however, the molecular mechanism underlying the anti-inflammatory effects of α-viniferin has not been completely elucidated thus far. Therefore, we determined the mechanism by which α-viniferin regulates lipopolysaccharide (LPS)-induced expression of proinflammatory mediators in BV2 microglial cells. Treatment with α-viniferin isolated from Clematis mandshurica decreased LPS-induced production of nitric oxide (NO) and prostaglandin E2 (PGE2). α-Viniferin also downregulated the LPS-induced expression of proinflammatory genes such as iNOS and COX-2 by suppressing the activity of nuclear factor kappa B (NF-κB) via dephosphorylation of Akt/PI3K. Treatment with a specific NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC), indirectly showed that NF-κB is a crucial transcription factor for expression of these genes in the early stage of inflammation. Additionally, our results indicated that α-viniferin suppresses NO and PGE2 production in the late stage of inflammation through induction of heme oxygenase-1 (HO-1) regulated by nuclear factor erythroid 2-related factor (Nrf2). Taken together, our data indicate that α-viniferin suppresses the expression of proinflammatory genes iNOS and COX-2 in the early stage of inflammation by inhibiting the Akt/PI3K-dependent NF-κB activation and inhibits the production of proinflammatory mediators NO and PGE2 in the late stage by stimulating Nrf2-mediated HO-1 signaling pathway in LPS-stimulated BV2 microglial cells. These results suggest that α-viniferin may be a potential candidate to regulate LPS-induced inflammation. PMID:24859013

  19. The Anti-Inflammatory Activity of Eucommia ulmoides Oliv. Bark. Involves NF-κB Suppression and Nrf2-Dependent HO-1 Induction in BV-2 Microglial Cells

    PubMed Central

    Kwon, Seung-Hwan; Ma, Shi-Xun; Hwang, Ji-Young; Ko, Yong-Hyun; Seo, Ji-Yeon; Lee, Bo-Ram; Lee, Seok-Yong; Jang, Choon-Gon

    2016-01-01

    In the present study, we investigated the anti-inflammatory properties of Eucommia ulmoides Oliv. Bark. (EUE) in lipopolysaccharide (LPS)-stimulated microglial BV-2 cells and found that EUE inhibited LPS-mediated up-regulation of pro-inflammatory response factors. In addition, EUE inhibited the elevated production of pro-inflammatory cytokines, mediators, and reactive oxygen species (ROS) in LPS-stimulated BV-2 microglial cells. Subsequent mechanistic studies revealed that EUE suppressed LPS-induced phosphorylation of mitogen-activated protein kinases (MAPKs), phosphoinositide-3-kinase (PI3K)/Akt, glycogen synthase kinase-3β (GSK-3β), and their downstream transcription factor, nuclear factor-kappa B (NF-κB). EUE also blocked the nuclear translocation of NF-κB and inhibited its binding to DNA. We next demonstrated that EUE induced the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and upregulated heme oxygenase-1 (HO-1) expression. We determined that the significant up-regulation of HO-1 expression by EUE was a consequence of Nrf2 nuclear translocation; furthermore, EUE increased the DNA binding of Nrf2. In contrast, zinc protoporphyrin (ZnPP), a specific HO-1 inhibitor, blocked the ability of EUE to inhibit NO and PGE2 production, indicating the vital role of HO-1. Overall, our results indicate that EUE inhibits pro-inflammatory responses by modulating MAPKs, PI3K/Akt, and GSK-3β, consequently suppressing NF-κB activation and inducing Nrf2-dependent HO-1 activation. PMID:27068259

  20. Anti-neuroinflammatory effects of citreohybridonol involving TLR4-MyD88-mediated inhibition of NF-кB and MAPK signaling pathways in lipopolysaccharide-stimulated BV2 cells.

    PubMed

    Cho, Kwang-Ho; Kim, Dong-Cheol; Yoon, Chi-Su; Ko, Won Min; Lee, Seung Jun; Sohn, Jae Hak; Jang, Jae-Hyuk; Ahn, Jong Seog; Kim, Youn-Chul; Oh, Hyuncheol

    2016-05-01

    In the course of searching for anti-neuroinflammatory metabolites from marine fungi, citreohybridonol was isolated from marine-derived fungal strain Toxicocladosporium sp. SF-5699. Citreohybridonol inhibited production of nitric oxide (NO) and prostaglandin E2 (PGE2) in BV2 cells stimulated by lipopolysaccharide (LPS). Citreohybridonol also suppressed the expression of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), and other pro-inflammatory cytokines including interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in the LPS-stimulated cells. In the further study, citreohybridonol disturbed nuclear translocation of nuclear factor-kappa B (NF-κB) in LPS-stimulated BV2 cells by inhibiting the phosphorylation of the inhibitor kappa B-α (IκB-α). Citreohybridonol also had inhibitory effect on the LPS-stimulated phosphorylation of p38 mitogen-activated protein kinase (MAPK). Finally, citreohybridonol suppressed the protein expression of Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88) in LPS-induced BV2 cells. These results suggest that citreohybridonol has anti-neuroinflammatory effect in LPS-stimulated BV2 cells by modulating TLR4-mediated several inflammatory pathways such as NF-κB and p38 MAPK pathways. PMID:26724567

  1. Inhibitory effect of ent-Sauchinone on amyloidogenesis via inhibition of STAT3-mediated NF-κB activation in cultured astrocytes and microglial BV-2 cells

    PubMed Central

    2014-01-01

    Background ent-Sauchinone is a polyphenolic compound found in plants belonging to the lignan family. ent-Sauchinone has been shown to modulate the expression of inflammatory factors through the nuclear factor-kappa B (NF-κB) signaling pathway. It is well known that neuroinflammation is associated with amyloidogenesis. Thus, in the present study, we investigated whether ent-Sauchinone could have anti-amyloidogenic effects through the inhibition of NF-κB pathways via its anti-inflammatory property. Methods To investigate the potential effect of ent-Sauchinone on anti-neuroinflammation and anti-amyloidogenesis in in vitro studies, we used microglial BV-2 cells and cultured astrocytes treated with ent-Sauchinone (1, 5, and 10 μM) for 24 hours. For the detection of anti-neuro-inflammatory responses, reative oxygen species (ROS) and Nitric oxide (NO) generation and inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression were measured with assay kits and western blotting. β-secretase and β-secretase activities and β-amyloid levels were determined for measuring the anti-amyloidogenic effects of ent-Sauchinone by enzyme assay kits. NF-κB and STAT3 signals were detected with electromobility shift assay (EMSA) to study the related signaling pathways. The binding of ent-Sauchinone to STAT3 was evaluated by a pull-down assay and by a docking model using Autodock VINA software (Hoover’s Inc., Texas, United states). Results ent-Sauchinone (1, 5, and 10 μM) effectively decreased lipopolysaccharide (LPS)-(1 μg/ml) induced inflammatory responses through the reduction of ROS and NO generations and iNOS and COX-2 expressions in cultured astrocytes and microglial BV-2 cells. ent-Sauchinone also inhibited LPS-induced amyloidogenesis through the inhibition of β-secretase and β-secretase activity. NF- κB amyloid and STAT3, critical transcriptional factors regulating not only inflammation but also amyloidogenesis, were also inhibited in a

  2. New compound, 5-O-isoferuloyl-2-deoxy-D-ribono-γ-lacton from Clematis mandshurica: Anti-inflammatory effects in lipopolysaccharide-stimulated BV2 microglial cells.

    PubMed

    Dilshara, Matharage Gayani; Lee, Kyoung-Tae; Lee, Chang-Min; Choi, Yung Hyun; Lee, Hak-Ju; Choi, Il-Whan; Kim, Gi-Young

    2015-01-01

    Microglia are main immune cells to exacerbate neural disorders in persistent overactivating. Therefore, it is a good strategy to regulate microglia for the treatment of neural disorders. In the present study, we isolated and characterized a novel compound, 5-O-isoferuloyl-2-deoxy-D-ribono-γ-lacton (5-DRL) from Clematis mandshurica, and evaluated its anti-inflammatory effect in lipopolysaccharide (LPS)-treated BV2 microglial cells. 5-DRL inhibited the expression of LPS-stimulated proinflammatory mediators such as nitric oxide (NO) and prostaglandin E2 (PGE2), as well as their regulatory genes inducible NO syntheses (iNOS) and cyclooxygenase-2 (COX-2). 5-DRL also downregulated the LPS-induced DNA-binding activity of nuclear factor-κB (NF-κB) through suppression of the nuclear translocation of the NF-κB subunits, p65 and p50. Consistent with the inhibition of iNOS and COX-2 via NF-κB activity with 5-DRL, an inhibitor of NF-κB, pyrrolidine dithiocarbamate (PDTC), also led to the suppression of LPS-induced iNOS and COX-2 expression. Additionally, 5-DRL corresponding with antioxidants, N-acetylcysteine (NAC) and glutathione (GSH), remarkably inhibited reactive oxygen species (ROS) generation. Both NAC and GSH, thus attenuated the expression of iNOS and COX-2 by suppressing NF-κB activation, indicating that 5-DRL suppresses LPS-induced iNOS and COX-2 expression through downregulation of the ROS-dependent NF-κB signaling pathway. The present study also indicated that 5-DRL suppresses NO and PGE2 production by inducing heme oxygenase-1 (HO-1) via nuclear factor erythroid 2-related factor 2 (Nrf2). Taken together, the present data indicate that 5-DRL attenuates the production of proinflammatory mediators such as NO and PGE2 as well as their regulatory genes in LPS-stimulated BV2 microglial cells by inhibiting ROS-dependent NF-κB activation and stimulating the Nrf2/HO-1 signal pathway. These data may be implicated in the application of 5-DRL in LPS

  3. Functional and expression analysis of the metal-inducible dmeRF system from Rhizobium leguminosarum bv. viciae.

    PubMed

    Rubio-Sanz, L; Prieto, R I; Imperial, J; Palacios, J M; Brito, B

    2013-10-01

    A gene encoding a homolog to the cation diffusion facilitator protein DmeF from Cupriavidus metallidurans has been identified in the genome of Rhizobium leguminosarum UPM791. The R. leguminosarum dmeF gene is located downstream of an open reading frame (designated dmeR) encoding a protein homologous to the nickel- and cobalt-responsive transcriptional regulator RcnR from Escherichia coli. Analysis of gene expression showed that the R. leguminosarum dmeRF genes are organized as a transcriptional unit whose expression is strongly induced by nickel and cobalt ions, likely by alleviating the repressor activity of DmeR on dmeRF transcription. An R. leguminosarum dmeRF mutant strain displayed increased sensitivity to Co(II) and Ni(II), whereas no alterations of its resistance to Cd(II), Cu(II), or Zn(II) were observed. A decrease of symbiotic performance was observed when pea plants inoculated with an R. leguminosarum dmeRF deletion mutant strain were grown in the presence of high concentrations of nickel and cobalt. The same mutant induced significantly lower activity levels of NiFe hydrogenase in microaerobic cultures. These results indicate that the R. leguminosarum DmeRF system is a metal-responsive efflux mechanism acting as a key element for metal homeostasis in R. leguminosarum under free-living and symbiotic conditions. The presence of similar dmeRF gene clusters in other Rhizobiaceae suggests that the dmeRF system is a conserved mechanism for metal tolerance in legume endosymbiotic bacteria. PMID:23934501

  4. Complete genome sequence of Rhizobium leguminosarum bv trifolii strain WSM2304, an effective microsymbiont of the South American clover Trifolium polymorphum

    SciTech Connect

    Reeve, Wayne; O'Hara, Graham; Chain, Patrick S. G.; Ardley, Julie; Brau, Lambert; Nandesena, Kemanthi; Tiwari, Ravi; Malfatti, Stephanie; Kiss, Hajnalka; Lapidus, Alla L.; Copeland, A; Nolan, Matt; Land, Miriam L; Ivanova, N; Mavromatis, K; Markowitz, Victor; Kyrpides, Nikos C; Melino, Vanessa; Denton, Matthew; Yates, Ron; Howieson, John

    2010-01-01

    Rhizobium leguminosarum bv trifolii is the effective nitrogen fixing microsymbiont of a diverse range of annual and perennial Trifolium (clover) species. Strain WSM2304 is an aerobic, motile, non-spore forming, Gram-negative rod, isolated from Trifolium polymorphum in Uruguay in 1998. This microsymbiont predominated in the perennial grasslands of Glencoe Research Station, in Uruguay, to competitively nodulate its host, and fix atmospheric nitrogen. Here we describe the basic features of WSM2304, together with the complete genome sequence, and annotation. This is the first completed genome sequence for a nitrogen fixing microsymbiont of a clover species from the American center of origin. We reveal that its genome size is 6,872,702 bp encoding 6,643 protein-coding genes and 62 RNA only encoding genes. This multipartite genome was found to contain 5 distinct replicons; a chromosome of size 4,537,948 bp and four circular plasmids of size 1,266,105 bp, 501,946 bp, 308,747 bp and 257,956 bp.

  5. Dihydroisocoumarin Derivatives from Marine-Derived Fungal Isolates and Their Anti-inflammatory Effects in Lipopolysaccharide-Induced BV2 Microglia.

    PubMed

    Kim, Dong-Cheol; Quang, Tran Hong; Ngan, Nguyen Thi Thanh; Yoon, Chi-Su; Sohn, Jae Hak; Yim, Joung Han; Feng, Yu; Che, Yongsheng; Kim, Youn-Chul; Oh, Hyuncheol

    2015-12-24

    Chemical investigation of the EtOAc extracts of marine-derived fungal isolates Aspergillus sp. SF-5974 and Aspergillus sp. SF-5976 yielded a new dihydroisocoumarin derivative (1) and 12 known metabolites. The structures of the isolated metabolites were established by extensive spectroscopic analyses, including 1D and 2D NMR spectra and MS data. Among the metabolites, the absolute configuration of 5'-hydroxyasperentin (6) was determined by single-crystal X-ray diffraction analysis. The in vitro antineuroinflammatory effects of the metabolites were also evaluated in lipopolysaccharide (LPS)-stimulated microglial cells. Among the isolated metabolites, dihydroisocoumarin derivatives 1-6 (10-80 μM) were shown to inhibit LPS-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production by suppressing the expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2), respectively, in LPS-stimulated BV2 microglia. Further, 1 (20-80 μM) was found to suppress the phosphorylation of the inhibitor of nuclear factor kappa B-α (IκB-α), interrupt the nuclear translocation of nuclear factor kappa B (NF-κB), and decrease the activation of p38 mitogen-activated protein kinase (MAPK). PMID:26651366

  6. Rhizobium leguminosarum bv. viciae 3841 Adapts to 2,4-Dichlorophenoxyacetic Acid with “Auxin-Like” Morphological Changes, Cell Envelope Remodeling and Upregulation of Central Metabolic Pathways

    PubMed Central

    Bhat, Supriya V.; Booth, Sean C.; McGrath, Seamus G. K.; Dahms, Tanya E. S.

    2015-01-01

    There is a growing need to characterize the effects of environmental stressors at the molecular level on model organisms with the ever increasing number and variety of anthropogenic chemical pollutants. The herbicide 2,4-dichlorophenoxyacetic acid (2,4-D), as one of the most widely applied pesticides in the world, is one such example. This herbicide is known to have non-targeted undesirable effects on humans, animals and soil microbes, but specific molecular targets at sublethal levels are unknown. In this study, we have used Rhizobium leguminosarum bv. viciae 3841 (Rlv) as a nitrogen fixing, beneficial model soil organism to characterize the effects of 2,4-D. Using metabolomics and advanced microscopy we determined specific target pathways in the Rlv metabolic network and consequent changes to its phenotype, surface ultrastructure, and physical properties during sublethal 2,4-D exposure. Auxin and 2,4-D, its structural analogue, showed common morphological changes in vitro which were similar to bacteroids isolated from plant nodules, implying that these changes are related to bacteroid differentiation required for nitrogen fixation. Rlv showed remarkable adaptation capabilities in response to the herbicide, with changes to integral pathways of cellular metabolism and the potential to assimilate 2,4-D with consequent changes to its physical and structural properties. This study identifies biomarkers of 2,4-D in Rlv and offers valuable insights into the mode-of-action of 2,4-D in soil bacteria. PMID:25919284

  7. Gasmin (BV2-5), a polydnaviral-acquired gene in Spodoptera exigua. Trade-off in the defense against bacterial and viral infections.

    PubMed

    Gasmi, Laila; Jakubowska, Agata K; Herrero, Salvador

    2016-03-01

    Thousands of Hymenopteran endoparasitoids have developed a unique symbiotic relationship with viruses named polydnavirus (PDVs). These viruses immunocompromise the lepidopteran host allowing the survival of the wasp eggs. In a previous work, we have shown the horizontal transfer of some polydnaviral genes into the genome of the Lepidoptera, Spodoptera exigua. One of these genes, BV2-5 (named gasmin) interferes with actin polymerization, negatively affecting the multiplication of baculovirus in cell culture. In this work, we have focused in the study of the effect of Gasmin expression on different aspects of the baculovirus production. In addition, and since actin polymerization is crucial for phagocytosis, we have studied the effect of Gasmin expression on the larval interaction with bacterial pathogens. Over-expression of Gasmin on hemocytes significantly reduces their capacity to phagocytize the pathogenic bacteria Bacillus thuringiensis. According to these results, gasmin domestication negatively affects baculovirus replication, but increases larvae susceptibility to bacterial infections as pay off. Although the effect of Gasmin on the insect interaction with other pathogens or parasitoids remain unknown, the opposite effects described here could shape the biological history of this species based on the abundance of certain type of pathogens as suggested by the presence of truncated forms of this protein in several regions of the world. PMID:26658027

  8. Temporal and spatial order of events during the induction of cortical cell divisions in white clover by Rhizobium leguminosarum bv. trifolii inoculation or localized cytokinin addition.

    PubMed

    Mathesius, U; Charon, C; Rolfe, B G; Kondorosi, A; Crespi, M

    2000-06-01

    We examined the timing and location of several early root responses to Rhizobium leguminosarum bv. trifolii infection, compared with a localized addition of cytokinin in white clover, to study the role of cytokinin in early signaling during nodule initiation. Induction of ENOD40 expression by either rhizobia or cytokinin was similar in timing and location and occurred in nodule progenitor cells in the inner cortex. Inoculation of rhizobia in the mature root failed to induce ENOD40 expression and cortical cell divisions (ccd). Nitrate addition at levels repressing nodule formation inhibited ENOD40 induction by rhizobia but not by cytokinin. ENOD40 expression was not induced by auxin, an auxin transport inhibitor, or an ethylene precursor. In contrast to rhizobia, cytokinin addition was not sufficient to induce a modulation of the auxin flow, the induction of specific chalcone synthase genes, and the accumulation of fluorescent compounds associated with nodule initiation. However, cytokinin addition was sufficient for the localized induction of auxin-induced GH3 gene expression and the initiation of ccd. Our results suggest that rhizobia induce cytokinin-mediated events in parallel to changes in auxin-related responses during nodule initiation and support a role of ENOD40 in regulating ccd. We propose a model for the interactions of cytokinin with auxin, ENOD40, flavonoids, and nitrate during nodulation. PMID:10830261

  9. Inhibitory effects of alternaramide on inflammatory mediator expression through TLR4-MyD88-mediated inhibition of NF-кB and MAPK pathway signaling in lipopolysaccharide-stimulated RAW264.7 and BV2 cells.

    PubMed

    Ko, Wonmin; Sohn, Jae Hak; Jang, Jae-Hyuk; Ahn, Jong Seog; Kang, Dae Gill; Lee, Ho Sub; Kim, Jong-Su; Kim, Youn-Chul; Oh, Hyuncheol

    2016-01-25

    Alternaramide (1), a novel lipophilic depsipeptide, has been isolated from the extract of the marine-derived fungus Alternaria sp. SF-5016. In the course of extensive biological evaluation of 1, its anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated RAW264.7 and BV2 cells were observed. In our initial study of the anti-inflammatory effects of 1, the compound suppressed production of nitric oxide (NO) and prostaglandin E2 (PGE2) in LPS-stimulated RAW264.7 and BV2 cells. Suppression of NO and PGE2 production was correlated with the inhibitory effect of 1 on expression of LPS-induced inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at the protein level in RAW264.7 and BV2 cells. In addition, 1 reduced production of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, and IL-12 in LPS-stimulated RAW264.7 and BV2 cells. In the evaluation of the molecular mechanisms underlying the anti-inflammatory effects of 1, the compound was found to suppress the nuclear factor-kappa B (NF-κB) signaling pathway in RAW264.7 and BV2 cells stimulated with LPS. This suppression was mediated by disruption of phosphorylation and degradation of IκBα, an inhibitor of NF-κB, in the cytoplasm, and blocking of nuclear translocation of the NF-κB p50-p65 heterodimer. Furthermore, 1 inhibited phosphorylation of c-Jun N-terminal kinases (JNKs) and p38 mitogen-activated protein kinase (MAPK), demonstrating its capacity to inhibit MAPK signaling. Finally, 1 markedly reduced expression of Toll-like receptor 4 (TLR4) and myeloid differentiation primary response gene 88 (MyD88) at the mRNA and protein levels in LPS-stimulated RAW264.7 and BV2 cells. Taken together, the results of the present study suggest that 1 modulates several TLR4-mediated inflammatory pathways, demonstrating its potential in the treatment of inflammatory and neuroinflammatory conditions. PMID:26620692

  10. Sinorhizobium teranga bv. acaciae ORS1073 and Rhizobium sp. strain ORS1001, two distantly related Acacia-nodulating strains, produce similar Nod factors that are O carbamoylated, N methylated, and mainly sulfated.

    PubMed Central

    Lorquin, J; Lortet, G; Ferro, M; Mear, N; Promé, J C; Boivin, C

    1997-01-01

    We have determined the structures of Nod factors produced by strains representative of Sinorhizobium teranga bv. acaciae and the so-called cluster U from the Rhizobium loti branch, two genetically different symbionts of particular Acacia species. Compounds from both strains were found to be similar, i.e., mainly sulfated, O carbamoylated, and N methylated, indicating a close relationship between host specificity and Nod factor structure, regardless of the taxonomy of the bacterial symbiont. PMID:9139935

  11. Anti-Inflammatory Effects of 3-(4'-Hydroxyl-3',5'-Dimethoxyphenyl)Propionic Acid, an Active Component of Korean Cabbage Kimchi, in Lipopolysaccharide-Stimulated BV2 Microglia.

    PubMed

    Jeong, Jin-Woo; Choi, Il-Whan; Jo, Guk-Heui; Kim, Gi-Young; Kim, Jinwoo; Suh, Hongsuk; Ryu, Chung-Ho; Kim, Wun-Jae; Park, Kun-Young; Choi, Yung Hyun

    2015-06-01

    We investigated the protective ability of 3-(4'-hydroxyl-3',5'-dimethoxyphenyl)propionic acid (HDMPPA), an active principle in Korean cabbage kimchi, against the production of proinflammatory mediators and cytokines, and the mechanisms involved in lipopolysaccharide (LPS)-stimulated BV2 microglial cells. HDMPPA significantly suppressed the production of nitric oxide (NO) and prostaglandin E2, along with the expression of inducible NO synthase and cyclooxygenase-2 in LPS-stimulated BV2 cells, at concentrations with no cytotoxicity. HDMPPA also attenuated the LPS-induced expression and secretion of proinflammatory cytokines, such as tumor necrosis factor-α and interleukin-1β. Furthermore, HDMPPA inhibited LPS-induced nuclear factor-κB (NF-κB) activation, which was associated with the abrogation of IκB-α degradation and phosphorylation, and subsequent decreases in NF-κB p65 levels. Moreover, the phosphorylation of mitogen-activated protein kinases (MAPKs) and Akt, a downstream molecule of phosphatidylinositol-3-kinase (PI3K), in LPS-stimulated BV2 cells was suppressed markedly by HDMPPA. This effect was associated with a significant reduction in the formation of intracellular reactive oxygen species. The findings in this study suggest that HDMPPA may exert anti-inflammatory responses by suppressing LPS-induced expression of proinflammatory mediators and cytokines through blockage of NF-κB, MAPKs, and PI3K/Akt signaling pathways and oxidative stress in microglia. PMID:25919915

  12. Retinoic acid receptor agonist Am80 inhibits CXCL2 production from microglial BV-2 cells via attenuation of NF-κB signaling.

    PubMed

    Takaoka, Yuichiro; Takahashi, Moeka; Kurauchi, Yuki; Hisatsune, Akinori; Seki, Takahiro; Shudo, Koichi; Katsuki, Hiroshi

    2016-09-01

    Accumulating lines of evidence suggest that retinoic acid receptor agonists such as Am80 exerts anti-inflammatory actions in the central nervous system, although detailed mechanisms of the action remain largely unknown. Our previous findings suggest that Am80 provides therapeutic effect on intracerebral hemorrhage in mice via suppression of expression of chemokine (C-X-C motif) ligand 2 (CXCL2). Here we investigated the mechanisms of inhibitory action of Am80 on expression of CXCL2 and other pro-inflammatory factors in microglial BV-2 cells. Pretreatment with Am80 markedly suppressed lipopolysaccharide (LPS)-induced expression of CXCL2 mRNA and release of CXCL2 protein. Am80 had no effect on LPS-induced activation of p38 mitogen-activated protein kinase and extracellular signal-regulated kinase. On the other hand, Am80 prevented LPS-induced nuclear translocation of p65 subunit of NF-κB complex. In addition, total expression levels of p65 and IκBα proteins, as well as of mRNAs encoding p65 and IκBα, were lowered by Am80. Dependence of CXCL2 expression on NF-κB was confirmed by the effect of an NF-κB inhibitor caffeic acid phenethyl ester that abolished LPS-induced CXCL2 expression. Caffeic acid phenethyl ester also abolished LPS-induced expression of inducible nitric oxide synthase, interleukin-1β and tumor necrosis factor α, which may be relevant to the inhibitory effect of Am80 on expression of these pro-inflammatory factors. We additionally found that Am80 attenuated LPS-induced up-regulation of CD14, a co-receptor for Toll-like receptor 4 (TLR4). These results suggest that inhibitory effect on TLR4 signaling mediated by NF-κB pathway underlies the anti-inflammatory action of retinoic acid receptor agonists in microglia. PMID:27351827

  13. Characterization of the membrane proteome and N-glycoproteome in BV-2 mouse microglia by liquid chromatography-tandem mass spectrometry

    PubMed Central

    2014-01-01

    Background Microglial cells are resident macrophages of the central nervous system and important cellular mediators of the immune response and neuroinflammatory processes. In particular, microglial activation and communication between microglia, astrocytes, and neurons are hallmarks of the pathogenesis of several neurodegenerative diseases. Membrane proteins and their N-linked glycosylation mediate this microglial activation and regulate many biological process including signal transduction, cell-cell communication, and the immune response. Although membrane proteins and N-glycosylation represent a valuable source of drug target and biomarker discovery, the knowledge of their expressed proteome in microglia is very limited. Results To generate a large-scale repository, we constructed a membrane proteome and N-glycoproteome from BV-2 mouse microglia using a novel integrated approach, comprising of crude membrane fractionation, multienzyme-digestion FASP, N-glyco-FASP, and various mass spectrometry. We identified 6928 proteins including 2850 membrane proteins and 1450 distinct N-glycosylation sites on 760 N-glycoproteins, of which 556 were considered novel N-glycosylation sites. Especially, a total of 114 CD antigens are identified via MS-based analysis in normal conditions of microglia for the first time. Our bioinformatics analysis provides a rich proteomic resource for examining microglial function in, for example, cell-to-cell communication and immune responses. Conclusions Herein, we introduce a novel integrated proteomic approach for improved identification of membrane protein and N-glycosylation sites. To our knowledge, this workflow helped us to obtain the first and the largest membrane proteomic and N-glycoproteomic datesets for mouse microglia. Collectively, our proteomics and bioinformatics analysis significantly expands the knowledge of the membrane proteome and N-glycoproteome expressed in microglia within the brain and constitutes a foundation for

  14. Quercetin Attenuates Inflammatory Responses in BV-2 Microglial Cells: Role of MAPKs on the Nrf2 Pathway and Induction of Heme Oxygenase-1

    PubMed Central

    Sun, Grace Y.; Chen, Zihong; Jasmer, Kimberly J.; Chuang, Dennis Y.; Gu, Zezong; Hannink, Mark; Simonyi, Agnes

    2015-01-01

    A large group of flavonoids found in fruits and vegetables have been suggested to elicit health benefits due mainly to their anti-oxidative and anti-inflammatory properties. Recent studies with immune cells have demonstrated inhibition of these inflammatory responses through down-regulation of the pro-inflammatory pathway involving NF-κB and up-regulation of the anti-oxidative pathway involving Nrf2. In the present study, the murine BV-2 microglial cells were used to compare anti-inflammatory activity of quercetin and cyanidin, two flavonoids differing by their alpha, beta keto carbonyl group. Quercetin was 10 folds more potent than cyanidin in inhibition of lipopolysaccharide (LPS)-induced NO production as well as stimulation of Nrf2-induced heme-oxygenase-1 (HO-1) protein expression. In addition, quercetin demonstrated enhanced ability to stimulate HO-1 protein expression when cells were treated with LPS. In an attempt to unveil mechanism(s) for quercetin to enhance Nrf2/HO-1 activity under endotoxic stress, results pointed to an increase in phospho-p38MAPK expression upon addition of quercetin to LPS. In addition, pharmacological inhibitors for phospho-p38MAPK and MEK1/2 for ERK1/2 further showed that these MAPKs target different sites of the Nrf2 pathway that regulates HO-1 expression. However, inhibition of LPS-induced NO by quercetin was not fully reversed by TinPPIX, a specific inhibitor for HO-1 activity. Taken together, results suggest an important role of quercetin to regulate inflammatory responses in microglial cells and its ability to upregulate HO-1 against endotoxic stress through involvement of MAPKs. PMID:26505893

  15. Kaempferol acts through mitogen-activated protein kinases and protein kinase B/AKT to elicit protection in a model of neuroinflammation in BV2 microglial cells

    PubMed Central

    Park, SE; Sapkota, K; Kim, S; Kim, H; Kim, SJ

    2011-01-01

    BACKGROUND AND PURPOSE Kaempferol, a dietary flavonoid and phyto-oestrogen, is known to have anti-inflammatory properties. Microglial activation has been implicated in various neurodegenerative diseases. Anti-inflammatory effects of kaempferol and the underlying mechanisms were investigated by using LPS-stimulated microglial BV2 cells. EXPERIMENTAL APPROACH Cell viability was measured using MTT and neutral red assays. elisa, Western blot, immunocytochemistry and electrophoretic mobility-shift assay were used to analyse NO, PGE2, TNF-α and IL-1β production, inducible NOS (iNOS), COX-2 expression and the involvement of signalling pathways such as toll-like receptor-4 (TLR4), MAPK cascades, PKB (AKT) and NF-κB. Accumulation of reaction oxygen species (ROS) was measured by nitroblue tetrazolium and 2′7′-dichlorofluorescein diacetate assay. Matrix metalloproteinase activity was investigated by zymography and immunoblot assay. Phagocytotic activity was assessed by use of latex beads. KEY RESULTS Kaempferol significantly attenuated LPS-induced NO, PGE2, TNF-α, IL-1β and ROS production and phagocytosis in a concentration-dependent manner. Kaempferol suppressed the expression of iNOS, COX-2, MMP-3 and blocked the TLR4 activation. Moreover, kaempferol inhibited LPS-induced NF-κB activation and p38 MAPK, JNK and AKT phosphorylation. CONCLUSION AND IMPLICATIONS Kaempferol was able to reduce LPS-induced inflammatory mediators through the down-regulation of TLR4, NF-κB, p38 MAPK, JNK and AKT suggesting that kaempferol has therapeutic potential for the treatment of neuroinflammatory diseases. PMID:21449918

  16. L-arabinose/D-galactose 1-dehydrogenase of Rhizobium leguminosarum bv. trifolii characterised and applied for bioconversion of L-arabinose to L-arabonate with Saccharomyces cerevisiae.

    PubMed

    Aro-Kärkkäinen, Niina; Toivari, Mervi; Maaheimo, Hannu; Ylilauri, Mikko; Pentikäinen, Olli T; Andberg, Martina; Oja, Merja; Penttilä, Merja; Wiebe, Marilyn G; Ruohonen, Laura; Koivula, Anu

    2014-12-01

    Four potential dehydrogenases identified through literature and bioinformatic searches were tested for L-arabonate production from L-arabinose in the yeast Saccharomyces cerevisiae. The most efficient enzyme, annotated as a D-galactose 1-dehydrogenase from the pea root nodule bacterium Rhizobium leguminosarum bv. trifolii, was purified from S. cerevisiae as a homodimeric protein and characterised. We named the enzyme as a L-arabinose/D-galactose 1-dehydrogenase (EC 1.1.1.-), Rl AraDH. It belongs to the Gfo/Idh/MocA protein family, prefers NADP(+) but uses also NAD(+) as a cofactor, and showed highest catalytic efficiency (k cat/K m) towards L-arabinose, D-galactose and D-fucose. Based on nuclear magnetic resonance (NMR) and modelling studies, the enzyme prefers the α-pyranose form of L-arabinose, and the stable oxidation product detected is L-arabino-1,4-lactone which can, however, open slowly at neutral pH to a linear L-arabonate form. The pH optimum for the enzyme was pH 9, but use of a yeast-in-vivo-like buffer at pH 6.8 indicated that good catalytic efficiency could still be expected in vivo. Expression of the Rl AraDH dehydrogenase in S. cerevisiae, together with the galactose permease Gal2 for L-arabinose uptake, resulted in production of 18 g of L-arabonate per litre, at a rate of 248 mg of L-arabonate per litre per hour, with 86 % of the provided L-arabinose converted to L-arabonate. Expression of a lactonase-encoding gene from Caulobacter crescentus was not necessary for L-arabonate production in yeast. PMID:25236800

  17. Novel endogenous N-acyl amides activate TRPV1-4 receptors, BV-2 microglia, and are regulated in brain in an acute model of inflammation

    PubMed Central

    Raboune, Siham; Stuart, Jordyn M.; Leishman, Emma; Takacs, Sara M.; Rhodes, Brandon; Basnet, Arjun; Jameyfield, Evan; McHugh, Douglas; Widlanski, Theodore; Bradshaw, Heather B.

    2014-01-01

    A family of endogenous lipids, structurally analogous to the endogenous cannabinoid, N-arachidonoyl ethanolamine (Anandamide), and called N-acyl amides have emerged as a family of biologically active compounds at TRP receptors. N-acyl amides are constructed from an acyl group and an amine via an amide bond. This same structure can be modified by changing either the fatty acid or the amide to form potentially hundreds of lipids. More than 70 N-acyl amides have been identified in nature. We have ongoing studies aimed at isolating and characterizing additional members of the family of N-acyl amides in both central and peripheral tissues in mammalian systems. Here, using a unique in-house library of over 70 N-acyl amides we tested the following three hypotheses: (1) Additional N-acyl amides will have activity at TRPV1-4, (2) Acute peripheral injury will drive changes in CNS levels of N-acyl amides, and (3) N-acyl amides will regulate calcium in CNS-derived microglia. Through these studies, we have identified 20 novel N-acyl amides that collectively activate (stimulating or inhibiting) TRPV1-4. Using lipid extraction and HPLC coupled to tandem mass spectrometry we showed that levels of at least 10 of these N-acyl amides that activate TRPVs are regulated in brain after intraplantar carrageenan injection. We then screened the BV2 microglial cell line for activity with this N-acyl amide library and found overlap with TRPV receptor activity as well as additional activators of calcium mobilization from these lipids. Together these data provide new insight into the family of N-acyl amides and their roles as signaling molecules at ion channels, in microglia, and in the brain in the context of inflammation. PMID:25136293

  18. Antibody-mediated inhibition of integrin α5β1 blocks neurotoxic prion peptide PrP106-126-induced activation of BV2 microglia.

    PubMed

    Chang, Jiaxin; Yang, Lifeng; Kouadir, Mohammed; Peng, Yun; Zhang, Siming; Shi, Fushan; Zhou, Xiangmei; Yin, Xiaomin; Zhao, Deming

    2012-09-01

    Microglial activation is a characteristic feature of the pathogenesis of prion diseases. The identification of cell surface molecules that mediate the prion protein (PrP) synthetic peptide interaction with microglia is of great significance as it represents potential target molecules to modulate the events leading to the pathophysiology of prion diseases. Here, we carried out in vitro experiments to investigate the involvement of α5β1 integrin in neurotoxic prion peptide PrP(106-126)-induced activation of BV2 microglia. The results showed that the exposure to PrP(106-126) upregulated the mRNA expression of proinflammatory factors (IL-1 β, IL-6, and iNOS) and NALP3 inflammasome components (NALP3 and ASC), increased the release of iNOS and its product nitric oxide, and stimulated NF-κB activation. Blockade of α5β1 integrin with monoclonal antibody BMC5 prior to PrP(106-126) treatment abrogated the upregulation of the mRNA expression of IL-1 β, IL-6, iNOS, and ASC, but had no effect on the mRNA expression of NALP3, blocked the release of iNOS and nitric oxide, and inhibited NF-κB activation. These results suggest that α5β1 integrin is involved in the PrP(106-126)-induced microglial activation through the participation in the activation of NF-κB and NALP3/ASC inflammasome. Our study unveils a previously unidentified role of α5β1 integrin as an intermediate signaling molecule in neurotoxic prion peptides-microglia interactions and identifies a potential molecular target for the modulation of prion-induced microglial activation. PMID:22648512

  19. Plasmid-Encoded RepA Proteins Specifically Autorepress Individual repABC Operons in the Multipartite Rhizobium leguminosarum bv. trifolii Genome

    PubMed Central

    Żebracki, Kamil; Koper, Piotr; Marczak, Małgorzata; Skorupska, Anna; Mazur, Andrzej

    2015-01-01

    Rhizobia commonly have very complex genomes with a chromosome and several large plasmids that possess genes belonging to the repABC family. RepA and RepB are members of the ParA and ParB families of partitioning proteins, respectively, whereas RepC is crucial for plasmid replication. In the repABC replicons, partitioning and replication functions are transcriptionally linked resulting in complex regulation of rep gene expression. The genome of R. leguminosarum bv. trifolii TA1 (RtTA1) consists of a chromosome and four plasmids (pRleTA1a-d), equipped with functional repABC genes. In this work, the regulation of transcription of the individual repABC cassettes of the four RtTA1 plasmids was studied. The involvement of the RepA and RepB as well as parS-like centromere sites in this process was depicted, demonstrating some dissimilarity in expression of respective rep regions. RtTA1 repABC genes of individual plasmids formed operons, which were negatively regulated by RepA and RepB. Individual RepA were able to bind to DNA without added nucleotides, but in the presence of ADP, bound specifically to their own operator sequences containing imperfect palindromes, and caused operon autorepression, whereas the addition of ATP stimulated non-specific binding of RepA to DNA. The RepA proteins were able to dimerize/oligomerize: in general dimers formed independently of ATP or ADP, although ATP diminished the concentration of oligomers that were produced. By the comprehensive approach focusing on a set of plasmids instead of individual replicons, the work highlighted subtle differences between the organization and regulation of particular rep operons as well as the structures and specificity of RepA proteins, which contribute to the fine-tuned coexistence of several replicons with similar repABC cassettes in the complex bacterial genome. PMID:26147968

  20. Crystallization and X-ray diffraction analysis of an l-arabinonate dehydratase from Rhizobium leguminosarum bv. trifolii and a d-xylonate dehydratase from Caulobacter crescentus

    PubMed Central

    Rahman, Mohammad Mubinur; Andberg, Martina; Koivula, Anu; Rouvinen, Juha; Hakulinen, Nina

    2016-01-01

    l-Arabinonate dehydratase (EC 4.2.1.25) and d-xylonate dehydratase (EC 4.2.1.82) are two enzymes that are involved in a nonphosphorylative oxidation pathway of pentose sugars. l-Arabinonate dehydratase converts l-arabinonate into 2-dehydro-3-deoxy-l-arabinonate, and d-xylonate dehydratase catalyzes the dehydration of d-xylonate to 2-dehydro-3-deoxy-d-xylonate. l-Arabinonate and d-xylonate dehydratases belong to the IlvD/EDD family, together with 6-phosphogluconate dehydratases and dihydroxyacid dehydratases. No crystal structure of any l-arabinonate or d-xylonate dehydratase is available in the PDB. In this study, recombinant l-arabinonate dehydratase from Rhizobium leguminosarum bv. trifolii (RlArDHT) and d-xylonate dehydratase from Caulobacter crescentus (CcXyDHT) were heterologously expressed in Escherichia coli and purified by the use of affinity chromatography followed by gel-filtration chromatography. The purified proteins were crystallized using the hanging-drop vapour-diffusion method at 293 K. Crystals of RlArDHT that diffracted to 2.40 Å resolution were obtained using sodium formate as a precipitating agent. They belonged to space group P21, with unit-cell parameters a = 106.07, b = 208.61, c = 147.09 Å, β = 90.43°. Eight RlArDHT molecules (two tetramers) in the asymmetric unit give a V M value of 3.2 Å3 Da−1 and a solvent content of 62%. Crystals of CcXyDHT that diffracted to 2.66 Å resolution were obtained using sodium formate and polyethylene glycol 3350. They belonged to space group C2, with unit-cell parameters a = 270.42, b = 236.13, c = 65.17 Å, β = 97.38°. Four CcXyDHT molecules (a tetramer) in the asymmetric unit give a V M value of 4.0 Å3 Da−1 and a solvent content of 69%. PMID:27487924

  1. Crystallization and X-ray diffraction analysis of an L-arabinonate dehydratase from Rhizobium leguminosarum bv. trifolii and a D-xylonate dehydratase from Caulobacter crescentus.

    PubMed

    Rahman, Mohammad Mubinur; Andberg, Martina; Koivula, Anu; Rouvinen, Juha; Hakulinen, Nina

    2016-08-01

    L-Arabinonate dehydratase (EC 4.2.1.25) and D-xylonate dehydratase (EC 4.2.1.82) are two enzymes that are involved in a nonphosphorylative oxidation pathway of pentose sugars. L-Arabinonate dehydratase converts L-arabinonate into 2-dehydro-3-deoxy-L-arabinonate, and D-xylonate dehydratase catalyzes the dehydration of D-xylonate to 2-dehydro-3-deoxy-D-xylonate. L-Arabinonate and D-xylonate dehydratases belong to the IlvD/EDD family, together with 6-phosphogluconate dehydratases and dihydroxyacid dehydratases. No crystal structure of any L-arabinonate or D-xylonate dehydratase is available in the PDB. In this study, recombinant L-arabinonate dehydratase from Rhizobium leguminosarum bv. trifolii (RlArDHT) and D-xylonate dehydratase from Caulobacter crescentus (CcXyDHT) were heterologously expressed in Escherichia coli and purified by the use of affinity chromatography followed by gel-filtration chromatography. The purified proteins were crystallized using the hanging-drop vapour-diffusion method at 293 K. Crystals of RlArDHT that diffracted to 2.40 Å resolution were obtained using sodium formate as a precipitating agent. They belonged to space group P21, with unit-cell parameters a = 106.07, b = 208.61, c = 147.09 Å, β = 90.43°. Eight RlArDHT molecules (two tetramers) in the asymmetric unit give a VM value of 3.2 Å(3) Da(-1) and a solvent content of 62%. Crystals of CcXyDHT that diffracted to 2.66 Å resolution were obtained using sodium formate and polyethylene glycol 3350. They belonged to space group C2, with unit-cell parameters a = 270.42, b = 236.13, c = 65.17 Å, β = 97.38°. Four CcXyDHT molecules (a tetramer) in the asymmetric unit give a VM value of 4.0 Å(3) Da(-1) and a solvent content of 69%. PMID:27487924

  2. Production and Excretion of Nod Metabolites by Rhizobium leguminosarum bv. trifolii Are Disrupted by the Same Environmental Factors That Reduce Nodulation in the Field

    PubMed Central

    McKay, Ian A.; Djordjevic, Michael A.

    1993-01-01

    Lipooligosaccharides (Nod metabolites) have been shown to be essential for the successful nodulation of legumes. In strains of Rhizobium leguminosarum bv. trifolii, Nod metabolites were detected predominantly within the cell and to a lesser extent in the periplasmic space and the growth medium. The production, and in particular the excretion, of Nod metabolites was restricted by a range of environmental conditions which are associated with poor nodulation in the field. Lowering the medium pH from 7.0 to 5.0, reducing the phosphate concentration from 1 mM to 5 μM KH2PO4, and lowering the incubation temperature from 28 to 18°C affected the number and relative concentrations of the Nod metabolites made. The form and concentration of the nitrogen source affected the relative concentrations of the Nod metabolites produced and excreted. KNO3 concentrations of >10 mM did not affect cell growth rate but substantially reduced the number of Nod metabolites released. Environmental stresses differentially altered Nod metabolite production and excretion in the same strain carrying different introduced nod regions. Strain ANU845(pWLH1) produced and excreted comparatively fewer Nod metabolites at pH 5.0 and at 18°C than strain ANU845(pRI4003). The excretion but not the production of Nod metabolites by strain ANU845(pRtO32) was dependent on the presence of both nodI and nodJ. Tn5-induced nodI and nodJ mutants did not accumulate any metabolites either outside the cell or within the outer membrane or periplasmic space. Recognition that Nod metabolite accumulation is a complex system of production and excretion, with each component responding differently to changes in environmental conditions, has many consequences, both at the molecular level and in the field. The ability of different strains to produce and release Nod metabolites is likely to be a major determinant of nodule occupancy and should be considered when screening strains suitable for adverse environments. Images PMID

  3. Plasmid-Encoded RepA Proteins Specifically Autorepress Individual repABC Operons in the Multipartite Rhizobium leguminosarum bv. trifolii Genome.

    PubMed

    Żebracki, Kamil; Koper, Piotr; Marczak, Małgorzata; Skorupska, Anna; Mazur, Andrzej

    2015-01-01

    Rhizobia commonly have very complex genomes with a chromosome and several large plasmids that possess genes belonging to the repABC family. RepA and RepB are members of the ParA and ParB families of partitioning proteins, respectively, whereas RepC is crucial for plasmid replication. In the repABC replicons, partitioning and replication functions are transcriptionally linked resulting in complex regulation of rep gene expression. The genome of R. leguminosarum bv. trifolii TA1 (RtTA1) consists of a chromosome and four plasmids (pRleTA1a-d), equipped with functional repABC genes. In this work, the regulation of transcription of the individual repABC cassettes of the four RtTA1 plasmids was studied. The involvement of the RepA and RepB as well as parS-like centromere sites in this process was depicted, demonstrating some dissimilarity in expression of respective rep regions. RtTA1 repABC genes of individual plasmids formed operons, which were negatively regulated by RepA and RepB. Individual RepA were able to bind to DNA without added nucleotides, but in the presence of ADP, bound specifically to their own operator sequences containing imperfect palindromes, and caused operon autorepression, whereas the addition of ATP stimulated non-specific binding of RepA to DNA. The RepA proteins were able to dimerize/oligomerize: in general dimers formed independently of ATP or ADP, although ATP diminished the concentration of oligomers that were produced. By the comprehensive approach focusing on a set of plasmids instead of individual replicons, the work highlighted subtle differences between the organization and regulation of particular rep operons as well as the structures and specificity of RepA proteins, which contribute to the fine-tuned coexistence of several replicons with similar repABC cassettes in the complex bacterial genome. PMID:26147968

  4. Universal trench design method for a high-voltage SOI trench LDMOS

    NASA Astrophysics Data System (ADS)

    Xiarong, Hu; Bo, Zhang; Xiaorong, Luo; Zhaoji, Li

    2012-07-01

    The design method for a high-voltage SOI trench LDMOS for various trench permittivities, widths and depths is introduced. A universal method for efficient design is presented for the first time, taking the trade-off between breakdown voltage (BV) and specific on-resistance (Rs,on) into account. The high-k (relative permittivity) dielectric is suitable to fill a shallow and wide trench while the low-k dielectric is suitable to fill a deep and narrow trench. An SOI LDMOS with a vacuum trench in the drift region is also discussed. Simulation results show that the high FOM BV2/Rs,on can be achieved with a trench filled with the low-k dielectric due to its shortened cell-pitch.

  5. Anti-inflammatory effects of egg white combined with chalcanthite in lipopolysaccharide-stimulated BV2 microglia through the inhibition of NF-κB, MAPK and PI3K/Akt signaling pathways.

    PubMed

    Choi, Eun A; Park, Hye Young; Yoo, Hwa-Seung; Choi, Yung Hyun

    2013-01-01

    Egg white-chalcanthite (EWCC) is a mixture of egg white and chalcanthite prepared by roasting chalcanthite (which is a natural mineral mainly composed of CuSO4•5H2O) to the point of dehydration, pulverizing the dehydrated chalcanthite and then mixing the pulverized chalcanthite to react with egg white to trigger a reaction. When egg white-chalcanthite is prepared in this manner, the toxicity of chalcanthite is neutralized by the egg white, so that the toxicity is reduced or removed and the pharmaceutical properties are increased. However, the cellular and molecular mechanisms underlying the pharmacological activity of EWCC remain poorly understood. In this study, we investigated the inhibitory effects of EWCC on the production of lipopolysaccharide (LPS)-induced pro-inflammatory mediators in BV2 microglia. Our data indicated that the EWCC treatment significantly inhibited the excessive production of nitric oxide and prostaglandin E2 in LPS-stimulated BV2 microglia in a concentration-dependent manner without causing cytotoxicity. It also attenuated the expression of inducible nitric oxide synthase, cyclooxygenase-2 and pro-inflammatory cytokines, including interleukin-1β and tumor necrosis factor-α. Moreover, EWCC exhibited anti-inflammatory properties by the suppression of nuclear factor‑κB (NF-κB) activation by blocking IκB-α degradation, downregulation of extracellular signal-regulated kinase, c-Jun N-terminal kinase, p38 mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/Akt pathways. Our results indicate that the inhibitory effects of EWCC on LPS-stimulated inflammatory mediator production in BV2 microglia are associated with the suppression of the NF-κB, MAPK and PI3K/Akt signaling pathways. These findings suggest that EWCC may offer a substantial therapeutic potential for the treatment of neurodegenerative diseases that are accompanied by microglial activation. PMID:23128312

  6. Downregulation of NO and PGE2 in LPS-stimulated BV2 microglial cells by trans-isoferulic acid via suppression of PI3K/Akt-dependent NF-κB and activation of Nrf2-mediated HO-1.

    PubMed

    Dilshara, Matharage Gayani; Lee, Kyoung-Tae; Jayasooriya, Rajapaksha Gedara Prasad Tharanga; Kang, Chang-Hee; Park, Sang Rul; Choi, Yung Hyun; Choi, Il-Whan; Hyun, Jin-Won; Chang, Weon-Young; Kim, Yeon-Su; Lee, Hak-Ju; Kim, Gi-Young

    2014-01-01

    Little is known about whether trans-isoferulic acid (TIA) regulates the production of lipopolysaccharide (LPS)-induced proinflammatory mediators. Therefore, we examined the effect of TIA isolated from Clematis mandshurica on LPS-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production in BV2 microglial cells. We found that TIA inhibited the production of LPS-induced NO and PGE2 without accompanying cytotoxicity in BV2 microglial cells. TIA also downregulated the expression levels of specific regulatory genes such as inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) by suppressing LPS-induced NF-κB activity via dephosphorylation of PI3K/Akt. In addition, we demonstrated that a specific NF-κB inhibitor PDTC and a selective PI3K/Akt inhibitor, LY294002 effectively attenuated the expression of LPS-stimulated iNOS and COX-2 mRNA, while LY294002 suppressed LPS-induced NF-κB activity, suggesting that TIA attenuates the expression of these proinflammatory genes by suppressing PI3K/Akt-mediated NF-κB activity. Our results showed that TIA suppressed NO and PGE2 production through the induction of nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent heme oxygenase-1 (HO-1). Taken together, our data indicate that TIA suppresses the production of proinflammatory mediators such as NO and PGE2, as well as their regulatory genes, in LPS-stimulated BV2 microglial cells, by inhibiting PI3K/Akt-dependent NF-κB activity and enhancing Nrf2-mediated HO-1 expression. PMID:24291391

  7. Cleome rutidosperma and Euphorbia thymifolia Suppress Inflammatory Response via Upregulation of Phase II Enzymes and Modulation of NF-κB and JNK Activation in LPS-Stimulated BV2 Microglia.

    PubMed

    Ding, Hsiou-Yu; Wu, Pei-Shan; Wu, Ming-Jiuan

    2016-01-01

    Cleome rutidosperma DC. and Euphorbia thymifolia L. are herbal medicines used in traditional Indian and Chinese medicine to treat various illnesses. Reports document that they have antioxidant and anti-inflammatory activities; nonetheless, the molecular mechanisms involved in their anti-inflammatory actions have not yet been elucidated. The anti-neuroinflammatory activities and underlying mechanisms of ethanol extracts of Cleome rutidosperma (CR) and Euphorbia thymifolia (ET) were studied using lipopolysaccharide (LPS)-stimulated microglial cell line BV2. The morphology changes and production of pro-inflammatory mediators were assayed. Gene expression of inflammatory genes such as inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, interleukin (IL)-1β, and CC chemokine ligand (CCL)-2, as well as phase II enzymes such as heme oxygenase (HO)-1, the modifier subunit of glutamate cysteine ligase (GCLM) and NAD(P)H quinone dehydrogenase 1 (NQO1), were further investigated using reverse transcription quantitative-PCR (RT-Q-PCR) and Western blotting. The effects of CR and ET on mitogen activated protein kinases (MAPKs) and nuclear factor (NF)-κB signaling pathways were examined using Western blotting and specific inhibitors. CR and ET suppressed BV2 activation, down-regulated iNOS and COX-2 expression and inhibited nitric oxide (NO) overproduction without affecting cell viability. They reduced LPS-mediated tumor necrosis factor (TNF) and IL-6 production, attenuated IL-1β and CCL2 expression, but upregulated HO-1, GCLM and NQO1 expression. They also inhibited p65 NF-κB phosphorylation and modulated Jun-N terminal kinase (JNK) activation in BV2 cells. SP600125, the JNK inhibitor, significantly augmented the anti-IL-6 activity of ET. NF-κB inhibitor, Bay 11-7082, enhanced the anti-IL-6 effects of both CR and ET. Znpp, a competitive inhibitor of HO-1, attenuated the anti-NO effects of CR and ET. Our results show that CR and ET exhibit anti

  8. Design of smart sensing components for volcano monitoring

    USGS Publications Warehouse

    Xu, M.; Song, W.-Z.; Huang, R.; Peng, Y.; Shirazi, B.; LaHusen, R.; Kiely, A.; Peterson, N.; Ma, A.; Anusuya-Rangappa, L.; Miceli, M.; McBride, D.

    2009-01-01

    In a volcano monitoring application, various geophysical and geochemical sensors generate continuous high-fidelity data, and there is a compelling need for real-time raw data for volcano eruption prediction research. It requires the network to support network synchronized sampling, online configurable sensing and situation awareness, which pose significant challenges on sensing component design. Ideally, the resource usages shall be driven by the environment and node situations, and the data quality is optimized under resource constraints. In this paper, we present our smart sensing component design, including hybrid time synchronization, configurable sensing, and situation awareness. Both design details and evaluation results are presented to show their efficiency. Although the presented design is for a volcano monitoring application, its design philosophy and framework can also apply to other similar applications and platforms. ?? 2009 Elsevier B.V.

  9. Morin downregulates nitric oxide and prostaglandin E2 production in LPS-stimulated BV2 microglial cells by suppressing NF-κB activity and activating HO-1 induction.

    PubMed

    Dilshara, Matharage Gayani; Jayasooriya, Rajapaksha Gedara Prasad Tharanga; Lee, Seungheon; Choi, Yung Hyun; Kim, Gi-Young

    2016-06-01

    Morin possesses anti-inflammatory activity against septic shock and allergic responses, and prevents acute liver damage. However, the biological mechanism of action of morin in neuroinflammation remains largely unknown. Therefore, the present study investigated whether morin has the ability to attenuate expression of proinflammatory mediators such as nitric oxide (NO) and prostaglandin E2 (PGE2) in lipopolysaccharide (LPS)-stimulated BV2 microglial cells. Morin inhibited the expression of LPS-induced proinflammatory mediators such as NO and PGE2, without any cytotoxic effects. Furthermore, LPS-induced inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) were inhibited both at the mRNA and protein levels in response to morin. Morin also attenuated LPS-induced DNA-binding activity of nuclear transcription factor-κB (NF-κB) and its promoter activity. Pyrrolidine dithiocarbamate (PDTC), a specific NF-κB inhibitor, downregulated the expression of LPS-induced iNOS and COX-2, which suggests that morin-mediated NF-κB inhibition is the main signaling pathway responsible for the inhibition of iNOS and COX-2 expression. Additionally, morin increased induction of heme oxygenase-1 (HO-1) activity, leading to the suppression of NO and PGE2 production. Our results indicate that morin downregulates the expression of proinflammatory genes, such as iNOS and COX-2, involved in the synthesis of NO and PGE2 in LPS-stimulated BV2 microglial cells by suppressing NF-κB activity and activation of HO-1. Taken together, the findings of the present study suggest that morin may have potential as a therapeutic for the prevention of neuroinflammation. PMID:27131287

  10. Hydrangenol inhibits lipopolysaccharide-induced nitric oxide production in BV2 microglial cells by suppressing the NF-κB pathway and activating the Nrf2-mediated HO-1 pathway.

    PubMed

    Kim, Hee-Ju; Kang, Chang-Hee; Jayasooriya, Rajapaksha Gedara Prasad Tharanga; Dilshara, Matharage Gayani; Lee, Seungheon; Choi, Yung Hyun; Seo, Yong Taek; Kim, Gi-Young

    2016-06-01

    We previously demonstrated the anti-inflammatory effect of water extract of Hydrangea macrophylla in lipopolysaccharide (LPS)-stimulated macrophage cells. Here, we investigated whether hydrangenol, a bioactive component of H. macrophylla, attenuates the expression of nitric oxide (NO) and its associated gene, inducible NO synthase (iNOS), in LPS-stimulated BV2 microglial cells. Our data showed that low dosages of hydrangenol inhibited LPS-stimulated NO release and iNOS expression without any accompanying cytotoxicity. Hydrangenol also suppressed LPS-induced nuclear translocation of nuclear factor-κB (NF-κB) subunits, consequently inhibiting DNA-binding activity of NF-κB. Additionally, the NF-κB inhibitors, pyrrolidine dithiocarbamate (PDTC) and PS-1145, significantly attenuated LPS-induced iNOS expression, indicating that hydrangenol-induced NF-κB inhibition might be a key regulator of iNOS expression. Furthermore, our data showed that hydrangenol suppresses NO production by inducing heme oxygenase-1 (HO-1). The presence of cobalt protoporphyrin, a specific HO-1 inducer, potently suppressed LPS-induced NO production. Hydrangenol also promoted nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and subsequently increased its binding activity at the specific antioxidant response element sites. Additionally, transient knockdown of Nrf2 significantly downregulated hydrangenol-induced HO-1 expression, indicating that hydrangenol-induced Nrf2 is an upstream regulator of HO-1. Taken together, these data suggest that hydrangenol attenuates NO production and iNOS expression in LPS-stimulated BV2 microglial cells by inhibiting NF-κB activation and by stimulating the Nrf2-mediated HO-1 signaling pathway. Therefore, hydrangenol is a promising therapeutic agent for treatment of LPS-mediated inflammatory diseases. PMID:27032067

  11. Hexane fraction of Zingiberis Rhizoma Crudus extract inhibits the production of nitric oxide and proinflammatory cytokines in LPS-stimulated BV2 microglial cells via the NF-kappaB pathway.

    PubMed

    Jung, Hyo Won; Yoon, Cheol-Ho; Park, Kwon Moo; Han, Hyung Soo; Park, Yong-Ki

    2009-06-01

    Excessive production of inflammatory mediators such as nitric oxide (NO), prostaglandin E(2) (PGE2), and proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) from activated microglia contributes to uncontrolled inflammation in neurodegenerative diseases. It seems possible that treatment with anti-inflammatory agents, including plants used in Oriental medicine, might delay the progression of neurodegeneration through the inhibition of microglial activation. The present study is focused on the inhibitory effect of the rhizome hexane fraction extract of Zingiber officinale Roscoe (ginger hexan extract; GHE) on the production of inflammatory mediators such as NO, PGE(2), and proinflammatory cytokines in lipopolysaccharide (LPS)-stimulated BV-2 cells, a mouse microglial cell line. GHE significantly inhibited the excessive production of NO, PGE(2), TNF-alpha, and IL-1beta in LPS-stimulated BV2 cells. In addition, GHE attenuated the mRNA expressions and protein levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and proinflammatory cytokines. The molecular mechanisms that underlie GHE-mediated attenuation are related to the inhibition of the phosphorylation of three mitogen-activated protein kinases (MAPKs), extracellular signal-regulated kinases 1 and 2 (ERK1/2), p38 MAPK, and c-Jun N-terminal kinase (JNK), and the activation of nuclear factor-kappaB (NF-kappaB). Our results indicate that GHE exhibits anti-inflammatory properties by suppressing the transcription of inflammatory mediator genes through the MAPK and NF-kappaB signaling pathways. The anti-inflammatory properties of GHE may make it useful as a therapeutic candidate for the treatment of human neurodegenerative diseases. PMID:19233241

  12. Acetylsalicylic acid enhances the anti-inflammatory effect of fluoxetine through inhibition of NF-κB, p38-MAPK and ERK1/2 activation in lipopolysaccharide-induced BV-2 microglia cells.

    PubMed

    Yang, J M; Rui, B B; Chen, C; Chen, H; Xu, T J; Xu, W P; Wei, W

    2014-09-01

    The latest advancements in neurobiological research provide increasing evidence that inflammatory and neurodegenerative pathways play an important role in depression. According to the cytokine hypothesis, depression could be due to the increased production of pro-inflammatory cytokines by microglia activation. Thus, using the BV-2 microglial cell line, the aim of the present study was to investigate whether fluoxetine (FLX) or acetylsalicylic acid (ASA) could inhibit this microglia activation and could achieve better results in combination. Our results showed that FLX could attenuate lipopolysaccharide (LPS)-induced production of interleukin-1β (IL-1β), the expression of the indoleamine 2,3 dioxygenase (IDO) enzyme and the depletion of 5-HT. Moreover, FLX could inhibit phosphorylation of nuclear factor-κB (NF-κB) and phosphorylation of p38 mitogen-activated protein kinase (MAPK), and the combined use with ASA could enhance these effects. Notably, the adjunctive agent ASA could also inhibit phosphorylation of extracellular-regulated kinase 1/2 (ERK1/2). Taken together, our results suggest that FLX may have some anti-inflammatory effects by modulating microglia activation and that ASA served as an effective adjunctive agent by enhancing these therapeutic effects. PMID:24952332

  13. A strategy for high-level expression of a single-chain variable fragment against TNFα by subcloning antibody variable regions from the phage display vector pCANTAB 5E into pBV220.

    PubMed

    Yang, Tao; Yang, Lijun; Chai, Weiran; Li, Renke; Xie, Jun; Niu, Bo

    2011-03-01

    A phage display single-chain variable fragment (scFv) library against TNFα was constructed using a recombinant phage antibody system (RPAS). The cloned scFv gene was introduced into the phage display vector pCANTAB 5E and expressed in Escherichia coli (E. coli) with a yield of up to 0.15 mg/l of total protein. With the attempt to improve the expression level of TNF-scFv, a strategy was established for subcloning the scFv gene from pCANTAB 5E into the plasmid pBV220. Under the control of a highly efficient tandem P(R)P(L) promoter system, scFv production was increased to 30% of total protein as inclusion bodies. After extraction from the cell pellet by sonication, the inclusion bodies were solubilized and denatured in the presence of 8M urea. Purification of denatured scFv was performed using nickel column chromatography followed by renaturation. The purity and activity of the refolded scFv were confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), Western blotting and by an enzyme-linked immunoabsorbent assay (ELISA). The results reveal that the overall yield of bioactive TNF-scFv from E. coli flask cultures was more than 45 mg/l culture medium and 15 mg/g wet weight cells. The renatured scFv exhibited binding activity similarly to soluble scFv. In conclusion we developed a method to over-express TNF-scFv, which have biological function after purification and renaturation. PMID:20951213

  14. An acpXL Mutant of Rhizobium leguminosarum bv. phaseoli Lacks 27-Hydroxyoctacosanoic Acid in Its Lipid A and Is Developmentally Delayed during Symbiotic Infection of the Determinate Nodulating Host Plant Phaseolus vulgaris ▿

    PubMed Central

    Brown, Dusty B.; Huang, Yu-Chu; Kannenberg, Elmar L.; Sherrier, D. Janine; Carlson, Russell W.

    2011-01-01

    Rhizobium leguminosarum is a Gram-negative bacterium that forms nitrogen-fixing symbioses with compatible leguminous plants via intracellular invasion and establishes a persistent infection within host membrane-derived subcellular compartments. Notably, an unusual very-long-chain fatty acid (VLCFA) is found in the lipid A of R. leguminosarum as well as in the lipid A of the medically relevant pathogens Brucella abortus, Brucella melitensis, Bartonella henselae, and Legionella pneumophila, which are also able to persist within intracellular host-derived membranes. These bacterial symbionts and pathogens each contain a homologous gene region necessary for the synthesis and transfer of the VLCFA to the lipid A. Within this region lies a gene that encodes the specialized acyl carrier protein AcpXL, on which the VLCFA is built. This study describes the biochemical and infection phenotypes of an acpXL mutant which lacks the VLCFA. The mutation was created in R. leguminosarum bv. phaseoli strain 8002, which forms symbiosis with Phaseolus vulgaris, a determinate nodulating legume. Structural analysis using gas chromatography and mass spectrometry revealed that the mutant lipid A lacked the VLCFA. Compared to the parent strain, the mutant was more sensitive to the detergents deoxycholate and dodecyl sulfate and the antimicrobial peptide polymyxin B, suggesting a compromise to membrane stability. In addition, the mutant was more sensitive to higher salt concentrations. Passage through the plant restored salt tolerance. Electron microscopic examination showed that the mutant was developmentally delayed during symbiotic infection of the host plant Phaseolus vulgaris and produced abnormal symbiosome structures. PMID:21764936

  15. High-throughput design and optimization of fast lithium ion conductors by the combination of bond-valence method and density functional theory

    NASA Astrophysics Data System (ADS)

    Xiao, Ruijuan; Li, Hong; Chen, Liquan

    2015-09-01

    Looking for solid state electrolytes with fast lithium ion conduction is an important prerequisite for developing all-solid-state lithium secondary batteries. By combining the simulation techniques in different levels of accuracy, e.g. the bond-valence (BV) method and the density functional theory (DFT), a high-throughput design and optimization scheme is proposed for searching fast lithium ion conductors as candidate solid state electrolytes for lithium rechargeable batteries. The screening from more than 1000 compounds is performed through BV-based method, and the ability to predict reliable tendency of the Li+ migration energy barriers is confirmed by comparing with the results from DFT calculations. β-Li3PS4 is taken as a model system to demonstrate the application of this combination method in optimizing properties of solid electrolytes. By employing the high-throughput DFT simulations to more than 200 structures of the doping derivatives of β-Li3PS4, the effects of doping on the ionic conductivities in this material are predicted by the BV calculations. The O-doping scheme is proposed as a promising way to improve the kinetic properties of this materials, and the validity of the optimization is proved by the first-principles molecular dynamics (FPMD) simulations.

  16. High-throughput design and optimization of fast lithium ion conductors by the combination of bond-valence method and density functional theory

    PubMed Central

    Xiao, Ruijuan; Li, Hong; Chen, Liquan

    2015-01-01

    Looking for solid state electrolytes with fast lithium ion conduction is an important prerequisite for developing all-solid-state lithium secondary batteries. By combining the simulation techniques in different levels of accuracy, e.g. the bond-valence (BV) method and the density functional theory (DFT), a high-throughput design and optimization scheme is proposed for searching fast lithium ion conductors as candidate solid state electrolytes for lithium rechargeable batteries. The screening from more than 1000 compounds is performed through BV-based method, and the ability to predict reliable tendency of the Li+ migration energy barriers is confirmed by comparing with the results from DFT calculations. β-Li3PS4 is taken as a model system to demonstrate the application of this combination method in optimizing properties of solid electrolytes. By employing the high-throughput DFT simulations to more than 200 structures of the doping derivatives of β-Li3PS4, the effects of doping on the ionic conductivities in this material are predicted by the BV calculations. The O-doping scheme is proposed as a promising way to improve the kinetic properties of this materials, and the validity of the optimization is proved by the first-principles molecular dynamics (FPMD) simulations. PMID:26387639

  17. Three-dimensional lithostratigraphic model at Yucca Mountain, Nevada: A framework for fluid transport modeling and engineering design

    SciTech Connect

    Buesch, D.C.; Spengler, R.W.; Nelson, J.E.; Dickerson, R.P.

    1993-12-31

    A three-dimensional lithostratigraphic model of the central block of Yucca MounEain. Nevada, illustrates how some activities can serve both site characterization and dcsign and construction of the Exploratory Studies Facility (ESF). Site-characterization activities supported bv this model include characterizing the three-dimensional geometry of lithologic units and faults, and providing boundary conditions for geostatistical models and site-scale fluid flow modeling. The model supports the conceptual design as construction efforts for the proposed ramps of the ESF and potential high-level nuclear waste repository.

  18. Potential chemoprevention of LPS-stimulated nitric oxide and prostaglandin E₂ production by α-L-rhamnopyranosyl-(1→6)-β-D-glucopyranosyl-3-indolecarbonate in BV2 microglial cells through suppression of the ROS/PI3K/Akt/NF-κB pathway.

    PubMed

    Dilshara, Matharage Gayani; Lee, Kyoung-Tae; Choi, Yung Hyun; Moon, Dong-Oh; Lee, Hak-Ju; Yun, Sung Gyu; Kim, Gi-Young

    2014-02-01

    α-l-Rhamnopyranosyl-(1→6)-β-d-glucopyranosyl-3-indolecarbonate (RG3I) is a chemical constituent isolated from the commonly used Asian traditional medicinal plant, Clematis mandshurica; however, no studies have been reported on its anti-inflammatory properties. In the present study, we found that RG3I attenuates the lipopolysaccharide (LPS)-induced DNA-binding activity of nuclear factor-κB (NF-κB) via the dephosphorylation of PI3K/Akt in BV2 microglial cells, leading to a suppression of nitric oxide (NO) and prostaglandin E2 (PGE2) production, along with that of their regulatory genes, inducible NO synthase (iNOS) and cyclooxygenase-2 (Cox-2). Further, the PI3K/Akt inhibitor, LY294002 diminished the expression of LPS-stimulated iNOS and COX-2 genes by suppressing NF-κB activity. Moreover, RG3I significantly inhibited LPS-induced reactive oxygen species (ROS) generation similar to the ROS inhibitors, N-acetylcysteine (NAC) and glutathione (GSH). Notably, NAC and GSH abolished the LPS-induced expression of iNOS and Cox-2 in BV2 microglial cells by inhibiting NF-κB activity. Taken together, our data indicate that RG3I suppresses the production of proinflammatory mediators such as NO and PGE2 as well as their regulatory genes in LPS-stimulated BV2 microglial cells by inhibiting the PI3K/Akt- and ROS-dependent NF-κB signaling pathway, suggesting that RG3I may be a good candidate to regulate LPS-induced inflammatory response. PMID:24486459

  19. Pump Design

    NASA Technical Reports Server (NTRS)

    1981-01-01

    A NASA handbook on a general purpose titanium alloy was used by Sundstrand Corporation in design calculation for casting titanium impellers. Information contributed substantially to improved impeller design.

  20. Design of a fixed-bed ion-exchange process for the treatment of rinse waters generated in the galvanization process using Laminaria hyperborea as natural cation exchanger.

    PubMed

    Mazur, Luciana P; Pozdniakova, Tatiana A; Mayer, Diego A; Boaventura, Rui A R; Vilar, Vítor J P

    2016-03-01

    In this study, the removal of zinc from galvanization wastewaters was performed in a fixed bed column packed with brown macro-algae Laminaria hyperborea, acting as a natural cation exchanger (resin). The rinse wastewater presents a zinc concentration between 9 and 22 mg/L, a high concentration of light metals (mainly Na and Ca), a high conductivity (0.5-1.5 mS/cm) and a low organic content (DOC = 7-15 mg C/L). The zinc speciation diagram showed that approximately 80% of zinc is in the form of Zn(2+) and ≅20% as ZnSO4, considering the effluent matrix. From all operational conditions tested for zinc uptake (17 < bed height<27 cm, 4.5 < flow rate<18.2 BV/h, 0.8 < particle equivalent diameter<2.0 mm), the highest useful capacity (7.1 mg Zn/g algae) was obtained for D/dp = 31, L/D = 11, 9.1 BV/h, τ = 6.4 min, corresponding to a service capacity of 124 BV (endpoint of 2 mg Zn/L). Elution was faster and near to 100% effective using 10 BV of HCl (1 M, 3.0%, 363 g HCl/L of resin), for flow rates higher than 4.5 BV/h. Calcium chloride solution (0.1 M) was selected as the best regenerant, allowing the reuse of the natural resin for more than 3 saturation/elution/regeneration cycles. The best operation conditions were scaled-up and tested in a pre-pilot plant. The scale-up design of the cation exchange process was proposed for the treatment of 2.4 m(3)/day of galvanization wastewater, resulting in an estimated reactants cost of 2.44 €/m(3). PMID:26766159

  1. Directed site exploration for permeable reactive barrier design

    USGS Publications Warehouse

    Lee, J.; Graettinger, A.J.; Moylan, J.; Reeves, H.W.

    2009-01-01

    Permeable reactive barriers (PRBs) are being employed for in situ site remediation of groundwater that is typically flowing under natural gradients. Site characterization is of critical importance to the success of a PRB. A design-specific site exploration approach called quantitatively directed exploration (QDE) is presented. The QDE approach employs three spatially related matrices: (1) covariance of input parameters, (2) sensitivity of model outputs, and (3) covariance of model outputs to identify the most important location to explore based on a specific design. Sampling at the location that most reduces overall site uncertainty produces a higher probability of success of a particular design. The QDE approach is demonstrated on the Kansas City Plant, Kansas City, MO, a case study where a PRB was installed and failed. It is shown that additional quantitatively directed site exploration during the design phase could have prevented the remedial failure that was caused by missing a geologic body having high hydraulic conductivity at the south end of the barrier. The most contributing input parameter approach using head uncertainty clearly indicated where the next sampling should be made toward the high hydraulic conductivity zone. This case study demonstrates the need to include the specific design as well as site characterization uncertainty when choosing the sampling locations. ?? 2008 Elsevier B.V.

  2. Design parameters for rotating cylindrical filtration

    NASA Technical Reports Server (NTRS)

    Schwille, John A.; Mitra, Deepanjan; Lueptow, Richard M.

    2002-01-01

    Rotating cylindrical filtration displays significantly reduced plugging of filter pores and build-up of a cake layer, but the number and range of parameters that can be adjusted complicates the design of these devices. Twelve individual parameters were investigated experimentally by measuring the build-up of particles on the rotating cylindrical filter after a fixed time of operation. The build-up of particles on the filter depends on the rotational speed, the radial filtrate flow, the particle size and the gap width. Other parameters, such as suspension concentration and total flow rate are less important. Of the four mechanisms present in rotating filters to reduce pore plugging and cake build-up, axial shear, rotational shear, centrifugal sedimentation and vortical motion, the evidence suggests rotational shear is the dominant mechanism, although the other mechanisms still play minor roles. The ratio of the shear force acting parallel to the filter surface on a particle to the Stokes drag acting normal to the filter surface on the particle due to the difference between particle motion and filtrate flow can be used as a non-dimensional parameter that predicts the degree of particle build-up on the filter surface for a wide variety of filtration conditions. c2002 Elsevier Science B.V. All rights reserved.

  3. Auto Design

    NASA Technical Reports Server (NTRS)

    1988-01-01

    The 1987 Honda Acura Legend Coupe was designed with aid of the NASA-developed NASTRAN computer program. NASTRAN takes an electronic look at a computerized design and predicts how the structure will react under a great many different conditions. Quick and inexpensive, it minimizes trial and error in the design process and makes possible better, lighter, safer structures while affording significant savings in development time. All Honda auto products designed in the 1980's have been analyzed by the NASTRAN program.

  4. Ship Design

    NASA Technical Reports Server (NTRS)

    1980-01-01

    Marine Consultants & Designers, Inc. is a leader in development of innovative designs for self unloading bulk cargo carriers. Company also performs engineering services related to design of tankers, tugboats and other forms of marine transportation. In its engineering work, the firm makes extensive use of COSMIC's SHCP, which provides highly accurate results, helps to increase product safety and reliability.

  5. Designing Philosophy

    ERIC Educational Resources Information Center

    Sless, David

    2007-01-01

    Drawing on the everyday experience of collaborative design, and using ordinary language, I examine the nature of design practices and rules, how they come about, and how we use them. I offer some arguments to suggest that our conventional ways of thinking about rules are wrong. I conclude by arguing that the practice of designing and doing…

  6. Automotive Design

    NASA Technical Reports Server (NTRS)

    1991-01-01

    Analytical Design Service Corporation, Ann Arbor, MI, used NASTRAN (a NASA Structural Analysis program that analyzes a design and predicts how parts will perform) in tests of transmissions, engine cooling systems, internal engine parts, and body components. They also use it to design future automobiles. Analytical software can save millions by allowing computer simulated analysis of performance even before prototypes are built.

  7. Chromatographic elution process design space development for the purification of saponins in Panax notoginseng extract using a probability-based approach.

    PubMed

    Chen, Teng; Gong, Xingchu; Chen, Huali; Zhang, Ying; Qu, Haibin

    2016-01-01

    A Monte Carlo method was used to develop the design space of a chromatographic elution process for the purification of saponins in Panax notoginseng extract. During this process, saponin recovery ratios, saponin purity, and elution productivity are determined as process critical quality attributes, and ethanol concentration, elution rate, and elution volume are identified as critical process parameters. Quadratic equations between process critical quality attributes and critical process parameters were established using response surface methodology. Then probability-based design space was computed by calculating the prediction errors using Monte Carlo simulations. The influences of calculation parameters on computation results were investigated. The optimized calculation condition was as follows: calculation step length of 0.02, simulation times of 10 000, and a significance level value of 0.15 for adding or removing terms in a stepwise regression. Recommended normal operation region is located in ethanol concentration of 65.0-70.0%, elution rate of 1.7-2.0 bed volumes (BV)/h and elution volume of 3.0-3.6 BV. Verification experiments were carried out and the experimental values were in a good agreement with the predicted values. The application of present method is promising to develop a probability-based design space for other botanical drug manufacturing process. PMID:26549198

  8. Targeted supplementation design for improved production and quality of enveloped viral particles in insect cell-baculovirus expression system.

    PubMed

    Monteiro, Francisca; Bernal, Vicente; Chaillet, Maxime; Berger, Imre; Alves, Paula M

    2016-09-10

    The recent approval of vaccines and gene therapy products for human use produced in the Insect Cell-Baculovirus Expression Vector System (IC-BEVS) underlines the high potential and versatility of this platform. The interest in developing robust production processes emerges to cope with manufacturing pressure, as well as stringent product quality guidelines. Previously, we addressed the impact of the baculovirus infection on the physiology of insect host cell lines, identifying key cellular pathways enrolled in heterologous gene/protein expression. In the present work, this knowledge was applied to design tailored media supplementation schemes to boost IC-BEVS production yields and quality of enveloped viral particles: influenza VLPs (Inf-VLP) and baculovirus vectors (BV). The addition of reduced glutathione, antioxidants and polyamines increased the cell specific yields of baculovirus particles up to 3 fold. Cholesterol was identified as the most critical system booster, capable of improving 2.5 and 6-fold cell specific yields of BV and Inf-VLPs, respectively. Surprisingly, the combination of polyamines and cholesterol supplementation improved baculovirus stock quality, by preventing the accumulation of non-infectious particles during viral replication while selectively increasing infectious particles production. In addition, the specific yields of both enveloped viral particles, BVs and Inf-VLPs, were also increased. The correlation between supplement addition and systems productivity was extensively analyzed, providing a critical assessment on final product quantity and quality as drivers of bioprocess optimization efforts. PMID:27378622

  9. Interior Design.

    ERIC Educational Resources Information Center

    Texas Tech Univ., Lubbock. Home Economics Curriculum Center.

    This document contains teacher's materials for an eight-unit secondary education vocational home economics course on interior design. The units cover period styles of interiors, furniture and accessories, surface treatments and lighting, appliances and equipment, design and space planning in home and business settings, occupant needs, acquisition…

  10. Universal Design.

    ERIC Educational Resources Information Center

    Rydeen, James E.

    1999-01-01

    Examines universal school design that is both user-friendly for all students and compliant with the Americans with Disabilities Act. This approach provides the basic functional design issues for easy traffic control, as well as orientation and classrooms that are adaptable to future curricular changes. Discusses new standards that impact design…

  11. Batik Designs

    ERIC Educational Resources Information Center

    Henn, Cynthia

    2004-01-01

    In this article, the author describes a unit she implemented on Batik designs. This unit helped second-graders gain an understanding of the batik process while learning about mask designs and the Senegalese culture. Batik has origins in many areas around the world, including Indonesia and West Africa. This fabric-resist process involves the…

  12. Name Design

    ERIC Educational Resources Information Center

    Kim, Nanyoung

    2009-01-01

    This article describes a name design project. The project is one way to teach how repetition makes a composition look harmonious and pleasing without even saying the word, and introduce the concept of "style" that can later be expanded to appreciating different styles of artworks. The main part of the project consists of drawing the chosen design,…

  13. Designing Complexity

    ERIC Educational Resources Information Center

    Glanville, Ranulph

    2007-01-01

    This article considers the nature of complexity and design, as well as relationships between the two, and suggests that design may have much potential as an approach to improving human performance in situations seen as complex. It is developed against two backgrounds. The first is a world view that derives from second order cybernetics and radical…

  14. Designing Skateboards

    ERIC Educational Resources Information Center

    Howard, Jim

    2009-01-01

    Having students buy in to the relevance of a lesson is always a challenge, even in a graphic design classroom. In this article, the author describes an activity on designing skateboards. The most successful element of this project was the addition of assessment and criticism from an outside audience. The inclusion of an outside audience upped the…

  15. Aircraft Design

    NASA Technical Reports Server (NTRS)

    Bowers, Albion H. (Inventor); Uden, Edward (Inventor)

    2016-01-01

    The present invention is an aircraft wing design that creates a bell shaped span load, which results in a negative induced drag (induced thrust) on the outer portion of the wing; such a design obviates the need for rudder control of an aircraft.

  16. Design Dilemma.

    ERIC Educational Resources Information Center

    Miller, Nory

    1980-01-01

    Two projects, the Milford (Pennsylvania) Reservation Solar Conservation Center and Prototype Passive Solar Townhouses, are designed for solar energy--one as a learning center, the other as urban infill housing. (Author/MLF)

  17. Designer Fish.

    ERIC Educational Resources Information Center

    Hall, William R., Jr.

    1990-01-01

    Described is an activity in which students are asked to design a fish that would survive in a natural system. A project to computerize the activity is discussed. The development of this artificial intelligence software is detailed. (CW)

  18. Effects of rhBMP-2 on Sandblasted and Acid Etched Titanium Implant Surfaces on Bone Regeneration and Osseointegration: Spilt-Mouth Designed Pilot Study.

    PubMed

    Kim, Nam-Ho; Lee, So-Hyoun; Ryu, Jae-Jun; Choi, Kyung-Hee; Huh, Jung-Bo

    2015-01-01

    This study was conducted to evaluate effects of rhBMP-2 applied at different concentrations to sandblasted and acid etched (SLA) implants on osseointegration and bone regeneration in a bone defect of beagle dogs as pilot study using split-mouth design. Methods. For experimental groups, SLA implants were coated with different concentrations of rhBMP-2 (0.1, 0.5, and 1 mg/mL). After assessment of surface characteristics and rhBMP-2 releasing profile, the experimental groups and untreated control groups (n = 6 in each group, two animals in each group) were placed in split-mouth designed animal models with buccal open defect. At 8 weeks after implant placement, implant stability quotients (ISQ) values were recorded and vertical bone height (VBH, mm), bone-to-implant contact ratio (BIC, %), and bone volume (BV, %) in the upper 3 mm defect areas were measured. Results. The ISQ values were highest in the 1.0 group. Mean values of VBH (mm), BIC (%), and BV (%) were greater in the 0.5 mg/mL and 1.0 mg/mL groups than those in 0.1 and control groups in buccal defect areas. Conclusion. In the open defect area surrounding the SLA implant, coating with 0.5 and 1.0 mg/mL concentrations of rhBMP-2 was more effective, compared with untreated group, in promoting bone regeneration and osseointegration. PMID:26504807

  19. Effects of rhBMP-2 on Sandblasted and Acid Etched Titanium Implant Surfaces on Bone Regeneration and Osseointegration: Spilt-Mouth Designed Pilot Study

    PubMed Central

    Kim, Nam-Ho; Lee, So-Hyoun; Ryu, Jae-Jun; Choi, Kyung-Hee; Huh, Jung-Bo

    2015-01-01

    This study was conducted to evaluate effects of rhBMP-2 applied at different concentrations to sandblasted and acid etched (SLA) implants on osseointegration and bone regeneration in a bone defect of beagle dogs as pilot study using split-mouth design. Methods. For experimental groups, SLA implants were coated with different concentrations of rhBMP-2 (0.1, 0.5, and 1 mg/mL). After assessment of surface characteristics and rhBMP-2 releasing profile, the experimental groups and untreated control groups (n = 6 in each group, two animals in each group) were placed in split-mouth designed animal models with buccal open defect. At 8 weeks after implant placement, implant stability quotients (ISQ) values were recorded and vertical bone height (VBH, mm), bone-to-implant contact ratio (BIC, %), and bone volume (BV, %) in the upper 3 mm defect areas were measured. Results. The ISQ values were highest in the 1.0 group. Mean values of VBH (mm), BIC (%), and BV (%) were greater in the 0.5 mg/mL and 1.0 mg/mL groups than those in 0.1 and control groups in buccal defect areas. Conclusion. In the open defect area surrounding the SLA implant, coating with 0.5 and 1.0 mg/mL concentrations of rhBMP-2 was more effective, compared with untreated group, in promoting bone regeneration and osseointegration. PMID:26504807

  20. Mechanical design

    NASA Technical Reports Server (NTRS)

    1976-01-01

    Design concepts for a 1000 mw thermal stationary power plant employing the UF6 fueled gas core breeder reactor are examined. Three design combinations-gaseous UF6 core with a solid matrix blanket, gaseous UF6 core with a liquid blanket, and gaseous UF6 core with a circulating blanket were considered. Results show the gaseous UF6 core with a circulating blanket was best suited to the power plant concept.

  1. Ship Design

    NASA Technical Reports Server (NTRS)

    1982-01-01

    Guided missile cruiser equipped with advanced Aegis fleet defense system which automatically tracks hundreds of attacking aircraft or missiles, then fires and guides the ship's own weapons in response. Designed by Ingalls Shipbuilding for the US Navy, the U.S.S. Ticonderoga is the first of four CG-47 cruisers to be constructed. NASTRAN program was used previously in another Navy/Ingalls project involving design and construction of four DDG-993 Kidd Class guided missile destroyers.

  2. Workplace Design

    NASA Technical Reports Server (NTRS)

    1984-01-01

    The Anthropometric Source Book was developed based on Johnson Space Center project of anthropometry, the study of the size, shape and motion characteristics of the human body. Designed primarily for use by NASA, the military services and aerospace contractors, the book was also intended to help non-aerospace engineers, architects, and others engaged in design of clothing, equipment and workplaces. An example of its use by Eastman Kodak Company is the company's application of the data to design efficient, productive and comfortable workplaces for employees in the Rochester, NY processing laboratories. The sourcebook was used to determine such dimensions as leg space, work surface height and thickness, employee reach distances, proper height for computer terminal screen, seat height and knee space.

  3. Design thinking.

    PubMed

    Brown, Tim

    2008-06-01

    In the past, design has most often occurred fairly far downstream in the development process and has focused on making new products aesthetically attractive or enhancing brand perception through smart, evocative advertising. Today, as innovation's terrain expands to encompass human-centered processes and services as well as products, companies are asking designers to create ideas rather than to simply dress them up. Brown, the CEO and president of the innovation and design firm IDEO, is a leading proponent of design thinking--a method of meeting people's needs and desires in a technologically feasible and strategically viable way. In this article he offers several intriguing examples of the discipline at work. One involves a collaboration between frontline employees from health care provider Kaiser Permanente and Brown's firm to reengineer nursing-staff shift changes at four Kaiser hospitals. Close observation of actual shift changes, combined with brainstorming and rapid prototyping, produced new procedures and software that radically streamlined information exchange between shifts. The result was more time for nursing, better-informed patient care, and a happier nursing staff. Another involves the Japanese bicycle components manufacturer Shimano, which worked with IDEO to learn why 90% of American adults don't ride bikes. The interdisciplinary project team discovered that intimidating retail experiences, the complexity and cost of sophisticated bikes, and the danger of cycling on heavily trafficked roads had overshadowed people's happy memories of childhood biking. So the team created a brand concept--"Coasting"--to describe a whole new category of biking and developed new in-store retailing strategies, a public relations campaign to identify safe places to cycle, and a reference design to inspire designers at the companies that went on to manufacture Coasting bikes. PMID:18605031

  4. Pyroshock design

    NASA Astrophysics Data System (ADS)

    Piersol, Allan G.

    2002-05-01

    The structural response velocities produced by pyroshocks are usually too low to cause structural damage beyond the immediate region of the pyrotechnic device where damage is intended. On the other hand, pyroshocks can cause malfunctions of equipment mounted near the pyrotechnic device, particularly equipment containing microelectronic or ceramic elements. These malfunctions are usually the result of the high frequency content (above 2 kHz) of pyroshocks, and are difficult to design against using conventional analysis procedures. On the other hand, adherence to simple design guidelines, which are summarized, can substantially suppress pyroshock-induced failures of equipment.

  5. Collaborative Design

    ERIC Educational Resources Information Center

    Broderick, Debora

    2014-01-01

    This practitioner research study investigates the power of multimodal texts within a real-world context and argues that a participatory culture focused on literary arts offers marginalized high school students opportunities for collaborative design and authoring. Additionally, this article invites educators to rethink the at-risk label. This…

  6. Designer Genes.

    ERIC Educational Resources Information Center

    Miller, Judith; Miller, Mark

    1983-01-01

    Genetic technologies may soon help fill some of the most important needs of humanity from food to energy to health care. The research of major designer genes companies and reasons why the initial mad rush for biotechnology has slowed are reviewed. (SR)

  7. Design Software

    NASA Technical Reports Server (NTRS)

    1991-01-01

    A NASA contractor and Small Business Innovation Research (SBIR) participant has converted its research into commercial software products for auto design, structural analysis and other applications. ViGYAN, Inc., utilizing the aeronautical research principle of computational fluid dynamics, has created - with VGRID3D and VPLOT3D - an easier alternative to conventional structured grids for fluid dynamic calculations.

  8. School Design.

    ERIC Educational Resources Information Center

    Erwin, Clyde A.

    This guide to basic principles of school design presents diagrammatic explanation of various developed standards and planning suggestions. The first section schematically develops patterns of school activity for primary, elementary, and high schools. The second discusses organization of activities--(1) contour adjustment, (2) landscaping, (3)…

  9. Dwelling Designers

    ERIC Educational Resources Information Center

    Szekely, George

    2012-01-01

    Children's inventions go far beyond track housing or Ethan Allen furniture; they foreshadow the most innovative ideas in building forms and interior designs. Children improvise with containers and find places in a home that suggest enticing dwellings. A drawer left open becomes a balcony, soap trays become cots, and the space between twin beds…

  10. Inhibition of endogenous heat shock protein 70 attenuates inducible nitric oxide synthase induction via disruption of heat shock protein 70/Na(+) /H(+) exchanger 1-Ca(2+) -calcium-calmodulin-dependent protein kinase II/transforming growth factor β-activated kinase 1-nuclear factor-κB signals in BV-2 microglia.

    PubMed

    Huang, Chao; Lu, Xu; Wang, Jia; Tong, Lijuan; Jiang, Bo; Zhang, Wei

    2015-08-01

    Inducible nitric oxide synthase (iNOS) critically contributes to inflammation and host defense. The inhibition of heat shock protein 70 (Hsp70) prevents iNOS induction in lipopolysaccharide (LPS)-stimulated macrophages. However, the role and mechanism of endogenous Hsp70 in iNOS induction in microglia remains unclear. This study addresses this issue in BV-2 microglia, showing that Hsp70 inhibition or knockdown prevents LPS-induced iNOS protein expression and nitric oxide production. Real-time PCR experiments showed that LPS-induced iNOS mRNA transcription was blocked by Hsp70 inhibition. Further studies revealed that the inhibition of Hsp70 attenuated LPS-stimulated nuclear translocation and phosphorylation of nuclear factor (NF)-κB as well as the degradation of inhibitor of κB (IκB)-α and phosphorylation of IκB kinase β (IKKβ). This prevention effect of Hsp70 inhibition on IKKβ-NF-κB activation was found to be dependent on the Ca(2+) /calcium-calmodulin-dependent protein kinase II (CaMKII)/transforming growth factor β-activated kinase 1 (TAK1) signals based on the following observations: 1) chelation of intracellular Ca(2+) or inhibition of CaMKII reduced LPS-induced increases in TAK1 phosphorylation and 2) Hsp70 inhibition reduced LPS-induced increases in CaMKII/TAK1 phosphorylation, intracellular pH value, [Ca(2+) ]i , and CaMKII/TAK1 association. Mechanistic studies showed that Hsp70 inhibition disrupted the association between Hsp70 and Na(+) /H(+) exchanger 1 (NHE1), which is an important exchanger responsible for Ca(2+) influx in LPS-stimulated cells. These studies demonstrate that the inhibition of endogenous Hsp70 attenuates the induction of iNOS, which likely occurs through the disruption of NHE1/Hsp70-Ca(2+) -CaMKII/TAK1-NF-κB signals in BV-2 microglia, providing further insight into the functions of Hsp70 in the CNS. PMID:25691123

  11. How to select study designs and parameters to investigate the effect of mouthrinses? Part II: comparisons between the parameters used.

    PubMed

    Lorenz, K; Bruhn, G; Heumann, C; Hoffmann, T; Netuschil, L

    2009-12-01

    A variety of parameters is available to assess the efficacy of oral antiseptics. Most study protocols select the parameters according to the specific study goal or according to preferences of the researchers. Beside general recommendations for home-use studies, no recommendations exist for other study types. Therefore, pre-selected parameters should be compared within several study designs and the most suitable parameters should be recommended for further application. The following parameters were selected before study start: plaque indices (PlI, Silness & Loe 1964, M-QHI, Turesky et al. 1970), plaque area (PlA), bacterial vitality (BV, Netuschil et al. 1989), gingivitis indices (GI, Loe 1967; M-GI, Lobene et al. 1986; BOP, Ainamo & Bay 1975), gingival crevicular fluid, colony forming units, and the discoloration index (DI, Brecx et al. 1993). The parameters were applied in four study designs: eight-hour substantivity studies, four-day plaque re-growth studies, 21-day experimental gingivitis studies, and six-month home-use studies. Pearson correlation coefficients were computed. The highest correlations were found between PlI and M-QHI and between GI and M-GI (p<0.01) in all corresponding studies and treatment groups. Few middle correlations existed between BOP and the other gingival indices. Neither GI nor M-GI correlated with GCF nor did BV with plaque indices. Inconsistent correlations were obtained between PlA and plaque indices and between PlI and GI. It is concluded, that primary parameters for these designs should be one plaque index and/or one gingivitis index to monitor plaque and gingivitis. The other parameters did not yield additional information about the study outcome. PMID:20400799

  12. Special Issue: Philosophy of Design, Design Education and Educational Design.

    ERIC Educational Resources Information Center

    Buchanan, Richard; Borgmann, Albert; Mitcham, Carl; Waks, Leonard J.; Huyke, Hector J.; Kellner, Douglas; Feenberg, Andrew

    2001-01-01

    Articles include: "Philosophy of Design, Design Education, and Educational Design: Introduction to the Special Issue"; "Opaque and Articulate Design"; "The Problem of Character in Design Education: Liberal Arts and Professional Specialization"; "'Dasein' Versus Design: The Problematics of Turning Making into Thinking"; "Donald Schon's Philosophy…

  13. The ARA Mark 3 solar array design and development

    NASA Technical Reports Server (NTRS)

    vanHassel, Rob H. A.

    1996-01-01

    The ARA (Advanced Rigid Array) Mark3 solar array of Fokker Space BV is currently in its final stages of qualification (wing tests to be completed in March, 1996; unit/part tests in April, 1996). With regard to its predecessor, the ARA Mark2, the design has not only been improved in terms of mechanical and electrical performance, but also with regard to production cost and throughput time. This 'state of the art' array is designed to fit the needs of a wide variety of geostationary telecommunications satellites and is qualified for launch on the complete range of medium/large size commercial launchers (Ariane IV & V, Atlas, Delta, Proton, Long March, H2). The first mission to fly the new ARA Mk3 array is Hot Bird 2 (customer: Eutelsat, prime contractor: Matra Marconi Space; launch: mid-1996). In this configuration, its end of life (EOL) power-to-mass ratio is 42 W/kg, with an operational life of more than 12 years. The main mechanisms on a solar array are typically found in the deployment system and in the hold down and release system. During the design and development phase of these mechanisms, extensive engineering and qualification tests have been performed. This paper presents the key design features of these mechanisms and the improvements that were made with regard to their predecessors. It also describes the qualification philosophy on unit/part and wing level. Finally, some of the development items that turned out to be critical, as well as the lessons learned from them, are discussed.

  14. Numerical analysis of modified Central Solenoid insert design

    SciTech Connect

    Khodak, Andrei; Martovetsky, Nicolai; Smirnov, Aleksandre; Titus, Peter

    2015-06-21

    The United States ITER Project Office (USIPO) is responsible for fabrication of the Central Solenoid (CS) for ITER project. The ITER machine is currently under construction by seven parties in Cadarache, France. The CS Insert (CSI) project should provide a verification of the conductor performance in relevant conditions of temperature, field, currents and mechanical strain. The US IPO designed the CSI that will be tested at the Central Solenoid Model Coil (CSMC) Test Facility at JAEA, Naka. To validate the modified design we performed three-dimensional numerical simulations using coupled solver for simultaneous structural, thermal and electromagnetic analysis. Thermal and electromagnetic simulations supported structural calculations providing necessary loads and strains. According to current analysis design of the modified coil satisfies ITER magnet structural design criteria for the following conditions: (1) room temperature, no current, (2) temperature 4K, no current, (3) temperature 4K, current 60 kA direct charge, and (4) temperature 4K, current 60 kA reverse charge. Fatigue life assessment analysis is performed for the alternating conditions of: temperature 4K, no current, and temperature 4K, current 45 kA direct charge. Results of fatigue analysis show that parts of the coil assembly can be qualified for up to 1 million cycles. Distributions of the Current Sharing Temperature (TCS) in the superconductor were obtained from numerical results using parameterization of the critical surface in the form similar to that proposed for ITER. Lastly, special ADPL scripts were developed for ANSYS allowing one-dimensional representation of TCS along the cable, as well as three-dimensional fields of TCS in superconductor material. Published by Elsevier B.V.

  15. Mechanical Design

    SciTech Connect

    Shook, Richard; /Marquette U. /SLAC

    2010-08-25

    The particle beam of the SXR (soft x-ray) beam line in the LCLS (Linac Coherent Light Source) has a high intensity in order to penetrate through samples at the atomic level. However, the intensity is so high that many experiments fail because of severe damage. To correct this issue, attenuators are put into the beam line to reduce this intensity to a level suitable for experimentation. Attenuation is defined as 'the gradual loss in intensity of any flux through a medium' by [1]. It is found that Beryllium and Boron Carbide can survive the intensity of the beam. At very thin films, both of these materials work very well as filters for reducing the beam intensity. Using a total of 12 filters, the first 9 being made of Beryllium and the rest made of Boron Carbide, the beam's energy range of photons can be attenuated between 800 eV and 9000 eV. The design of the filters allows attenuation for different beam intensities so that experiments can obtain different intensities from the beam if desired. The step of attenuation varies, but is relative to the thickness of the filter as a power function of 2. A relationship for this is f(n) = x{sub 0}2{sup n} where n is the step of attenuation desired and x{sub 0} is the initial thickness of the material. To allow for this desired variation, a mechanism must be designed within the test chamber. This is visualized using a 3D computer aided design modeling tool known as Solid Edge.

  16. Designer milk.

    PubMed

    Sabikhi, Latha

    2007-01-01

    Dairy biotechnology is fast gaining ground in the area of altering milk composition for processing and/or animal and human health by employing nutritional and genetic approaches. Modification of the primary structure of casein, alteration in the lipid profile, increased protein recovery, milk containing nutraceuticals, and replacement for infant formula offer several advantages in the area of processing. Less fat in milk, altered fatty acid profiles to include more healthy fatty acids such as CLA and omega-fats, improved amino acid profiles, more protein, less lactose, and absence of beta-lactoglobulin (beta-LG) are some opportunities of "designing" milk for human health benefits. Transgenic technology has also produced farm animals that secrete in their milk, human lactoferrin, lysozyme, and lipase so as to simulate human milk in terms of quality and quantity of these elements that are protective to infants. Cow milk allergenicity in children could be reduced by eliminating the beta-LG gene from bovines. Animals that produce milk containing therapeutic agents such as insulin, plasma proteins, drugs, and vaccines for human health have been genetically engineered. In order to cater to animal health, transgenic animals that express in their mammary glands, various components that work against mastitis have been generated. The ultimate acceptability of the "designer" products will depend on ethical issues such as animal welfare and safety, besides better health benefits and increased profitability of products manufactured by the novel techniques. PMID:17900499

  17. Group Design Problems in Engineering Design Graphics.

    ERIC Educational Resources Information Center

    Kelley, David

    2001-01-01

    Describes group design techniques used within the engineering design graphics sequence at Western Washington University. Engineering and design philosophies such as concurrent engineering place an emphasis on group collaboration for the solving of design problems. (Author/DDR)

  18. Design or "Design"--Envisioning a Future Design Education

    ERIC Educational Resources Information Center

    Sless, David

    2012-01-01

    Challenging the common grand vision of Design, this article considers "design" as a humble re-forming process based on evidence to substantiate its results. The designer is likened to a tinker who respects previous iterations of a design and seeks to retain what is useful while improving its performance. A design process is offered, illustrated…

  19. Apply Design Patterns to Refactor Software Design

    NASA Technical Reports Server (NTRS)

    Baggs, Rhoda; Shaykhian, Gholam Ali

    2007-01-01

    Refactoring software design is a method of changing software design while explicitly preserving its unique design functionalities. Presented approach is to utilize design patterns as the basis for refactoring software design. Comparison of a design solution will be made through C++ programming language examples to exploit this approach. Developing reusable component will be discussed, the paper presents that the construction of such components can diminish the added burden of both refactoring and the use of design patterns.

  20. Exploring Pupils' Beliefs about Designers and Designing

    ERIC Educational Resources Information Center

    Trebell, Donna

    2011-01-01

    The purpose of this paper is to report on an investigation into pupil beliefs about designers and designing conducted as part of a research project focusing on Designerly Activity in Secondary Design and Technology which builds upon a pilot study (Barlex and Trebell in "Int J Technol Design Educ," 2007). Four research questions drove this element…

  1. Characterization of swarming motility in Rhizobium leguminosarum bv. viciae.

    PubMed

    Tambalo, Dinah D; Yost, Christopher K; Hynes, Michael F

    2010-06-01

    We have characterized swarming motility in Rhizobium leguminosarum strains 3841 and VF39SM. Swarming was dependent on growth on energy-rich media, and both agar concentration and incubation temperature were critical parameters for surface migration. A cell density-dependent lag period was observed before swarming motility was initiated. Surface migration began 3-5 days after inoculation and a full swarming phenotype was observed 3 weeks after inoculation. The swarming front was preceded by a clear extracellular matrix, from which we failed to detect surfactants. The edge of the swarming front formed by VF39SM was characterized by hyperflagellated cells arranged in rafts, whereas the cells at the point of inoculation were indistinguishable from vegetative cells. Swarmer cells formed by 3841, in contrast, showed a minor increase in flagellation, with each swarmer cell exhibiting an average of three flagellar filaments, compared with an average of two flagella per vegetative cell. Reflective of their hyperflagellation, the VF39SM swarmer cells demonstrated an increased expression of flagellar genes. VF39SM swarmed better than 3841 under all the conditions tested, and the additional flagellation in VF39SM swarm cells may contribute to this difference. Metabolism of the supplemented carbon source appeared to be necessary for surface migration as strains incapable of utilizing the carbon source failed to swarm. We also observed that swarmer cells have increased resistance to several antibiotics. PMID:20455952

  2. What Are the Treatments for Bacterial Vaginosis (BV)?

    MedlinePlus

    ... NICHD in the News NICHD Spotlights Media Resources Interviews & Selected Staff Profiles Multimedia About NICHD Institute Overview Organization Budget & Appropriations Advisory Groups FOIA Jobs at NICHD Meetings, Conferences & Events Partnering & Donating to ...

  3. System design projects for undergraduate design education

    NASA Technical Reports Server (NTRS)

    Batill, S. M.; Pinkelman, J.

    1993-01-01

    Design education has received considerable in the recent past. This paper is intended to address one aspect of undergraduate design education and that is the selection and development of the design project for a capstone design course. Specific goals for a capstone design course are presented and their influence on the project selection are discussed. The evolution of a series of projects based upon the design of remotely piloted aircraft is presented along with students' perspective on the capstone experience.

  4. Differentiation of Brucella abortus bv. 1, 2, and 4, Brucella melitensis, Brucella ovis, and Brucella suis bv. 1 by PCR.

    PubMed Central

    Bricker, B J; Halling, S M

    1994-01-01

    Several PCR assays which identify the genus Brucella but do not discriminate among species have been reported. We describe a PCR assay that comprises five oligonucleotide primers which can identify selected biovars of four species of Brucella. Individual biovars within a species are not differentiated. The assay can identify three biovars (1, 2, and 4) of B. abortus, all three biovars of B. melitensis, biovar 1 of B. suis, and all B. ovis biovars. These biovars include all of the Brucella species typically isolated from cattle in the United States, a goal of the present research. The assay exploits the polymorphism arising from species-specific localization of the genetic element IS711 in the Brucella chromosome. Identity is determined by the size(s) of the product(s) amplified from primers hybridizing at various distances from the element. The performance of the assay with U.S. field isolates was highly effective. When 107 field isolates were screened by the described method, there was 100% agreement with the identifications made by conventional methods. Six closely related bacteria (Agrobacterium radiobacter, Agrobacterium rhizogenes, Ochrobactrum anthropi, Rhizobium leguminosarum, Rhizobium meliloti, and Rhodospirillum rubrum) and two control bacteria (Bordetella bronchiseptica and Escherichia coli) tested negative by the assay. Images PMID:7852552

  5. Role-Based Design: Design Experiences

    ERIC Educational Resources Information Center

    Miller, Charles; Hokanson, Brad; Doering, Aaron; Brandt, Tom

    2010-01-01

    This is the fourth and final installment in a series of articles presenting a new outlook on the methods of instructional design. These articles examine the nature of the process of instructional design and are meant to stimulate discussion about the roles of designers in the fields of instructional design, the learning sciences, and interaction…

  6. Adaptive Immune Responses Elicited by Baculovirus and Impacts on Subsequent Transgene Expression In Vivo

    PubMed Central

    Luo, Wen-Yi; Lin, Shih-Yeh; Lo, Kai-Wei; Lu, Chia-Hsin; Hung, Chang-Lin; Chen, Chi-Yuan; Chang, Chien-Chung

    2013-01-01

    Baculovirus (BV) is a promising gene therapy vector and typically requires readministration because BV mediates transient expression. However, how the prime-boost regimen triggers BV-specific adaptive responses and their impacts on BV readministration, transgene expression, and therapeutic/vaccine efficacy remain unknown. Here we unraveled that BV injection into BALB/c mice induced the production of BV-specific antibodies, including IgG1 and IgG2a, which could neutralize BV by antagonizing the envelope protein gp64 and impede BV-mediated transgene expression. Moreover, humans did not possess preexisting anti-BV antibodies. BV injection also elicited BV-specific Th1 and Th2 responses as well as CD4+ and CD8+ T cell responses. gp64 was a primary immunogen to activate the antibody and CD8+ T cell response, with its peptide at positions 457 to 465 (peptide 457-465) being the major histocompatibility complex (MHC) class I epitope to stimulate CD8+ T cell and cytotoxic responses. Nonetheless, a hybrid Sleeping Beauty-based BV enabled long-term expression for >1 year by a single injection, indicating that the T cell responses did not completely eradicate BV-transduced cells and implicating the potential of this hybrid BV vector for gene therapy. These data unveil that BV injection triggers adaptive immunity and benefit rational design of BV administration schemes for gene therapy and vaccination. PMID:23408634

  7. Information Design: A Bibliography.

    ERIC Educational Resources Information Center

    Albers, Michael J.; Lisberg, Beth Conney

    2000-01-01

    Presents a 17-item annotated list of essential books on information design chosen by members of the InfoDesign e-mail list. Includes a 113-item unannotated bibliography of additional works, on topics of creativity and critical thinking; visual thinking; graphic design; infographics; information design; instructional design; interface design;…

  8. Intelligent design system for design automation

    NASA Astrophysics Data System (ADS)

    Shakeri, Cirrus; Deif, Ismail; Katragadda, Prasanna; Knutson, Stanley

    2000-10-01

    In order to succeed in today's global, competitive market, companies need continuous improvements in their product development processes. These improvements should result in expending fewer resources on the design process while achieving better quality. Automating the design process reduces resources needed and allows designers to spend more time on creative aspects that improve the quality of design. For the last three decades, engineers and designers have been searching for better ways to automate the product development process. For certain classes of design problems, which cover a large portion of real world design situations, the process can be automated using knowledge-based systems. These are design problems in which the knowledge sources are known in advance. Using techniques from Knowledge-Based Engineering, knowledge is codified and inserted into a knowledge-based system. The system activates the design knowledge, automatically generating designs that satisfy the design constraints. To increase the return on investment of building automated design systems, Knowledge management methodologies and techniques are required for capturing, formalizing, storing, and searching design knowledge.

  9. Looking for design in materials design.

    PubMed

    Eberhart, M E; Clougherty, D P

    2004-10-01

    Despite great advances in computation, materials design is still science fiction. The construction of structure-property relations on the quantum scale will turn computational empiricism into true design. PMID:15467684

  10. Looking for design in materials design

    NASA Astrophysics Data System (ADS)

    Eberhart, M. E.; Clougherty, D. P.

    2004-10-01

    Despite great advances in computation, materials design is still science fiction. The construction of structure-property relations on the quantum scale will turn computational empiricism into true design.

  11. Nickel hydrogen cell design: A designer's aspect

    NASA Technical Reports Server (NTRS)

    Rehm, Raymond

    1992-01-01

    Information is given to give insight into the methodology of nickel hydrogen cell design and the decipherment of the battery cell reference guide that was distributed to many of Gates Energy Products' customers. Cell design, stacking design, charge capacity, and dynamic response are discussed in general terms.

  12. Existential Design Applied in Universal Design Settings.

    PubMed

    Torkildsby, Anne Britt

    2016-01-01

    The critical design method aims to discuss ways of opening up the (design) brief when planning, designing, building, operating and maintaining the future of the built environment - public as well as private, indoor as well as outdoor. Focusing on "designials" (fundamental forms of design being), the methodology intends to illustrate the fact that objects; including buildings, parks, transportation systems, etc. may directly encroach upon certain "existentials" (fundamental forms of human being) - thus shed light on how a design process is normally conducted, and furthermore, how that affects people's existential well-being. PMID:27534284

  13. VLSI system design

    NASA Astrophysics Data System (ADS)

    Muroga, S.

    A complete picture of LSI/VLSI system design is provided, encompassing both engineering and economic considerations. The subjects discussed include: cost analysis based on production volume, yield, chip size, design manpower and other factors; bipolar and MOS logic families, logic design procedures, and mask designs; use of ROMs and PLAs in logic design, along with design algorithms; a survey of CAD used in LSI/VLSI chip design. Also covered are: full-custom and semicustom designs; microprocessor and dedicated processor chips; system design and hardware-software tradeoffs; LSI/VLSI technological trends; new products realized by LSI/VLSI technology; future production and management problems.

  14. Future integrated design process

    NASA Technical Reports Server (NTRS)

    Meyer, D. D.

    1980-01-01

    The design process is one of the sources used to produce requirements for a computer system to integrate and manage product design data, program management information, and technical computation and engineering data management activities of the aerospace design process. Design activities were grouped chronologically and explored for activity type, activity interface, data quantity, and data flow. The work was based on analysis of the design process of several typical aerospace products, including both conventional and supersonic airplanes and a hydrofoil design. Activities examined included research, preliminary design, detail design, manufacturing interface, product verification, and product support. The design process was then described in an IPAD environment--the future.

  15. Effects of sample survey design on the accuracy of classification tree models in species distribution models

    USGS Publications Warehouse

    Edwards, T.C., Jr.; Cutler, D.R.; Zimmermann, N.E.; Geiser, L.; Moisen, G.G.

    2006-01-01

    We evaluated the effects of probabilistic (hereafter DESIGN) and non-probabilistic (PURPOSIVE) sample surveys on resultant classification tree models for predicting the presence of four lichen species in the Pacific Northwest, USA. Models derived from both survey forms were assessed using an independent data set (EVALUATION). Measures of accuracy as gauged by resubstitution rates were similar for each lichen species irrespective of the underlying sample survey form. Cross-validation estimates of prediction accuracies were lower than resubstitution accuracies for all species and both design types, and in all cases were closer to the true prediction accuracies based on the EVALUATION data set. We argue that greater emphasis should be placed on calculating and reporting cross-validation accuracy rates rather than simple resubstitution accuracy rates. Evaluation of the DESIGN and PURPOSIVE tree models on the EVALUATION data set shows significantly lower prediction accuracy for the PURPOSIVE tree models relative to the DESIGN models, indicating that non-probabilistic sample surveys may generate models with limited predictive capability. These differences were consistent across all four lichen species, with 11 of the 12 possible species and sample survey type comparisons having significantly lower accuracy rates. Some differences in accuracy were as large as 50%. The classification tree structures also differed considerably both among and within the modelled species, depending on the sample survey form. Overlap in the predictor variables selected by the DESIGN and PURPOSIVE tree models ranged from only 20% to 38%, indicating the classification trees fit the two evaluated survey forms on different sets of predictor variables. The magnitude of these differences in predictor variables throws doubt on ecological interpretation derived from prediction models based on non-probabilistic sample surveys. ?? 2006 Elsevier B.V. All rights reserved.

  16. Virtual Bridge Design Challenge

    ERIC Educational Resources Information Center

    Mitts, Charles R.

    2013-01-01

    This design/problem-solving activity challenges students to design a replacement bridge for one that has been designated as either structurally deficient or functionally obsolete. The Aycock MS Technology/STEM Magnet Program Virtual Bridge Design Challenge is an authentic introduction to the engineering design process. It is a socially relevant…

  17. Software Design Analyzer System

    NASA Technical Reports Server (NTRS)

    Tausworthe, R. C.

    1985-01-01

    CRISP80 software design analyzer system a set of programs that supports top-down, hierarchic, modular structured design, and programing methodologies. CRISP80 allows for expression of design as picture of program.

  18. Solar Control design package

    NASA Technical Reports Server (NTRS)

    1978-01-01

    Information used in the evaluation of design of Solar Control's solar heating and cooling system controller and the Solarstat is given. Some of the information includes system performance specifications, design data brochures, and detailed design drawings.

  19. Design Activity Framework for Visualization Design.

    PubMed

    McKenna, Sean; Mazur, Dominika; Agutter, James; Meyer, Miriah

    2014-12-01

    An important aspect in visualization design is the connection between what a designer does and the decisions the designer makes. Existing design process models, however, do not explicitly link back to models for visualization design decisions. We bridge this gap by introducing the design activity framework, a process model that explicitly connects to the nested model, a well-known visualization design decision model. The framework includes four overlapping activities that characterize the design process, with each activity explicating outcomes related to the nested model. Additionally, we describe and characterize a list of exemplar methods and how they overlap among these activities. The design activity framework is the result of reflective discussions from a collaboration on a visualization redesign project, the details of which we describe to ground the framework in a real-world design process. Lastly, from this redesign project we provide several research outcomes in the domain of cybersecurity, including an extended data abstraction and rich opportunities for future visualization research. PMID:26356933

  20. Printed Circuit Board Design with HDL Designer

    NASA Technical Reports Server (NTRS)

    Winkert, Thomas K.; LaFourcade, Teresa

    2004-01-01

    Staying up to date with the latest CAD tools both from a cost and time perspective is difficult. Within a given organization there may be experts in Printed Circuit Board Design tools and experts in FPGA/VHDL tools. Wouldn't it be great to have someone familiar with HDL Designer be able to design PCBs without having to learn another tool? This paper describes a limited experiment to do this.

  1. Solar Design Workbook

    SciTech Connect

    Franta, G.; Baylin, F.; Crowther, R.; Dubin, F.; Grace, A., Griffith, J.W.; Holtz, M.; Kutscher, C.; Nordham, D.; Selkowitz, S.; Villecco, M.

    1981-06-01

    This Solar Design Workbook presents solar building design applications for commercial buildir^s. The book is divided into four sections. The first section describes the variety of solar applications in buildings including conservation aspects, solar fundamentals, passive systems, active systems, daylighting, and other solar options. Solar system design evaluation techniques including considerations for building energy requirements, passive systems, active systems, and economics are presented in Section II. The third section attempts to assist the designer in the building design process for energy conservation and solar applications including options and considerations for pre-design, design, and post-design phases. The information required for the solar design proee^ has not been fully developed at this time. Therefore, Section III is incomplete, but an overview of the considerations with some of the design proces elements is presented. Section IV illustrates ease studies that utilize solar applications in the building design.

  2. DOE handbook: Design considerations

    SciTech Connect

    1999-04-01

    The Design Considerations Handbook includes information and suggestions for the design of systems typical to nuclear facilities, information specific to various types of special facilities, and information useful to various design disciplines. The handbook is presented in two parts. Part 1, which addresses design considerations, includes two sections. The first addresses the design of systems typically used in nuclear facilities to control radiation or radioactive materials. Specifically, this part addresses the design of confinement systems and radiation protection and effluent monitoring systems. The second section of Part 1 addresses the design of special facilities (i.e., specific types of nonreactor nuclear facilities). The specific design considerations provided in this section were developed from review of DOE 6430.1A and are supplemented with specific suggestions and considerations from designers with experience designing and operating such facilities. Part 2 of the Design Considerations Handbook describes good practices and design principles that should be considered in specific design disciplines, such as mechanical systems and electrical systems. These good practices are based on specific experiences in the design of nuclear facilities by design engineers with related experience. This part of the Design Considerations Handbook contains five sections, each of which applies to a particular engineering discipline.

  3. Designing Award Winning Graphics.

    ERIC Educational Resources Information Center

    Kintigh, Cynthia

    1990-01-01

    Graphic designers, marketing specialists, and campus activities professionals who have won awards for the design of campus programing publicity offer tips in the process of designing successful promotional items, including ingredients of winning pieces and aspects of a productive designer-client relationship. (MSE)

  4. Document Design: Part 1.

    ERIC Educational Resources Information Center

    Andrews, Deborah C., Ed.; Dyrud, Marilyn, Ed.

    1996-01-01

    Presents four articles that provide suggestions for teaching document design: (1) "Teaching the Rhetoric of Document Design" (Michael J. Hassett); (2) "Teaching by Example: Suggestions for Assignment Design" (Marilyn A. Dyrud); (3) "Teaching the Page as a Visual Unit" (Bill Hart-Davidson); and (4) "Designing a Home Page for the Web" (Lynette…

  5. Designing Learning through Learning to Design

    ERIC Educational Resources Information Center

    Mishra, Punya; Girod, Mark

    2006-01-01

    This paper represents a conversation between a high school science teacher and a university researcher as they found common ground in the theory and experiences of designing powerful learning experiences. The teacher describes an instructional unit in which students designed a complex, interactive display showing what life may have been like…

  6. Designing Learning through Learning To Design.

    ERIC Educational Resources Information Center

    Girod, Mark; Mishra, Punya

    This paper emerged from a conversation between a high school science teacher and a university researcher as they found common ground in the theory and experiences of designing transformative learning experiences. The teacher describes an instructional unit in which students designed a complex, interactive display showing what life may have been…

  7. Applying Software Design Methodology to Instructional Design

    ERIC Educational Resources Information Center

    East, J. Philip

    2004-01-01

    The premise of this paper is that computer science has much to offer the endeavor of instructional improvement. Software design processes employed in computer science for developing software can be used for planning instruction and should improve instruction in much the same manner that design processes appear to have improved software. Techniques…

  8. Designing Design Challenges: Getting the Details Right

    ERIC Educational Resources Information Center

    Meyer, Daniel

    2012-01-01

    In looking at successful inquiry activities, patterns in pedagogical approach emerge (Meyer et al. 2011). This article discusses one such approach--the design challenge. A design challenge can be defined as an activity in which students are given an explicit task to create a product that meets a defined goal. However, simply asking students to…

  9. Design for reflection.

    PubMed

    Bagnara, Sebastiano; Pozzi, Simone

    2012-01-01

    Since a few years, a number of academic papers have been proposing to shift from user-centered design to human-centered (or person) design. In this contribution, we discuss as the common tread underlying these works the idea that design should also address the reflective part of our human experience, and not only aim to maximize the experiential aspects. Our review is complemented with examples derived from the internet world and from ICT consumer products. The main research areas we see as promising for the approach of "design for reflection" are: design for pauses, design for detachment, design for serendipity. PMID:22316867

  10. Novel fundus camera design

    NASA Astrophysics Data System (ADS)

    Dehoog, Edward A.

    A fundus camera a complex optical system that makes use of the principle of reflex free indirect ophthalmoscopy to image the retina. Despite being in existence as early as 1900's, little has changed in the design of a fundus camera and there is minimal information about the design principles utilized. Parameters and specifications involved in the design of fundus camera are determined and their affect on system performance are discussed. Fundus cameras incorporating different design methods are modeled and a performance evaluation based on design parameters is used to determine the effectiveness of each design strategy. By determining the design principles involved in the fundus camera, new cameras can be designed to include specific imaging modalities such as optical coherence tomography, imaging spectroscopy and imaging polarimetry to gather additional information about properties and structure of the retina. Design principles utilized to incorporate such modalities into fundus camera systems are discussed. Design, implementation and testing of a snapshot polarimeter fundus camera are demonstrated.

  11. Software Architecture Design Reasoning

    NASA Astrophysics Data System (ADS)

    Tang, Antony; van Vliet, Hans

    Despite recent advancements in software architecture knowledge management and design rationale modeling, industrial practice is behind in adopting these methods. The lack of empirical proofs and the lack of a practical process that can be easily incorporated by practitioners are some of the hindrance for adoptions. In particular, the process to support systematic design reasoning is not available. To rectify this issue, we propose a design reasoning process to help architects cope with an architectural design environment where design concerns are cross-cutting and diversified.We use an industrial case study to validate that the design reasoning process can help improve the quality of software architecture design. The results have indicated that associating design concerns and identifying design options are important steps in design reasoning.

  12. Reliable Design Versus Trust

    NASA Technical Reports Server (NTRS)

    Berg, Melanie; LaBel, Kenneth A.

    2016-01-01

    This presentation focuses on reliability and trust for the users portion of the FPGA design flow. It is assumed that the manufacturer prior to hand-off to the user tests FPGA internal components. The objective is to present the challenges of creating reliable and trusted designs. The following will be addressed: What makes a design vulnerable to functional flaws (reliability) or attackers (trust)? What are the challenges for verifying a reliable design versus a trusted design?

  13. Control system design guide

    SciTech Connect

    Sellers, David; Friedman, Hannah; Haasl, Tudi; Bourassa, Norman; Piette, Mary Ann

    2003-05-01

    The ''Control System Design Guide'' (Design Guide) provides methods and recommendations for the control system design process and control point selection and installation. Control systems are often the most problematic system in a building. A good design process that takes into account maintenance, operation, and commissioning can lead to a smoothly operating and efficient building. To this end, the Design Guide provides a toolbox of templates for improving control system design and specification. HVAC designers are the primary audience for the Design Guide. The control design process it presents will help produce well-designed control systems that achieve efficient and robust operation. The spreadsheet examples for control valve schedules, damper schedules, and points lists can streamline the use of the control system design concepts set forth in the Design Guide by providing convenient starting points from which designers can build. Although each reader brings their own unique questions to the text, the Design Guide contains information that designers, commissioning providers, operators, and owners will find useful.

  14. A synthetic design environment for ship design

    NASA Technical Reports Server (NTRS)

    Chipman, Richard R.

    1995-01-01

    Rapid advances in computer science and information system technology have made possible the creation of synthetic design environments (SDE) which use virtual prototypes to increase the efficiency and agility of the design process. This next generation of computer-based design tools will rely heavily on simulation and advanced visualization techniques to enable integrated product and process teams to concurrently conceptualize, design, and test a product and its fabrication processes. This paper summarizes a successful demonstration of the feasibility of using a simulation based design environment in the shipbuilding industry. As computer science and information science technologies have evolved, there have been many attempts to apply and integrate the new capabilities into systems for the improvement of the process of design. We see the benefits of those efforts in the abundance of highly reliable, technologically complex products and services in the modern marketplace. Furthermore, the computer-based technologies have been so cost effective that the improvements embodied in modern products have been accompanied by lowered costs. Today the state-of-the-art in computerized design has advanced so dramatically that the focus is no longer on merely improving design methodology; rather the goal is to revolutionize the entire process by which complex products are conceived, designed, fabricated, tested, deployed, operated, maintained, refurbished and eventually decommissioned. By concurrently addressing all life-cycle issues, the basic decision making process within an enterprise will be improved dramatically, leading to new levels of quality, innovation, efficiency, and customer responsiveness. By integrating functions and people with an enterprise, such systems will change the fundamental way American industries are organized, creating companies that are more competitive, creative, and productive.

  15. Applying Software Design Methodology to Instructional Design

    NASA Astrophysics Data System (ADS)

    East, J. Philip

    2004-12-01

    The premise of this paper is that computer science has much to offer the endeavor of instructional improvement. Software design processes employed in computer science for developing software can be used for planning instruction and should improve instruction in much the same manner that design processes appear to have improved software. Techniques for examining the software development process can be applied to an examination of the instructional process. Furthermore, the computer science discipline is particularly well suited to these tasks. Thus, computer science can develop instructional design expertise for export to other disciplines to improve education in all disciplines and, eventually, at all levels.

  16. Radiological design guide

    SciTech Connect

    Evans, R.A.

    1994-08-16

    The purpose of this design guide is to provide radiological safety requirements, standards, and information necessary for designing facilities that will operate without unacceptable risk to personnel, the public, or the environment as required by the US Department of Energy (DOE). This design guide, together with WHC-CM-4-29, Nuclear Criticality Safety, WHC-CM-4-46, Nonreactor Facility Safety Analysis, and WHC-CM-7-5, Environmental Compliance, covers the radiation safety design requirements at Westinghouse Hanford Company (WHC). This design guide applies to the design of all new facilities. The WHC organization with line responsibility for design shall determine to what extent this design guide shall apply to the modifications to existing facilities. In making this determination, consideration shall include a cost versus benefit study. Specifically, facilities that store, handle, or process radioactive materials will be covered. This design guide replaces WHC-CM-4-9 and is designated a living document. This design guide is intended for design purposes only. Design criteria are different from operational criteria and often more stringent. Criteria that might be acceptable for operations might not be adequate for design.

  17. Improving designer productivity

    NASA Technical Reports Server (NTRS)

    Hill, Gary C.

    1992-01-01

    Designer and design team productivity improves with skill, experience, and the tools available. The design process involves numerous trials and errors, analyses, refinements, and addition of details. Computerized tools have greatly speeded the analysis, and now new theories and methods, emerging under the label Artificial Intelligence (AI), are being used to automate skill and experience. These tools improve designer productivity by capturing experience, emulating recognized skillful designers, and making the essence of complex programs easier to grasp. This paper outlines the aircraft design process in today's technology and business climate, presenting some of the challenges ahead and some of the promising AI methods for meeting those challenges.

  18. Space Station design integration

    NASA Technical Reports Server (NTRS)

    Carlisle, Richard F.

    1988-01-01

    This paper discusses the top Program level design integration process which involves the integration of a US Space Station manned base that consists of both US and international Elements. It explains the form and function of the Program Requirements Review (PRR), which certifies that the program is ready for preliminary design, the Program Design Review (PDR), which certifies the program is ready to start the detail design, and the Critical Design Review (CDR), which certifies that the program is completing a design that meets the Program objectives. The paper also discusses experience, status to date, and plans for continued system integration through manufacturing, testing and final verification of the Space Station system performance.

  19. Photonic Design for Photovoltaics

    SciTech Connect

    Kosten, E.; Callahan, D.; Horowitz, K.; Pala, R.; Atwater, H.

    2014-08-28

    We describe photonic design approaches for silicon photovoltaics including i) trapezoidal broadband light trapping structures ii) broadband light trapping with photonic crystal superlattices iii) III-V/Si nanowire arrays designed for broadband light trapping.

  20. Energy design for architects

    SciTech Connect

    Shaw, A.

    1989-01-01

    This book contains techniques for energy efficiency in architectural design. Many aspects are covered including: cost; comfort and health; energy use; the design process; and analytical techniques. 202 figs. (JF)

  1. Design software for reuse

    NASA Technical Reports Server (NTRS)

    Tracz, Will

    1990-01-01

    Viewgraphs are presented on the designing of software for reuse. Topics include terminology, software reuse maxims, the science of programming, an interface design example, a modularization example, and reuse and implementation guidelines.

  2. Computer Lens Design Program

    NASA Astrophysics Data System (ADS)

    Shiue, S. G.; Chang, M. W.

    1986-02-01

    An interactive computer lens design program has been developed. It has capabilities for editing lens data, optimizing zoom lens, evaluating image qualities, etc.. A Tessar lens and an IR zoom telescope designed by using this program are discussed.

  3. Book Design, Part I.

    ERIC Educational Resources Information Center

    Harms, Jeanne McClain; Lettow, Lucille

    1996-01-01

    Encourages teachers or school librarians to conduct a lesson in visual literacy by having children examine book design. Discusses book jackets and endpapers as book design elements, and highlights illustrations from five children's picture books. (PEN)

  4. Encouraging Creativity in Design.

    ERIC Educational Resources Information Center

    Kawenski, Mary

    1991-01-01

    This article describes a six-week course for design students called "Needs Awareness and Design" which stresses the development of creative thinking skills. Brainstorming is recommended for identifying many ideas, and synectics is stressed for actual problem solving. (DB)

  5. Medicines by Design

    MedlinePlus

    ... Education > Medicines By Design Medicines By Design Spotlight Nature's Medicine Cabinet A Medicine's Life Inside the Body ... CYP 450 enzymes » more Chapter 3: Drugs from Nature, Then and Now Drugs from plants, oceans and ...

  6. Nutrient Control Design Manual

    EPA Science Inventory

    The Nutrient Control Design Manual will present an extensive state-of-the-technology review of the engineering design and operation of nitrogen and phosphorous control technologies and techniques applied at municipal wastewater treatment plants (WWTPs). This manual will present ...

  7. Education for Urban Design

    ERIC Educational Resources Information Center

    Eckstut, Stanton

    1978-01-01

    Presents 39 questions concerning urban design educational programs to be discussed at a workshop. The questions represent five groups: schools with programs, schools wanting to establish programs, practitioners, students, and the AIA committee on urban planning and design. (MA)

  8. Proxemics and Design

    ERIC Educational Resources Information Center

    Hall, Edward T.

    1971-01-01

    Proxemics deals with man's use and structuring of space, particularly the unconscious patterns that deeply influence life. It can never tell the designer how to design but can tell him important things to consider. (Author/PR)

  9. Conceptual design optimization study

    NASA Technical Reports Server (NTRS)

    Hollowell, S. J.; Beeman, E. R., II; Hiyama, R. M.

    1990-01-01

    The feasibility of applying multilevel functional decomposition and optimization techniques to conceptual design of advanced fighter aircraft was investigated. Applying the functional decomposition techniques to the conceptual design phase appears to be feasible. The initial implementation of the modified design process will optimize wing design variables. A hybrid approach, combining functional decomposition techniques for generation of aerodynamic and mass properties linear sensitivity derivatives with existing techniques for sizing mission performance and optimization, is proposed.

  10. Spacelab EMC design

    NASA Astrophysics Data System (ADS)

    Rempke, H.

    1982-07-01

    Spacelab electrical bonds, grounding, power filters, harness design and safety margin/signal interfaces of EMC design features are discussed. Electromagnetic compatibility experience acquired with Spacelab is summarized. It is argued that MIL-STD-461 is useful only as a starting point for design. Design requirements should be established for each system, and detailed definitions of interfaces should be given to contractors. The combination of EMC and power quality requirements into one specification is suggested.

  11. Science sequence design

    NASA Technical Reports Server (NTRS)

    Koskela, P. E.; Bollman, W. E.; Freeman, J. E.; Helton, M. R.; Reichert, R. J.; Travers, E. S.; Zawacki, S. J.

    1973-01-01

    The activities of the following members of the Navigation Team are recorded: the Science Sequence Design Group, responsible for preparing the final science sequence designs; the Advanced Sequence Planning Group, responsible for sequence planning; and the Science Recommendation Team (SRT) representatives, responsible for conducting the necessary sequence design interfaces with the teams during the mission. The interface task included science support in both advance planning and daily operations. Science sequences designed during the mission are also discussed.

  12. Power Station Design

    NASA Technical Reports Server (NTRS)

    1985-01-01

    Kuljian Corporation provides design engineering and construction management services for power generating plants in more than 20 countries. They used WASP (Calculating Water and Steam Properties), a COSMIC program to optimize power station design. This enabled the company to substantially reduce lead time and software cost in a recent design project.

  13. Computer Guided Instructional Design.

    ERIC Educational Resources Information Center

    Merrill, M. David; Wood, Larry E.

    1984-01-01

    Describes preliminary efforts to create the Lesson Design System, a computer-guided instructional design system written in Pascal for Apple microcomputers. Its content outline, strategy, display, and online lesson editors correspond roughly to instructional design phases of content and strategy analysis, display creation, and computer programing…

  14. Designing a Good Graph.

    ERIC Educational Resources Information Center

    Vinberg, Anders

    Although computer graphics professionals usually consider only technical graphic design issues, recent improvements may make the only limiting design factors the user's purpose, imagination, style, and taste rather than computer hardware or software technology. Computer graphics designers can be helped to avoid pitfalls by understanding the visual…

  15. Designing Safe Schools.

    ERIC Educational Resources Information Center

    Atlas, Randall

    Incorporating the principles and practices of crime prevention through environmental design (CPTED) in the design and remodeling of schools can contribute to the safety of the school while reducing the target-hardening and fortressing effects of a bunker mentality. The basic CPTED premise is that through the effective use and design of the built…

  16. Nature's Design Rules.

    ERIC Educational Resources Information Center

    Reicher, Dan

    2000-01-01

    Discusses school design considerations for energy-efficient schools that provide learning environments that lead to improved student performance. Design myths are addressed as are use of daylighting and designing schools that can teach students and adults about the importance of conserving energy and money. Two online resources are included. (GR)

  17. Designing synthetic biology.

    PubMed

    Agapakis, Christina M

    2014-03-21

    Synthetic biology is frequently defined as the application of engineering design principles to biology. Such principles are intended to streamline the practice of biological engineering, to shorten the time required to design, build, and test synthetic gene networks. This streamlining of iterative design cycles can facilitate the future construction of biological systems for a range of applications in the production of fuels, foods, materials, and medicines. The promise of these potential applications as well as the emphasis on design has prompted critical reflection on synthetic biology from design theorists and practicing designers from many fields, who can bring valuable perspectives to the discipline. While interdisciplinary connections between biologists and engineers have built synthetic biology via the science and the technology of biology, interdisciplinary collaboration with artists, designers, and social theorists can provide insight on the connections between technology and society. Such collaborations can open up new avenues and new principles for research and design, as well as shed new light on the challenging context-dependence-both biological and social-that face living technologies at many scales. This review is inspired by the session titled "Design and Synthetic Biology: Connecting People and Technology" at Synthetic Biology 6.0 and covers a range of literature on design practice in synthetic biology and beyond. Critical engagement with how design is used to shape the discipline opens up new possibilities for how we might design the future of synthetic biology. PMID:24156739

  18. Designing for Mathematical Abstraction

    ERIC Educational Resources Information Center

    Pratt, Dave; Noss, Richard

    2010-01-01

    Our focus is on the design of systems (pedagogical, technical, social) that encourage mathematical abstraction, a process we refer to as "designing for abstraction." In this paper, we draw on detailed design experiments from our research on children's understanding about chance and distribution to re-present this work as a case study in designing…

  19. Turbine design review text

    NASA Technical Reports Server (NTRS)

    1975-01-01

    Three-volume publication covers theoretical, design, and performance aspects of turbines. Volumes cover thermodynamic and fluid-dynamic concepts, velocity diagram design, turbine blade aerodynamic design, turbine energy losses, supersonic turbines, radial-inflow turbines, turbine cooling, and aerodynamic performance testing.

  20. Universal Design Problem Solving

    ERIC Educational Resources Information Center

    Sterling, Mary C.

    2004-01-01

    Universal design is made up of four elements: accessibility, adaptability, aesthetics, and affordability. This article addresses the concept of universal design problem solving through experiential learning for an interior design studio course in postsecondary education. Students' experiences with clients over age 55 promoted an understanding of…

  1. Teaching Text Design.

    ERIC Educational Resources Information Center

    Kramer, Robert; Bernhardt, Stephen A.

    1996-01-01

    Reports that although a rhetoric of visible text based on page layout and various design features has been defined, what a writer should know about design is rarely covered. Describes and demonstrates a scope and sequence of learning that encourages writers to develop skills as text designers. Introduces helpful literature that displays visually…

  2. Measuring software design

    NASA Technical Reports Server (NTRS)

    1986-01-01

    An extensive series of studies of software design measures conducted by the Software Engineering Laboratory is described. Included are the objectives and results of the studies, the method used to perform the studies, and the problems encountered. The document should be useful to researchers planning similar studies as well as to managers and designers concerned with applying quantitative design measures.

  3. Child Care Design Guide.

    ERIC Educational Resources Information Center

    Olds, Anita Rui

    This book provides architects, interior designers, developers, and child-care professionals with detailed information on the planning and design of child care centers. Part 1 examines the current state of child care in the United States and offers an overall philosophical concert--the spirit of place--as the framework for all center design. Part 2…

  4. Design on Your Face

    ERIC Educational Resources Information Center

    Funk, Roger L.

    2004-01-01

    This feature article has two goals. The first is to muse about the role of style and styling in the world of design and designing. The second is to present a project with which to engage students in several aspects of industrial design. This brief has been developed to use it either solely as a research activity or as a combined research and…

  5. Lehigh Design Course

    ERIC Educational Resources Information Center

    Grassi, Vincent G.; Luyben, William L.; Silebi, Cesar A.

    2011-01-01

    This paper discusses a two-semester senior design course that combines traditional steady-state economic process design with dynamic plantwide control. This unique course has been taught at Lehigh for more than a decade and has garnered rave reviews from students, industry, and ABET. Each student design group has its own industrial consultant who…

  6. Lighting in Architectural Design.

    ERIC Educational Resources Information Center

    Phillips, Derek

    The primary function of this book is to treat the topic of lighting design in such a manner as to bridge the gap between architects and illuminating engineers. The work is divided into three parts: Part I, Principles of Design, offers information and analysis of how natural and artificial lighting affects building design, how illumination levels…

  7. Revisiting "Beyond Instructional Design"

    ERIC Educational Resources Information Center

    Sims, Rod

    2015-01-01

    Since the article "Beyond Instructional Design: Making Learning Design a Reality" (Sims, 2006) was published, much has changed in the opportunities we have for learning, and Professor Rod Sims's thinking has evolved. In this article, Professor Rod Sims reflects upon his original article, and he offers an evolved model of learning design,…

  8. Energy efficient building design

    SciTech Connect

    Not Available

    1992-03-01

    The fundamental concepts of the building design process, energy codes and standards, and energy budgets are introduced. These tools were combined into Energy Design Guidelines and design contract requirements. The Guidelines were repackaged for a national audience and a videotape for selling the concept to government executives. An effort to test transfer of the Guidelines to outside agencies is described.

  9. The Backpack Design Challenge

    ERIC Educational Resources Information Center

    Roman, Harry T.

    2010-01-01

    Something as simple as carrying books to school can be an interesting design challenge for students. It's an old problem that gets reinvented from time to time. In this article, the author discusses a backpack design challenge in which teachers work with students to design another way to carry books to school. The challenge started by trying to…

  10. Education by Design

    ERIC Educational Resources Information Center

    Davis, Meredith C.

    2004-01-01

    This paper discusses the 1997 National Endowment for the Arts (NEA) two-year study("Design as a Catalyst for Learning") of how design is being used in pre-K-12 schools. The NEA acknowledged the thirty-year contributions of professional designers who bring their content and expertise to the school classroom; however, the focus of the report was on…

  11. Designers in Britain 7.

    ERIC Educational Resources Information Center

    New York Graphic Society, Greenwich, CT.

    The Society of Industrial Artists and Designers (SIAD) has for over 40 years been working to establish design as a profession with a status equivalent to that of architecture or engineering. Intended as a selective review of recent British illustration and design in industry, advertising, and publishing, this volume is the seventh in a series…

  12. Global Interaction in Design

    ERIC Educational Resources Information Center

    Bennett, Audrey Grace

    2010-01-01

    Based on a virtual conference, Glide'08 (Global Interaction in Design Education), that brought international design scholars together online, this special issue expands on the topics of cross-cultural communication and design and the technological affordances that support such interaction. The author discusses the need for global interaction in…

  13. Thermodynamics with Design Problems.

    ERIC Educational Resources Information Center

    Cilento, E. V.; Sears, J. T.

    1983-01-01

    Discusses how basic thermodynamics concepts are integrated with design problems. Includes course goals, instructional strategies, and major advantages/disadvantages of the integrated design approach. Advantages include making subject more concrete, emphasizing interrelation of variables, and reinforcing concepts by use in design analysis; whereas…

  14. Designing the Instructional Interface.

    ERIC Educational Resources Information Center

    Lohr, L. L.

    2000-01-01

    Designing the instructional interface is a challenging endeavor requiring knowledge and skills in instructional and visual design, psychology, human-factors, ergonomic research, computer science, and editorial design. This paper describes the instructional interface, the challenges of its development, and an instructional systems approach to its…

  15. Design for All Children.

    ERIC Educational Resources Information Center

    Stoecklin, Vicki L.

    This paper examines four key elements in the designing-for-all-children concept for school environments. Designing-for-all-children designs acknowledge that children pass through differing, yet recognizable, stages of development; and that children need usable environments free from physical and social barriers. Key elements address equitable use,…

  16. Designing for Energy Conservation.

    ERIC Educational Resources Information Center

    Estes, R. C.

    This document is a description of the energy efficient designs for new schools in the Alief Independent School District of Houston, Texas. Exhibit A shows how four major school projects differ from conventional designs. Parameters and designs for heating, ventilating, air conditioning, and lighting are given. Twenty year projected energy costs and…

  17. Designing Simulation Systems

    ERIC Educational Resources Information Center

    Twelker, Paul A.

    1969-01-01

    "The purpose of this paper is to outline the approach to designing instructional simulation systems developed at Teaching Research. The 13 phases of simulation design will be summarized, and an effort will be made to expose the vital decision points that confront the designer as he develops simulation experiences. (Author)

  18. Nurturing Talented Design Students.

    ERIC Educational Resources Information Center

    Boyd, Rae; Field, Sue

    1987-01-01

    The paper argues that students talented in design usually demonstrate advanced development in some but not all aspects of design. A battery of tests was developed to enable the art teacher to identify strengths and weaknesses of able students. Noted also is the family's role in nurturing design talent. (Author/DB)

  19. Telephone Survey Designs.

    ERIC Educational Resources Information Center

    Casady, Robert J.

    The concepts, definitions, and notation that have evolved with the development of telephone survey design methodology are discussed and presented as a unified structure. This structure is then applied to some of the more well-known telephone survey designs and alternative designs are developed. The relative merits of the different survey designs…

  20. Design as Storytelling

    ERIC Educational Resources Information Center

    Parrish, Patrick

    2006-01-01

    Technical problem solving as a model for instructional design (ID) has its strengths, and it has done much to provide designers strategies for their work, but it has substantial limitations as well. For one, it does not do a good job in describing how designers actually think. Slavish adherence to its methods can also be considered responsible for…

  1. Computerized design of CAD

    NASA Astrophysics Data System (ADS)

    Paul, B. E.; Pham, T. A.

    1982-11-01

    A computerized ballistic design technique for CAD/PAD is described by which a set of ballistic design parameters are determined, all of which satisfy a particular performance requirement. In addition, the program yields the remaining performance predictions, so that only a very few computer runs of the design program can quickly bring the ballistic design within the specification limits prescribed. An example is presented for a small propulsion device, such as a remover or actuator, for which the input specifications define a maximum allowable thrust and minimum end-of-stroke velocity. The resulting output automatically satisfies the input requirements, and will always yield an acceptable ballistic design.

  2. Foundation Design Handbook

    SciTech Connect

    Carmody, John; Mosiman, Garrett; Handeen, Daniel; Huelman, Patrick; Christian, Jeffery

    2013-10-01

    The purpose of this handbook is to provide information that will enable designers, builders, and homeowners to understand foundation design problems and solutions. The foundation of a house is a somewhat invisible and sometimes ignored component of the building. It is increasingly evident, however, that attention to good foundation design and construction has significant benefits to the homeowner and the builder, and can avoid some serious future problems. Good foundation design and construction practice means not only insulating to save energy, but also providing effective structural design as well as moisture, termite, and radon control techniques where appropriate.

  3. PRISM Spectrograph Optical Design

    NASA Technical Reports Server (NTRS)

    Chipman, Russell A.

    1995-01-01

    The objective of this contract is to explore optical design concepts for the PRISM spectrograph and produce a preliminary optical design. An exciting optical configuration has been developed which will allow both wavelength bands to be imaged onto the same detector array. At present the optical design is only partially complete because PRISM will require a fairly elaborate optical system to meet its specification for throughput (area*solid angle). The most complex part of the design, the spectrograph camera, is complete, providing proof of principle that a feasible design is attainable. This camera requires 3 aspheric mirrors to fit inside the 20x60 cm cross-section package. A complete design with reduced throughput (1/9th) has been prepared. The design documents the optical configuration concept. A suitable dispersing prism material, CdTe, has been identified for the prism spectrograph, after a comparison of many materials.

  4. Roller bearing geometry design

    NASA Technical Reports Server (NTRS)

    Savage, M.; Pinkston, B. H. W.

    1976-01-01

    A theory of kinematic stabilization of rolling cylinders is extended and applied to the design of cylindrical roller bearings. The kinematic stabilization mechanism puts a reverse skew into the rolling elements by changing the roller taper. Twelve basic bearing modification designs are identified amd modeled. Four have single transverse convex curvature in their rollers while eight have rollers which have compound transverse curvature made up of a central cylindrical band surrounded by symmetric bands with slope and transverse curvature. The bearing designs are modeled for restoring torque per unit axial displacement, contact stress capacity, and contact area including dynamic loading, misalignment sensitivity and roller proportion. Design programs are available which size the single transverse curvature roller designs for a series of roller slopes and load separations and which design the compound roller bearings for a series of slopes and transverse radii of curvature. The compound rollers are proportioned to have equal contact stresses and minimum size. Design examples are also given.

  5. Visualization Design Environment

    SciTech Connect

    Pomplun, A.R.; Templet, G.J.; Jortner, J.N.; Friesen, J.A.; Schwegel, J.; Hughes, K.R.

    1999-02-01

    Improvements in the performance and capabilities of computer software and hardware system, combined with advances in Internet technologies, have spurred innovative developments in the area of modeling, simulation and visualization. These developments combine to make it possible to create an environment where engineers can design, prototype, analyze, and visualize components in virtual space, saving the time and expenses incurred during numerous design and prototyping iterations. The Visualization Design Centers located at Sandia National Laboratories are facilities built specifically to promote the ''design by team'' concept. This report focuses on designing, developing and deploying this environment by detailing the design of the facility, software infrastructure and hardware systems that comprise this new visualization design environment and describes case studies that document successful application of this environment.

  6. The Building Design Advisor

    SciTech Connect

    Papamichael, K.; LaPorta, J.; Chauvet, H.; Collins, D.; Trzcinski, T.; Thorpe, J.; Selkowitz, S.

    1996-03-01

    The Building Design Advisor (BDA) is a software environment that supports the integrated use of multiple analysis and visualization tools throughout the building design process, from the initial, schematic design phases to the detailed specification of building components and systems. Based on a comprehensive design theory, the BDA uses an object-oriented representation of the building and its context, and acts as a data manager and process controller to allow building designers to quickly navigate through the multitude of descriptive and performance parameters addressed by the analysis and visualization tools linked to the BDA. Through the Browser the user can edit the values of input parameters and select any number of input and/or output parameters for display in the Decision Desktop. The Desktop allows building designers to compare multiple design alternatives with respect to any number of parameters addressed by the tools linked to the BDA.

  7. Situating universal design architecture: designing with whom?

    PubMed Central

    Jones, Paul

    2014-01-01

    Abstract Purpose: To respond to growing calls for a theoretical unpacking of Universal Design (UD), a disparate movement cohering around attempts to design spaces and technologies that seek to allow use by all people (to the fullest extent possible). The on-going embedding of UD into architectural practice and pedagogy represents an opportune juncture at which to draw learning from other distinct-but-related transformatory architectural movements. Methods: Sociological-theoretical commentary. Results: UD has to date, and necessarily, been dominated by the practice contexts from which it emerged. Appealing as a short-hand for description of “designing-for-all”, in most cases UD has come to stand in as a term to signal a general intent in this direction and as an umbrella term for the range of technical design resources that have been developed under these auspices. There remains a fundamental ambivalence vis-à-vis the question of users’ power/capacity to influence decision-making in the design process in UD; technically-oriented typologies of bodies predominate in influential UD architectural accounts. Conclusions: UD represents rich technical and pedagogical resources for those architects committed to transforming the existing built environment so as to be less hostile to a wide range of users. However, within UD, unpacking the social role of the professional architect vis-à-vis a variety of publics is an important, but hitherto underdeveloped, challenge; issues concerning professional-citizen power relations continue to animate parallel architectural politics, and UD can both contribute and draw much from these on-going explorations. Implications for RehabilitationUniversal Design (UD) architecture shares a close affinity with rehabilitation practice, with the creation of built environments that allow use by individuals with a wide range of capacities a priority for both.While an effective communicative “bridge” between professions, UD’s deployment

  8. Development of the Design Laboratory.

    ERIC Educational Resources Information Center

    Silla, Harry

    1986-01-01

    Describes the design laboratory at the Stevens Institute of Technology (SIT). Considers course objectives, design projects, project structure, mechanical design, project management, and laboratory operation. This laboratory complements SIT's course in process design, giving students a complete design experience. (JN)

  9. Designers' unified cost model

    NASA Technical Reports Server (NTRS)

    Freeman, W.; Ilcewicz, L.; Swanson, G.; Gutowski, T.

    1992-01-01

    The Structures Technology Program Office (STPO) at NASA LaRC has initiated development of a conceptual and preliminary designers' cost prediction model. The model will provide a technically sound method for evaluating the relative cost of different composite structural designs, fabrication processes, and assembly methods that can be compared to equivalent metallic parts or assemblies. The feasibility of developing cost prediction software in a modular form for interfacing with state-of-the-art preliminary design tools and computer aided design programs is being evaluated. The goal of this task is to establish theoretical cost functions that relate geometric design features to summed material cost and labor content in terms of process mechanics and physics. The output of the designers' present analytical tools will be input for the designers' cost prediction model to provide the designer with a database and deterministic cost methodology that allows one to trade and synthesize designs with both cost and weight as objective functions for optimization. This paper presents the team members, approach, goals, plans, and progress to date for development of COSTADE (Cost Optimization Software for Transport Aircraft Design Evaluation).

  10. Designer's unified cost model

    NASA Technical Reports Server (NTRS)

    Freeman, William T.; Ilcewicz, L. B.; Swanson, G. D.; Gutowski, T.

    1992-01-01

    A conceptual and preliminary designers' cost prediction model has been initiated. The model will provide a technically sound method for evaluating the relative cost of different composite structural designs, fabrication processes, and assembly methods that can be compared to equivalent metallic parts or assemblies. The feasibility of developing cost prediction software in a modular form for interfacing with state of the art preliminary design tools and computer aided design programs is being evaluated. The goal of this task is to establish theoretical cost functions that relate geometric design features to summed material cost and labor content in terms of process mechanics and physics. The output of the designers' present analytical tools will be input for the designers' cost prediction model to provide the designer with a data base and deterministic cost methodology that allows one to trade and synthesize designs with both cost and weight as objective functions for optimization. The approach, goals, plans, and progress is presented for development of COSTADE (Cost Optimization Software for Transport Aircraft Design Evaluation).

  11. SKITTER foot design

    NASA Technical Reports Server (NTRS)

    Choi, Gene; Jones, David L.; Morris, James; Parham, Martin; Stephens, Jim; Yancey, Gregg

    1987-01-01

    A mechanical design team was formed to design a foot for the lunar utility vehicle SKITTER. The primary design was constrained to be a ski pole design compatible with the existing femur-tibia design legs. The lunar environment had several important effects on the foot design. Three materials were investigated for the SKITTER foot: aluminum alloys, cold worked stainless steel alloys, and titanium alloys. Thin film coatings were investigated as a method of wear reduction for the foot. The performance of the foot is dependent on the action of the legs. The range of motion for the legs was determined to be vertical to 15 degrees above horizontal. An impact analysis was performed for the foot movement, but the results were determined to be inconclusive due to unknown soil parameters. The initial foot design configuration consisted of an annulus attached to the pointed pole. The annulus was designed to prevent excess sinkage. Later designs call for a conical shaped foot with a disk at the point of the tibia attachment. The conical design was analyzed for strength and deflection by two different approaches. A deformable body analysis was performed for the foot under crane load in crane position, and also under actuator load in the vertical position. In both cases, the deflection of the foot was insignificant and the stresses well below the strength of the titanium alloy.

  12. Evolution design requirements and design strategy

    NASA Technical Reports Server (NTRS)

    Monell, D. W.

    1992-01-01

    Space Station Freedom (SSF) has undergone numerous design changes during the rephasing and restructuring activities occurring in 1989 and 1990/91, respectively. One direct result of these changes is that the Station has become more complex and compact which requires that future modifications to the Station be carefully planned and analyzed in conjunction with the baseline design process. This will ensure that the configuration has adequate design features and flexibility to accommodate the future capability and element upgrades. Six critical growth requirements (electrical power, thermal control, pressurized volume, structures, EVA equipment, and data management) have been identified and baselined in the Level I Program Requirements Document (PRD) and the Level II Program Definition and Requirements Document (PDRD). The approach to meeting the growth requirements will be to minimize the impact on the baseline design in the areas of weight, power, and development cost. The specifics of these requirements, with regard to scarring and implementation during the Follow-On and Evolution phases of SSF, are detailed in this paper.

  13. Collection Development "Universal Design": Design for Everyone

    ERIC Educational Resources Information Center

    Felix, Lisa

    2008-01-01

    As the first wave of baby boomers hit their "golden years," there is a growing demand for housing that meets their changing physical needs. The older and disabled population face a lot of physical challenges in a traditional home. Before homeowners can modify their houses, they must first understand the key design terminology involved.…

  14. Reusing Design Knowledge Based on Design Cases and Knowledge Map

    ERIC Educational Resources Information Center

    Yang, Cheng; Liu, Zheng; Wang, Haobai; Shen, Jiaoqi

    2013-01-01

    Design knowledge was reused for innovative design work to support designers with product design knowledge and help designers who lack rich experiences to improve their design capacity and efficiency. First, based on the ontological model of product design knowledge constructed by taxonomy, implicit and explicit knowledge was extracted from some…

  15. Design Languages: A Powerful Medium for Communicating Designs.

    ERIC Educational Resources Information Center

    Seo, Kay Kyeongju; Gibbons, Andrew S.

    2003-01-01

    Defines design languages as collections of terms that can be used as the primitive words for expressing design sentences. Explains the use of design languages in an instructional design context, including identifying design language terms, design language flexibility, and sharing design languages for cooperative dialogs. (Author/LRW)

  16. Printed Circuit Board Design (PCB) with HDL Designer

    NASA Technical Reports Server (NTRS)

    Winkert, Thomas K.; LaFourcade, Teresa

    2004-01-01

    Contents include the following: PCB design with HDL designer, design process and schematic capture - symbols and diagrams: 1. Motivation: time savings, money savings, simplicity. 2. Approach: use single tool PCB for FPGA design, more FPGA designs than PCB designers. 3. Use HDL designer for schematic capture.

  17. Central ballast tanker design

    SciTech Connect

    1997-01-01

    The purpose of this paper is to present the CENTRAL BALLAST TANKER Design. This design is intended to reduce the volume of oil spilled from tankers by giving the crew a tanker properly designed and equipped to allow large quantities of oil from ruptured tank(s) to flow safely to a fully-inerted central ballast tank. In addition to reducing the volume of oil spilled, the design also addresses many of the shortcomings of the DOUBLE HULL DESIGN which are increasingly becoming a concern. The following is a brief review of the development of the CENTRAL BALLAST TANKER. The simple operational features, stability, low cost and ease of maintenance of the single hull tanker were important and can be retained with the CENTRAL BALLAST DESIGN.

  18. Liaison based assembly design

    SciTech Connect

    Ames, A.; Kholwadwala, D.; Wilson, R.H.

    1996-12-01

    Liaison Based Assembly Design extends the current information infrastructure to support design in terms of kinematic relationships between parts, or liaisons. These liaisons capture information regarding contact, degrees-of-freedom constraints and containment relationships between parts in an assembly. The project involved defining a useful collection of liaison representations, investigating their properties, and providing for maximum use of the data in downstream applications. We tested our ideas by implementing a prototype system involving extensions to Pro/Engineer and the Archimedes assembly planner. With an expanded product model, the design system is more able to capture design intent. When a product update is attempted, increased knowledge availability improves our ability to understand the effect of design changes. Manufacturing and analysis disciplines benefit from having liaison information available, so less time is wasted arguing over incomplete design specifications and our enterprise can be more completely integrated.

  19. Integrated building design

    NASA Astrophysics Data System (ADS)

    Sanguinetti, Jennifer

    2005-04-01

    For many years, building design has been a very linear process with owners speaking to architects who then design building shells that they pass along to sub-consultants who must fit their systems into the allotted spaces. While this process has some advantages, it provides little opportunity to optimize systems based on such factors as energy use or occupant comfort. This presentation will focus on the evolution and implications of integrated building design, a method that has provided greater opportunities for interaction between design disciplines and with building users early on in the design process. Integration has resulted in buildings that are more sustainable than typical buildings and that can respond better to the needs of the owner and users. Examples of the application of the process and the resulting buildings will be presented from the view of a design engineer with experience of both processes. Specifically, the potential contribution of an acoustical consultant in the integrated process will be explored.

  20. Propeller design by optimization

    NASA Technical Reports Server (NTRS)

    Rizk, M. H.; Jou, W.-H.

    1986-01-01

    The feasibility of designing propellers by an optimization procedure is investigated. A scheme, which solves the full potential flow equation about a propeller by line relaxation, is modified so that the iterative solutions of the flow equation and the design parameters are updated simultaneously. Some technical problems in using optimization for designing propellers with maximum efficiency are identified. Approaches for overcoming these problems are presented.

  1. Aviation Design Software

    NASA Technical Reports Server (NTRS)

    1997-01-01

    DARcorporation developed a General Aviation CAD package through a Small Business Innovation Research contract from Langley Research Center. This affordable, user-friendly preliminary design system for General Aviation aircraft runs on the popular 486 IBM-compatible personal computers. Individuals taking the home-built approach, small manufacturers of General Aviation airplanes, as well as students and others interested in the analysis and design of aircraft are possible users of the package. The software can cut design and development time in half.

  2. Designing in Clay

    ERIC Educational Resources Information Center

    Nigrosh, Leon I.

    1977-01-01

    What can be done to transform a lump of wet clay into something more than a lump of glaze-fired clay? It is at this point when forming techniques have been mastered that good design becomes most important. Discusses six criteria involved in the search for good design so that students can discover what good design is and how important it is.…

  3. Rotorcraft Conceptual Design Environment

    NASA Technical Reports Server (NTRS)

    Johnson, Wayne; Sinsay, Jeffrey D.

    2010-01-01

    Requirements for a rotorcraft conceptual design environment are discussed, from the perspective of a government laboratory. Rotorcraft design work in a government laboratory must support research, by producing technology impact assessments and defining the context for research and development; and must support the acquisition process, including capability assessments and quantitative evaluation of designs, concepts, and alternatives. An information manager that will enable increased fidelity of analysis early in the design effort is described. This manager will be a framework to organize information that describes the aircraft, and enable movement of that information to and from analyses. Finally, a recently developed rotorcraft system analysis tool is described.

  4. Introduction to battery design

    SciTech Connect

    Nees, J.M.

    1983-05-01

    It is the purpose of this presentation on battery design to provide data and procedures that will enable the lead acid battery engineer to design replacement batteries for automotive application. Although the data and procedures cited in this presentation refer primarily to automotive batteries, they can be applied in principal to the design of other types of lead acid batteries. As the materials and processes will differ between battery manufacturers, the design criteria for each manufacturer will be subject to these differences and the data presented should be used accordingly.

  5. Filter construction and design.

    PubMed

    Jornitz, Maik W

    2006-01-01

    Sterilizing and pre-filters are manufactured in different formats and designs. The criteria for the specific designs are set by the application and the specifications of the filter user. The optimal filter unit or even system requires evaluation, such as flow rate, throughput, unspecific adsorption, steam sterilizability and chemical compatibility. These parameters are commonly tested within a qualification phase, which ensures that an optimal filter design and combination finds its use. If such design investigations are neglected it could be costly in the process scale. PMID:16570863

  6. LF460 detail design

    NASA Technical Reports Server (NTRS)

    1971-01-01

    This is the final technical report documenting the detail design of the LF460, and advanced turbotip lift fan intended for application with the YJ97-GE-100 turbojet jet generator to a V/STOL transport research aircraft. Primary objective of the design was to achieve a low noise level while maintaining the high thrust/weight ratio capability of a high pressure ratio lift fan. Report covers design requirements and summarizes activities and final results in the areas of aerodynamic and mechanical design, component and system performance, acoustic features and final noise predictions.

  7. LSST Camera Optics Design

    SciTech Connect

    Riot, V J; Olivier, S; Bauman, B; Pratuch, S; Seppala, L; Gilmore, D; Ku, J; Nordby, M; Foss, M; Antilogus, P; Morgado, N

    2012-05-24

    The Large Synoptic Survey Telescope (LSST) uses a novel, three-mirror, telescope design feeding a camera system that includes a set of broad-band filters and three refractive corrector lenses to produce a flat field at the focal plane with a wide field of view. Optical design of the camera lenses and filters is integrated in with the optical design of telescope mirrors to optimize performance. We discuss the rationale for the LSST camera optics design, describe the methodology for fabricating, coating, mounting and testing the lenses and filters, and present the results of detailed analyses demonstrating that the camera optics will meet their performance goals.

  8. Asphere design for dummies

    NASA Astrophysics Data System (ADS)

    Oka, Keita; Sparrold, Scott

    2012-10-01

    The use of aspheres has become common in minimizing aberrations, reducing weight and the overall package. With new technology for fabrication and metrology being introduced, aspheres have experienced increasing use in wide applications. Although new techniques allow for tighter tolerance and steeper geometries, there still remains a significant challenge in designing aspheres for manufacturability and testing. While the topic of designing for fabrication and metrology limitations has been highlighted over the years, the design process continues to be complex and may prevent the optical designer from reaching an optimum solution that meets both optical performance and manufacturing capabilities. In achieving such goals, it is important to not only have a fundamental understanding of aspheres and its uses, but also the flow for a design process using such elements. Without adding the correct constraints and varying them at the correct time, the design may take extreme forms and hence eliminate fabrication options. In this paper, we present a method for optimizing aspheres which can be applied to designing simple on-axis single elements all the way to high numerical aperture multi-element systems. It will outline the procedure of the necessary steps, configurations to pay attention to, and potential courses of action in order to design for the appropriate solution. Understanding these issues will enable the optical designer to efficiently produce an asphere meeting optical requirements and fabrication capabilities.

  9. Conservation by design.

    PubMed

    Root-Bernstein, Meredith; Ladle, Richard J

    2010-10-01

    Conservation researchers are increasingly aware of the need to conduct interdisciplinary research and to engage nonscientists in practical applications of conservation biology. But so far, industrial designers have been left out of such collaboration and outreach efforts. Conservation of wildlife often depends on products such as nest boxes, feeders, barriers, and corridors, all of which have a designed component that is frequently overlooked. Furthermore, many products are adopted without testing on short or long time scales. We argue that the design of products for conservation, and hence their functionality, effectiveness, and value, can be improved through collaboration with industrial designers. We see four key benefits that can arise from interactions with industrial designers: improvement of product quality and value, innovation and improvement in functionality of products, harmonization of conservation products with local values, and development of a psychological biomimesis approach to design. The role of industrial designers in conservation projects would be to improve factors such as product durability, affordability, functionality, and aesthetic appeal to local people. Designers can also help to create multiple product options whose success can be tested in the field. We propose that collaborations with industrial designers can contribute to the development of improvements to existing products and innovations in the practice of animal conservation. PMID:20408866

  10. Rotorcraft Conceptual Design Environment

    NASA Technical Reports Server (NTRS)

    Johnson, Wayne; Sinsay, Jeffrey

    2009-01-01

    Requirements for a rotorcraft conceptual design environment are discussed, from the perspective of a government laboratory. Rotorcraft design work in a government laboratory must support research, by producing technology impact assessments and defining the context for research and development; and must support the acquisition process, including capability assessments and quantitative evaluation of designs, concepts, and alternatives. An information manager that will enable increased fidelity of analysis early in the design effort is described. This manager will be a framework to organize information that describes the aircraft, and enable movement of that information to and from analyses. Finally, a recently developed rotorcraft system analysis tool is described.

  11. NASA Exploration Design Challenge

    NASA Video Gallery

    From the International Space Station, astronaut Sunita Williams welcomes participants to the NASA Exploration Design Challenge and explains the uncertainties about the effects of space radiation on...

  12. Managing Software Design and Design Changes

    NASA Technical Reports Server (NTRS)

    Loesh, R. E.

    1985-01-01

    Microprocessor-based system for document production work scheduling, and change control and management information aids in design, development, and control of software. Main components Z80 microprocessor, floppydisk and hard-disk drives, and a character printer. System linked to large computer. Major software components are control program monitor (CP/M), text-editing and wordprocessing system, workbreakdown-schedule processor, and data-base management tool.

  13. Design friendly double patterning

    NASA Astrophysics Data System (ADS)

    Yesilada, Emek

    2012-03-01

    Double patterning using 193nm immersion has been adapted as the solution to enable 2x nm technology nodes until the arrival of EUV tools. As a result the past few years have seen a huge effort in creating double patterning friendly design flows. These flows have so far proposed a combination of decomposition rules at cell level and/or at placement level as well as sophisticated decomposition tools with varying density, design iteration and decomposition complexity penalties. What is more, designers have to familiarize themselves with double patterning challenges and decomposition tools. In this paper an alternative approach is presented that allows the development of dense standard cells with minimal impact on design flow due to double patterning. A real case study is done on 20nm node first metal layer where standard cells are designed without considering decomposition restrictions. The resulting layout is carefully studied in order to establish decomposition or color rules that can map the layout into two masks required for double patterning but without the need of complex coloring algorithms. Since the rules are derived from a decomposition unaware design they do not in return impose heavy restrictions on the design at the cell or placement level and show substantial density gains compared to previously proposed methods. Other key advantages are a simplified design flow without complex decomposition tools that can generate a faster time to market solution all at the same time keeping designers isolated from the challenges of the double patterning. The derived design rules highlight process development path required for design driven manufacturing.

  14. The design of the MAD Design Program

    SciTech Connect

    Niederer, J.

    1992-01-01

    The study of long term stability in particle accelerators has long been served by a group of widely circulated computer programs. The progress in these programs has mirrored the growth and versatility in accelerator size, complexity, and purpose, as well as evolving technologies in computing software and hardware. A number of large accelerator projects during the last decade were designed with the aid of physics programs either written for, or tailored for the project at hand, each invariably benefiting from contributions of previous workers. This paper outlines the recent history of of expample of an accelerator lattice model tool kit, the Methodical Accelerator Design (MAD) Program, which has tried to knit together this collective wisdom of the accelerator community, The ideas behind the software design of the program itself are traced here; the accelerator physics contents and origins are thoroughly documented elsewhere. These informal notes have a Brookhaven flavor, in part because of early BNL efforts to generalize the ways that technical problems are organized and presented to computers. Some recent BNL applications not covered in the extensive CERN documentation are also included.

  15. The design of the MAD Design Program

    SciTech Connect

    Niederer, J.

    1992-12-31

    The study of long term stability in particle accelerators has long been served by a group of widely circulated computer programs. The progress in these programs has mirrored the growth and versatility in accelerator size, complexity, and purpose, as well as evolving technologies in computing software and hardware. A number of large accelerator projects during the last decade were designed with the aid of physics programs either written for, or tailored for the project at hand, each invariably benefiting from contributions of previous workers. This paper outlines the recent history of of expample of an accelerator lattice model tool kit, the Methodical Accelerator Design (MAD) Program, which has tried to knit together this collective wisdom of the accelerator community, The ideas behind the software design of the program itself are traced here; the accelerator physics contents and origins are thoroughly documented elsewhere. These informal notes have a Brookhaven flavor, in part because of early BNL efforts to generalize the ways that technical problems are organized and presented to computers. Some recent BNL applications not covered in the extensive CERN documentation are also included.

  16. Elementary Design Challenges

    ERIC Educational Resources Information Center

    Gerlach, Jonathan W.

    2010-01-01

    How many of our students come to the classroom with little background knowledge about the world around them and how things work? To help students develop conceptual understanding and explore the design process, the author brought the NASA "Engineering Design Challenges" program to his school district, redeveloped for elementary students. In this…

  17. Rooftop Garden Design Challenge

    ERIC Educational Resources Information Center

    Roman, Harry T.

    2010-01-01

    A small commercial building in a nearby industrial park has decided to install a rooftop garden for its employees to enjoy. The garden will be about 100 feet long and 75 feet wide. This article presents a design challenge for technology and engineering students wherein they will assist in the initial conceptual design of the rooftop garden. The…

  18. Passionate about Designing

    ERIC Educational Resources Information Center

    Atkinson, Stephanie; Sandwith, Angela

    2014-01-01

    In the school based subject of design and technology (D&T) a fundamental element is designing and making functional products using critical and creative thinking whilst developing skills in the use of a variety of processes and materials. Teachers of the subject need to be more then just "enthusiastic" about the processes involved if…

  19. Power plant design

    SciTech Connect

    Khalil, E.E. )

    1990-01-01

    This overviews basic theories and concepts of power plant design using an accessible approach that moves smoothly from simple to real configurations. Utilizing a large number of worked examples the book provides a treatment and understanding of all aspects of power plant design from basic thermodynamics to complex applications.

  20. Textiles and Apparel Design.

    ERIC Educational Resources Information Center

    Texas Tech Univ., Lubbock. Home Economics Curriculum Center.

    This document contains teacher's materials for a seven-unit secondary education vocational home economics course on textiles and apparel design. The units cover: (1) fiber/fiber characteristics and textile development (including fabrication and dyeing, printing, and finishing); (2) textile and apparel design industries (including their history and…

  1. Fracture design modelling

    SciTech Connect

    Crichlow, H.B.; Crichlow, H.B.

    1980-02-07

    A design tool is discussed whereby the various components that enter the design process of a hydraulic fracturing job are combined to provide a realistic appraisal of a stimulation job in the field. An interactive computer model is used to solve the problem numerically to obtain the effects of various parameters on the overall behavior of the system.

  2. Design-Based Science.

    ERIC Educational Resources Information Center

    Fortus, David; Reddy, Srikaran; Dershimer, Ralph Charles

    2003-01-01

    Describes design-based science, which aims to develop useful skills for a wide range of actual problem-solving situations involving science. Discusses units of design activities concerning the voltage and lifetime of batteries and the potential in science education. (KHR)

  3. Transonic airfoil design code

    NASA Technical Reports Server (NTRS)

    Bauer, F.; Garabedian, P.; Korn, D.

    1980-01-01

    Program aids in design of shockless airfoils, assists development of fuel-conserving, supercritical wings. Algorithm calculates approximate airfoil shape given prescribed pressure distribution. This allows design of families of transonic airfoils for use in aircraft wings or turbine and compressor blades. Program is written in FORTRAN IV for batch execution on CDC-6000.

  4. Designing Electronic Books.

    ERIC Educational Resources Information Center

    Barker, Philip; Manji, Karim

    1991-01-01

    Discussion of the design of interactive environments focuses on three types of electronic book metaphors that use optical discs and can facilitate computer-based learning: (1) static picture books, (2) moving picture books, and (3) multimedia books. Guidelines for designing electronic books are presented, and future directions are discussed. (17…

  5. Graphite design handbook

    SciTech Connect

    Ho, F.H.

    1988-09-01

    The objectives of the Graphite Design Handbook (GDH) are to provide and maintain a single source of graphite properties and phenomenological model of mechanical behavior to be used for design of MHTGR graphite components of the Reactor System, namely, core support, permanent side reflector, hexagonal reflector elements, and prismatic fuel elements; to provide a single source of data and material models for use in MHTGR graphite component design, performance, and safety analyses; to present properties and equations representing material models in a form which can be directly used by the designer or analyst without the need for interpretation and is compatible with analytical methods and structural criteria used in the MHTGR project, and to control the properties and material models used in the MHTGR design and analysis to proper Quality Assurance standards and project requirements. The reference graphite in the reactor internal components is the nuclear grade 2020. There are two subgrades of interest, the cylinder nuclear grade and the large rectangular nuclear grade. The large rectangular nuclear grade is molded in large rectangular blocks. It is the reference material for the permanent side reflector and the central column support structure. The cylindrical nuclear grade is isostatically pressed and is intended for use as the core support component. This report gives the design properties for both H-451 and 2020 graphite as they apply to their respective criteria. The properties are presented in a form for design, performance, and safety calculations that define or validate the component design. 103 refs., 20 figs., 19 tabs.

  6. Design for Visual Arts.

    ERIC Educational Resources Information Center

    Skeries, Larry

    Experiences suggested within this visual arts packet provide high school students with awareness of visual expression in graphic design, product design, architecture, and crafts. The unit may be used in whole or in part and includes information about art careers and art-related jobs found in major occupational fields. Specific lesson topics…

  7. Designing with superconductors

    SciTech Connect

    Hammond, R.B.; Hey-Shipton, G.L. ); Matthaei, G.L. )

    1993-04-01

    This article examines the basics of designing with superconducting microwave ICs. The topics of this article include high-temperature superconductors of copper-oxide compounds, the shortcomings of designing ICs with CAD, building small, high-Q bandpass or bandstop filters, combining high-temperature superconductors and conventional components, oscillator stability, tuning, digital interconnects, and cryogenic cooling options.

  8. Computer Designed Instruction & Testing.

    ERIC Educational Resources Information Center

    New Mexico State Univ., Las Cruces.

    Research findings on computer designed instruction and testing at the college level are discussed in 13 papers from the first Regional Conference on University Teaching at New Mexico State University. Titles and authors are as follows: "Don't Bother Me with Instructional Design, I'm Busy Programming! Suggestions for More Effective Educational…

  9. Johannes Kepler's Intelligent Design

    NASA Astrophysics Data System (ADS)

    Wallace, Paul M.

    2006-12-01

    In the last decade, the theory labeled "Intelligent Design" has exacerbated long-standing conflicts between religion and science. This issue will be addressed from the perspective of the philosophy and science of Johannes Kepler (1571-1630), whose unconventional belief in design lived in harmony with his revolutionary physical astronomy.

  10. Jewelry Design by Example

    ERIC Educational Resources Information Center

    Mahoney, Ellen

    2011-01-01

    Presidential campaigns bring out the expression of strong political sentiments in the jewelry and pins that people wear to declare their allegiances. Images, flags, symbols, and words are all elements that are incorporated into designs that make decisive visual statements. In this article, the author's high-school metals class students design a…

  11. Designing Safer Schools.

    ERIC Educational Resources Information Center

    Crowe, Timothy D.

    1990-01-01

    Crime Prevention through Environmental Design (CPTED) is being used in schools and communities to improve the management of human space. Outlines CPTED concepts and strategies to implement crime reduction through environmental design of school grounds, parking lots, locker rooms, corridors, restrooms, and classrooms. (MLF)

  12. Instructional Design: System Strategies.

    ERIC Educational Resources Information Center

    Ledford, Bruce R.; Sleeman, Phillip J.

    This book is intended as a source for those who desire to apply a coherent system of instructional design, thereby insuring accountability. Chapter 1 covers the instructional design process, including: instructional technology; the role of evaluation; goal setting; the psychology of teaching and learning; task analysis; operational objectives;…

  13. Design-to-cost

    NASA Technical Reports Server (NTRS)

    Bradley, F. E.

    1974-01-01

    Attempts made to design to costs equipment, vehicles and subsystems for various space projects are discussed. A systematic approach, based on mission requirement analysis, definition of a mission baseline design, benefit and cost analysis, and a benefit-cost analysis was proposed for implementing the cost control program.

  14. ORION mobile unit design

    NASA Technical Reports Server (NTRS)

    Brunn, D. L.; Wu, S. C.; Thom, E. H.; Mclaughlin, F. D.; Sweetser, B. M.

    1980-01-01

    An overview of the design of the ORION mobile system is presented. System capability and performance characteristics are outlined. Functional requirements and key performance parameters are stated for each of the nine subsystems. A master design and implementation schedule is given.

  15. Optimization of digital designs

    NASA Technical Reports Server (NTRS)

    Whitaker, Sterling R. (Inventor); Miles, Lowell H. (Inventor)

    2009-01-01

    An application specific integrated circuit is optimized by translating a first representation of its digital design to a second representation. The second representation includes multiple syntactic expressions that admit a representation of a higher-order function of base Boolean values. The syntactic expressions are manipulated to form a third representation of the digital design.

  16. Designing ROW Methods

    NASA Technical Reports Server (NTRS)

    Freed, Alan D.

    1996-01-01

    There are many aspects to consider when designing a Rosenbrock-Wanner-Wolfbrandt (ROW) method for the numerical integration of ordinary differential equations (ODE's) solving initial value problems (IVP's). The process can be simplified by constructing ROW methods around good Runge-Kutta (RK) methods. The formulation of a new, simple, embedded, third-order, ROW method demonstrates this design approach.

  17. Hypersonic aircraft design

    NASA Technical Reports Server (NTRS)

    Alkamhawi, Hani; Greiner, Tom; Fuerst, Gerry; Luich, Shawn; Stonebraker, Bob; Wray, Todd

    1990-01-01

    A hypersonic aircraft is designed which uses scramjets to accelerate from Mach 6 to Mach 10 and sustain that speed for two minutes. Different propulsion systems were considered and it was decided that the aircraft would use one full scale turbofan-ramjet. Two solid rocket boosters were added to save fuel and help the aircraft pass through the transonic region. After considering aerodynamics, aircraft design, stability and control, cooling systems, mission profile, and landing systems, a conventional aircraft configuration was chosen over that of a waverider. The conventional design was chosen due to its landing characteristics and the relative expense compared to the waverider. Fuel requirements and the integration of the engine systems and their inlets are also taken into consideration in the final design. A hypersonic aircraft was designed which uses scramjets to accelerate from Mach 6 to Mach 10 and sustain that speed for two minutes. Different propulsion systems were considered and a full scale turbofan-ramjet was chosen. Two solid rocket boosters were added to save fuel and help the aircraft pass through the transonic reqion. After the aerodynamics, aircraft design, stability and control, cooling systems, mission profile, landing systems, and their physical interactions were considered, a conventional aircraft configuration was chosen over that of a waverider. The conventional design was chosen due to its landing characteristics and the relative expense compared to the waverider. Fuel requirements and the integration of the engine systems and their inlets were also considered in the designing process.

  18. Designing for Watershed Inquiry

    ERIC Educational Resources Information Center

    Bodzin, Alec; Shive, Louise

    2004-01-01

    In this article, we describe a collaborative design initiative with three secondary school teachers to promote the use of Web-based inquiry in the context of a watershed investigation. Design interviews that focus on instructional goals and pedagogical beliefs of classroom teachers were conducted. The interview protocol used a curricular framework…

  19. A coilgun design primer

    NASA Astrophysics Data System (ADS)

    Marder, B.

    How an induction coilgun works is explained, and the factors which go into its design are presented. Our purpose is to obtain algebraic expressions which, although crude, provide useful predictors of behavior, illustrate the dependence on various parameters, and suggest ways to optimize the design. Detailed prediction of the gun's behavior can be obtained from simulation codes, such as SLINGSHOT.

  20. A coilgun design primer

    SciTech Connect

    Marder, B.

    1991-01-01

    This paper explains how an induction coilgun works and presents the factors which go into its design. Our purpose is to obtain algebraic expressions which, although crude, provide useful predictors of behavior, illustrate the dependence on various parameters, and suggest ways to optimize the design. Detailed prediction of the gun's behavior can be obtained from simulation codes, such as SLINGSHOT.

  1. A coilgun design primer

    SciTech Connect

    Marder, B.

    1991-12-31

    This paper explains how an induction coilgun works and presents the factors which go into its design. Our purpose is to obtain algebraic expressions which, although crude, provide useful predictors of behavior, illustrate the dependence on various parameters, and suggest ways to optimize the design. Detailed prediction of the gun`s behavior can be obtained from simulation codes, such as SLINGSHOT.

  2. Core Design Applications

    1995-07-12

    CORD-2 is intended for core desigh applications of pressurized water reactors. The main objective was to assemble a core design system which could be used for simple calculations (such as frequently required for fuel management) as well as for accurate calculations (for example, core design after refueling).

  3. Engineering Design Thinking

    ERIC Educational Resources Information Center

    Lammi, Matthew; Becker, Kurt

    2013-01-01

    Engineering design thinking is "a complex cognitive process" including divergence-convergence, a systems perspective, ambiguity, and collaboration (Dym, Agogino, Eris, Frey, & Leifer, 2005, p. 104). Design is often complex, involving multiple levels of interacting components within a system that may be nested within or connected to other systems.…

  4. Design-Focused Evaluation

    ERIC Educational Resources Information Center

    Smith, Calvin

    2008-01-01

    In this paper an approach to the writing of evaluation questions is outlined and developed which focuses attention on the question of the effectiveness of an educational design for bringing about the learning it is intended to facilitate. The approach develops from the idea that all educational designs rely on instructional alignment, implicitly…

  5. Energy Systems Design

    NASA Technical Reports Server (NTRS)

    1986-01-01

    PRESTO, a COSMIC program, handles energy system specifications and predicts design efficiency of cogeneration systems. These systems allow a company to use excess energy produced to generate electricity. PRESTO is utilized by the Energy Systems Division of Thermo Electron Corporation in the custom design of cogeneration systems.

  6. Assessing Intercultural Training Designs

    ERIC Educational Resources Information Center

    Graf, Andrea

    2004-01-01

    Training designs are critical to the success of intercultural training programmes. A common typology for classifying intercultural training designs distinguishes among the following dimensions: experiential discovery versus didactic expository and culture-specific versus culture-general training. The purpose of this paper is to assess different…

  7. Nutrient Control Design Manual

    EPA Science Inventory

    The purpose of this EPA design manual is to provide updated, state‐of‐the‐technology design guidance on nitrogen and phosphorus control at municipal Wastewater Treatment Plants (WWTPs). Similar to previous EPA manuals, this manual contains extensive information on the principles ...

  8. Programming for Design

    NASA Technical Reports Server (NTRS)

    1976-01-01

    Structures under stress are designed much more rapidly -- allowing for remarkable increases in productivity -- since NASTRAN (for NASA Structural Analysis) has become available. The versatile computer program, written originally to help design more efficient space vehicles, finds additional applications each year.

  9. Managing Course Design.

    ERIC Educational Resources Information Center

    Foster, Geoff

    1993-01-01

    Presents a framework for academic staff that explains aspects of managing course design. The main activities described are planning, including setting objectives and budgeting; leading, including decision making, motivating, and communicating; organizing, including designing an organizational structure; and controlling, including developing…

  10. Design Thinking for Life

    ERIC Educational Resources Information Center

    Watson, Andrew D.

    2015-01-01

    According to Vande Zande (2007), understanding the Design Process can help students become stronger critical thinkers. With this in mind, Andrew Watson decided to undertake an observational case study in which he focused directly on Design Thinking and addressed it more intentionally in his teaching. The hope was to understand how students saw…

  11. Learning Biology by Designing

    ERIC Educational Resources Information Center

    Janssen, Fred; Waarlo, Arend Jan

    2010-01-01

    According to a century-old tradition in biological thinking, organisms can be considered as being optimally designed. In modern biology this idea still has great heuristic value. In evolutionary biology a so-called design heuristic has been formulated which provides guidance to researchers in the generation of knowledge about biological systems.…

  12. Design a Hummingbird Flower.

    ERIC Educational Resources Information Center

    Bailey, Kim

    2002-01-01

    Presents an activity that engages students in designing and making an artificial flower adapted for pollination by hummingbirds. Students work in teams to design flowers that maximize the benefit from attracting hummingbirds. Examines characteristics of real flowers adapted to pollination by hummingbirds. (DLH)

  13. Designing for the Disabled.

    ERIC Educational Resources Information Center

    Goldsmith, Selwyn

    Implications of the merits of normality and independence for the disabled, and their relevance to architectural design criteria are discussed. The introduction reflects the philosophical approach to the design and construction of public buildings and housing. Nine principle sections provide data and recommendations on the following topics:…

  14. Standardizing Interaction Design Education

    ERIC Educational Resources Information Center

    Thomassen, Aukje; Ozcan, Oguzhan

    2010-01-01

    The objective of this paper is to which extend the didactic format of studio-based group-work is applicable for creating a common-ground for Interaction Design Education in European Perspective. The current debate on design education shows us a landscape of different initiatives. So far difficulties have arisen in the area of accreditation and…

  15. Security by Design.

    ERIC Educational Resources Information Center

    Sabo, Sandra R.

    1993-01-01

    School districts across the country are taking measures in the design and renovation of school buildings that will protect students and staff members. Exterior and interior design possibilities are listed. Schools are also advised to have a districtwide crisis intervention plan, a school safety plan, and an annual safety audit. (MLF)

  16. School Design and Construction.

    ERIC Educational Resources Information Center

    Bete, Tim, Ed.

    1998-01-01

    Presents the opinions of five school design and construction experts on the future of school facility design and use. Issues discussed involve changes in classroom size, school facilities doubling as community-use buildings, emphasis on life cycle costing on construction projects, the future of modular school buildings, and the possibility of…

  17. Barrier Free Site Design.

    ERIC Educational Resources Information Center

    Dee, Richard K., Ed.

    The booklet provides information for the design and evaluation of a barrier free outdoor environment for handicapped individuals. Section 1 discusses the scope of the study, defines terms, cites pertinent laws and legislation, describes cost/benefit factors, and surveys population statistics. Section 2 considers recommended design details in the…

  18. DESIGNING GREENER SOLVENTS

    EPA Science Inventory

    Computer-aided design of chemicals and chemical mixtures provides a powerful tool to help engineers identify cleaner process designs and more-benign alternatives to toxic industrial solvents. Three software programs are discussed: (1) PARIS II (Program for Assisting the Replaceme...

  19. Designing School Gardens

    ERIC Educational Resources Information Center

    Van Dexter, Kurt

    2008-01-01

    Schoolyards can be a blank canvas of opportunity for students, teachers, and the community to create physical and psychological changes in their schools and communities. Through design, art teachers can guide their students, providing them with the tools to work in the world of spatial design. In this article, the author provides strategies for…

  20. Designing a Weather Station

    ERIC Educational Resources Information Center

    Roman, Harry T.

    2012-01-01

    The collection and analysis of weather data is crucial to the location of alternate energy systems like solar and wind. This article presents a design challenge that gives students a chance to design a weather station to collect data in advance of a large wind turbine installation. Data analysis is a crucial part of any science or engineering…

  1. Effective Monitor Display Design.

    ERIC Educational Resources Information Center

    Harrell, William

    1999-01-01

    Describes some of the factors that affect computer monitor display design and provides suggestions and insights into how screen displays can be designed more effectively. Topics include color, font choices, organizational structure of text, space outline, and general principles. (Author/LRW)

  2. Space Station Engineering Design Issues

    NASA Technical Reports Server (NTRS)

    Mcruer, Duane T.; Boehm, Barry W.; Debra, Daniel B.; Green, C. Cordell; Henry, Richard C.; Maycock, Paul D.; Mcelroy, John H.; Pierce, Chester M.; Stafford, Thomas P.; Young, Laurence R.

    1989-01-01

    Space Station Freedom topics addressed include: general design issues; issues related to utilization and operations; issues related to systems requirements and design; and management issues relevant to design.

  3. NIF capsule design update

    SciTech Connect

    Dittrich, T.R.; Haan, S.W.; Pollaine, S.; Burnham, A.K.; Strobel, G.L.

    1996-10-01

    We describe several ignition capsule designs, for use in the National Ignition Facility. We will compare these designs for ablator efficiency, ignition margin, implosion and stability performance. This study includes capsule designs driven by x-ray drive profiles with both 300 eV and 250 eV peak temperatures. All of the 300 eV designs are tuned to implode the DT fuel in a nearly identical manner. Capsule designs consist of an ablator material (CH with Br dopant; Be with Cu dopant; and B{sub 4}C) encasing a layer of solid DT. The dopants alter material opacities sufficiently to (1) shield the DT fuel from preheat effects; and (2) develop an ablation front density profile favorable to implosion stability. B{sub 4}C has sufficient opacity at 300 eV that a dopant is not necessary. Issues relating to material properties and fabrication will be described.

  4. LOXT mirror design study

    NASA Technical Reports Server (NTRS)

    Vanspeybroeck, L.; Antrim, W.; Boyd, D.; Giacconi, R.; Sinnamon, G.; Stille, F.

    1972-01-01

    The final report for the large orbiting X-ray telescope (LOXT) high resolution mirror design study is presented. The following tasks were performed: (1) Generation of a reference and alternate preliminary design for the LOXT high resolution mirror assembly, which will meet the LOXT scientific requirements, and are within the present state of the art of materials and fabrication techniques. (2) Measurement, in X-rays, of the scattering properties of a variety of optical flats, embodying materials, coatings, and polishing techniques which might be applicable to the flight configuration LOXT high resolution mirror. (3) Preparation of a procurement specification for a paraboloid test mirror of the size of the innermost paraboloid of the high resolution mirror assembly, including the design requirements for the reference design evolved from this preliminary design study. The results of the engineering and scientific analysis and the conclusions drawn are presented. The procurement specification for the test mirror is included.

  5. Beam director design report

    SciTech Connect

    Younger, F.C.

    1986-08-01

    A design and fabrication effort for a beam director is documented. The conceptual design provides for the beam to pass first through a bending and focusing system (or ''achromat''), through a second achromat, through an air-to-vacuum interface (the ''beam window''), and finally through the vernier steering system. Following an initial concept study for a beam director, a prototype permanent magnet 30/sup 0/ beam-bending achromat and prototype vernier steering magnet were designed and built. In volume II, copies are included of the funding instruments, requests for quotations, purchase orders, a complete set of as-built drawings, magnetic measurement reports, the concept design report, and the final report on the design and fabrication project. (LEW)

  6. Entanglement and designs

    NASA Astrophysics Data System (ADS)

    Graydon, Matthew A.; Appleby, D. M.

    2016-08-01

    We describe a connection between entanglement and designs. It involves the conical two-designs introduced in a previous paper. These are a generalization of projective two-designs which includes full sets of arbitrary rank mutually unbiased measurements (mums) and arbitrary rank symmetric informationally complete measurements (sims), as well as the more familiar mubs and sics. We show that a povm is a conical two-design if and only if there exists what we call a regular entanglement monotone whose restriction to the pure states is a function of the norm of the probability vector. In that case the concurrence is such a monotone. We also generalize and develop previous work on designs and entanglement detection.

  7. Biomimetic sensor design

    NASA Astrophysics Data System (ADS)

    Lee, Ju Hun; Jin, Hyo-Eon; Desai, Malav S.; Ren, Shuo; Kim, Soyoun; Lee, Seung-Wuk

    2015-11-01

    Detection of desired target chemicals in a sensitive and selective manner is critically important to protect human health, environment and national security. Nature has been a great source of inspiration for the design of sensitive and selective sensors. In this mini-review, we overview the recent developments in bio-inspired sensor development. There are four major components of sensor design: design of receptors for specific targets; coating materials to integrate receptors to transducing machinery; sensitive transducing of signals; and decision making based on the sensing results. We discuss the biomimetic methods to discover specific receptors followed by a discussion about bio-inspired nanocoating material design. We then review the recent developments in phage-based bioinspired transducing systems followed by a discussion of biomimetic pattern recognition-based decision making systems. Our review will be helpful to understand recent approaches to reverse-engineer natural systems to design specific and sensitive sensors.

  8. Biomimetic sensor design.

    PubMed

    Lee, Ju Hun; Jin, Hyo-Eon; Desai, Malav S; Ren, Shuo; Kim, Soyoun; Lee, Seung-Wuk

    2015-11-28

    Detection of desired target chemicals in a sensitive and selective manner is critically important to protect human health, environment and national security. Nature has been a great source of inspiration for the design of sensitive and selective sensors. In this mini-review, we overview the recent developments in bio-inspired sensor development. There are four major components of sensor design: design of receptors for specific targets; coating materials to integrate receptors to transducing machinery; sensitive transducing of signals; and decision making based on the sensing results. We discuss the biomimetic methods to discover specific receptors followed by a discussion about bio-inspired nanocoating material design. We then review the recent developments in phage-based bioinspired transducing systems followed by a discussion of biomimetic pattern recognition-based decision making systems. Our review will be helpful to understand recent approaches to reverse-engineer natural systems to design specific and sensitive sensors. PMID:26498660

  9. 78 FR 59766 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-27

    ... Office of Foreign Assets Control Additional Designations, Foreign Narcotics Kingpin Designation Act... Narcotics Kingpin Designation Act (``Kingpin Act''). DATES: The designation by the Director of OFAC of the... establishes a program targeting the activities of significant foreign narcotics ] traffickers and...

  10. 75 FR 65554 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-25

    ... Office of Foreign Assets Control Additional Designations, Foreign Narcotics Kingpin Designation Act... interests in property are blocked pursuant to the Foreign Narcotics Kingpin Designation Act (``Kingpin Act... they are owned or controlled by a specially designated narcotics trafficker. FOR FURTHER...

  11. 77 FR 48609 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-14

    ... Office of Foreign Assets Control Additional Designations, Foreign Narcotics Kingpin Designation Act... Narcotics Kingpin Designation Act (``Kingpin Act''). DATES: The designation by the Director of OFAC of the... of significant foreign narcotics traffickers and their organizations on a worldwide basis....

  12. Computational enzyme design

    NASA Astrophysics Data System (ADS)

    Bolon, Daniel N.

    2002-08-01

    The long-term objective of computational enzyme design is the ability to generate efficient protein catalysts for any chemical reaction. This thesis develops and experimentally validates a general computational approach for the design of enzymes with novel function. In order to include catalytic mechanism in protein design, a high-energy state (HES) rotamer (side chain representation) was constructed. In this rotamer, substrate atoms are in a HES. In addition, at least one amino acid side chain is positioned to interact favorably with substrate atoms in their HES and facilitate the reaction. Including an amino acid side chain in the HES rotamer automatically positions substrate relative to a protein scaffold and allows protein design algorithms to search for sequences capable of interacting favorably with the substrate. Because chemical similarity exists between the transition state and the high-energy state, optimizing the protein sequence to interact favorably with the HES rotamer should lead to transition state stabilization. In addition, the HES rotamer model focuses the subsequent computational active site design on a relevant phase space where an amino acid is capable of interacting in a catalytically active geometry with substrate. Using a HES rotamer model of the histidine mediated nucleophilic hydrolysis of p-nitrophenyl acetate, the catalytically inert 108 residue E. coli thioredoxin as a scaffold, and the ORBIT protein design software to compute sequences, an active site scan identified two promising active site designs. Experimentally, both candidate ?protozymes? demonstrated catalytic activity significantly above background. In addition, the rate enhancement of one of these ?protozymes? was the same order of magnitude as the first catalytic antibodies. Because polar groups are frequently buried at enzyme-substrate interfaces, improved modeling of buried polar interactions may benefit enzyme design. By studying native protein structures, rules have been

  13. Design, science and naturalism

    NASA Astrophysics Data System (ADS)

    Deming, David

    2008-09-01

    The Design Argument is the proposition that the presence of order in the universe is evidence for the existence of God. The Argument dates at least to the presocratic Greek philosophers, and is largely based on analogical reasoning. Following the appearance of Aquinas' Summa Theologica in the 13th century, the Christian Church in Europe embraced a Natural Theology based on observation and reason that allowed it to dominate the entire world of knowledge. Science in turn advanced itself by demonstrating that it could be of service to theology, the recognized queen of the sciences. During the heyday of British Natural Theology in the 17th and 18th centuries, the watchmaker, shipbuilder, and architect analogies were invoked reflexively by philosophers, theologians, and scientists. The Design Argument was not systematically and analytically criticized until David Hume wrote Dialogues on Natural Religion in the 1750s. After Darwin published Origin of Species in 1859, Design withered on the vine. But in recent years, the Argument has been resurrected under the appellation "intelligent design," and been the subject of political and legal controversy in the United States. Design advocates have argued that intelligent design can be formulated as a scientific hypothesis, that new scientific discoveries validate a design inference, and that naturalism must be removed as a methodological requirement in science. If science is defined by a model of concentric epistemological zonation, design cannot be construed as a scientific hypothesis because it is inconsistent with the core aspects of scientific methodology: naturalism, uniformity, induction, and efficient causation. An analytical examination of claims by design advocates finds no evidence of any type to support either scientific or philosophical claims that design can be unambiguously inferred from nature. The apparent irreducible complexity of biological mechanisms may be explained by exaptation or scaffolding. The argument

  14. The Design Space for Solving Instructional-Design Problems.

    ERIC Educational Resources Information Center

    Dijkstra, Sanne

    2001-01-01

    Outlines the development of design science and describes the concept of design space. Discusses rules of good design, rules of good instructional design, goals of education and instructional design, the concept of situatedness, and the developments of an instructional design science, both in Europe and in the United States. (Author/LRW)

  15. 40 CFR 130.9 - Designation and de-designation.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 23 2012-07-01 2012-07-01 false Designation and de-designation. 130.9 Section 130.9 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS WATER QUALITY PLANNING AND MANAGEMENT § 130.9 Designation and de-designation. (a) Designation. Areawide planning agencies may be designated by...

  16. Engineering Design vs. Artistic Design: Some Educational Consequences

    ERIC Educational Resources Information Center

    Eder, Wolfgang Ernst

    2013-01-01

    "Design" can be a noun, or a verb. Six paths for research into engineering design (as verb) are identified, they must be coordinated for internal consistency and plausibility. Design research tries to clarify design processes and their underlying theories--for designing in general, and for particular forms, e.g., design engineering. Theories are a…

  17. WASTE PACKAGE TRANSPORTER DESIGN

    SciTech Connect

    D.C. Weddle; R. Novotny; J. Cron

    1998-09-23

    The purpose of this Design Analysis is to develop preliminary design of the waste package transporter used for waste package (WP) transport and related functions in the subsurface repository. This analysis refines the conceptual design that was started in Phase I of the Viability Assessment. This analysis supports the development of a reliable emplacement concept and a retrieval concept for license application design. The scope of this analysis includes the following activities: (1) Assess features of the transporter design and evaluate alternative design solutions for mechanical components. (2) Develop mechanical equipment details for the transporter. (3) Prepare a preliminary structural evaluation for the transporter. (4) Identify and recommend the equipment design for waste package transport and related functions. (5) Investigate transport equipment interface tolerances. This analysis supports the development of the waste package transporter for the transport, emplacement, and retrieval of packaged radioactive waste forms in the subsurface repository. Once the waste containers are closed and accepted, the packaged radioactive waste forms are termed waste packages (WP). This terminology was finalized as this analysis neared completion; therefore, the term disposal container is used in several references (i.e., the System Description Document (SDD)) (Ref. 5.6). In this analysis and the applicable reference documents, the term ''disposal container'' is synonymous with ''waste package''.

  18. Designing Hydrolytic Zinc Metalloenzymes

    PubMed Central

    2015-01-01

    Zinc is an essential element required for the function of more than 300 enzymes spanning all classes. Despite years of dedicated study, questions regarding the connections between primary and secondary metal ligands and protein structure and function remain unanswered, despite numerous mechanistic, structural, biochemical, and synthetic model studies. Protein design is a powerful strategy for reproducing native metal sites that may be applied to answering some of these questions and subsequently generating novel zinc enzymes. From examination of the earliest design studies introducing simple Zn(II)-binding sites into de novo and natural protein scaffolds to current studies involving the preparation of efficient hydrolytic zinc sites, it is increasingly likely that protein design will achieve reaction rates previously thought possible only for native enzymes. This Current Topic will review the design and redesign of Zn(II)-binding sites in de novo-designed proteins and native protein scaffolds toward the preparation of catalytic hydrolytic sites. After discussing the preparation of Zn(II)-binding sites in various scaffolds, we will describe relevant examples for reengineering existing zinc sites to generate new or altered catalytic activities. Then, we will describe our work on the preparation of a de novo-designed hydrolytic zinc site in detail and present comparisons to related designed zinc sites. Collectively, these studies demonstrate the significant progress being made toward building zinc metalloenzymes from the bottom up. PMID:24506795

  19. Design of Critical Components

    NASA Technical Reports Server (NTRS)

    Hendricks, Robert C.; Zaretsky, Erwin V.

    2001-01-01

    Critical component design is based on minimizing product failures that results in loss of life. Potential catastrophic failures are reduced to secondary failures where components removed for cause or operating time in the system. Issues of liability and cost of component removal become of paramount importance. Deterministic design with factors of safety and probabilistic design address but lack the essential characteristics for the design of critical components. In deterministic design and fabrication there are heuristic rules and safety factors developed over time for large sets of structural/material components. These factors did not come without cost. Many designs failed and many rules (codes) have standing committees to oversee their proper usage and enforcement. In probabilistic design, not only are failures a given, the failures are calculated; an element of risk is assumed based on empirical failure data for large classes of component operations. Failure of a class of components can be predicted, yet one can not predict when a specific component will fail. The analogy is to the life insurance industry where very careful statistics are book-kept on classes of individuals. For a specific class, life span can be predicted within statistical limits, yet life-span of a specific element of that class can not be predicted.

  20. MEGARA cryostat advanced design

    NASA Astrophysics Data System (ADS)

    Ferrusca, D.; Castillo-Domínguez, Edgar; Velázquez, M.; Gil de Paz, A.; Carrasco, E.; Gallego, J.; Cedazo, R.; Iglesias-Páramo, J.

    2014-08-01

    MEGARA (Multi-Espectrógrafo en GTC de Alta Resolución para Astronomía) is an optical Integral-Field Unit and Multi-Object Spectrograph designed for the GTC (Gran Telescopio de Canarias) 10.4m telescope in La Palma. MEGARA project has already passed preliminary design review and the optics critical design review, first-light it is expected to take place at the end of 2016. MEGARA is a development under a GRANTECAN contract. In this paper we summarize the current status of the LN2 open-cycle cryostat which has been designed by the "Astronomical Instrumentation Lab for Millimeter Wavelengths" at the Instituto Nacional de Astrofísica, Óptica y Electrónica (INAOE) and emphasize the key parts of the system that have updated since the Preliminary Design, the main activities related to acceptance, integration, fabrication and maintenance plans which fit into the overall structure of the management plan of MEGARA are also described. The cryogenic work package of MEGARA has completed all the design stages and is ready for its Critical Design Review and then proceed to fabrication.

  1. NCSX Trim Coil Design

    SciTech Connect

    M. Kalish, A. Brooks, J. Rushinski, R. Upcavage

    2009-05-29

    The National Compact Stellarator Experiment (NCSX) was being constructed at the Princeton Plasma Physics Laboratory in partnership with Oak Ridge National Laboratory before work was stopped in 2008. The objective of this experiment was to develop the stellarator concept and evaluate it's potential as a model for future fusion power plants. Stellarator design requires very precisely positioned Modular Coils of complex shape to form 3D plasmas. In the design of NCSX, Trim Coils were required to compensate for both the positioning of the coils during assembly and the fabrication tolerances of the Modular Coils. Use of the Trim Coils allowed for larger tolerances increasing ease of assembly and decreasing overall cost. A set of Trim coils was developed to suppress the toroidal flux in island regions due to misalignment, magnetic materials, and eddy currents. The requirement imposed upon the design forced the toroidal flux in island regions below 10% of the total toroidal flux in the plasma. An analysis was first performed to evaluate candidate Trim Coil configurations iterating both the size, number, and position of the coils. The design was optimized considering both performance and cost while staying within the tight restraints presented by the space limited geometry. The final design of the Trim Coils incorporated a 48 Coil top bottom symmetric set. Fabrication costs were minimized by having only two coil types and using a planar conventional design with off the shelf commercial conductor. The Trim Coil design incorporated supports made from simple structural shapes assembled together in a way which allowed for adjustment as well as accommodation for the tolerance build up on the mating surfaces. This paper will summarize the analysis that led to the optimization of the Trim Coils set, the trim coil mechanical design, thermal and stress analysis, and the design of the supporting Trim Coil structure.

  2. Electronic aids to conceptual design

    NASA Technical Reports Server (NTRS)

    Bouchard, Eugene E.

    1990-01-01

    Presented in viewgraph form are techniques to improve the conceptual design of complex systems. The paper discusses theory of design, flexible software tools for computer aided design, and methods for enhancing communication among design teams.

  3. Lunar surface magnetometer design review

    NASA Technical Reports Server (NTRS)

    1970-01-01

    Design and fabrication parameters of a lunar surface magnetometer are discussed. Drawings and requirements for mechanical design, electronic packaging design, thermal design, quality assurance and systems testing are included.

  4. Advanced wind turbine design

    SciTech Connect

    Jamieson, P.M.; Jaffrey, A.

    1995-09-01

    Garrad Hassan have a project in progress funded by the UK Department of Trade and Industry (DTI) to assess the prospects and cost benefits of advanced wind turbine design. In the course of this work, a new concept, the coned rotor design, has been developed. This enables a wind turbine system to operate in effect with variable rotor diameter augmenting energy capture in light winds and shedding loads in storm conditions. Comparisons with conventional design suggest that a major benefit in reduced cost of wind generated electricity may be possible.

  5. Designing Echelle Spectrographs

    NASA Technical Reports Server (NTRS)

    Dantzler, A.

    1987-01-01

    Performance numbers and output maps computed from inputs supplied by user. Echelle Spectrograph Design Aid program (EGRAM) aids in design of spectrographic systems that utilize echelle/first-order crossdisperser combinations. Optical combination causes two-dimensional echellogram to fall on detector. Describes echellogram with enough detail to enable user to judge effectively feasibility of spectrograph design. By iteratively altering system parameters, desired echellogram achieved without making physical model. Calculates system parameters accurately to first order and compare favorably to results from raytracing techniques. EGRAM written in two versions. FORTRAN 77, and Microsoft BASIC A.

  6. Rampressor Turbine Design

    SciTech Connect

    Ramgen Power Systems

    2003-09-30

    The design of a unique gas turbine engine is presented. The first Rampressor Turbine engine rig will be a configuration where the Rampressor rotor is integrated into an existing industrial gas turbine engine. The Rampressor rotor compresses air which is burned in a traditional stationary combustion system in order to increase the enthalpy of the compressed air. The combustion products are then expanded through a conventional gas turbine which provides both compressor and electrical power. This in turn produces shaft torque, which drives a generator to provide electricity. The design and the associated design process of such an engine are discussed in this report.

  7. Fastener Design Manual

    NASA Technical Reports Server (NTRS)

    Barrett, Richard T.

    1990-01-01

    This manual was written for design engineers to enable them to choose appropriate fasteners for their designs. Subject matter includes fastener material selection, platings, lubricants, corrosion, locking methods, washers, inserts, thread types and classes, fatigue loading, and fastener torque. A section on design criteria covers the derivation of torque formulas, loads on a fastener group, combining simultaneous shear and tension loads, pullout load for tapped holes, grip length, head styles, and fastener strengths. The second half of this manual presents general guidelines and selection criteria for rivets and lockbolts.

  8. Transformer design tradeoffs

    NASA Technical Reports Server (NTRS)

    Mclyman, W. T.

    1976-01-01

    Material was presented to assist transformer designers in the transition from long-used English units to the less familiar metric equivalents. A coordination between the area product numbers ap (product of window and core cross-section areas) and current density J was developed for a given regulation and temperature rise. Straight-line relationships for Ap and Volume, Ap and surface area At and, Ap and weight were developed. These relationships can now be used as new tools to simplify and standardize the process of transformer design. They also made it possible to design transformers of small bulk and volume or to optimize efficiency.

  9. Consensus protein design.

    PubMed

    Porebski, Benjamin T; Buckle, Ashley M

    2016-07-01

    A popular and successful strategy in semi-rational design of protein stability is the use of evolutionary information encapsulated in homologous protein sequences. Consensus design is based on the hypothesis that at a given position, the respective consensus amino acid contributes more than average to the stability of the protein than non-conserved amino acids. Here, we review the consensus design approach, its theoretical underpinnings, successes, limitations and challenges, as well as providing a detailed guide to its application in protein engineering. PMID:27274091

  10. Generic composite flywheel designs

    NASA Technical Reports Server (NTRS)

    Steele, R. S.

    1984-01-01

    Fiber reinforced composites belong to a new class of materials and allow great flexibility in flywheel design. The most efficient flywheel may no longer have the classic Stodola taper and indeed, may not even be round. Some of the flywheel designs that have been developed in the past are discussed. Although choice of material, mounts and service requirements often dictate the final design choice for a particular application, the composite flywheels in this paper are classified within a geometric framework, a simple stress analysis of a circular disk is carried out.

  11. Consensus protein design

    PubMed Central

    Porebski, Benjamin T.; Buckle, Ashley M.

    2016-01-01

    A popular and successful strategy in semi-rational design of protein stability is the use of evolutionary information encapsulated in homologous protein sequences. Consensus design is based on the hypothesis that at a given position, the respective consensus amino acid contributes more than average to the stability of the protein than non-conserved amino acids. Here, we review the consensus design approach, its theoretical underpinnings, successes, limitations and challenges, as well as providing a detailed guide to its application in protein engineering. PMID:27274091

  12. Policies for green design

    SciTech Connect

    Fullerton, D.; Wu, W.

    1998-09-01

    A simple general equilibrium model is used to analyze disposal-content fees, subsidies for recyclable designs, unit-pricing of household disposal, deposit-refund systems, and manufacturer take-back requirements. Firms use primary and recycled inputs to produce output that has two attributes: packaging per unit output, and recyclability. If households pay the social cost of disposal, then they send the right signals to producers to reduce packaging and to design products that can more easily be recycled. If garbage is collected for free, then socially optimum attributes can still be achieved by a tax on producers` use of packaging and subsidy to recyclable designs.

  13. Header design evaluation. Final report

    SciTech Connect

    Stubenhofer, R.L.

    1993-08-01

    An evaluation was conducted of two new six-pin header designs. This evaluation consisted of designing, evaluating, procuring, and building contact module subassemblies with each of the two designs. The study was initiated as a result of the high scrap costs associated with the current product design. Two new designs were found to be feasible alternative to the current design.

  14. Developing Designer Identity through Reflection

    ERIC Educational Resources Information Center

    Tracey, Monica W.; Hutchinson, Alisa

    2013-01-01

    As designers utilize design thinking while moving through a design space between problem and solution, they must rely on design intelligence, precedents, and intuition in order to arrive at meaningful and inventive outcomes. Thus, instructional designers must constantly re-conceptualize their own identities and what it means to be a designer.…

  15. Genesis Trajectory Design

    NASA Technical Reports Server (NTRS)

    Bell, Julia L.; Lo, Martin W.; Wilson, Roby S.

    2000-01-01

    The Genesis mission will launch in 2001, sending the spacecraft into a halo orbit about the Sun-Earth L1 point to collect and return solar wind samples to the Earth for analysis in 2003. One of the most constraining aspects of the mission design is the requirement to return to the designated landing site (the Utah Test and Training Range, UTTR) during daylight hours. The ongoing mission design has led the development of a family of solutions that characterize a broad range of conditions at Earth entry. Characterizing this family provides insight into the possible existence of additional trajectories while also helping to narrow the search space by indicating where additional solutions are unlikely to exist; this contributes to a more efficient utilization of mission design resources.

  16. Scrolls and Designs

    ERIC Educational Resources Information Center

    Skelton, Mary Lou

    1972-01-01

    Third-graders wrote stories, then made them into books using adapted early Egyptian technique of scrolls. Scroll backs were covered with designs made from melted wax crayons and oil pastels. Article details materials and technique used. (PD)

  17. Ideas by Design

    ERIC Educational Resources Information Center

    Nation's Schools, 1974

    1974-01-01

    Describes two new design ideas -- a combination study carrel-locker for use in high schools and a geodesic dome made of transparent vinyl for housing ping pong games in densely populated activity area on a college campus. (DN)

  18. Transformer design tradeoffs

    NASA Technical Reports Server (NTRS)

    Mclyman, W. T.

    1977-01-01

    In space, power system transformer components are frequently the heaviest and bulkiest items in the power conversion circuit. They also have a significant effect upon the overall performance and efficiency of the system. Accordingly, the design of such transformers has an important effect on overall system weight, power-inversion efficiency, and cost. Relationships were between the parameters used by transformer designers that can be used as new tools to standardize and simplify transformer design. They can be used to optimize the design either for small size and weight or efficiency. The metric system of units, rather than the familiar English units, is used; however, material is presented to assist the reader in the transition from one system to the other.

  19. Probabilistic Approaches: Composite Design

    NASA Technical Reports Server (NTRS)

    Chamis, Christos C.

    1997-01-01

    Probabilistic composite design is described in terms of a computational simulation. This simulation tracks probabilistically the composite design evolution from constituent materials, fabrication process through composite mechanics, and structural component. Comparisons with experimental data are provided to illustrate selection of probabilistic design allowables, test methods/specimen guidelines, and identification of in situ versus pristine strength. For example, results show that: in situ fiber tensile strength is 90 percent of its pristine strength; flat-wise long-tapered specimens are most suitable for setting ply tensile strength allowables; a composite radome can be designed with a reliability of 0.999999; and laminate fatigue exhibits wide spread scatter at 90 percent cyclic-stress to static-strength ratios.

  20. Helicopter Design Analysis

    NASA Technical Reports Server (NTRS)

    1982-01-01

    Design of military and civil helicopters, produced by Bell Helicopter Textron, and aided by the use of COSMIC'S computer program VASP enables performance of more accurate analyses to insure product safety and improved production efficiency.