Science.gov

Sample records for a-interior design bv

  1. C-9A Interior Noise Evaluation.

    DTIC Science & Technology

    1983-02-01

    OEHL REPORK 83-101EH174BNA Cqk C-9A INTERIOR NOISE EVALUATION FEBRUARY 1983 DTIC $! ELECTE 0 Lj" __ B DIUTFION STATEMENT A [ Appoved for public releasq...may in any way be related thereto. The mention of trade names or commercial products in this publication is for illustration purposes and does not...the Public Affa.rs Office and is releasable to the National Technical Information Service (NTIS). At NTIS, it will be available to the general public

  2. Classical BV Theories on Manifolds with Boundary

    NASA Astrophysics Data System (ADS)

    Cattaneo, Alberto S.; Mnev, Pavel; Reshetikhin, Nicolai

    2014-12-01

    In this paper we extend the classical BV framework to gauge theories on spacetime manifolds with boundary. In particular, we connect the BV construction in the bulk with the BFV construction on the boundary and we develop its extension to strata of higher codimension in the case of manifolds with corners. We present several examples including electrodynamics, Yang-Mills theory and topological field theories coming from the AKSZ construction, in particular, the Chern-Simons theory, the BF theory, and the Poisson sigma model. This paper is the first step towards developing the perturbative quantization of such theories on manifolds with boundary in a way consistent with gluing.

  3. 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

  4. BRST-BV approach to continuous-spin field

    NASA Astrophysics Data System (ADS)

    Metsaev, R. R.

    2018-06-01

    Using BRST-BV approach, massless and massive continuous-spin fields propagating in the flat space are studied. For such fields, BRST-BV gauge invariant Lagrangian is obtained. The Lagrangian and gauge transformations are constructed out of traceless gauge fields and traceless gauge transformation parameters. Interrelation between the BRST-BV Lagrangian and the Lagrangian for the continuous-spin fields in metric-like approach is demonstrated. Considering the BRST-BV Lagrangian in the Siegel gauge, we get gauge-fixed Lagrangian which is invariant under global BRST and antiBRST transformations.

  5. Integration over families of Lagrangian submanifolds in BV formalism

    NASA Astrophysics Data System (ADS)

    Mikhailov, Andrei

    2018-03-01

    Gauge fixing is interpreted in BV formalism as a choice of Lagrangian submanifold in an odd symplectic manifold (the BV phase space). A natural construction defines an integration procedure on families of Lagrangian submanifolds. In string perturbation theory, the moduli space integrals of higher genus amplitudes can be interpreted in this way. We discuss the role of gauge symmetries in this construction. We derive the conditions which should be imposed on gauge symmetries for the consistency of our integration procedure. We explain how these conditions behave under the deformations of the worldsheet theory. In particular, we show that integrated vertex operator is actually an inhomogeneous differential form on the space of Lagrangian submanifolds.

  6. 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...

  7. Effects of hypnotic bromovalerylurea on microglial BV2 cells.

    PubMed

    Kawasaki, Shun; Abe, Naoki; Ohtake, Fumito; Islam, Afsana; Choudhury, Mohammed Emamussalehin; Utsunomiya, Ryo; Kikuchi, Satoshi; Nishihara, Tasuku; Kuwabara, Jun; Yano, Hajime; Watanabe, Yuji; Aibiki, Mayuki; Yorozuya, Toshihiro; Tanaka, Junya

    2017-06-01

    An old sedative and hypnotic bromovalerylurea (BU) has anti-inflammatory effects. BU suppressed nitric oxide (NO) release and proinflammatory cytokine expression by lipopolysaccharide (LPS)-treated BV2 cells, a murine microglial cell line. However, BU did not inhibit LPS-induced nuclear translocation of nuclear factor-κB and subsequent transcription. BU suppressed LPS-induced phosphorylation of signal transducer and activator of transcription 1 (STAT1) and expression of interferon regulatory factor 1 (IRF1). The Janus kinase 1 (JAK1) inhibitor filgotinib suppressed the NO release much more weakly than that of BU, although filgotinib almost completely prevented LPS-induced STAT1 phosphorylation. Knockdown of JAK1, STAT1, or IRF1 did not affect the suppressive effects of BU on LPS-induced NO release by BV2 cells. A combination of BU and filgotinib synergistically suppressed the NO release. The mitochondrial complex I inhibitor rotenone, which did not prevent STAT1 phosphorylation or IRF1 expression, suppressed proinflammatory mediator expression less significantly than BU. BU and rotenone reduced intracellular ATP (iATP) levels to a similar extent. A combination of rotenone and filgotinib suppressed NO release by LPS-treated BV2 cells as strongly as BU. These results suggest that anti-inflammatory actions of BU may be attributable to the synergism of inhibition of JAK1/STAT1-dependent pathways and reduction in iATP level. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  8. Clinical characterization of bvFTD due to FUS neuropathology

    PubMed Central

    Lee, Suzee E.; Seeley, William W.; Poorzand, Pardis; Rademakers, Rosa; Karydas, Anna; Stanley, Christine M.; Miller, Bruce L.; Rankin, Katherine P.

    2011-01-01

    In 2009, inclusions containing the fused in sarcoma (FUS) protein were identified as a third major molecular class of pathology underlying the behavioral variant frontotemporal dementia (bvFTD) syndrome. Due to the low prevalence of FUS pathology, few clinical descriptions have been published and none provides information about specific social-emotional deficits despite evidence for severe behavioral manifestations in this disorder. We evaluated a patient with bvFTD due to FUS pathology using a comprehensive battery of cognitive and social-emotional tests. A structural MRI scan and genetic tests for tau, progranulin, and FUS mutations were also performed. The patient showed preserved general cognitive functioning and superior working memory, but severe deficits in emotion attribution, sensitivity to punishment, and the capacity for interpersonal warmth and empathy. The gray matter atrophy pattern corresponded to this focal deficit profile, with preservation of dorsolateral fronto-parietal regions associated with executive functioning but severe damage to right worse than left frontoinsula, temporal pole, subgenual anterior cingulate, medial orbitofrontal cortex, amygdala, and caudate. This patient demonstrates the striking focality associated with FUS neuropathology in patients with bvFTD. PMID:22060063

  9. BV Quantization of the Rozansky-Witten Model

    NASA Astrophysics Data System (ADS)

    Chan, Kwokwai; Leung, Naichung Conan; Li, Qin

    2017-10-01

    We investigate the perturbative aspects of Rozansky-Witten's 3d {σ}-model (Rozansky and Witten in Sel Math 3(3):401-458, 1997) using Costello's approach to the Batalin-Vilkovisky (BV) formalism (Costello in Renormalization and effective field theory, American Mathematical Society, Providence, 2011). We show that the BV quantization (in Costello's sense) of the model, which produces a perturbative quantum field theory, can be obtained via the configuration space method of regularization due to Kontsevich (First European congress of mathematics, Paris, 1992) and Axelrod-Singer (J Differ Geom 39(1):173-213, 1994). We also study the factorization algebra structure of quantum observables following Costello-Gwilliam (Factorization algebras in quantum field theory, Cambridge University Press, Cambridge 2017). In particular, we show that the cohomology of local quantum observables on a genus g handle body is given by {H^*(X, (\\wedge^*T_X)^{⊗ g})} (where X is the target manifold), and we prove that the partition function reproduces the Rozansky-Witten invariants.

  10. Vaginal symptoms and bacterial vaginosis (BV): how useful is self-report? Development of a screening tool for predicting BV status.

    PubMed

    Nelson, D B; Bellamy, S; Odibo, A; Nachamkin, I; Ness, R B; Allen-Taylor, L

    2007-11-01

    Vaginal complaints compel an evaluation of bacterial vaginosis (BV), however, many cases of BV are asymptomatic. We evaluated the sensitivity and specificity of vaginal symptoms in the diagnosis of BV and examined the utility of creating a BV screening tool using clinical, behavioural and demographic characteristics. A total of 1916 pregnant women were included in this analysis. In total, 757 women screened positive for BV and over one third of BV-positive women presented without any lower genital tract symptoms (39.4%). African American race, abnormal vaginal odour, and smoking were independently related to BV positivity. A BV screening tool including these three factors was fairly predictive of BV status with the area under the ROC curve equal to 0.669. This three-item prediction rule may be useful in identifying high- risk pregnant women in need of BV screening and, given the high specificity, accurately identify the group of BV-negative pregnant women.

  11. Incident bacterial vaginosis (BV) in women who have sex with women is associated with behaviors that suggest sexual transmission of BV.

    PubMed

    Vodstrcil, Lenka A; Walker, Sandra M; Hocking, Jane S; Law, Matthew; Forcey, Dana S; Fehler, Glenda; Bilardi, Jade E; Chen, Marcus Y; Fethers, Katherine A; Fairley, Christopher K; Bradshaw, Catriona S

    2015-04-01

    Female same-sex partnerships provide a unique opportunity to study the pathogenesis and transmissibility of bacterial vaginosis (BV) because it can be diagnosed in both members of the partnership. We conducted a nationwide community-enrolled cohort study of women who have sex with women, including women coenrolled with their regular female sexual partner (FSP), to investigate the BV incidence rate and factors associated with incident BV. Women who have sex with women, without prevalent BV in a cross-sectional study, were enrolled in a 24-month cohort study involving 3-monthly questionnaires and self-collected vaginal swabs that were scored by the Nugent method. We assessed the BV incidence rate per 100 woman-years (WY) and used univariate and multivariable Cox regression analysis to establish factors associated with BV acquisition. Two hundred ninety-eight participants were enrolled in the cohort; 122 were coenrolled with their regular FSP. There were 51 incident cases of BV (rate, 9.75/100 WY; 95% confidence interval [CI], 7.41-12.83). Incident BV was associated with exposure to a new sexual partner (adjusted hazard ratio [AHR], 2.51; 95% CI, 1.30-4.82), a partner with BV symptoms (AHR, 3.99; 95% CI, 1.39-11.45), receptive oral sex (AHR, 3.52; 95% CI, 1.41-8.79), and onset of BV symptoms (AHR, 2.80; 95% CI, 1.39-5.61). Women coenrolled with their BV-negative partner had a greatly reduced risk of incident BV (AHR, 0.26; 95% CI, .11-.61), and high concordance of Nugent category (74%), which was predominantly normal vaginal flora throughout follow-up. These data highlight the strong influence of sexual relationships and behaviors on BV acquisition and the vaginal microbiota. They provide epidemiological evidence to support exchange of vaginal bacterial species between women and the concept that BV is sexually transmitted. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For

  12. 78 FR 9884 - Approval of Subzone Status; Zimmer Manufacturing BV; Ponce, Puerto Rico

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-12

    ...; Zimmer Manufacturing BV; Ponce, Puerto Rico Pursuant to its authority under the Foreign-Trade Zones Act... subzone at the facility of Zimmer Manufacturing BV located in Ponce, Puerto Rico (FTZ Docket B-81-2012... hereby approves subzone status at the facility of Zimmer Manufacturing BV located in Ponce, Puerto Rico...

  13. 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.

  14. BV-BFV approach to general relativity: Einstein-Hilbert action

    NASA Astrophysics Data System (ADS)

    Cattaneo, Alberto S.; Schiavina, Michele

    2016-02-01

    The present paper shows that general relativity in the Arnowitt-Deser-Misner formalism admits a BV-BFV formulation. More precisely, for any d + 1 ≠ 2 (pseudo-) Riemannian manifold M with space-like or time-like boundary components, the BV data on the bulk induces compatible BFV data on the boundary. As a byproduct, the usual canonical formulation of general relativity is recovered in a straightforward way.

  15. 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

  16. On the BV formalism of open superstring field theory in the large Hilbert space

    NASA Astrophysics Data System (ADS)

    Matsunaga, Hiroaki; Nomura, Mitsuru

    2018-05-01

    We construct several BV master actions for open superstring field theory in the large Hilbert space. First, we show that a naive use of the conventional BV approach breaks down at the third order of the antifield number expansion, although it enables us to define a simple "string antibracket" taking the Darboux form as spacetime antibrackets. This fact implies that in the large Hilbert space, "string fields-antifields" should be reassembled to obtain master actions in a simple manner. We determine the assembly of the string anti-fields on the basis of Berkovits' constrained BV approach, and give solutions to the master equation defined by Dirac antibrackets on the constrained string field-antifield space. It is expected that partial gauge-fixing enables us to relate superstring field theories based on the large and small Hilbert spaces directly: reassembling string fields-antifields is rather natural from this point of view. Finally, inspired by these results, we revisit the conventional BV approach and construct a BV master action based on the minimal set of string fields-antifields.

  17. On the global well-posedness of BV weak solutions to the Kuramoto-Sakaguchi equation

    NASA Astrophysics Data System (ADS)

    Amadori, Debora; Ha, Seung-Yeal; Park, Jinyeong

    2017-01-01

    The Kuramoto model is a prototype phase model describing the synchronous behavior of weakly coupled limit-cycle oscillators. When the number of oscillators is sufficiently large, the dynamics of Kuramoto ensemble can be effectively approximated by the corresponding mean-field equation, namely "the Kuramoto-Sakaguchi (KS) equation". This KS equation is a kind of scalar conservation law with a nonlocal flux function due to the mean-field interactions among oscillators. In this paper, we provide a unique global solvability of bounded variation (BV) weak solutions to the kinetic KS equation for identical oscillators using the method of front-tracking in hyperbolic conservation laws. Moreover, we also show that our BV weak solutions satisfy local-in-time L1-stability with respect to BV-initial data. For the ensemble of identical Kuramoto oscillators, we explicitly construct an exponentially growing BV weak solution generated from BV perturbation of incoherent state for any positive coupling strength. This implies the nonlinear instability of incoherent state in a positive coupling strength regime. We provide several numerical examples and compare them with our analytical results.

  18. Sensitization of transient receptor potential vanilloid 1 by the prokineticin receptor agonist Bv8.

    PubMed

    Vellani, Vittorio; Colucci, Mariantonella; Lattanzi, Roberta; Giannini, Elisa; Negri, Lucia; Melchiorri, Pietro; McNaughton, Peter A

    2006-05-10

    Small mammalian proteins called the prokineticins [prokineticin 1 (PK1) and PK2] and two corresponding G-protein-coupled receptors [prokineticin receptor 1 (PKR1) and PKR2] have been identified recently, but the physiological role of the PK/PKR system remains mostly unexplored. Bv8, a protein extracted from frog skin, is a convenient and potent agonist for both PKR1 and PKR2, and injection of Bv8 in vivo causes a potent and long-lasting hyperalgesia. Here, we investigate the cellular basis of hyperalgesia caused by activation of PKRs. Bv8 caused increases in [Ca]i in a population of isolated dorsal root ganglion (DRG) neurons, which we identified as nociceptors, or sensors for painful stimuli, from their responses to capsaicin, bradykinin, mustard oil, or proteases. Bv8 enhanced the inward current carried by the heat and capsaicin receptor, transient receptor potential vanilloid 1 (TRPV1) via a pathway involving activation of protein kinase Cepsilon (PKCepsilon), because Bv8 caused translocation of PKCepsilon to the neuronal membrane and because PKC antagonists reduced both the enhancement of current carried by TRPV1 and behavioral hyperalgesia in rodents. The neuronal population expressing PKRs consisted partly of small peptidergic neurons and partly of neurons expressing the N52 marker for myelinated fibers. Using single-cell reverse transcriptase-PCR, we found that mRNA for PKR1 was mainly expressed in small DRG neurons. Exposure to GDNF (glial cell line-derived neurotrophic factor) induced de novo expression of functional receptors for Bv8 in a nonpeptidergic population of neurons. These results show that prokineticin receptors are expressed in nociceptors and cause heat hyperalgesia by sensitizing TRPV1 through activation of PKCepsilon. The results suggest a role for prokineticins in physiological inflammation and hyperalgesia.

  19. 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.

  20. 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

  1. 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

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

    PubMed

    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

    2016-09-01

    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.

  3. JNK and NADPH Oxidase Involved in Fluoride-Induced Oxidative Stress in BV-2 Microglia Cells

    PubMed Central

    Yan, Ling; Liu, Shengnan; Wang, Chen; Wang, Fei; Song, Yingli; Yan, Nan; Xi, Shuhua; Liu, Ziyou; Sun, Guifan

    2013-01-01

    Excessive fluoride may cause central nervous system (CNS) dysfunction, and oxidative stress is a recognized mode of action of fluoride toxicity. In CNS, activated microglial cells can release more reactive oxygen species (ROS), and NADPH oxidase (NOX) is the major enzyme for the production of extracellular superoxide in microglia. ROS have been characterized as an important secondary messenger and modulator for various mammalian intracellular signaling pathways, including the MAPK pathways. In this study we examined ROS production and TNF-α, IL-1β inflammatory cytokines releasing, and the expression of MAPKs in BV-2 microglia cells treated with fluoride. We found that fluoride increased JNK phosphorylation level of BV-2 cells and pretreatment with JNK inhibitor SP600125 markedly reduced the levels of intracellular O2 ·− and NO. NOX inhibitor apocynin and iNOS inhibitor SMT dramatically decreased NaF-induced ROS and NO generations, respectively. Antioxidant melatonin (MEL) resulted in a reduction in JNK phosphorylation in fluoride-stimulated BV-2 microglia. The results confirmed that NOX and iNOS played an important role in fluoride inducing oxidative stress and NO production and JNK took part in the oxidative stress induced by fluoride and meanwhile also could be activated by ROS in fluoride-treated BV-2 cells. PMID:24072958

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

    PubMed

    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.

  5. 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

  6. 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

  7. Complete Closed Genome Sequence of Nontoxigenic Invasive Corynebacterium diphtheriae bv. mitis Strain ISS 3319.

    PubMed

    Azevedo Antunes, Camila; Richardson, Emily J; Quick, Joshua; Fuentes-Utrilla, Pablo; Isom, Georgia L; Goodall, Emily C; Möller, Jens; Hoskisson, Paul A; Mattos-Guaraldi, Ana Luiza; Cunningham, Adam F; Loman, Nicholas J; Sangal, Vartul; Burkovski, Andreas; Henderson, Ian R

    2018-02-01

    The genome sequence of the human pathogen Corynebacterium diphtheriae bv. mitis strain ISS 3319 was determined and closed in this study. The genome is estimated to have 2,404,936 bp encoding 2,257 proteins. This strain also possesses a plasmid of 1,960 bp. Copyright © 2018 Azevedo Antunes et al.

  8. 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

  9. 77 FR 9871 - Airworthiness Directives; Fokker Services B.V. Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-21

    ... revising the airworthiness limitations section (ALS) of the instructions for continued airworthiness for... Limitations section (ALS) of the Instructions for Continued Airworthiness by incorporating Fokker Services B.V... 1, 2000, may be removed from the ALS of the Instructions for Continued Airworthiness. Doing the...

  10. Excretory and Secretory Proteins of Naegleria fowleri Induce Inflammatory Responses in BV-2 Microglial Cells.

    PubMed

    Lee, Jinyoung; Kang, Jung-Mi; Kim, Tae Im; Kim, Jong-Hyun; Sohn, Hae-Jin; Na, Byoung-Kuk; Shin, Ho-Joon

    2017-03-01

    Naegleria fowleri, a free-living amoeba that is found in diverse environmental habitats, can cause a type of fulminating hemorrhagic meningoencephalitis, primary amoebic meningoencephalitis (PAM), in humans. The pathogenesis of PAM is not fully understood, but it is likely to be primarily caused by disruption of the host's nervous system via a direct phagocytic mechanism by the amoeba. Naegleria fowleri trophozoites are known to secrete diverse proteins that may indirectly contribute to the pathogenic function of the amoeba, but this factor is not clearly understood. In this study, we analyzed the inflammatory responses in BV-2 microglial cells induced by excretory and secretory proteins of N. fowleri (NfESP). Treatment of BV-2 cells with NfESP induced the expression of various cytokines and chemokines, including the proinflammatory cytokines IL-1α and TNF-α. NfESP-induced IL-1α and TNF-α expression in BV-2 cells were regulated by p38, JNK, and ERK MAPKs. NfESP-induced IL-1α and TNF-α production in BV-2 cells were effectively downregulated by inhibition of NF-kB and AP-1. These results collectively suggest that NfESP stimulates BV-2 cells to release IL-1α and TNF-α via NF-kB- and AP-1-dependent MAPK signaling pathways. The released cytokines may contribute to inflammatory responses in microglia and other cell types in the brain during N. fowleri infection. © 2016 The Author(s) Journal of Eukaryotic Microbiology © 2016 International Society of Protistologists.

  11. 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

  12. The dwarf spheroidal galaxy in Draco. I - New BV photometry. II - Galactic foreground reddening

    NASA Technical Reports Server (NTRS)

    Stetson, P. B.

    1979-01-01

    BV photoelectric photometry for 39 stars and BV photographic photometry for 514 stars in the field of the Draco dwarf spheroidal galaxy are presented. The color-magnitude diagram for 512 of these field stars is found to display a well-defined red horizontal branch as well as a red giant branch whose observed width is comparable to the accidental photometric error. The results also indicate that a more diffuse sequence of stars lies about 0.1 mag to the blue of the giant branch and that an upper horizontal branch of more massive core helium-burning stars may also be present. The foreground reddening toward Draco is then determined by narrow-band uvby-beta photometry of galactic B-A-F stars.

  13. A Role of Fluoride on Free Radical Generation and Oxidative Stress in BV-2 Microglia Cells

    PubMed Central

    Shuhua, Xi; Ziyou, Liu; Ling, Yan; Fei, Wang; Sun, Guifan

    2012-01-01

    The generation of ROS and lipid peroxidation has been considered to play an important role in the pathogenesis of chronic fluoride toxicity. In the present study, we observed that fluoride activated BV-2 microglia cell line by observing OX-42 expression in immunocytochemistry. Intracellular superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), reactive oxygen species (ROS), superoxide anions (O2 ∙−), nitric oxide synthase (NOS), nitrotyrosine (NT) and nitric oxide (NO), NOS in cell medium were determined for oxidative stress assessment. Our study found that NaF of concentration from 5 to 20 mg/L can stimuli BV-2 cells to change into activated microglia displaying upregulated OX-42 expression. SOD activities significantly decreased in fluoride-treated BV-2 cells as compared with control, and MDA concentrations and contents of ROS and O2 ∙− increased in NaF-treated cells. Activities of NOS in cells and medium significantly increased with fluoride concentrations in a dose-dependent manner. NT concentrations also increased significantly in 10 and 50 mg/L NaF-treated cells compared with the control cells. Our present study demonstrated that toxic effects of fluoride on the central nervous system possibly partly ascribed to activiting of microglia, which enhanced oxidative stress induced by ROS and reactive nitrogen species. PMID:22933830

  14. AMPK and SIRT1 activation contribute to inhibition of neuroinflammation by thymoquinone in BV2 microglia.

    PubMed

    Velagapudi, Ravikanth; El-Bakoush, Abdelmeneim; Lepiarz, Izabela; Ogunrinade, Folashade; Olajide, Olumayokun A

    2017-11-01

    Thymoquinone is a known inhibitor of neuroinflammation. However, the mechanism(s) involved in its action remain largely unknown. In this study, we investigated the roles of cellular reactive oxygen species (ROS), 5' AMP-activated protein kinase (AMPK) and sirtuin 1 (SIRT1) in the anti-neuroinflammatory activity of thymoquinone. We investigated effects of the compound on ROS generation in LPS-activated microglia using the fluorescent 2',7'-dichlorofluorescin diacetate (DCFDA)-cellular ROS detection. Immunoblotting was used to detect protein levels of p40 phox , gp91 phox , AMPK, LKB1 and SIRT1. Additionally, ELISA and immunofluorescence were used to detect nuclear accumulation of SIRT1. NAD + /NADH assay was also performed. The roles of AMPK and SIRT1 in anti-inflammatory activity of thymoquinone were investigated using RNAi and pharmacological inhibition. Our results show that thymoquinone reduced cellular ROS generation, possibly through inhibition of p40 phox and gp91 phox protein. Treatment of BV2 microglia with thymoquinone also resulted in elevation in the levels of LKB1 and phospho-AMPK proteins. We further observed that thymoquinone reduced cytoplasmic levels and increased nuclear accumulation of SIRT1 protein and increased levels of NAD + . Results also show that the anti-inflammatory activity of thymoquinone was abolished when the expressions of AMPK and SIRT1 were suppressed by RNAi or pharmacological antagonists. Pharmacological antagonism of AMPK reversed thymoquinone-induced increase in SIRT1. Taken together, we propose that thymoquinone inhibits cellular ROS generation in LPS-activated BV2 microglia. It is also suggested that activation of both AMPK and NAD + /SIRT1 may contribute to the anti-inflammatory, but not antioxidant activity of the compound in BV2 microglia.

  15. 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

  16. 76 FR 50111 - Airworthiness Directives; Fokker Services B.V. Model F.28 Mark 1000, 2000, 3000, and 4000 Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-12

    ... Directives; Fokker Services B.V. Model F.28 Mark 1000, 2000, 3000, and 4000 Airplanes AGENCY: Federal... Services B.V. Model F.28 Mark 1000, 2000, 3000, and 4000 airplanes, certificated in any category, all...

  17. Anti-Inflammatory Effect of Ginsenoside Rg5 in Lipopolysaccharide-Stimulated BV2 Microglial Cells

    PubMed Central

    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-1β, 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-κB 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

  18. 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

  19. Inhibitory effects of antihistamines, diphenhydramine and chlorpheniramine, on proton currents in BV2 microglial cells.

    PubMed

    Kim, Jiwon; Song, Jin-Ho

    2017-03-05

    Microglial NADPH oxidase is a major source of toxic reactive oxygen species produced during chronic neuroinflammation. Voltage-gated proton channel (H V 1) functions to maintain the intense activity of NADPH oxidase, and channel inhibition alleviates the pathology of neurodegenerative diseases such as ischemic stroke and multiple sclerosis associated with oxidative neuroinflammation. Antagonists of histamine H 1 receptors have beneficial effects against microglia-mediated oxidative stress and neurotoxicity. We examined the effects of the H 1 antihistamines, diphenhydramine and chlorpheniramine, on proton currents in BV2 microglial cells recorded using the whole-cell patch clamp technique. Diphenhydramine and chlorpheniramine reduced the proton currents with almost the same potency, yielding IC 50 values of 42 and 43μM, respectively. Histamine did not affect proton currents, excluding the involvement of histamine receptors in their action. Neither drug shifted the voltage-dependence of activation or the reversal potential of the proton currents, even though diphenhydramine slowed the activation and deactivation kinetics. The inhibitory effects of the two antihistamines on proton currents could be utilized to develop therapeutic agents for neurodegenerative diseases and other diseases associated with H V 1 proton channel abnormalities. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. FimH adhesin of Escherichia coli K1 type 1 fimbriae activates BV-2 microglia

    SciTech Connect

    Lee, Jongseok; Shin, Sooan; Teng, C.-H.

    2005-09-02

    The generation of intense inflammation in the subarachnoid space in response to meningitis-causing bacteria contributes to brain dysfunction and neuronal injury in bacterial meningitis. Microglia, the major immune effector cells in the central nervous system (CNS), become activated by bacterial components to produce proinflammatory immune mediators. In this study, we showed that FimH adhesin, a tip component of type 1 fimbriae of meningitis-causing Escherichia coli K1, activated the murine microglial cell line, BV-2, which resulted in the production of nitric oxide and the release of tumor necrosis factor-{alpha}. Mitogen-activated protein kinases, ERK and p-38, and nuclear factor-{kappa}B were involved inmore » FimH adhesin-mediated microglial activation. These findings suggest that FimH adhesin contributes to the CNS inflammatory response by virtue of activating microglia in E. coli meningitis.« less

  1. Chern-Simons theory with Wilson lines and boundary in the BV-BFV formalism

    NASA Astrophysics Data System (ADS)

    Alekseev, Anton; Barmaz, Yves; Mnev, Pavel

    2013-05-01

    We consider the Chern-Simons theory with Wilson lines in 3D and in 1D in the BV-BFV formalism of Cattaneo-Mnev-Reshetikhin. In particular, we allow for Wilson lines to end on the boundary of the space-time manifold. In the toy model of 1D Chern-Simons theory, the quantized BFV boundary action coincides with the Kostant cubic Dirac operator which plays an important role in representation theory. In the case of 3D Chern-Simons theory, the boundary action turns out to be the odd (degree 1) version of the BF model with source terms for the B field at the points where the Wilson lines meet the boundary. The boundary space of states arising as the cohomology of the quantized BFV action coincides with the space of conformal blocks of the corresponding WZW model.

  2. Dextromethorphan inhibition of voltage-gated proton currents in BV2 microglial cells.

    PubMed

    Song, Jin-Ho; Yeh, Jay Z

    2012-05-10

    Dextromethorphan, an antitussive drug, has a neuroprotective property as evidenced by its inhibition of microglial production of pro-inflammatory cytokines and reactive oxygen species. The microglial activation requires NADPH oxidase activity, which is sustained by voltage-gated proton channels in microglia as they dissipate an intracellular acid buildup. In the present study, we examined the effect of dextromethorphan on proton currents in microglial BV2 cells. Dextromethorphan reversibly inhibited proton currents with an IC(50) value of 51.7 μM at an intracellular/extracellular pH gradient of 5.5/7.3. Dextromethorphan did not change the reversal potential or the voltage dependence of the gating. Dextrorphan and 3-hydroxymorphinan, major metabolites of dextromethorphan, and dextromethorphan methiodide were ineffective in inhibiting proton currents. The results indicate that dextromethorphan inhibition of proton currents would suppress NADPH oxidase activity and, eventually, microglial activation. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  3. Oligonucleotide microarray analysis of apoptosis induced by 15-methoxypinusolidic acid in microglial BV2 cells

    PubMed Central

    Choi, Y; Lim, SY; Jeong, HS; Koo, KA; Sung, SH; Kim, YC

    2009-01-01

    Background and purpose: We conducted a genome wide gene expression analysis to explore the biological aspects of 15-methoxypinusolidic acid (15-MPA) isolated from Biota orientalis and tried to confirm the suitability of 15-MPA as a therapeutic candidate for CNS injuries focusing on microglia. Experimental approach: Murine microglial BV2 cells were treated with 15-MPA, and their transcriptome was analysed by using oligonucleotide microarrays. Genes differentially expressed upon 15-MPA treatment were selected for RT-PCR (reverse transcription-polymerase chain reaction) analysis to confirm the gene expression. Inhibition of cell proliferation and induction of apoptosis by 15-MPA were examined by bromodeoxyuridine assay, Western blot analysis of poly-ADP-ribose polymerase and flow cytometry. Key results: A total of 514 genes were differentially expressed by 15-MPA treatment. Biological pathway analysis revealed that 15-MPA induced significant changes in expression of genes in the cell cycle pathway. Genes involved in growth arrest and DNA damage [gadd45α, gadd45γ and ddit3 (DNA damage-inducible transcript 3)] and cyclin-dependent kinase inhibitor (cdkn2b) were up-regulated, whereas genes involved in cell cycle progression (ccnd1, ccnd3 and ccne1), DNA replication (mcm4, orc1l and cdc6) and cell proliferation (fos and jun) were down-regulated. RT-PCR analysis for representative genes confirmed the expression levels. 15-MPA significantly reduced bromodeoxyuridine incorporation, increased poly-ADP-ribose polymerase cleavage and the number of apoptotic cells, indicating that 15-MPA induces apoptosis in BV2 cells. Conclusion and implications: 15-MPA induced apoptosis in murine microglial cells, presumably via inhibition of the cell cycle progression. As microglial activation is detrimental in CNS injuries, these data suggest a strong therapeutic potential of 15-MPA. PMID:19466985

  4. Antipsychotics, chlorpromazine and haloperidol inhibit voltage-gated proton currents in BV2 microglial cells.

    PubMed

    Shin, Hyewon; Song, Jin-Ho

    2014-09-05

    Microglial dysfunction and neuroinflammation are thought to contribute to the pathogenesis of schizophrenia. Some antipsychotic drugs have anti-inflammatory activity and can reduce the secretion of pro-inflammatory cytokines and reactive oxygen species from activated microglial cells. Voltage-gated proton channels on the microglial cells participate in the generation of reactive oxygen species and neuronal toxicity by supporting NADPH oxidase activity. In the present study, we examined the effects of two typical antipsychotics, chlorpromazine and haloperidol, on proton currents in microglial BV2 cells using the whole-cell patch clamp method. Chlorpromazine and haloperidol potently inhibited proton currents with IC50 values of 2.2 μM and 8.4 μM, respectively. Chlorpromazine and haloperidol are weak bases that can increase the intracellular pH, whereby they reduce the proton gradient and affect channel gating. Although the drugs caused a marginal positive shift of the activation voltage, they did not change the reversal potential. This suggested that proton current inhibition was not due to an alteration of the intracellular pH. Chlorpromazine and haloperidol are strong blockers of dopamine receptors. While dopamine itself did not affect proton currents, it also did not alter proton current inhibition by the two antipsychotics, indicating dopamine receptors are not likely to mediate the proton current inhibition. Given that proton channels are important for the production of reactive oxygen species and possibly pro-inflammatory cytokines, the anti-inflammatory and antipsychotic activities of chlorpromazine and haloperidol may be partly derived from their ability to inhibit microglial proton currents. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Effect of oral supplementation of the probiotic capsule UB-01BV in the treatment of patients with bacterial vaginosis.

    PubMed

    Sudha, M Ratna; Maurya, A K

    2012-06-01

    Bacterial vaginosis (BV) is a common condition affecting millions of women annually and is characterised by a reduction in native lactobacilli. Antimicrobial therapy used to cure the disease is often found to be ineffective. We postulate that the potential probiotic capsule UB-01BV might be efficient in the treatment of BV. In the present study, 30 Indian women diagnosed with BV presenting symptoms such as white discharge, pH greater than 4.7, increased discharge, odour, colour of discharge and pruritus were included. All subjects were assigned to receive two potential probiotic capsules UB-01BV a day for 7 days. At the end of the treatment all subjects showed significant (P<0.001) positive response as revealed by a reduction in vaginosis symptoms. Therefore, the results of the present study provide the first preliminary evidence that the potential probiotic capsule UB-01BV can exert a significant reduction in vaginal infection.

  6. Thermally controlled growth of surface nanostructures on ion-modified AIII-BV semiconductor crystals

    NASA Astrophysics Data System (ADS)

    Trynkiewicz, Elzbieta; Jany, Benedykt R.; Wrana, Dominik; Krok, Franciszek

    2018-01-01

    The primary motivation for our systematic study is to provide a comprehensive overview of the role of sample temperature on the pattern evolution of several AIII-BV semiconductor crystal (001) surfaces (i.e., InSb, InP, InAs, GaSb) in terms of their response to low-energy Ar+ ion irradiation conditions. The surface morphology and the chemical diversity of such ion-modified binary materials has been characterized by means of scanning electron microscopy (SEM). In general, all surface textures following ion irradiation exhibit transitional behavior from small islands, via vertically oriented 3D nanostructures, to smoothened surface when the sample temperature is increased. This result reinforces our conviction that the mass redistribution of adatoms along the surface plays a vital role during the formation and growth process of surface nanostructures. We would like to emphasize that this paper addresses in detail for the first time the topic of the growth kinetics of the nanostructures with regard to thermal surface diffusion, while simultaneously offering some possible approaches to supplementing previous studies and therein gaining a new insight into this complex issue. The experimental results are discussed with reference to models of the pillars growth, abutting on preferential sputtering, the self-sustained etch masking effect and the redeposition process recently proposed to elucidate the observed nanostructuring mechanism.

  7. Costunolide inhibits proinflammatory cytokines and iNOS in activated murine BV2 microglia.

    PubMed

    Rayan, Nirmala Arul; Baby, Nimmi; Pitchai, Daisy; Indraswari, Fransisca; Ling, Eng-Ang; Lu, Jia; Dheen, Thameem

    2011-06-01

    Costunolide, a sesquiterpene lactone present in Costus speciosus root exerts a variety of pharmacological activity but its effects on neuroinflammation have not been studied. Microglia, the resident phagocytic cells in the central nervous system respond to neuroinflammation and their overwhelming response in turn aggravate brain damage during infection, ischemia and neurodegenerative diseases. In this study, we report the effect of Costunolide on the production of proinflammatory mediators and mechanisms involved in BV2 microglial cells stimulated with LPS. Costunolide attenuated the expression of tumour necrosis factor-alpha, interleukin-1,6, inducible nitric oxide synthase, monocyte chemotactic protein 1 and cyclooxygenase 2 in activated microglia. This Costunolide-mediated inhibition was correspondent with the inhibition of NFkappaB activation. It has been further shown that Costunolide suppressed MAPK pathway activation by inducing MKP-1 production. Collectively our results suggest that Costunolide shows an ability to inhibit expression of multiple neuroinflammatory mediators and this is attributable to the compounds inhibition of NFkappaB and MAPK activation. This novel role of Costunolide upon investigation may aid in developing better therapeutic strategies for treatment of neuroinflammatory diseases.

  8. A Genetic Locus Necessary for Rhamnose Uptake and Catabolism in Rhizobium leguminosarum bv. trifolii

    PubMed Central

    Richardson, Jason S.; Hynes, Michael F.; Oresnik, Ivan J.

    2004-01-01

    Rhizobium leguminosarum bv. trifolii mutants unable to catabolize the methyl-pentose rhamnose are unable to compete effectively for nodule occupancy. In this work we show that the locus responsible for the transport and catabolism of rhamnose spans 10,959 bp. Mutations in this region were generated by transposon mutagenesis, and representative mutants were characterized. The locus contains genes coding for an ABC-type transporter, a putative dehydrogenase, a probable isomerase, and a sugar kinase necessary for the transport and subsequent catabolism of rhamnose. The regulation of these genes, which are inducible by rhamnose, is carried out in part by a DeoR-type negative regulator (RhaR) that is encoded within the same transcript as the ABC-type transporter but is separated from the structural genes encoding the transporter by a terminator-like sequence. RNA dot blot analysis demonstrated that this terminator-like sequence is correlated with transcript attenuation only under noninducing conditions. Transport assays utilizing tritiated rhamnose demonstrated that uptake of rhamnose was inducible and dependent upon the presence of the ABC transporter at this locus. Phenotypic analyses of representative mutants from this locus provide genetic evidence that the catabolism of rhamnose differs from previously described methyl-pentose catabolic pathways. PMID:15576793

  9. Protective Effects of Curcumin on Manganese-Induced BV-2 Microglial Cell Death.

    PubMed

    Park, Euteum; Chun, Hong Sung

    2017-08-01

    Curcumin, a bioactive component in tumeric, has been shown to exert antioxidant, anti-inflammatory, anticarcinogenic, hepatoprotective, and neuroprotective effects, but the effects of curcumin against manganese (Mn)-mediated neurotoxicity have not been studied. This study examined the protective effects of curcumin on Mn-induced cytotoxicity in BV-2 microglial cells. Curcumin (0.1-10 µM) dose-dependently prevented Mn (250 µM)-induced cell death. Mn-induced mitochondria-related apoptotic characteristics, such as caspase-3 and -9 activation, cytochrome c release, Bax increase, and Bcl-2 decrease, were significantly suppressed by curcumin. In addition, curcumin significantly increased intracellular glutathione (GSH) and moderately potentiated superoxide dismutase (SOD), both which were diminished by Mn treatment. Curcumin pretreatment effectively suppressed Mn-induced upregulation of malondialdehyde (MDA), total reactive oxygen species (ROS). Moreover, curcumin markedly inhibited the Mn-induced mitochondrial membrane potential (MMP) loss. Furthermore, curcumin was able to induce heme oxygenase (HO)-1 expression. Curcumin-mediated inhibition of ROS, down-regulation of caspases, restoration of MMP, and recovery of cell viability were partially reversed by HO-1 inhibitor (SnPP). These results suggest the first evidence that curcumin can prevent Mn-induced microglial cell death through the induction of HO-1 and regulation of oxidative stress, mitochondrial dysfunction, and apoptotic events.

  10. Quantitative Proteomics Reveals Temporal Proteomic Changes in Signaling Pathways during BV2 Mouse Microglial Cell Activation.

    PubMed

    Woo, Jongmin; Han, Dohyun; Wang, Joseph Injae; Park, Joonho; Kim, Hyunsoo; Kim, Youngsoo

    2017-09-01

    The development of systematic proteomic quantification techniques in systems biology research has enabled one to perform an in-depth analysis of cellular systems. We have developed a systematic proteomic approach that encompasses the spectrum from global to targeted analysis on a single platform. We have applied this technique to an activated microglia cell system to examine changes in the intracellular and extracellular proteomes. Microglia become activated when their homeostatic microenvironment is disrupted. There are varying degrees of microglial activation, and we chose to focus on the proinflammatory reactive state that is induced by exposure to such stimuli as lipopolysaccharide (LPS) and interferon-gamma (IFN-γ). Using an improved shotgun proteomics approach, we identified 5497 proteins in the whole-cell proteome and 4938 proteins in the secretome that were associated with the activation of BV2 mouse microglia by LPS or IFN-γ. Of the differentially expressed proteins in stimulated microglia, we classified pathways that were related to immune-inflammatory responses and metabolism. Our label-free parallel reaction monitoring (PRM) approach made it possible to comprehensively measure the hyper-multiplex quantitative value of each protein by high-resolution mass spectrometry. Over 450 peptides that corresponded to pathway proteins and direct or indirect interactors via the STRING database were quantified by label-free PRM in a single run. Moreover, we performed a longitudinal quantification of secreted proteins during microglial activation, in which neurotoxic molecules that mediate neuronal cell loss in the brain are released. These data suggest that latent pathways that are associated with neurodegenerative diseases can be discovered by constructing and analyzing a pathway network model of proteins. Furthermore, this systematic quantification platform has tremendous potential for applications in large-scale targeted analyses. The proteomics data for

  11. The Globular Cluster NGC 5286. I. A New CCD BV Color-Magnitude Diagram

    NASA Astrophysics Data System (ADS)

    Zorotovic, M.; Catelan, M.; Zoccali, M.; Pritzl, B. J.; Smith, H. A.; Stephens, A. W.; Contreras, R.; Escobar, M. E.

    2009-01-01

    We present BV photometry of the Galactic globular cluster NGC 5286, based on 128 V frames and 133 B frames, and covering the entire face of the cluster. Our photometry reaches almost two magnitudes below the turn-off level, and is accordingly suitable for age analysis. Field stars were removed statistically from the cluster's color-magnitude diagram (CMD), and a differential reddening correction applied, thus allowing a precise ridgeline to be calculated. Using the latter, a metallicity of [Fe/H] = -1.70 ± 0.05 in the Zinn & West scale, and [Fe/H] = -1.47 ± 0.02 in the Carretta & Gratton scale, was derived on the basis of several parameters measured from the red giant branch, in good agreement with the value provided in the Harris catalog. Comparing the NGC 5286 CMD with the latest photometry for M3 by P. B. Stetson, and using VandenBerg isochrones for a suitable chemical composition, we find evidence that NGC 5286 is around 1.7 ± 0.9 Gyr older than M3. This goes in the right sense to help account for the blue horizontal branch of NGC 5286, for which we provide a measurement of several morphological indicators. If NGC 5286 is a bona fide member of the Canis Major dwarf spheroidal galaxy, as previously suggested, our results imply that the latter's oldest components may be at least as old as the oldest Milky Way globular clusters. Based on observations obtained with the 1.3 m Warsaw telescope at the Las Campanas Observatory, Chile.

  12. 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).

  13. Identifying bvFTD Within the Wide Spectrum of Late Onset Frontal Lobe Syndrome: A Clinical Approach.

    PubMed

    Krudop, Welmoed A; Kerssens, Cora J; Dols, Annemiek; Prins, Niels D; Möller, Christiane; Schouws, Sigfried; van der Flier, Wiesje M; Scheltens, Philip; Sikkes, Sietske; Stek, Max L; Pijnenburg, Yolande A L

    2015-10-01

    The behavioral variant of frontotemporal dementia (bvFTD) can be difficult to diagnose because of the extensive differential diagnosis, including many other diseases presenting with a frontal lobe syndrome. We aimed to identify the diagnostic spectrum causing a late onset frontal lobe syndrome and examine the quality of commonly used instruments to distinguish between bvFTD and non-bvFTD patients, within this syndrome. A total of 137 patients fulfilling the criteria of late onset frontal lobe syndrome, aged 45 to 75 years, were included in a prospective observational study. Diagnoses were made after clinical and neuropsychological examination, and neuroimaging and cerebral spinal fluid results were taken into account. Baseline characteristics and the scores on the Mini-Mental State Exam (MMSE), frontal assessment battery (FAB), Frontal Behavioral Inventory (FBI), and Stereotypy Rating Inventory (SRI) were compared between the bvFTD and the non-bvFTD group. Fifty-five (40%) of the patients received a bvFTD diagnosis (33% probable and 7% possible bvFTD). Fifty-one patients (37%) had a psychiatric disorder, including 20 with major depressive disorder. Thirty-one patients received an alternative neurological, including neurodegenerative, diagnosis. MMSE and FAB scores were unspecific for a particular diagnosis. A score above 12 on the positive FBI subscale or a score above 5 on the SRI were indicative of a bvFTD diagnosis. A broad spectrum of both neurological and psychiatric disorders underlies late onset frontal lobe syndrome, of which bvFTD was the most prevalent diagnosis in our cohort. The commonly used MMSE and the FAB could not successfully distinguish between bvFTD and non-bvFTD, but this could be achieved with the more specific FBI and SRI. Copyright © 2015 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

  14. BmNHR96 participate BV entry of BmN-SWU1 cells via affecting the cellular cholesterol level.

    PubMed

    Dong, Xiao-Long; Liu, Tai-Hang; Wang, Wei; Pan, Cai-Xia; Du, Guo-Yu; Wu, Yun-Fei; Pan, Min-Hui; Lu, Cheng

    2017-01-22

    B.mori nucleopolyhedrovirus (BmNPV), which produces BV and ODV two virion phenotypes in its life cycle, caused the amount of economic loss in sericulture. But the mechanism of its infection was still unclear. In this study we characterized B.mori nuclear hormone receptor 96 (BmNHR96) as a NHR96 family member, which was localized in the nucleus. We also found BmNHR96 over-expression could enhance the entry of BV as well as cellular cholesterol level. Furthermore, we validated that BmNHR96 increased membrane fusion mediated by GP64, which could probably promote BV-infection. In summary, our study suggested that BmNHR96 plays an important role in BV infection and this function probably actualized by affecting cellular cholesterol level, and our results provided insights to the mechanisms of BV-infection of B.mori. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Estimation of Human Body Volume (BV) from Anthropometric Measurements Based on Three-Dimensional (3D) Scan Technique.

    PubMed

    Liu, Xingguo; Niu, Jianwei; Ran, Linghua; Liu, Taijie

    2017-08-01

    This study aimed to develop estimation formulae for the total human body volume (BV) of adult males using anthropometric measurements based on a three-dimensional (3D) scanning technique. Noninvasive and reliable methods to predict the total BV from anthropometric measurements based on a 3D scan technique were addressed in detail. A regression analysis of BV based on four key measurements was conducted for approximately 160 adult male subjects. Eight total models of human BV show that the predicted results fitted by the regression models were highly correlated with the actual BV (p < 0.001). Two metrics, the mean value of the absolute difference between the actual and predicted BV (V error ) and the mean value of the ratio between V error and actual BV (RV error ), were calculated. The linear model based on human weight was recommended as the most optimal due to its simplicity and high efficiency. The proposed estimation formulae are valuable for estimating total body volume in circumstances in which traditional underwater weighing or air displacement plethysmography is not applicable or accessible. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

  16. 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

  17. 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

    2016-02-04

    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. Copyright © 2016 Zuljan et al.

  18. Use of OM-85 BV in children suffering from recurrent respiratory tract infections and subnormal IgG subclass levels.

    PubMed

    Del-Río-Navarro, B E; Luis Sienra-Monge, J J; Berber, A; Torres-Alcántara, S; Avila-Castañón, L; Gómez-Barreto, D

    2003-01-01

    Recurrent acute respiratory tract infections (RARTIs) in children are related to IgG subclass deficiencies. The aim of the trial was to evaluate the effect of OM-85 BV in the number of RARTIs as well as in the IgG subclass levels. This was a randomized, double-blind, placebo-controlled clinical trial. Patients of ages three to six years, having three or more documented ARTIs during the last six months with subnormal IgG subclass levels were included. Patients took either one capsule of OM-85 BV (3.5 mg) or placebo orally every day for ten consecutive days per month during three consecutive months. Patients were followed three further months without drug intake. IgG subclass levels were determined before and after treatment. IgG4 levels diminished after the OM-85 BV treatment (-3 [-8.0, -1.0] median difference [95 % CI] p < 0.05 by Wilcoxon test). No other significant changes in IgG subclasses were observed. After six months the patients in the OM-85 BV group (n = 20) experienced 2.8 1.4 (mean SD) ARTIs, while the patients in the placebo group (n = 20) suffered 5.2 1.5 ARTIs (-2.4 [3.3, -1.5] mean difference [95 % CI] p < 0.001 by Student's t test). Three patients with OM-85 BV had gastrointestinal events related to drug administration, as well as three placebo patients. This study demonstrated the clinical benefit of OM-85 BV in patients suffering from RARTIs and subnormal levels of IgG subclasses. This trial opens new perspectives in the research of the mechanism of action of OM-85 BV.

  19. Neuroprotective effect of curcumin against oxidative damage in BV-2 microglia and high intraocular pressure animal model.

    PubMed

    Yue, Yan-Kun; Mo, Bin; Zhao, Jun; Yu, Ya-Jie; Liu, Lu; Yue, Chang-Li; Liu, Wu

    2014-10-01

    The involvement of local and systemic oxidative stress in intraocular pressure (IOP) elevation and optic nerve damage has been hypothesized in the pathogenesis of glaucoma. In this study, we aim to evaluate the antioxidant effects of curcumin in BV-2 microglia oxidative damage and assess its neuroprotective effects in a chronic high IOP rat model. BV-2 microglia cell line was used in an in vitro study and Wistar rats were used in an in vivo study. Cultured BV-2 microglia cells were pretreated with 10, 1, or 0.1 μM curcumin for 1 h, and sustained oxidative stress was induced by subjecting BV-2 microglia to 200 μM hydrogen peroxide (H2O2) for 24 h. MTT assay was used to determine cell viability. Changes of intracellular reactive oxygen species (ROS) and apoptosis were analyzed by flow cytometry. Three episcleral veins were cauterized to induce high IOP in Wistar rats and measured by Tonopen. After 6 weeks of treatment with curcumin (10 mg/kg/day) by intragastric administration, surviving of retinal ganglion cells was quantified. Activation of caspase 3, cytochrome c, BAX, and BCL2 was quantified by Western blotting both in BV-2 microglia and in animal model. Data were analyzed with the GraphPad Prism 5.0 software, and P<0.05 was considered to be statistically significant. The in vitro study showed that when BV-2 microglia was pretreated with curcumin, the cell viability increased and the intracellular ROS and apoptosis significantly decreased. In the in vivo study, chronic mild IOP elevation was induced for 4 weeks. In the curcumin-treated group, curcumin protected rat BV-2 microglia from death significantly. In both H2O2-treated BV-2 microglia and glaucoma models, caspase 3, cytochrome c, and BAX were downregulated and BCL2 was upregulated in the curcumin-treated group. Curcumin affords neuroprotective effects by inhibiting oxidative damage and could be a new or adjunctive treatment for glaucoma.

  20. Sugar beet proteinase inhibitor (BvSTI) gene promoter is regulated by insects and wounding in transgenic Nicotiana benthamiana

    USDA-ARS?s Scientific Manuscript database

    A regulatory sequence from a serine proteinase inhibitor gene (BvSTIpro) shown to be up-regulated in resistant interactions with a root pest of sugar beet, the sugar beet root maggot, was fused to the ß-glucuronidase (GUS) reporter gene to characterize its expression patterns in transgenic Nicotiana...

  1. Activation of PPARδ attenuates neurotoxicity by inhibiting lipopolysaccharide-triggered glutamate release in BV-2 microglial cells.

    PubMed

    Lee, Won Jin; Ham, Sun Ah; Yoo, Hyunjin; Hwang, Jung Seok; Yoo, Taesik; Paek, Kyung Shin; Lim, Dae-Seog; Han, Sung Gu; Lee, Chi-Ho; Hong, Kwonho; Seo, Han Geuk

    2018-02-01

    Neuroinflammation-associated release of glutamate from activated microglia has been implicated in the progression of neurodegenerative diseases. However, the regulatory mechanisms underlying this glutamate release are poorly understood. Here, we show that peroxisome proliferator-activated receptor delta (PPARδ) modulates neurotoxicity by inhibiting glutamate release in lipopolysaccharide (LPS)-activated BV-2 microglial cells. Activation of PPARδ by GW501516, a specific PPARδ agonist, inhibited glutamate release in BV-2 cells. This effect of GW501516 was significantly blocked by shRNA-mediated knockdown of PPARδ and by treatment with GSK0660, a specific PPARδ antagonist, indicating that PPARδ is associated with blockade of glutamate release. Additionally, GW501516-activated PPARδ suppressed generation of reactive oxygen species and expression of gp91phox, a functional subunit of NADPH oxidase 2, in BV-2 cells stimulated with LPS. The inhibitory effect of GW501516 on gp91phox expression and glutamate release was further potentiated in the presence of AG490, a specific inhibitor of janus kinase 2 (JAK2), leading to the inhibition of signal transducer and activator of transcription 1 (STAT1). By contrast, GW501516 upregulated the expression of suppressor of cytokine signaling 1 (SOCS1), an endogenous inhibitor of JAK2. Furthermore, neurotoxicity induced by conditioned media from LPS-stimulated BV-2 cells was significantly reduced when conditioned media from BV-2 cells treated with both LPS and GW501516 were used. These results indicate that PPARδ attenuates LPS-triggered neuroinflammation by enhancing SOCS1-mediated inhibition of JAK2/STAT1 signaling, thereby inhibiting neurotoxicity associated with glutamate release. © 2018 Wiley Periodicals, Inc.

  2. 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

  3. 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

  4. 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

  5. Bombyx mori nucleopolyhedrovirus (BmNPV) Bm64 is required for BV production and per os infection.

    PubMed

    Chen, Lin; Shen, Yunwang; Yang, Rui; Wu, Xiaofeng; Hu, Wenjun; Shen, Guoxin

    2015-10-24

    Bombyx mori nucleopolyhedrovirus (BmNPV) orf64 (Bm64, a homologue of ac78) is a core baculovirus gene. Recently, Li et al. reported that Ac78 was not essential for budded viruses (BVs) production and occlusion-derived viruses (ODVs) formation (Virus Res 191:70-82, 2014). Conversely, Tao et al. demonstrated that Ac78 was localized to the BV and ODV envelopes and was required for BV production and ODV formation (J Virol 87:8441-50, 2013). In this study, the function of Bm64 was characterized to determine the role of Bm64 in the BmNPV infection cycle. The temporal expression of Bm64 was examined using total RNA extracted from BmNPV-infected BmN cells at different time points by reverse-transcription PCR (RT-PCR) and 5' RACE analysis. To determine the functions of Bm64 in viral replication and the viral phenotype throughout the viral life cycle, a deletion virus (vBm(64KO)) was generated via homologous recombination in Escherichia coli. Viral replication and BV production were determined by real-time PCR. Electron microscopy was used to detect virion morphogenesis. The subcellular localization of Bm64 was determined by microscopy, and per os infectivity was used to determine its role in the baculovirus oral infection cycle. Viral plaque and titer assay results showed that a few infectious BVs were produced by vBm(64KO), suggesting that deletion of Bm64 affected BV production. Viral DNA replication was detected and polyhedra were observed in vBm(64KO)-transfected cells. Microscopy analysis revealed that Bm64 was predominantly localized to the ring zone of the nuclei during the infection cycle. Electron microscopy showed that Bm64 was not essential for the formation of ODVs or the subsequent occlusion of ODV into polyhedra. The per os infectivity results showed that the polyhedra of vBm(64KO) were unable to infect silkworm larvae. In conclusion, our results suggest that Bm64 plays an important role in BV production and per os infection, but is not required for viral DNA

  6. MiR-200c regulates ROS-induced apoptosis in murine BV-2 cells by targeting FAP-1.

    PubMed

    Yu, D S; Lv, G; Mei, X F; Cao, Y; Wang, Y F; Wang, Y S; Bi, Y L

    2014-12-02

    Objective:Reactive oxygen species (ROS) are significantly upregulated after spinal cord injury (SCI). MicroRNAs (miRNAs) are reported to be widely involved in regulating gene expression. This paper aims to explore the correlation between ROS-induced cell apoptosis and abnormal miRNA expression after SCI.Methods:To profile the expression of miRNAs after SCI, miRNA microarray was applied and the result was verified by reverse transcription quantitative PCR (RT-qPCR). ROS production following H 2 O 2 stimulation was examined using dihydroethidium staining and flow cytometry. The levels of miR-200c after H 2 O 2 treatment were determined using RT-qPCR. Cell viability and apoptosis were examined in murine BV-2 cells transfected with miR-200c mimics, inhibitor or negative control. Immunofluorescence and western blot were used to further explore the effects of miR-200c on Fas-associated phosphatase-1 (FAP-1) expression.Results:MiR-200c was showed to be significantly increased after SCI by miRNA microassay and RT-qPCR. ROS production enhanced miR-200c expression in a dose-dependent manner and induced significant apoptosis in BV-2 cells. The upregulation of miR-200c reduced cell viability and induced BV-2 cell apoptosis. MiR-200c negatively regulated the expression of FAP-1, thereby inducing FAS signaling-induced apoptosis. RT-qPCR analysis showed that the FAP-1-targeting small interfering RNA (siRNA) did not affect the level of miR-200c in murine BV-2 cells. In addition, suppression of FAP-1 by siRNA promoted apoptosis, even in cells that were co-transfected with the miR-200c inhibitor.Conclusions:The current data suggested that miR-200c contributes to apoptosis in murine BV-2 cells by regulating the expression of FAP-1. This proposes a therapeutic target for enhancing neural cell functional recovery after SCI.Spinal Cord advance online publication, 2 December 2014; doi:10.1038/sc.2014.185.

  7. Anti-inflammatory effects of the cannabidiol derivative dimethylheptyl-cannabidiol - studies in BV-2 microglia and encephalitogenic T cells.

    PubMed

    Juknat, Ana; Kozela, Ewa; Kaushansky, Nathali; Mechoulam, Raphael; Vogel, Zvi

    2016-05-01

    Dimethylheptyl-cannabidiol (DMH-CBD), a non-psychoactive, synthetic derivative of the phytocannabinoid cannabidiol (CBD), has been reported to be anti-inflammatory in RAW macrophages. Here, we evaluated the effects of DMH-CBD at the transcriptional level in BV-2 microglial cells as well as on the proliferation of encephalitogenic T cells. BV-2 cells were pretreated with DMH-CBD, followed by stimulation with the endotoxin lipopolysaccharide (LPS). The expression levels of selected genes involved in stress regulation and inflammation were determined by quantitative real-time PCR. In addition, MOG35-55-reactive T cells (TMOG) were cultured with antigen-presenting cells in the presence of DMH-CBD and MOG35-55 peptide, and cell proliferation was determined by measuring [3H]thymidine incorporation. DMH-CBD treatment downregulated in a dose-dependent manner the mRNA expression of LPS-upregulated pro-inflammatory genes (Il1b, Il6, and Tnf) in BV-2 microglial cells. The expression of these genes was also downregulated by DMH-CBD in unstimulated cells. In parallel, DMH-CBD upregulated the expression of genes related to oxidative stress and glutathione homeostasis such as Trb3, Slc7a11/xCT, Hmox1, Atf4, Chop, and p8 in both stimulated and unstimulated microglial cells. In addition, DMH-CBD dose-dependently inhibited MOG35-55-induced TMOG proliferation. The results show that DMH-CBD has similar anti-inflammatory properties to those of CBD. DMH-CBD downregulates the expression of inflammatory cytokines and protects the microglial cells by inducing an adaptive cellular response against inflammatory stimuli and oxidative injury. In addition, DMH-CBD decreases the proliferation of pathogenic activated TMOG cells.

  8. Involvement of PINK1/parkin-mediated mitophagy in ZnO nanoparticle-induced toxicity in BV-2 cells.

    PubMed

    Wei, Limin; Wang, Jianfeng; Chen, Aijie; Liu, Jia; Feng, Xiaoli; Shao, Longquan

    2017-01-01

    With the increasing application of zinc oxide nanoparticles (ZnO NPs) in biological materials, the neurotoxicity caused by these particles has raised serious concerns. However, the underlying molecular mechanisms of the toxic effect of ZnO NPs on brain cells remain unclear. Mitochondrial damage has been reported to be a factor in the toxicity of ZnO NPs. PINK1/parkin-mediated mitophagy is a newly emerging additional function of autophagy that selectively degrades impaired mitochondria. Here, a PINK1 gene knockdown BV-2 cell model was established to determine whether PINK1/parkin-mediated mitophagy was involved in ZnO NP-induced toxicity in BV-2 cells. The expression of total parkin, mito-parkin, cyto-parkin, and PINK1 both in wild type and PINK1 -/- BV-2 cells was evaluated using Western blot analysis after the cells were exposed to 10 μg/mL of 50 nm ZnO NPs for 2, 4, 8, 12, and 24 h. The findings suggested that the downregulation of PINK1 resulted in a significant reduction in the survival rate after ZnO NP exposure compared with that of control cells. ZnO NPs were found to induce the transportation of parkin from the cytoplasm to the mitochondria, implying the involvement of mitophagy in ZnO NP-induced toxicity. The deletion of the PINK1 gene inhibited the recruitment of parkin to the mitochondria, causing failure of the cell to trigger mitophagy. The present study demonstrated that apart from autophagy, PINK1/parkin-mediated mitophagy plays a protective role in ZnO NP-induced cytotoxicity.

  9. Borrelia burgdorferi basic membrane protein A could induce chemokine production in murine microglia cell line BV2.

    PubMed

    Zhao, Hua; Liu, Aihua; Cui, Yuhui; Liang, Zhang; Li, Bingxue; Bao, Fukai

    2017-10-01

    Lyme neuroborreliosis is a nervous system infectious disease caused by Borrelia burgdorferi (B. burgdorferi). It has been demonstrated that cytokines induced by B. burgdorferi are related to Lyme neuroborreliosis. Microglia is known as a key player in the immune responses that occur within the central nervous system. In response to inflammation, it will be activated and generate cytokines and chemokines. Experiments in vitro cells have showed that B. Burgdorferi membrane protein A (BmpA), a major immunogen of B. Burgdorferi, could induce Lyme arthritis and stimulate human and murine lymphocytes to produce inflammatory cytokines. In our study, the murine microglia BV2 cell line was used as a cell model to explore the stimulating effects of recombinant BmpA (rBmpA); Chemokine chip, ELISA and QPCR technology were used to measure the production of chemokines from microglial cells stimulated by rBmpA. Compared with the negative control group, CXCL2, CCL22, and CCL5 concentrations in the cell supernatant increased significantly after the rBmpA stimulation; the concentration of these chemokines increased with rBmpA concentration increasing; the mRNA expression levels of chemokines (CXCL2, CCL22, and CCL5) in murine BV2 cells increased significantly with 10 μg/mL and 20 μg/mL rBmpA stimulation; CXCL13 was not change after the rBmpA stimulation. Our study shows that chemokines, such as CXCL2, CCL22, and CCL5 were up-regulated by the rBmpA in the BV2 cells. The production of chemokines in Lyme neuroborreliosis may be mainly from microglia cells and the rBmpA may be closely related with the development of Lyme neuroborreliosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Effect of the semen extract of Cuscuta chinensis on inflammatory responses in LPS-stimulated BV-2 microglia.

    PubMed

    Kang, Seok Yong; Jung, Hyo Won; Lee, Mi-Young; Lee, Hye Won; Chae, Seong Wook; Park, Yong-Ki

    2014-08-01

    To investigate the anti-inflammatory activities of the semen extract of Cuscuta chinensis Lam. (Cuscutae Semen; CS) on the production of inflammatory mediators, nitric oxide (NO), prostaglandin 2 (PGE2), and proinflammatory cytokines in lipopolysaccharide (LPS)-stimulated BV-2 microglia. BV-2 cells were treated with CS extract for 30 min, and then stimulated with LPS or without for 24 h. The levels of NO, PGE2 and proinflammatory cytokines were measured by Griess assay and ELISA. The expression of inducible nitric oxide synthase (iNOS), and cyclooxygenase (COX)-2 mRNA and protein was determined by RT-PCR and Western blot, respectively. The phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (MAPK), and the nuclear expression of nuclear factor (NF)-κB p65 were investigated by Western blot analysis. CS extract significantly decreased the production of NO and PGE2 by suppressing the expression of iNOS and COX-2 in activated microglia. CS extract decreased the production of TNF-α, IL-1β, and IL-6 by down-regulating their transcription levels. In addition, CS extract suppressed the phosphorylation of ERK1/2, JNK, and p38 MAPK, and the nuclear translocation of NF-κB p65 in activated microglia. These results indicate that CS extract is capable of suppressing the inflammatory response by microglia activation, suggesting that CS extract has potential in the treatment of brain inflammation. Copyright © 2014 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

  11. Involvement of PINK1/parkin-mediated mitophagy in ZnO nanoparticle-induced toxicity in BV-2 cells

    PubMed Central

    Wei, Limin; Wang, Jianfeng; Chen, Aijie; Liu, Jia; Feng, Xiaoli; Shao, Longquan

    2017-01-01

    With the increasing application of zinc oxide nanoparticles (ZnO NPs) in biological materials, the neurotoxicity caused by these particles has raised serious concerns. However, the underlying molecular mechanisms of the toxic effect of ZnO NPs on brain cells remain unclear. Mitochondrial damage has been reported to be a factor in the toxicity of ZnO NPs. PINK1/parkin-mediated mitophagy is a newly emerging additional function of autophagy that selectively degrades impaired mitochondria. Here, a PINK1 gene knockdown BV-2 cell model was established to determine whether PINK1/parkin-mediated mitophagy was involved in ZnO NP-induced toxicity in BV-2 cells. The expression of total parkin, mito-parkin, cyto-parkin, and PINK1 both in wild type and PINK1−/− BV-2 cells was evaluated using Western blot analysis after the cells were exposed to 10 μg/mL of 50 nm ZnO NPs for 2, 4, 8, 12, and 24 h. The findings suggested that the downregulation of PINK1 resulted in a significant reduction in the survival rate after ZnO NP exposure compared with that of control cells. ZnO NPs were found to induce the transportation of parkin from the cytoplasm to the mitochondria, implying the involvement of mitophagy in ZnO NP-induced toxicity. The deletion of the PINK1 gene inhibited the recruitment of parkin to the mitochondria, causing failure of the cell to trigger mitophagy. The present study demonstrated that apart from autophagy, PINK1/parkin-mediated mitophagy plays a protective role in ZnO NP-induced cytotoxicity. PMID:28331313

  12. RNA sequencing analysis reveals quiescent microglia isolation methods from postnatal mouse brains and limitations of BV2 cells.

    PubMed

    He, Yingbo; Yao, Xiang; Taylor, Natalie; Bai, Yuchen; Lovenberg, Timothy; Bhattacharya, Anindya

    2018-05-22

    Microglia play key roles in neuron-glia interaction, neuroinflammation, neural repair, and neurotoxicity. Currently, various microglial in vitro models including primary microglia derived from distinct isolation methods and immortalized microglial cell lines are extensively used. However, the diversity of these existing models raises difficulty in parallel comparison across studies since microglia are sensitive to environmental changes, and thus, different models are likely to show widely varied responses to the same stimuli. To better understand the involvement of microglia in pathophysiological situations, it is critical to establish a reliable microglial model system. With postnatal mouse brains, we isolated microglia using three general methods including shaking, mild trypsinization, and CD11b magnetic-associated cell sorting (MACS) and applied RNA sequencing to compare transcriptomes of the isolated cells. Additionally, we generated a genome-wide dataset by RNA sequencing of immortalized BV2 microglial cell line to compare with primary microglia. Furthermore, based on the outcomes of transcriptional analysis, we compared cellular functions between primary microglia and BV2 cells including immune responses to LPS by quantitative RT-PCR and Luminex Multiplex Assay, TGFβ signaling probed by Western blot, and direct migration by chemotaxis assay. We found that although the yield and purity of microglia were comparable among the three isolation methods, mild trypsinization drove microglia in a relatively active state, evidenced by high amount of amoeboid microglia, enhanced expression of microglial activation genes, and suppression of microglial quiescent genes. In contrast, CD11b MACS was the most reliable and consistent method, and microglia isolated by this method maintained a relatively resting state. Transcriptional and functional analyses revealed that as compared to primary microglia, BV2 cells remain most of the immune functions such as responses to LPS

  13. Effect of Chinese herbal compound Naofucong () on the inflammatory process induced by high glucose in BV-2 cells.

    PubMed

    Jing, Guang-Chan; Zhang, Meng-Ren; Ji, Chao; Zuo, Ping-Ping; Liu, Yu-Qin; Gu, Bei

    2016-11-01

    To determine the effect of medicated serum of Chinese herbal compound Naofucong (, NFC) on the microglia BV-2 cells viability and the transcription and expression of interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) in microglia BV-2 cells to further explore the mechanisms underlying the protective effect of NFC on inflammatory process induced by high glucose. The microglia BV-2 cells incubated in vitro were divided into different groups: the control group (25 mmol/L glucose), the model group (75 mmol/L glucose), high glucose media containing different dose medicated serum of NFC. After being cultured for 24 h, changes in IL-6 and TNF-α were measured by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay. The expression of surface marker CD11b of activated microglia was measured by confocal laser scanning microscope and Western blot. Nuclear factor-κB (NF-κB) p-p65 expression was analyzed by Western blot. The model group obviously increased the expression of microglial surface marker CD11b and NF-κB p-p65 (all P<0.01), induced a signifificant up-regulation of release and the mRNA expression of IL-6 and TNF-α (P<0.01 or P<0.05). The medicated serum of NFC could obviously down-regulate the transcription and expression of surface marker CD11 b and NF-κB p-p65 (all P<0.01), and inhibit the mRNA and protein expression (P<0.01 or P<0.05) of inflflammatory cytokines, such as IL-6 and TNF-α, in microglia BV-2 cells cultured with high glucose for 24 h. The inhibition of microglial activation and IL-6 and TNF-α expression induced by high glucose may at least partly explain NFC therapeutic effects on diabetes-associated cognitive decline diseases. Its underlying mechanism could probably be related to the inhibition of NFC on NF-κB phosphorylation.

  14. 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.

  15. 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

  16. 6-Shogaol attenuates LPS-induced inflammation in BV2 microglia cells by activating PPAR-γ

    PubMed Central

    Han, Qinghe; Yuan, Qinghai; Meng, Xiaolin; Huo, Junyuan; Bao, Yuxin; Xie, Guanghong

    2017-01-01

    6-Shogaol, a pungent agent isolated from Zingiber officinale Roscoe, has been known to have anti-tumor and anti-inflammatory effects. However, the anti-inflammatory effects and biological mechanism of 6-Shogaol in LPS-activated BV2 microglia remains largely unknown. In this study, we evaluated the anti-inflammatory effects of 6-Shogaol in LPS-activated BV2 microglia. 6-Shogaol was administrated 1 h before LPS treatment. The production of inflammatory mediators were detected by ELISA. The expression of NF-κB and PPAR-γ were detected by western blot analysis. Our results revealed that 6-Shogaol inhibited LPS-induced TNF-α, IL-1β, IL-6, and PGE2 production in a concentration dependent manner. Furthermore, 6-Shogaol inhibited LPS-induced NF-κB activation by inhibiting phosphorylation and nuclear translocation of NF-κB p65. In addition, 6-Shogaol could increase the expression of PPAR-γ. Moreover, inhibition of PPAR-γ by GW9662 could prevent the inhibition of 6-Shogaol on LPS-induced inflammatory mediator production. In conclusion, 6-Shogaol inhibits LPS-induced inflammation by activating PPAR-γ. PMID:28410218

  17. 6-Shogaol attenuates LPS-induced inflammation in BV2 microglia cells by activating PPAR-γ.

    PubMed

    Han, Qinghe; Yuan, Qinghai; Meng, Xiaolin; Huo, Junyuan; Bao, Yuxin; Xie, Guanghong

    2017-06-27

    6-Shogaol, a pungent agent isolated from Zingiber officinale Roscoe, has been known to have anti-tumor and anti-inflammatory effects. However, the anti-inflammatory effects and biological mechanism of 6-Shogaol in LPS-activated BV2 microglia remains largely unknown. In this study, we evaluated the anti-inflammatory effects of 6-Shogaol in LPS-activated BV2 microglia. 6-Shogaol was administrated 1 h before LPS treatment. The production of inflammatory mediators were detected by ELISA. The expression of NF-κB and PPAR-γ were detected by western blot analysis. Our results revealed that 6-Shogaol inhibited LPS-induced TNF-α, IL-1β, IL-6, and PGE2 production in a concentration dependent manner. Furthermore, 6-Shogaol inhibited LPS-induced NF-κB activation by inhibiting phosphorylation and nuclear translocation of NF-κB p65. In addition, 6-Shogaol could increase the expression of PPAR-γ. Moreover, inhibition of PPAR-γ by GW9662 could prevent the inhibition of 6-Shogaol on LPS-induced inflammatory mediator production. In conclusion, 6-Shogaol inhibits LPS-induced inflammation by activating PPAR-γ.

  18. 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…

  19. Anti-inflammatory effects of sodium alginate/gelatine porous scaffolds merged with fucoidan in murine microglial BV2 cells.

    PubMed

    Nguyen, Van-Tinh; Ko, Seok-Chun; Oh, Gun-Woo; Heo, Seong-Yeong; Jeon, You-Jin; Park, Won Sun; Choi, Il-Whan; Choi, Sung-Wook; Jung, Won-Kyo

    2016-12-01

    Microglia are the immune cells of the central nervous system (CNS). Overexpression of inflammatory mediators by microglia can induce several neurological diseases. Thus, the underlying basic requirement for neural tissue engineering is to develop materials that exhibit little or no neuro-inflammatory effects. In this study, we have developed a method to create porous scaffolds by adding fucoidan (Fu) into porous sodium alginate (Sa)/gelatine (G) (SaGFu). For mechanical characterization, in vitro degradation, stress/strain, swelling, and pore size were measured. Furthermore, the biocompatibility was evaluated by assessing the adhesion and proliferation of BV2 microglial cells on the SaGFu porous scaffolds using scanning electron microscopy (SEM) and lactate dehydrogenase (LDH) assay, respectively. Moreover, we studied the neuro-inflammatory effects of SaGFu on BV2 microglial cells. The effect of gelatine and fucoidan content on the various properties of the scaffold was investigated and the results showed that mechanical properties increased porosity and swelling ratio with an increase in the gelatine and fucoidan, while the in vitro biodegradability decreased. The average SaGFu diameter attained by fabrication of SaGFu ranged from 60 to 120μm with high porosity (74.44%-88.30%). Cell culture using gelatine 2.0% (SaG2Fu) and 4.0% (SaG4Fu), showed good cell proliferation; more than 60-80% that with Sa alone. Following stimulation with 0.5μg/mL LPS, microglia cultured in porous SaGFu decreased their expression of nitric oxide (NO), prostaglandin E2 (PGE2), and reactive oxygen species (ROS). SaG2Fu and SaG4Fu also inhibited the activation and translocation of p65 NF-κB protein levels, resulting in reduction of NO, ROS, and PGE2 production. These results provide insights into the diverse biological effects and opens new avenues for the applications of SaGFu in neuroscience. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Protective Effect of Cactus Cladode Extracts on Peroxisomal Functions in Microglial BV-2 Cells Activated by Different Lipopolysaccharides.

    PubMed

    Saih, Fatima-Ezzahra; Andreoletti, Pierre; Mandard, Stéphane; Latruffe, Norbert; El Kebbaj, M'Hammed Saïd; Lizard, Gérard; Nasser, Boubker; Cherkaoui-Malki, Mustapha

    2017-01-07

    In this study, we aimed to evaluate the antioxidant and anti-inflammatory properties of Opuntia ficus-indica cactus cladode extracts in microglia BV-2 cells. Inflammation associated with microglia activation in neuronal injury can be achieved by LPS exposure. Using four different structurally and biologically well-characterized LPS serotypes, we revealed a structure-related differential effect of LPS on fatty acid β-oxidation and antioxidant enzymes in peroxisomes: Escherichia coli -LPS decreased ACOX1 activity while Salmonella minnesota -LPS reduced only catalase activity. Different cactus cladode extracts showed an antioxidant effect through microglial catalase activity activation and an anti-inflammatory effect by reducing nitric oxide (NO) LPS-dependent production. These results suggest that cactus extracts may possess a neuroprotective activity through the induction of peroxisomal antioxidant activity and the inhibition of NO production by activated microglial cells.

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

    SciTech Connect

    Park, Hye Young; Department of Pharmacy, Pusan National University, Busan 609-735; Kim, Nam Deuk

    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) andmore » 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.« less

  2. [Effects of electromagnetic pulse exposure on the morphological change and excretion function of BV-2 cells and possible mechanism].

    PubMed

    Yang, Long-long; Zhou, Yan; Li, Hai-juan; Guo, Juan; Zhang, Yan-jun; Ding, Gui-rong; Guo, Guo-zhen

    2012-03-01

    To study the effects of electromagnetic pulse (EMP) exposure on the morphological change and excretion functions of mouse microglia (BV-2) cells and possible mechanism. BV-2 cells were divided into two groups: the group exposed to EMP at 200 kV/m for 200 pulses and sham exposure group. At 1, 6, 12 and 24 hour after exposure the cells and culture supernatant were collected. Cellular morphological change was observed under invert microscope, the levels of TNF-α, IL-1β and IL-10 in culture supernatant were determined by enzyme-linked immunosorbent assay (ELISA), nitric oxide (NO) and reactive oxygen species (ROS) were detected by nitrate reductase method and DCFH-DA probe, respectively. The protein and phosphorylation levels of ERK, JNK and p38 were measured by Western Blot method. After the cells pre-treated with the inhibitor of p38 (SB203580) were exposed to EMP, the levels of NO and ROS in culture supernatant were detected. It was found that the large ameboid shape appeared in some microglia cells exposed to EMP for 1, 6 and 12 h. Moreover, the number of microglia cells with ameboid shape increased significantly at 1 h, 6 h and 12 h after EMP exposure compared with sham group (P < 0.05). The levels of cytokines, such as TNF-α, IL-1β and IL-10, in culture supernatant did not change obviously after EMP exposure. The levels of NO and ROS increased significantly at 1h after EMP exposure, reached the peak at 6 h, began to recover at 12 h and recovered to sham group level at 24 h (P < 0.05). Western blot results showed that the protein and protein phosphorylation levels of ERK and JNK did not change significantly after EMP exposure, however, the protein and protein phosphorylation levels of p38 increased obviously at 1 h and 6 h after EMP exposure, compared with sham group (P < 0.05). In addition, the pretreatment of p38 inhibitor (SB203580) significantly decreased NO and ROS production induced by EMP. EMP exposure may activate microglia cells and promote the

  3. VizieR Online Data Catalog: BV(RI)c light curves of DD Indi (Samec+, 2016)

    NASA Astrophysics Data System (ADS)

    Samec, R. G.; Norris, C. L.; van Hamme, W.; Faulkner, D. R.; Hill, R. L.

    2017-01-01

    Our photometry was taken with the Southeastern Association for Research in Astronomy (SARA South) Telescope at Cerro Tololo InterAmerican Observatory (CTIO) in remote mode. The 24 inch F/11 Boller and Chivens reflector was used on five nights, 2013 June 21, July 30, August 01 and 29, and September 01 with the ARC Camera cooled to -110°C. Sample nightly B, V, and B-V color light curves are given for 2013 July 30, August 29, and September 01 using standard BVRcIc Johnson-Cousins filters in Figures 2(a), (b), and (c) in the paper. The precision of a single observation was excellent, 4, 7, 5, and 6mmag in Ic, Rc, V, and B, respectively. The observations included, 313 in B, and 310 in V, 301 in Rc and 261 in Ic. Exposure times varied from 40 to 60s in B, 16 to 25s in V, and 20s in R and I. Our complete set of observations is given in Table1. (1 data file).

  4. Visualization of symbiotic tissue in intact root nodules of Vicia tetrasperma using GFP-marked Rhizobium leguminosarum bv. viciae.

    PubMed

    Chovanec, P; Hovorka, O; Novák, K

    2008-01-01

    In rhizobial symbiosis with legume plant hosts, the symbiotic tissue in the root nodules of indeterminate type is localized to the basal part of the nodule where the symbiotic zones contain infected cells (IC) interspersed with uninfected cells (UC) that are devoid of rhizobia. Although IC are easily distinguished in nodule sections using standard histochemical techniques, their observation in intact nodules is hampered by nodule tissue characteristics. Tagging of Rhizobium leguminosarum bv. viciae strain 128C30 with a constitutively expressed gene for green fluorescent protein (nonshifted mutant form cycle3) in combination with the advantages of the tiny nodules formed by Vicia tetrasperma (L.) SCHREB . allowed for vital observation of symbiotic tissue using fluorescence microscopy. Separation of a red-shifted background channel and digital image stacking along z-axis enabled us to construct a nodule image in a classical fluorescence microscopy of nodules exceeding 1 mm in diameter. In parallel, visualization of nodule bacteria inside the symbiotic tissue by confocal microscopy at the excitation wavelength 488 nm clearly distinguished IC/UC pattern in the nodule virtual sections and revealed red-shifted fluorescence of nonrhizobial origin. This signal was located on the periphery of IC and increased with their degradation, thus suggesting accumulation of secondary metabolites, presumably flavonoids. The simultaneous detection of bacteria and secondary metabolites can be used for monitoring changes to intact nodule physiology in the model legumes. The advantage of V. tetrasperma as a suggested laboratory model for pea cross-inoculation group has been demonstrated.

  5. 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

  6. 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

  7. Functional characterisation and cell specificity of BvSUT1, the transporter that loads sucrose into the phloem of sugar beet (Beta vulgaris L.) source leaves.

    PubMed

    Nieberl, P; Ehrl, C; Pommerrenig, B; Graus, D; Marten, I; Jung, B; Ludewig, F; Koch, W; Harms, K; Flügge, U-I; Neuhaus, H E; Hedrich, R; Sauer, N

    2017-05-01

    Sugar beet (Beta vulgaris L.) is one of the most important sugar-producing plants worldwide and provides about one third of the sugar consumed by humans. Here we report on molecular characterisation of the BvSUT1 gene and on the functional characterisation of the encoded transporter. In contrast to the recently identified tonoplast-localised sucrose transporter BvTST2.1 from sugar beet taproots, which evolved within the monosaccharide transporter (MST) superfamily, BvSUT1 represents a classical sucrose transporter and is a typical member of the disaccharide transporter (DST) superfamily. Transgenic Arabidopsis plants expressing the β-GLUCURONIDASE (GUS) reporter gene under control of the BvSUT1-promoter showed GUS histochemical staining of their phloem; an anti-BvSUT1-antiserum identified the BvSUT1 transporter specifically in phloem companion cells. After expression of BvSUT1 cDNA in bakers' yeasts (Saccharomyces cerevisiae) uptake characteristics of the BvSUT1 protein were studied. Moreover, the sugar beet transporter was characterised as a proton-coupled sucrose symporter in Xenopus laevis oocytes. Our findings indicate that BvSUT1 is the sucrose transporter that is responsible for loading of sucrose into the phloem of sugar beet source leaves delivering sucrose to the storage tissue in sugar beet taproot sinks. © 2017 German Botanical Society and The Royal Botanical Society of the Netherlands.

  8. Population Size and Distribution of Rhizobium leguminosarum bv. trifolii in Relation to Total Soil Bacteria and Soil Depth †

    PubMed Central

    Bottomley, Peter J.; Dughri, Muktar H.

    1989-01-01

    Bacterial cells small enough to pass through 0.4-μm-pore-size filters made up 5 to 9% of the indigenous bacterial population in 0- to 20-cm-depth samples of Abiqua silty clay loam. Within the same soil samples, cells of a similar dimension were stained with fluorescent antibodies specific to each of four antigenically distinct indigenous serogroups of Rhizobium leguminosarum bv. trifolii and made up 22 to 34% of the soil population of the four serogroups. Despite the extensive contribution of small cells to these soil populations, no evidence of their being capable of either growth or nodulation was obtained. The density of soil bacteria which could be cultured ranged between 0.5 and 8.5% of the >0.4-μm direct count regardless of media, season of sampling, or soil depth. In the same soil samples, the viable nodulating populations of biovar trifolii determined by the plant infection soil dilution technique ranged between 1 and 10% of the >0.4-μm direct-immunofluorescence count of biovar trifolii. The <0.4-μm cell populations of both total soil bacteria and biovar trifolii changed abruptly between the 10- to 15-cm and 15- to 20-cm soil depth increments, increasing from 5 to 20% and from 20 to 50%, respectively, of their direct-count totals. The increase in density of the small-cell population corresponded to a significant increase in soil bulk density (1.07 to 1.21 g cm−3). The percent contribution of the <0.4-μm direct count to individual serogroup totals increased with soil depth by approximately 2-fold (39 to 87%) for serogroups 17 and 21 and by 12-fold (6 to 75%) for serogroups 6 and 36. PMID:16347896

  9. Functional relationships between plasmids and their significance for metabolism and symbiotic performance of Rhizobium leguminosarum bv. trifolii.

    PubMed

    Stasiak, Grażyna; Mazur, Andrzej; Wielbo, Jerzy; Marczak, Małgorzata; Zebracki, Kamil; Koper, Piotr; Skorupska, Anna

    2014-11-01

    Rhizobium leguminosarum bv. trifolii TA1 (RtTA1) is a soil bacterium establishing a highly specific symbiotic relationship with clover, which is based on the exchange of molecular signals between the host plant and the microsymbiont. The RtTA1 genome is large and multipartite, composed of a chromosome and four plasmids, which comprise approximately 65 % and 35 % of the total genome, respectively. Extrachromosomal replicons were previously shown to confer significant metabolic versatility to bacteria, which is important for their adaptation in the soil and nodulation competitiveness. To investigate the contribution of individual RtTA1 plasmids to the overall cell phenotype, metabolic properties and symbiotic performance, a transposon-based elimination strategy was employed. RtTA1 derivatives cured of pRleTA1b or pRleTA1d and deleted in pRleTA1a were obtained. In contrast to the in silico predictions of pRleTA1b and pRleTA1d, which were described as chromid-like replicons, both appeared to be completely curable. On the other hand, for pRleTA1a (symbiotic plasmid) and pRleTA1c, which were proposed to be unessential for RtTA1 viability, it was not possible to eliminate them at all (pRleTA1c) or entirely (pRleTA1a). Analyses of the phenotypic traits of the RtTA1 derivatives obtained revealed the functional significance of individual plasmids and their indispensability for growth, certain metabolic pathways, production of surface polysaccharides, autoaggregation, biofilm formation, motility and symbiotic performance. Moreover, the results allow us to suggest broad functional cooperation among the plasmids in shaping the phenotypic properties and symbiotic capabilities of rhizobia.

  10. 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

  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. Role of O2 in the Growth of Rhizobium leguminosarum bv. viciae 3841 on Glucose and Succinate

    PubMed Central

    Wheatley, Rachel M.; Ramachandran, Vinoy K.; Geddes, Barney A.; Perry, Benjamin J.; Yost, Chris K.

    2016-01-01

    ABSTRACT Insertion sequencing (INSeq) analysis of Rhizobium leguminosarum bv. viciae 3841 (Rlv3841) grown on glucose or succinate at both 21% and 1% O2 was used to understand how O2 concentration alters metabolism. Two transcriptional regulators were required for growth on glucose (pRL120207 [eryD] and RL0547 [phoB]), five were required on succinate (pRL100388, RL1641, RL1642, RL3427, and RL4524 [ecfL]), and three were required on 1% O2 (pRL110072, RL0545 [phoU], and RL4042). A novel toxin-antitoxin system was identified that could be important for generation of new plasmidless rhizobial strains. Rlv3841 appears to use the methylglyoxal pathway alongside the Entner-Doudoroff (ED) pathway and tricarboxylic acid (TCA) cycle for optimal growth on glucose. Surprisingly, the ED pathway was required for growth on succinate, suggesting that sugars made by gluconeogenesis must undergo recycling. Altered amino acid metabolism was specifically needed for growth on glucose, including RL2082 (gatB) and pRL120419 (opaA, encoding omega-amino acid:pyruvate transaminase). Growth on succinate specifically required enzymes of nucleobase synthesis, including ribose-phosphate pyrophosphokinase (RL3468 [prs]) and a cytosine deaminase (pRL90208 [codA]). Succinate growth was particularly dependent on cell surface factors, including the PrsD-PrsE type I secretion system and UDP-galactose production. Only RL2393 (glnB, encoding nitrogen regulatory protein PII) was specifically essential for growth on succinate at 1% O2, conditions similar to those experienced by N2-fixing bacteroids. Glutamate synthesis is constitutively activated in glnB mutants, suggesting that consumption of 2-ketoglutarate may increase flux through the TCA cycle, leading to excess reductant that cannot be reoxidized at 1% O2 and cell death. IMPORTANCE Rhizobium leguminosarum, a soil bacterium that forms N2-fixing symbioses with several agriculturally important leguminous plants (including pea, vetch, and lentil), has

  13. 76 FR 13921 - Airworthiness Directives; Fokker Services B.V. Model F.28 Mark 0070 and 0100 Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-15

    ... corrective actions. The percentage of operating time during which fuel tanks are exposed to flammable..., which, in combination with flammable fuel vapors, could result in fuel tank explosions and consequent... Design Authority (or their delegated agent). You are required to assure the product is airworthy before...

  14. GRANULOCYTE INFILTRATION AND EXPRESSION OF THE PRO-ANGIOGENIC BV8 PROTEIN IN EXPERIMENTAL EL4 AND LEWIS LUNG CARCINOMA TUMORS.

    PubMed

    Jiang, Kan; Kwak, Hyeongil; Tosato, Giovanna

    2013-01-18

    Although Vascular Endothelial Growth Factor (VEGF)-targeted therapies have shown efficacy in the treatment of certain advanced cancers, benefits to patients have been modest, which is attributed to tumor resistance to VEGF neutralization. Recent efforts to identify new targets to inhibit tumor angiogenesis have identified Bv8 (prokineticin 2), a myeloid cell-derived protein that promotes endothelial cell growth and tumor angiogenesis, but many mechanistic aspects of the pro-tumorigenic function of Bv8 are unclear. Here we demonstrate that CD11b+, Ly6C+, Ly6G+ granulocytes are the predominant cell source of Bv8 expression in bone marrow, spleen and in tumor tissues. Using granulocyte-deficient Growth factor independence-1 (Gfi1)-null mutant mice and normal littermates, we found that EL4 lymphoma tumors grow significantly larger in the granulocyte and Bv8-deficient mutant mice in comparison to the normal mice that display abundant tumor-associated granulocytes and Bv8 expression. Conversely, Lewis lung carcinoma (LLC-1) tumors grew to a significantly greater size in the normal mice in comparison to the Gfi1-null mice, but normal granulocyte tumor infiltration was modest. Quantitative analysis of tissue vascularization showed that EL4 and LLC-1 tumors from normal and Gfi1-mutant mice are similarly vascularized. These results confirm the critical contribution of the tumor microenvironment in determining the rate of tumor progression independently of tumor angiogenesis, and reveal some of the complexities of granulocyte and Bv8 functions in modulating tumor growth.

  15. GRANULOCYTE INFILTRATION AND EXPRESSION OF THE PRO-ANGIOGENIC BV8 PROTEIN IN EXPERIMENTAL EL4 AND LEWIS LUNG CARCINOMA TUMORS

    PubMed Central

    Jiang, Kan; Kwak, Hyeongil; Tosato, Giovanna

    2014-01-01

    Although Vascular Endothelial Growth Factor (VEGF)-targeted therapies have shown efficacy in the treatment of certain advanced cancers, benefits to patients have been modest, which is attributed to tumor resistance to VEGF neutralization. Recent efforts to identify new targets to inhibit tumor angiogenesis have identified Bv8 (prokineticin 2), a myeloid cell-derived protein that promotes endothelial cell growth and tumor angiogenesis, but many mechanistic aspects of the pro-tumorigenic function of Bv8 are unclear. Here we demonstrate that CD11b+, Ly6C+, Ly6G+ granulocytes are the predominant cell source of Bv8 expression in bone marrow, spleen and in tumor tissues. Using granulocyte-deficient Growth factor independence-1 (Gfi1)-null mutant mice and normal littermates, we found that EL4 lymphoma tumors grow significantly larger in the granulocyte and Bv8-deficient mutant mice in comparison to the normal mice that display abundant tumor-associated granulocytes and Bv8 expression. Conversely, Lewis lung carcinoma (LLC-1) tumors grew to a significantly greater size in the normal mice in comparison to the Gfi1-null mice, but normal granulocyte tumor infiltration was modest. Quantitative analysis of tissue vascularization showed that EL4 and LLC-1 tumors from normal and Gfi1-mutant mice are similarly vascularized. These results confirm the critical contribution of the tumor microenvironment in determining the rate of tumor progression independently of tumor angiogenesis, and reveal some of the complexities of granulocyte and Bv8 functions in modulating tumor growth. PMID:25493215

  16. 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

  17. Functional and Expression Analysis of the Metal-Inducible dmeRF System from Rhizobium leguminosarum bv. viciae

    PubMed Central

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

    2013-01-01

    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

  18. A synthetic diosgenin primary amine derivative attenuates LPS-stimulated inflammation via inhibition of NF-κB and JNK MAPK signaling in microglial BV2 cells.

    PubMed

    Cai, Bangrong; Seong, Kyung-Joo; Bae, Sun-Woong; Chun, Changju; Kim, Won-Jae; Jung, Ji-Yeon

    2018-06-08

    Diosgenin, a precursor of steroid hormones in plants, is known to exhibit diverse pharmacological activities including anti-inflammatory properties. In this study, (3β, 25R)‑spirost‑5‑en‑3‑oxyl (2‑((2((2‑aminoethyl)amino)ethyl)amino)ethyl) carbamate (DGP), a new synthetic diosgenin derivative incorporating primary amine was used to investigate its anti-inflammatory effects and underlying mechanisms of action in lipopolysaccharide (LPS)-stimulated microglial BV2 cells. Pretreatment with DGP resulted in significant inhibition of nitric oxide (NO) synthesis, and down-regulation of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in LPS-stimulated microglial BV2 cells. In addition, DGP decreased the production of reactive oxygen species (ROS) and pro-inflammatory cytokines such as interleukin (IL)-6, IL-1β, and tumor necrosis factor alpha (TNF-α). The inhibitory effects of DGP on these inflammatory mediators in LPS-stimulated microglial BV2 cells were regulated by NF-κB signaling through blocking p65 nuclear translocation and NF-κB p65/DNA binding activity. DGP also blocked the phosphorylation of c-Jun amino-terminal kinase (JNK), but not p38 kinase or extracellular signal-regulated kinases (ERK). The NF-κB inhibitor JSH-23 and JNK-specific inhibitor SP600125 significantly decreased NO production and IL-6 release in LPS-stimulated BV2 cells, respectively. The overall results demonstrate that DGP has anti-inflammatory effects on LPS-stimulated BV2 cells via inhibition of NF-κB and JNK activation, suggesting that DGP is a potential prophylactic agent in various neurodegenerative disorders. Copyright © 2018. Published by Elsevier B.V.

  19. HIV-1 gp120 Upregulates Brain-Derived Neurotrophic Factor (BDNF) Expression in BV2 Cells via the Wnt/β-Catenin Signaling Pathway.

    PubMed

    Wang, Yongdi; Liao, Jinxu; Tang, Shao-Jun; Shu, Jianhong; Zhang, Wenping

    2017-06-01

    HIV-1 gp120 plays a critical role in the pathogenesis of HIV-associated pain, but the underlying molecular mechanisms are incompletely understood. This study aims to determine the effect and possible mechanism of HIV-1 gp120 on BDNF expression in BV2 cells (a murine-derived microglial cell line). We observed that gp120 (10 ng/ml) activated BV2 cells in cultures and upregulated proBDNF/mBDNF. Furthermore, gp120-treated BV2 also accumulated Wnt3a and β-catenin, suggesting the activation of the Wnt/β-catenin pathway. We demonstrated that activation of the pathway by Wnt3a upregulated BDNF expression. In contrast, inhibition of the Wnt/β-catenin pathway by either DKK1 or IWR-1 attenuated BDNF upregulation induced by gp120 or Wnt3a. These findings collectively suggest that gp120 stimulates BDNF expression in BV2 cells via the Wnt/β-catenin signaling pathway.

  20. Neuroprotective effects of pretreatment with propofol in LPS-induced BV-2 microglia cells: role of TLR4 and GSK-3β.

    PubMed

    Gui, Bo; Su, Mingyan; Chen, Jie; Jin, Lai; Wan, Rong; Qian, Yanning

    2012-10-01

    Surgery often leads to neuroinflammation, which mainly acts as the activation of microglia cells. Propofol is always used for induction and maintenance of anesthesia prior to surgical trauma, whereas whether or not it could attenuate neuroinflammation used prophylactically is not well defined. In the present study, we incubated BV-2 microglia cells with 1 μg/ml lipopolysaccharide (LPS) to mimic neuroinflammation in vitro. Firstly, cell viability was measured using 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and the data indicated that propofol would not reduce cell viability unless its concentration reached 300 μM. Secondly, BV-2 microglia cells were pretreated with 30 μM propofol (clinically relevant concentration), and then stimulated with LPS. The results showed that the production of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-10 was considerably increased by LPS, but the change could be markedly attenuated by pretreatment with propofol. Meanwhile, pretreatment with propofol inhibited LPS-induced augmentation of toll-like receptor 4 (TLR4) expression at both mRNA and protein levels and further upregulated LPS-induced inactivation of glycogen synthase kinase-3β (GSK-3β) in BV-2 microglia cells. These results indicated, at least in part, that pretreatment with propofol can protect BV-2 microglia cells against LPS-induced inflammation. Downregulation of TLR4 expression and inactivation of GSK-3β may be involved in its protective effect.

  1. Inhibitory effects of the methylene chloride fraction of JP05 on the production of inflammatory mediators in LPS-activated BV2 microglia.

    PubMed

    Jung, Hyo Won; Oh, Tae Woo; Jung, Jin Ki; Lee, Je-Hyun; Shin, Gil Jo; Park, Yong-Ki

    2012-02-01

    Excessive production of inflammatory mediators such as nitric oxide (NO) and proinflammatory cytokines from activated microglia in the central nervous system contributes to uncontrolled inflammation in neurodegenerative disorders. In this study, we investigated the anti-inflammatory activities of the methylene chloride fraction of JP05 (JP05-MC) on the production of inflammatory mediators in lipopolysaccharide (LPS)-stimulated BV2 mouse microglial cells, and its mechanism of action. JP05-MC significantly inhibited LPS-induced production of NO and the proinflammatory cytokines, TNF-α and IL-6, in BV2 cells. JP05-MC also attenuated the mRNA expression and protein levels of inducible nitric oxide synthase in LPS-induced BV2 cells. JP05-MC significantly attenuated LPS-elicited phosphorylation of the mitogen-activated protein kinase (MAPK), extracellular-signal-regulated kinase 1/2, and nuclear factor-κB (NF-κB) nuclear translocation in BV2 cells. Our results indicate that JP05-MC exerts anti-inflammatory properties via downregulation of inflammatory mediator gene transcription by suppressing the MAPK and NF-κB pathways, suggesting that JP05-MC may have therapeutic potential as an anti-inflammatory agent in neurodegenerative diseases.

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

    USDA-ARS?s Scientific Manuscript database

    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...

  3. Proinflammatory effects of S100A8/A9 via TLR4 and RAGE signaling pathways in BV-2 microglial cells

    PubMed Central

    Ma, Li; Sun, Peng; Zhang, Jian-Cheng; Zhang, Qing; Yao, Shang-Long

    2017-01-01

    S100A8/A9, a heterodimer of the two calcium-binding proteins S100A8 and S100A9, has emerged as an important proinflammatory mediator in acute and chronic inflammation. However, whether S100A8/A9 is implicated in microglial-induced neuroinflammatory response remains unclear. Here, we found that S100A8/A9 significantly increased the secretion of proinflammatory cytokines including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in cultured BV-2 microglial cells. Inhibition of the Toll-like receptor 4 (TLR4) and the receptor for advanced glycation end-products (RAGE) with C225 and a RAGE-blocking antibody, respectively significantly reduced the secretion of TNF-α and IL-6 from S100A8/A9-stimulated BV-2 microglial cells. Furthermore, S100A8/A9 markedly enhanced the nuclear translocation of NF-κB p65 and the DNA-binding activities of NF-κB in BV-2 microglial cells, and suppression of ERK and JNK/MAPK signaling pathways by PD98059 or SP600125 significantly inhibited NF-κB activity and the release of TNF-α and IL-6 in the S100A8/A9-treated BV-2 microglial cells. Our data also showed that inhibition of NF-κB with pyrrolidine dithiocarbamate (PDTC) significantly reduced the secretion of TNF-α and IL-6 from BV-2 microglial cells treated with S100A8/A9. Taken together, our data suggest that S100A8/A9 acts directly on BV-2 microglial cells via binding to TLR4 and RAGE on the membrane and then stimulates the secretion of proinflammatory cytokines through ERK and JNK-mediated NF-κB activity in BV-2 microglial cells. Targeting S100A8/A9 may provide a novel therapeutic strategy in microglial-induced neuroinflammatory diseases. PMID:28498464

  4. Proinflammatory effects of S100A8/A9 via TLR4 and RAGE signaling pathways in BV-2 microglial cells.

    PubMed

    Ma, Li; Sun, Peng; Zhang, Jian-Cheng; Zhang, Qing; Yao, Shang-Long

    2017-07-01

    S100A8/A9, a heterodimer of the two calcium-binding proteins S100A8 and S100A9, has emerged as an important proinflammatory mediator in acute and chronic inflammation. However, whether S100A8/A9 is implicated in microglial‑induced neuroinflammatory response remains unclear. Here, we found that S100A8/A9 significantly increased the secretion of proinflammatory cytokines inclu-ding tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in cultured BV-2 microglial cells. Inhibition of the Toll-like receptor 4 (TLR4) and the receptor for advanced glycation end-products (RAGE) with C225 and a RAGE-blocking antibody, respectively significantly reduced the secretion of TNF-α and IL-6 from S100A8/A9-stimulated BV-2 microglial cells. Furthermore, S100A8/A9 markedly enhanced the nuclear translocation of NF-κB p65 and the DNA-binding activities of NF-κB in BV-2 microglial cells, and suppression of ERK and JNK/MAPK signaling pathways by PD98059 or SP600125 significantly inhibited NF-κB activity and the release of TNF-α and IL-6 in the S100A8/A9-treated BV-2 microglial cells. Our data also showed that inhibition of NF-κB with pyrrolidine dithiocarbamate (PDTC) significantly reduced the secretion of TNF-α and IL-6 from BV-2 microglial cells treated with S100A8/A9. Taken together, our data suggest that S100A8/A9 acts directly on BV-2 microglial cells via binding to TLR4 and RAGE on the membrane and then stimulates the secretion of proinflammatory cytokines through ERK and JNK-mediated NF-κB activity in BV-2 microglial cells. Targeting S100A8/A9 may provide a novel therapeutic strategy in microglial-induced neuroinflammatory diseases.

  5. 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. Copyright © 2015 the American Physiological Society.

  6. T-cell receptor BV gene usage in colorectal carcinoma patients immunised with recombinant Ep-CAM protein or anti-idiotypic antibody.

    PubMed

    Mosolits, Szilvia; Markovic, Katja; Fagerberg, Jan; Frödin, Jan-Erik; Rezvany, Mohammad-Reza; Kiaii, Shahryar; Mellstedt, Håkan; Jeddi-Tehrani, Mahmood

    2005-06-01

    The tumour-associated antigen, Ep-CAM, is over-expressed in colorectal carcinoma (CRC). In the present study, a recombinant Ep-CAM protein or a human anti-idiotypic antibody (anti-Id) mimicking Ep-CAM, either alone or in combination, was used for vaccination of CRC patients (n=9). GM-CSF was given as an adjuvant cytokine. A cellular immune response was assessed by measuring anti-Ep-CAM lymphoproliferation, IFN-gamma production (ELISPOT) and by analysing the TCR BV gene usage within the CD4+ and CD8+ T-cell subsets followed by CDR3 fragment analysis. A proliferative and/or IFN-gamma T-cell response was induced against the Ep-CAM protein in eight out of nine patients, and against Ep-CAM-derived peptides in nine out of nine patients. Analysis of the TCR BV gene usage showed a significantly higher usage of BV12 family in CD4+ T cells of patients both before and after immunisation than in those of healthy control donors (p<0.05). In the CD8+ T-cell subset, a significant (p<0.05) increase in the BV19 usage was noted in patients after immunisation. In individual patients, a number of TCR BV gene families in both CD4+ and CD8+ T cells were over-expressed mainly in post-immunisation samples. Analysis of the CDR3 length polymorphism revealed a higher degree of clonality in post-immunisation samples than in pre-immunisation samples. In vitro stimulation with Ep-CAM protein confirmed the expansion of anti-Ep-CAM T-cell clones. The results indicate that immunisation with the Ep-CAM protein and/or anti-Id entails the induction of an anti-Ep-CAM T-cell response in CRC patients, and suggest that BV19+ CD8+ T cells might be involved in a vaccine-induced immune response.

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

    DOE PAGES

    Mazur, Andrzej; De Meyer, Sofie E.; Tian, Rui; ...

    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

  8. 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

    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

  9. Inducible nitric oxide synthase is key to peroxynitrite-mediated, LPS-induced protein radical formation in murine microglial BV2 cells

    PubMed Central

    Kumar, Ashutosh; Chen, Shih-Heng; Kadiiska, Maria B.; Hong, Jau-Shyong; Zielonka, Jacek; Kalyanaraman, Balaraman; Mason, Ronald P.

    2014-01-01

    Microglia are the resident immune cells in the brain. Microglial activation is characteristic of several inflammatory and neurodegenerative diseases including Alzheimer’s disease, multiple sclerosis, and Parkinson’s disease. Though LPS-induced microglial activation in models of Parkinson’s disease (PD) is well documented, the free radical-mediated protein radical formation and its underlying mechanism during LPS-induced microglial activation is not known. Here we have used immuno-spin trapping and RNA interference to investigate the role of inducible nitric oxide synthase (iNOS) in peroxynitrite-mediated protein radical formation in murine microglial BV2 cells treated with LPS. Treatment of BV2 cells with LPS resulted in morphological changes, induction of iNOS and increased protein radical formation. Pretreatments with FeTPPS (a peroxynitrite decomposition catalyst), L-NAME (total NOS inhibitor), 1400W (iNOS inhibitor) and apocynin significantly attenuated LPS-induced protein radical formation and tyrosine nitration. Results obtained with coumarin-7-boronic acid, a highly specific probe for peroxynitrite detection, correlated with LPS-induced tyrosine nitration, which demonstrated involvement of peroxynitrite in protein radical formation. A similar degree of protection conferred by 1400W and L-NAME led us to conclude that only iNOS, and no other forms of NOS, are involved in LPS-induced peroxynitrite formation. Subsequently, siRNA for iNOS, the iNOS-specific inhibitor 1400W, the NF-kB inhibitor PDTC and the P38 MAPK inhibitor SB202190 were used to inhibit iNOS directly or indirectly. Inhibition of iNOS precisely correlated with decreased protein radical formation in LPS-treated BV2 cells. The time course of protein radical formation also matched the time course of iNOS expression. Taken together, these results prove the role of iNOS in peroxynitrite-mediated protein radical formation in LPS-treated microglial BV2 cells. PMID:24746617

  10. Prevention of recurrent rhinopharyngitis in at-risk children in France: a cost-effectiveness model for a nonspecific immunostimulating bacterial extract (OM-85 BV).

    PubMed

    Pessey, Jean-Jacques; Mégas, Françoise; Arnould, Benoît; Baron-Papillon, Florence

    2003-01-01

    To estimate the pharmacoeconomic impact for the French Social Security System of preventing recurrent acute rhinopharyngitis (RARP) in at-risk children with OM-85 BV, an immunostimulating agent indicated for the prevention of recurrences. A decision-analysis model. The probability of progression of the infection and of its associated care, the principal direct costs linked to them, and the effectiveness of OM-85 BV were established or calculated by reviewing the available literature (published between 1984 and 2000). Four experts validated the parameters and the model. For the French Social Security System, the mean direct cost for an acute rhinopharyngitis (ARP) infection was 49.39 Euro(2000 values). By using OM-85 BV prevention, 1.52 infections were prevented in 6 months saving 67.83 Euro on the costs of care for the recurrently infected child. Sensitivity analyses confirmed the robustness of the model and indicated a saving of between 6.28 Euro and 303.64 Euro in direct costs for each individual treated preventively. Threshold analyses showed that OM-85 BV prophylaxis is economically profitable if more than 0.15 infections are prevented and if direct costs of care of an ARP are greater than 4.78 Euro. Non-specific immunotherapy should be considered for the child at risk of RARP and administered in addition to other recommended measures. The economic savings for the community of using a medication for which the clinical effectiveness has been demonstrated should also be taken into account in assessing its usefulness.

  11. [Influence of OM-85 BV on hBD-1 and immunoglobulin in children with asthma and recurrent respiratory tract infection].

    PubMed

    Liao, Jia-Yi; Zhang, Tao

    2014-05-01

    To observe the clinical therapeutic effect of OM-85 BV(OM-85 Broncho-Vaxom) in children with asthma and recurrent respiratory tract infection, and the effect of OM-85 BV on human β-defensins 1 (hBD-1) and immunoglobulin levels. Sixty-two children with asthma and recurrent respiratory infection treated between 2011 January and December were divided into two groups by the randomized, double blind method: a treatment group and a control group. With inhaling corticosteroids, the treatment group was given OM-85 BV, and the control group was given a placebo. Clinical curative effects and adverse reactions were observed. Serum levels of hBD-1, IgA, IgG, IgM and urea and alanine aminotransferase (ALT) were measured before treatment and 6 months and 12 months after treatment. Compared with the control group and before treatment, the frequency of respiratory tract infection was reduced in the treatment group 6 months and 12 months after treatment (P<0.05), and serum levels of hBD-1, IgA and IgG in the treatment group increased significantly (P<0.05). There was no significant difference in serum levels of urea, ALT and IgM between the control and treatment groups (P>0.05). Mild adverse reactions occurred in 3 cases in the two groups, 2 cases of abdominal pain and 1 cases of constipation. OM-85 BV can improve serum levels of hBD-1, IgA and IgG, reduce the occurrence of acute respiratory tract infection and cause mild adverse reactions, suggesting its satisfactory therapeutic effect and safety in the treatment of asthma combined with recurrent respiratory tract infection in children.

  12. Mutation in the pssA gene involved in exopolysaccharide synthesis leads to several physiological and symbiotic defects in Rhizobium leguminosarum bv. trifolii.

    PubMed

    Janczarek, Monika; Rachwał, Kamila

    2013-12-05

    The symbiotic nitrogen-fixing bacterium Rhizobium leguminosarum bv. trifolii 24.2 secretes large amounts of acidic exopolysaccharide (EPS), which plays a crucial role in establishment of effective symbiosis with clover. The biosynthesis of this heteropolymer is conducted by a multi-enzymatic complex located in the bacterial inner membrane. PssA protein, responsible for the addition of glucose-1-phosphate to a polyprenyl phosphate carrier, is involved in the first step of EPS synthesis. In this work, we characterize R. leguminosarum bv. trifolii strain Rt270 containing a mini-Tn5 transposon insertion located in the 3'-end of the pssA gene. It has been established that a mutation in this gene causes a pleiotropic effect in rhizobial cells. This is confirmed by the phenotype of the mutant strain Rt270, which exhibits several physiological and symbiotic defects such as a deficiency in EPS synthesis, decreased motility and utilization of some nutrients, decreased sensitivity to several antibiotics, an altered extracellular protein profile, and failed host plant infection. The data of this study indicate that the protein product of the pssA gene is not only involved in EPS synthesis, but also required for proper functioning of Rhizobium leguminosarum bv. trifolii cells.

  13. Shikonin Isolated from Lithospermum erythrorhizon Downregulates Proinflammatory Mediators in Lipopolysaccharide-Stimulated BV2 Microglial Cells by Suppressing Crosstalk between Reactive Oxygen Species and NF-κB.

    PubMed

    Prasad, Rajapaksha Gedara; Choi, Yung Hyun; Kim, Gi-Young

    2015-03-01

    According to the expansion of lifespan, neuronal disorder based on inflammation has been social problem. Therefore, we isolated shikonin from Lithospermum erythrorhizon and evaluated anti-inflammatory effects of shikonin in lipopolysaccharide (LSP)-stimulated BV2 microglial cells. Shikonin dose-dependently inhibits the expression of the proinflammatory mediators, nitric oxide (NO), prostaglandin E2 (PGE2), and tumor necrosis factor-α (TNF-α) as well as their main regulatory genes and products such as inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), and TNF-α in LPS-stimulated BV2 microglial cells. Additionally, shikonin suppressed the LPS-induced DNA-binding activity of nuclear factor-κB (NF-κB) to regulate the key regulatory genes of the proinflammatory mediators, such as iNOS, COX-2, and TNF-α, accompanied with downregulation of reactive oxygen species (ROS) generation. The results indicate that shikonin may downregulate the expression of proinflammatory genes involved in the synthesis of NO, PGE2, and TNF-α in LPS-treated BV2 microglial cells by suppressing ROS and NF-κB. Taken together, our results revealed that shikonin exerts downregulation of proinflammatory mediators by interference the ROS and NF-κB signaling pathway.

  14. Shikonin Isolated from Lithospermum erythrorhizon Downregulates Proinflammatory Mediators in Lipopolysaccharide-Stimulated BV2 Microglial Cells by Suppressing Crosstalk between Reactive Oxygen Species and NF-κB

    PubMed Central

    Prasad, Rajapaksha Gedara; Choi, Yung Hyun; Kim, Gi-Young

    2015-01-01

    According to the expansion of lifespan, neuronal disorder based on inflammation has been social problem. Therefore, we isolated shikonin from Lithospermum erythrorhizon and evaluated anti-inflammatory effects of shikonin in lipopolysaccharide (LSP)-stimulated BV2 microglial cells. Shikonin dose-dependently inhibits the expression of the proinflammatory mediators, nitric oxide (NO), prostaglandin E2 (PGE2), and tumor necrosis factor-α (TNF-α) as well as their main regulatory genes and products such as inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), and TNF-α in LPS-stimulated BV2 microglial cells. Additionally, shikonin suppressed the LPS-induced DNA-binding activity of nuclear factor-κB (NF-κB) to regulate the key regulatory genes of the proinflammatory mediators, such as iNOS, COX-2, and TNF-α, accompanied with downregulation of reactive oxygen species (ROS) generation. The results indicate that shikonin may downregulate the expression of proinflammatory genes involved in the synthesis of NO, PGE2, and TNF-α in LPS-treated BV2 microglial cells by suppressing ROS and NF-κB. Taken together, our results revealed that shikonin exerts downregulation of proinflammatory mediators by interference the ROS and NF-κB signaling pathway. PMID:25767678

  15. Sulforaphane attenuates microglia-mediated neuronal necroptosis through down-regulation of MAPK/NF-κB signaling pathways in LPS-activated BV-2 microglia.

    PubMed

    Qin, Sisi; Yang, Canhong; Huang, Weihua; Du, Shuhua; Mai, Hantao; Xiao, Jijie; Lü, Tianming

    2018-01-31

    Sulforaphane (SFN), a natural dietary isothiocyanate in cruciferous vegetables such as broccoli and cabbage, has very strong anti-inflammatory activity. Activation of microglia leads to overexpression of a series of pro-inflammatory mediators, which play a vital role in neuronal damage. SFN may have neuroprotective effects in different neurodegenerative diseases related to inflammation. However, the mechanisms underlying SFN's protection of neurons against microglia-mediated neuronal damage are not fully understood. Here, we investigated how SFN attenuated microglia-mediated neuronal damage. Our results showed that SFN could not directly protect the viability of neurons following pro-inflammatory mediators, but increased the viability of BV-2 microglia and down-regulated the mRNA and protein levels of pro-inflammatory mediators including TNF-α, IL-1β, IL-6 and iNOS in a concentration-dependent manner in BV-2 cells. SFN also significantly blocked the phosphorylation of MAPKs (p38, JNK, and ERK1/2) and NF-κB p65, both by itself and with MAPK inhibitors (SB203580, SP 600125, and U0126) or an NF-κB inhibitor (PDTC). The expression of pro-inflammatory proteins was also blocked by SFN with or without inhibitors. Further, SFN indirectly increased the viability and maintained the morphology of neurons, and the protein expression of RIPK3 and MLKL was significantly suppressed by SFN in neuronal necroptosis through p38, JNK, and NF-κB p65 but not ERK1/2 signaling pathways. Together, our results demonstrate that SFN attenuates LPS-induced pro-inflammatory responses through down-regulation of MAPK/NF-κB signaling pathway in BV-2 microglia and thus indirectly suppresses microglia-mediated neuronal damage. Copyright © 2018 Elsevier Ltd. All rights reserved.

  16. The T-cell receptor beta chain CDR3 region of BV8S1/BJ1S5 transcripts in type 1 diabetes.

    PubMed

    Naserke, H E; Durinovic-Bellò, I; Seidel, D; Ziegler, A G

    1996-01-01

    We recently described the T-cell receptor (TCR) beta chain CDR3 motif S-SDRLG-NQPQH (BV8S1-BJ1S5) in an islet-specific T-cell clone (K2.12) from a type 1 diabetic patient (AS). A similar motif (RLGNQ) was also reported in a T-cell clone of non-obese diabetic (NOD) mice by others. In order to determine the frequency of our motif in selected and unselected T-cell populations, we cloned and sequenced the CDR3 region of BV8S1-BJ1S5 transcripts. These transcripts were derived from unstimulated peripheral blood T lymphocytes from two type 1 diabetic patients (AS and FS) and their non-diabetic sibling (WS), as well as from an islet-specific T-cell line of one of the patients. In addition, we compared the structure and composition of the CDR3 region in BV8S1-BJ1S5 transcripts from peripheral blood T cells between the patients and their non-diabetic sibling (>50 sequences each). We found that 30% of the islet-specific T-cell line cDNA clones expressed the entire sequence-motif, whereas it was absent in the clones of unstimulated peripheral blood T cells from both patients and their non-diabetic sibling. The average length of the CDR3 region was shorter in the patients (mean AS 9.9, FS 9.9, versus WS 10.7, p = 0.0037) and the number of inserted nucleotides in N nucleotide addition at the DJ-junction lower (mean AS 3.5, FS 3. 2, versus WS 5.2, P = <10(-4)) as compared with their non-diabetic sibling. Moreover, the pattern of amino acid usage in the CDR3 region was dissimilar at positions 5 and 6, where polar amino acids predominated in both diabetic siblings. In contrast, basic amino acids are preferentially used at position 5 in the clones of the non-diabetic sibling. These data provide information on the general structure of the TCR(BV8S1-BJ1S5) CDR3 region in type 1 diabetes and may indicate differences in the amino and nucleic acid composition of the TCR beta chain CDR3 region between two type 1 diabetic patients and their non-diabetic sibling.

  17. Quantitative Analysis and Biological Efficacies regarding the Neuroprotective and Antineuroinflammatory Actions of the Herbal Formula Jodeungsan in HT22 Hippocampal Cells and BV-2 Microglia

    PubMed Central

    Lim, Hye-Sun

    2017-01-01

    Jodeungsan (JDS) is a traditional herbal formula that comprises seven medicinal herbs and is broadly utilized to treat hypertension, dementia, and headache. However, the effects of JDS and its herbal components on neurodegenerative diseases have not been reported. We examined the inhibitory effects of JDS and its seven components on neuronal cell death and inflammation using HT22 hippocampal cells and BV-2 microglia, respectively. Among its seven herbal components, Uncaria sinensis (US), Chrysanthemum morifolium (CM), Zingiber officinale (ZO), Pinellia ternata (PT), Citrus unshiu (CU), and Poria cocos (PC) exhibited significant neuroprotective effects in HT22 cells. In BV-2 cells, JDS significantly suppressed the production of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), indicating the antineuroinflammatory activity of JDS. In addition, the herbal extracts from ZO, Panax ginseng (PG), PT, CU, and PC exhibited inhibitory effects on the inflammatory response in microglia. These data imply that the JDS effect on neurodegeneration occurs via coordination among its seven components. To establish a quality control for JDS, a simultaneous analysis using five standard compounds identified hesperidin (37.892 ± 1.228 mg/g) as the most abundant phytochemical of JDS. Further investigation of the combinatorial activities of two or more standard compounds will be necessary to verify their antineurodegenerative regulatory mechanisms. PMID:29391873

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

    PubMed

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

    2010-05-03

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

  19. Anthocyanins Downregulate Lipopolysaccharide-Induced Inflammatory Responses in BV2 Microglial Cells by Suppressing the NF-κB and Akt/MAPKs Signaling Pathways

    PubMed Central

    Jeong, Jin-Woo; Lee, Won Sup; Shin, Sung Chul; Kim, Gi-Young; Choi, Byung Tae; Choi, Yung Hyun

    2013-01-01

    Anthocyanins are naturally occurring polyphenols that impart bright color to fruits, vegetables and plants and have a variety of protective properties, which have generally been attributed to their antioxidant capacity. However, little is known about the molecular mechanisms underlying anti-inflammatory effects of anthocyanins related to neurodegenerative diseases. Therefore, we determined whether anthocyanins isolated from black soybean seed coats would inhibit pro-inflammatory mediators and cytokines in lipopolysaccharide (LPS)-stimulated murine BV2 microglial cells. Our results showed that anthocyanins significantly inhibited LPS-induced pro-inflammatory mediators, such as nitric oxide (NO) and prostaglandin E2, and pro-inflammatory cytokines including tumor necrosis factor (TNF)-α and interleukin (IL)-1β, without significant cytotoxicity. Anthocyanins also downregulated excessive expression of inducible NO synthase, cyclooxygenase-2, TNF-α, and IL-1β in LPS-stimulated BV2 cells. Moreover, anthocyanins inhibited nuclear translocation of nuclear factor-kappa B (NF-κB) by reducing inhibitor of NF-κB alpha degradation as well as phosphorylating extracellular signal-regulated kinase, c-Jun N-terminal kinase, p38 mitogen-activated protein kinase, and Akt. These findings suggest that anthocyanins may offer substantial therapeutic potential for treating inflammatory and neurodegenerative diseases accompanied by microglial activation. PMID:23344054

  20. 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

  1. 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

    2016-05-13

    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.

  2. Inhibitory effects of palm α-, γ- and δ-tocotrienol on lipopolysaccharide-induced nitric oxide production in BV2 microglia.

    PubMed

    Tan, Shi Wei; Ramasamy, Rajesh; Abdullah, Maha; Vidyadaran, Sharmili

    2011-01-01

    Anti-inflammatory actions of the vitamin E fragment tocotrienol have not been described for microglia. Here, we screened palm α-, γ- and δ-tocotrienol isoforms and Tocomin® 50% (contains spectrum of tocotrienols and tocopherols) for their ability to limit nitric oxide (NO) production by BV2 microglia. Microglia were treated with varying doses of tocotrienols for 24h and stimulated with 1 μg/ml lipopolysaccharide (LPS). All tocotrienol isoforms reduced NO release by LPS-stimulated microglia, with 50 μM being the most potent tocotrienol dose. Of the isoforms tested, δ-tocotrienol lowered NO levels the most, reducing NO by approximately 50% at 48 h post-LPS treatment (p<.05). None of the tocotrienol doses tested affected microglia viability. Copyright © 2011 Elsevier Inc. All rights reserved.

  3. Lactolisterin BU, a Novel Class II Broad-Spectrum Bacteriocin from Lactococcus lactis subsp. lactis bv. diacetylactis BGBU1-4.

    PubMed

    Lozo, Jelena; Mirkovic, Nemanja; O'Connor, Paula M; Malesevic, Milka; Miljkovic, Marija; Polovic, Natalija; Jovcic, Branko; Cotter, Paul D; Kojic, Milan

    2017-11-01

    Lactococcus lactis subsp. lactis bv. diacetylactis BGBU1-4 produces a novel bacteriocin, lactolisterin BU, with strong antimicrobial activity against many species of Gram-positive bacteria, including important food spoilage and foodborne pathogens, such as Listeria monocytogenes , Staphylococcus aureus , Bacillus spp., and streptococci. Lactolisterin BU was extracted from the cell surface of BGBU1-4 by 2-propanol and purified to homogeneity by C 18 solid-phase extraction and reversed-phase high-performance liquid chromatography. The molecular mass of the purified lactolisterin BU was 5,160.94 Da, and an internal fragment, AVSWAWQH, as determined by N-terminal sequencing, showed low-level similarity to existing antimicrobial peptides. Curing and transformation experiments revealed the presence of a corresponding bacteriocin operon on the smallest plasmid, pBU6 (6.2 kb), of strain BGBU1-4. Analysis of the bacteriocin operon revealed a leaderless bacteriocin of 43 amino acids that exhibited similarity to bacteriocin BHT-B (63%) from Streptococcus ratti , a bacteriocin with analogy to aureocin A. IMPORTANCE Lactolisterin BU, a broad-spectrum leaderless bacteriocin produced by L. lactis subsp. lactis bv. diacetylactis BGBU1-4, expresses strong antimicrobial activity against food spoilage and foodborne pathogens, such as Listeria monocytogenes , Staphylococcus aureus , Bacillus spp., and streptococci. Lactolisterin BU showed the highest similarity to aureocin-like bacteriocins produced by different bacteria. The operon for synthesis is located on the smallest plasmid, pBU6 (6.2 kb), of strain BGBU1-4, indicating possible horizontal transfer among producers. Copyright © 2017 American Society for Microbiology.

  4. Lactolisterin BU, a Novel Class II Broad-Spectrum Bacteriocin from Lactococcus lactis subsp. lactis bv. diacetylactis BGBU1-4

    PubMed Central

    Lozo, Jelena; Mirkovic, Nemanja; O'Connor, Paula M.; Malesevic, Milka; Miljkovic, Marija; Polovic, Natalija; Cotter, Paul D.

    2017-01-01

    ABSTRACT Lactococcus lactis subsp. lactis bv. diacetylactis BGBU1-4 produces a novel bacteriocin, lactolisterin BU, with strong antimicrobial activity against many species of Gram-positive bacteria, including important food spoilage and foodborne pathogens, such as Listeria monocytogenes, Staphylococcus aureus, Bacillus spp., and streptococci. Lactolisterin BU was extracted from the cell surface of BGBU1-4 by 2-propanol and purified to homogeneity by C18 solid-phase extraction and reversed-phase high-performance liquid chromatography. The molecular mass of the purified lactolisterin BU was 5,160.94 Da, and an internal fragment, AVSWAWQH, as determined by N-terminal sequencing, showed low-level similarity to existing antimicrobial peptides. Curing and transformation experiments revealed the presence of a corresponding bacteriocin operon on the smallest plasmid, pBU6 (6.2 kb), of strain BGBU1-4. Analysis of the bacteriocin operon revealed a leaderless bacteriocin of 43 amino acids that exhibited similarity to bacteriocin BHT-B (63%) from Streptococcus ratti, a bacteriocin with analogy to aureocin A. IMPORTANCE Lactolisterin BU, a broad-spectrum leaderless bacteriocin produced by L. lactis subsp. lactis bv. diacetylactis BGBU1-4, expresses strong antimicrobial activity against food spoilage and foodborne pathogens, such as Listeria monocytogenes, Staphylococcus aureus, Bacillus spp., and streptococci. Lactolisterin BU showed the highest similarity to aureocin-like bacteriocins produced by different bacteria. The operon for synthesis is located on the smallest plasmid, pBU6 (6.2 kb), of strain BGBU1-4, indicating possible horizontal transfer among producers. PMID:28842543

  5. AN EXAMINATION OF RECENT TRANSFORMATIONS TO THE BV(RI){sub C} PHOTOMETRIC SYSTEM FROM THE PERSPECTIVE OF STELLAR MODELS FOR OLD STARS

    SciTech Connect

    VandenBerg, Don A.; Casagrande, L.; Stetson, Peter B., E-mail: vandenbe@uvic.c, E-mail: Luca@MPA-Garching.mpg.d, E-mail: Peter.Stetson@nrc.gc.c

    2010-10-15

    Isochrones for ages {approx}>4 Gyr and metallicities in the range -2.5{approx}< [Fe/H] {approx}<+0.3 that take the diffusion of helium and recent advances in stellar physics into account are compared with observations in the Johnson-Cousins BV(RI){sub C} photometric system for several open and globular star clusters. The adopted color-T{sub eff} relations include those which we have derived from the latest MARCS model atmospheres and the empirical transformations for dwarf and subgiant stars given by Casagrande et al. (CRMBA). Those reported by VandenBerg and Clem have also been considered, mainly to resolve some outstanding questions concerning them. Indeed, for the latter, Vmore » - I{sub C} colors should be corrected by {approx}-0.02 mag, for all metal abundances, in order to obtain consistent interpretations of the observed (B - V, V), (V - R{sub C} , V), and (V - I{sub C} , V) diagrams for M 67 and the Hyades as well as for local subdwarfs. Remarkably, when the subdwarfs in the CRMBA data set that have {sigma}{sub {pi}/{pi}} {<=} 0.15 are superimposed on a set of 12 Gyr isochrones spanning a wide range in [Fe/H], the inferred metallicities and effective temperatures agree, in the mean, with those given by CRMBA to within {+-}0.05 dex and {+-}10 K, respectively. Thus, the hot T{sub eff} scale derived by CRMBA is nearly identical with that predicted by stellar models; and consequently, there is excellent consistency between theory and observations on the Hertzsprung-Russell diagram and the different color-magnitude diagrams considered in this investigation. To obtain similar consistency, the colors obtained from the MARCS and VandenBerg and Clem (B - V)-T{sub eff} relations for metal-poor dwarf stars should be adjusted to the red by 0.02-0.03 mag. In general, isochrones that employ the CRMBA transformations provide reasonably consistent fits to our BV(RI){sub C} photometry for main-sequence stars in the globular clusters 47 Tuc, M 3, M 5, M 92, and NGC 1851

  6. An Examination of Recent Transformations to the BV(RI) C Photometric System from the Perspective of Stellar Models for Old Stars

    NASA Astrophysics Data System (ADS)

    VandenBerg, Don A.; Casagrande, L.; Stetson, Peter B.

    2010-10-01

    Isochrones for ages gsim4 Gyr and metallicities in the range -2.5lsim [Fe/H] lsim+0.3 that take the diffusion of helium and recent advances in stellar physics into account are compared with observations in the Johnson-Cousins BV(RI) C photometric system for several open and globular star clusters. The adopted color-T eff relations include those which we have derived from the latest MARCS model atmospheres and the empirical transformations for dwarf and subgiant stars given by Casagrande et al. (CRMBA). Those reported by VandenBerg & Clem have also been considered, mainly to resolve some outstanding questions concerning them. Indeed, for the latter, V - IC colors should be corrected by ≈-0.02 mag, for all metal abundances, in order to obtain consistent interpretations of the observed (B - V, V), (V - RC , V), and (V - IC , V) diagrams for M 67 and the Hyades as well as for local subdwarfs. Remarkably, when the subdwarfs in the CRMBA data set that have σπ/π <= 0.15 are superimposed on a set of 12 Gyr isochrones spanning a wide range in [Fe/H], the inferred metallicities and effective temperatures agree, in the mean, with those given by CRMBA to within ±0.05 dex and ±10 K, respectively. Thus, the hot T eff scale derived by CRMBA is nearly identical with that predicted by stellar models; and consequently, there is excellent consistency between theory and observations on the Hertzsprung-Russell diagram and the different color-magnitude diagrams considered in this investigation. To obtain similar consistency, the colors obtained from the MARCS and VandenBerg & Clem (B - V)-T eff relations for metal-poor dwarf stars should be adjusted to the red by 0.02-0.03 mag. In general, isochrones that employ the CRMBA transformations provide reasonably consistent fits to our BV(RI) C photometry for main-sequence stars in the globular clusters 47 Tuc, M 3, M 5, M 92, and NGC 1851—but not the cluster giants (when adopting the synthetic MARCS colors). We speculate that

  7. Immunoglobulins G from Sera of Amyotrophic Lateral Sclerosis Patients Induce Oxidative Stress and Upregulation of Antioxidative System in BV-2 Microglial Cell Line

    PubMed Central

    Milošević, Milena; Milićević, Katarina; Božić, Iva; Lavrnja, Irena; Stevanović, Ivana; Bijelić, Dunja; Dubaić, Marija; Živković, Irena; Stević, Zorica; Giniatullin, Rashid; Andjus, Pavle

    2017-01-01

    Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder with a very fast progression, no diagnostic tool for the presymptomatic phase, and still no effective treatment of the disease. Although ALS affects motor neurons, the overall pathophysiological condition points out to the non-cell autonomous mechanisms, where astrocytes and microglia play crucial roles in the disease progression. We have already shown that IgG from sera of ALS patients (ALS IgG) induce calcium transients and an increase in the mobility of acidic vesicles in cultured rat astrocytes. Having in mind the role of microglia in neurodegeneration, and a well-documented fact that oxidative stress is one of the many components contributing to the disease, we decided to examine the effect of ALS IgG on activation, oxidative stress and antioxidative system of BV-2 microglia, and to evaluate their acute effect on cytosolic peroxide, pH, and on reactive oxygen species (ROS) generation. All tested ALS IgGs (compared to control IgG) induced oxidative stress (rise in nitric oxide and the index of lipid peroxidation) followed by release of TNF-α and higher antioxidative defense (elevation of Mn- and CuZn-superoxide dismutase, catalase, and glutathione reductase with a decrease of glutathione peroxidase and glutathione) after 24 h treatment. Both ALS IgG and control IgG showed same localization on the membrane of BV-2 cells following 24 h treatment. Cytosolic peroxide and pH alteration were evaluated with fluorescent probes HyPer and SypHer, respectively, having in mind that HyPer also reacts to pH changes. Out of 11 tested IgGs from ALS patients, 4 induced slow exponential rise of HyPer signal, with maximal normalized fluorescence in the range 0.2–0.5, also inducing similar increase of SypHer intensity, but of a lower amplitude. None of the control IgGs induced changes with neither of the indicators. Acute ROS generation was detected in one out of three tested ALS samples with carboxy-H2

  8. 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. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. 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

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

    2014-01-01

    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.

  10. 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

  11. Ac102 Participates in Nuclear Actin Polymerization by Modulating BV/ODV-C42 Ubiquitination during Autographa californica Multiple Nucleopolyhedrovirus Infection.

    PubMed

    Zhang, Yongli; Hu, Xue; Mu, Jingfang; Hu, Yangyang; Zhou, Yuan; Zhao, He; Wu, Chunchen; Pei, Rongjuan; Chen, Jizheng; Chen, Xinwen; Wang, Yun

    2018-06-15

    As a virus-encoded actin nucleation promoting factor (NPF), P78/83 induces actin polymerization to assist in Autographa californica multiple nucleopolyhedrovirus (AcMNPV) propagation. According to our previous study, although P78/83 actively undergoes ubiquitin-independent proteasomal degradation, AcMNPV encodes budded virus/occlusion derived virus (BV/ODV)-C42 (C42), which allows P78/83 to function as a stable NPF by inhibiting its degradation during viral infection. However, whether there are other viral proteins involved in regulating P78/83-induced actin polymerization has yet to be determined. In this study, we found that Ac102, an essential viral gene product previously reported to play a key role in mediating the nuclear accumulation of actin during AcMNPV infection, is a novel regulator of P78/83-induced actin polymerization. By characterizing an ac102 knockout bacmid, we demonstrated that Ac102 participates in regulating nuclear actin polymerization as well as the morphogenesis and distribution of capsid structures in the nucleus. These regulatory effects are heavily dependent on an interaction between Ac102 and C42. Further investigation revealed that Ac102 binds to C42 to suppress K48-linked ubiquitination of C42, which decreases C42 proteasomal degradation and consequently allows P78/83 to function as a stable NPF to induce actin polymerization. Thus, Ac102 and C42 form a regulatory cascade to control viral NPF activity, representing a sophisticated mechanism for AcMNPV to orchestrate actin polymerization in both a ubiquitin-dependent and ubiquitin-independent manner. IMPORTANCE Actin is one of the most functionally important proteins in eukaryotic cells. Morphologically, actin can be found in two forms: a monomeric form called globular actin (G-actin) and a polymeric form called filamentous actin (F-actin). G-actin can polymerize to form F-actin, and nucleation promoting factor (NPF) is the initiator of this process. Many viral pathogens harness the

  12. High spatial variation in population size and symbiotic performance of Rhizobium leguminosarum bv. trifolii with white clover in New Zealand pasture soils.

    PubMed

    Wakelin, Steven; Tillard, Guyléne; van Ham, Robert; Ballard, Ross; Farquharson, Elizabeth; Gerard, Emily; Geurts, Rene; Brown, Matthew; Ridgway, Hayley; O'Callaghan, Maureen

    2018-01-01

    Biological nitrogen fixation through the legume-rhizobia symbiosis is important for sustainable pastoral production. In New Zealand, the most widespread and valuable symbiosis occurs between white clover (Trifolium repens L.) and Rhizobium leguminosarum bv. trifolii (Rlt). As variation in the population size (determined by most probable number assays; MPN) and effectiveness of N-fixation (symbiotic potential; SP) of Rlt in soils may affect white clover performance, the extent in variation in these properties was examined at three different spatial scales: (1) From 26 sites across New Zealand, (2) at farm-wide scale, and (3) within single fields. Overall, Rlt populations ranged from 95 to >1 x 108 per g soil, with variation similar at the three spatial scales assessed. For almost all samples, there was no relationship between rhizobia population size and ability of the population to fix N during legume symbiosis (SP). When compared with the commercial inoculant strain, the SP of soils ranged between 14 to 143% efficacy. The N-fixing ability of rhizobia populations varied more between samples collected from within a single hill country field (0.8 ha) than between 26 samples collected from diverse locations across New Zealand. Correlations between SP and calcium and aluminium content were found in all sites, except within a dairy farm field. Given the general lack of association between SP and MPN, and high spatial variability of SP at single field scale, provision of advice for treating legume seed with rhizobia based on field-average MPN counts needs to be carefully considered.

  13. Clarithromycin expands CD11b+Gr-1+ cells via the STAT3/Bv8 axis to ameliorate lethal endotoxic shock and post-influenza bacterial pneumonia

    PubMed Central

    Fujii, Hideki; Yagi, Kazuma; Suzuki, Shoji; Hegab, Ahmed E.; Tasaka, Sadatomo; Nakamoto, Nobuhiro; Iwata, Satoshi; Honda, Kenya; Kanai, Takanori; Hasegawa, Naoki; Betsuyaku, Tomoko

    2018-01-01

    Macrolides are used to treat various inflammatory diseases owing to their immunomodulatory properties; however, little is known about their precise mechanism of action. In this study, we investigated the functional significance of the expansion of myeloid-derived suppressor cell (MDSC)-like CD11b+Gr-1+ cells in response to the macrolide antibiotic clarithromycin (CAM) in mouse models of shock and post-influenza pneumococcal pneumonia as well as in humans. Intraperitoneal administration of CAM markedly expanded splenic and lung CD11b+Gr-1+ cell populations in naïve mice. Notably, CAM pretreatment enhanced survival in a mouse model of lipopolysaccharide (LPS)-induced shock. In addition, adoptive transfer of CAM-treated CD11b+Gr-1+ cells protected mice against LPS-induced lethality via increased IL-10 expression. CAM also improved survival in post-influenza, CAM-resistant pneumococcal pneumonia, with improved lung pathology as well as decreased interferon (IFN)-γ and increased IL-10 levels. Adoptive transfer of CAM-treated CD11b+Gr-1+ cells protected mice from post-influenza pneumococcal pneumonia. Further analysis revealed that the CAM-induced CD11b+Gr-1+ cell expansion was dependent on STAT3-mediated Bv8 production and may be facilitated by the presence of gut commensal microbiota. Lastly, an analysis of peripheral blood obtained from healthy volunteers following oral CAM administration showed a trend toward the expansion of human MDSC-like cells (Lineage−HLA-DR−CD11b+CD33+) with increased arginase 1 mRNA expression. Thus, CAM promoted the expansion of a unique population of immunosuppressive CD11b+Gr-1+ cells essential for the immunomodulatory properties of macrolides. PMID:29621339

  14. Cannabinoids Δ9-Tetrahydrocannabinol and Cannabidiol Differentially Inhibit the Lipopolysaccharide-activated NF-κB and Interferon-β/STAT Proinflammatory Pathways in BV-2 Microglial Cells*

    PubMed Central

    Kozela, Ewa; Pietr, Maciej; Juknat, Ana; Rimmerman, Neta; Levy, Rivka; Vogel, Zvi

    2010-01-01

    Cannabinoids have been shown to exert anti-inflammatory activities in various in vivo and in vitro experimental models as well as ameliorate various inflammatory degenerative diseases. However, the mechanisms of these effects are not completely understood. Using the BV-2 mouse microglial cell line and lipopolysaccharide (LPS) to induce an inflammatory response, we studied the signaling pathways engaged in the anti-inflammatory effects of cannabinoids as well as their influence on the expression of several genes known to be involved in inflammation. We found that the two major cannabinoids present in marijuana, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), decrease the production and release of proinflammatory cytokines, including interleukin-1β, interleukin-6, and interferon (IFN)β, from LPS-activated microglial cells. The cannabinoid anti-inflammatory action does not seem to involve the CB1 and CB2 cannabinoid receptors or the abn-CBD-sensitive receptors. In addition, we found that THC and CBD act through different, although partially overlapping, mechanisms. CBD, but not THC, reduces the activity of the NF-κB pathway, a primary pathway regulating the expression of proinflammatory genes. Moreover, CBD, but not THC, up-regulates the activation of the STAT3 transcription factor, an element of homeostatic mechanism(s) inducing anti-inflammatory events. Following CBD treatment, but less so with THC, we observed a decreased level of mRNA for the Socs3 gene, a main negative regulator of STATs and particularly of STAT3. However, both CBD and THC decreased the activation of the LPS-induced STAT1 transcription factor, a key player in IFNβ-dependent proinflammatory processes. In summary, our observations show that CBD and THC vary in their effects on the anti-inflammatory pathways, including the NF-κB and IFNβ-dependent pathways. PMID:19910459

  15. 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

  16. The host-encoded RNase E endonuclease as the crRNA maturation enzyme in a CRISPR-Cas subtype III-Bv system.

    PubMed

    Behler, Juliane; Sharma, Kundan; Reimann, Viktoria; Wilde, Annegret; Urlaub, Henning; Hess, Wolfgang R

    2018-03-01

    Specialized RNA endonucleases for the maturation of clustered regularly interspaced short palindromic repeat (CRISPR)-derived RNAs (crRNAs) are critical in CRISPR-CRISPR-associated protein (Cas) defence mechanisms. The Cas6 and Cas5d enzymes are the RNA endonucleases in many class 1 CRISPR-Cas systems. In some class 2 systems, maturation and effector functions are combined within a single enzyme or maturation proceeds through the combined actions of RNase III and trans-activating CRISPR RNAs (tracrRNAs). Three separate CRISPR-Cas systems exist in the cyanobacterium Synechocystis sp. PCC 6803. Whereas Cas6-type enzymes act in two of these systems, the third, which is classified as subtype III-B variant (III-Bv), lacks cas6 homologues. Instead, the maturation of crRNAs proceeds through the activity of endoribonuclease E, leaving unusual 13- and 14-nucleotide-long 5'-handles. Overexpression of RNase E leads to overaccumulation and knock-down to the reduced accumulation of crRNAs in vivo, suggesting that RNase E is the limiting factor for CRISPR complex formation. Recognition by RNase E depends on a stem-loop in the CRISPR repeat, whereas base substitutions at the cleavage site trigger the appearance of secondary products, consistent with a two-step recognition and cleavage mechanism. These results suggest the adaptation of an otherwise very conserved housekeeping enzyme to accommodate new substrates and illuminate the impressive plasticity of CRISPR-Cas systems that enables them to function in particular genomic environments.

  17. Tetrathiomolybdate Treatment Leads to the Suppression of Inflammatory Responses through the TRAF6/NFκB Pathway in LPS-Stimulated BV-2 Microglia

    PubMed Central

    Wang, Zhuo; Zhang, Ya-Hong; Guo, Chuang; Gao, Hui-Ling; Zhong, Man-Li; Huang, Ting-Ting; Liu, Na-Na; Guo, Rui-Fang; Lan, Tian; Zhang, Wei; Wang, Zhan-You; Zhao, Pu

    2018-01-01

    Although the positive relationship between copper and Alzheimer's disease (AD) was reported by a lot of epidemiological data, the mechanism is not completely known. Copper is a redox metal and serves as a mediator of inflammation. Because the homeostasis of copper is altered in Aβ precursor protein (APP) and presenilin 1 (PS1) transgenic (Tg) mice, the using of copper chelators is a potential therapeutic strategy for AD. Here we report that a copper chelator, tetrathiomolybdate (TM), is a potential therapeutic drug of AD. We investigated whether TM treatment led to a decrease of pro-inflammatory cytokines in vivo and in vitro, and found that TM treatment reduced the expression of iNOS and TNF-α in APP/PS1 Tg mice through up-regulating superoxide dismutase 1 (SOD1) activity. In vitro, once stimulated, microglia secretes a variety of proinflammatory cytokines, so we utilized LPS-stimulated BV-2 cells as the inflammatory cell model to detect the anti-inflammatory effects of TM. Our results indicated that TM-pretreatment suppressed the ubiquitination of TRAF6 and the activation of NFκB without affecting the expression of TLR4 and Myd88 in vitro. By detecting the activity of SOD1 and the production of reactive oxygen species (ROS), we found that the anti-inflammatory effects of TM could be attributed to its ability to reduce the amount of intracellular bioavailable copper, and the production of ROS which is an activator of the TRAF6 auto-ubiquitination. Hence, our results revealed that TM-treatment could reduce the production of inflammatory cytokines by the suppression of ROS/TRAF6/AKT/NFκB signaling pathway. PMID:29535623

  18. Small molecule activators of the Nrf2-HO-1 antioxidant axis modulate heme metabolism and inflammation in BV2 microglia cells.

    PubMed

    Foresti, Roberta; Bains, Sandip K; Pitchumony, Tamil Selvi; de Castro Brás, Lisandra E; Drago, Filippo; Dubois-Randé, Jean-Luc; Bucolo, Claudio; Motterlini, Roberto

    2013-10-01

    The nuclear factor erythroid derived 2-related factor 2 (Nrf2) and the antioxidant protein heme oxygenase-1 (HO-1) are crucial components of the cellular stress response. These two systems work together to combat oxidative stress and inflammation and are attractive drug targets for counteracting different pathologies, including neuroinflammation. We aimed to identify the most effective Nrf2/HO-1 activators that modulate the inflammatory response in microglia cells. In the present study, we searched the literature and selected 56 compounds reported to activate Nrf2 or HO-1 and analyzed them for HO-1 induction at 6 and 24h and cytotoxicity in BV2 microglial cells in vitro. Approximately 20 compounds up-regulated HO-1 at the concentrations tested (5-20 μM) with carnosol, supercurcumin, cobalt protoporphyrin-IX and dimethyl fumarate exhibiting the best induction/low cytotoxicity profile. Up-regulation of HO-1 by some compounds resulted in increased cellular bilirubin levels but did not augment the expression of proteins involved in heme synthesis (ALAS 1) or biliverdin reductase. Bilirubin production by HO-1 inducers correlated with their potency in inhibiting nitrite production after challenge with interferon-γ (INF-γ) or lipopolysaccharide (LPS). The compounds down-regulated the inflammatory response (TNF-α, PGE2 and nitrite) more strongly in cells challenged with INF-γ than LPS, and silencing HO-1 or Nrf2 with shRNA differentially affected the levels of inflammatory markers. These findings indicate that some small activators of Nrf2/HO-1 are effective modulators of microglia inflammation and highlight the chemical scaffolds that can serve for the synthesis of potent new derivatives to counteract neuroinflammation and neurodegeneration. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. 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

  20. High spatial variation in population size and symbiotic performance of Rhizobium leguminosarum bv. trifolii with white clover in New Zealand pasture soils

    PubMed Central

    Tillard, Guyléne; van Ham, Robert; Ballard, Ross; Farquharson, Elizabeth; Gerard, Emily; Geurts, Rene; Brown, Matthew; Ridgway, Hayley; O’Callaghan, Maureen

    2018-01-01

    Biological nitrogen fixation through the legume-rhizobia symbiosis is important for sustainable pastoral production. In New Zealand, the most widespread and valuable symbiosis occurs between white clover (Trifolium repens L.) and Rhizobium leguminosarum bv. trifolii (Rlt). As variation in the population size (determined by most probable number assays; MPN) and effectiveness of N-fixation (symbiotic potential; SP) of Rlt in soils may affect white clover performance, the extent in variation in these properties was examined at three different spatial scales: (1) From 26 sites across New Zealand, (2) at farm-wide scale, and (3) within single fields. Overall, Rlt populations ranged from 95 to >1 x 108 per g soil, with variation similar at the three spatial scales assessed. For almost all samples, there was no relationship between rhizobia population size and ability of the population to fix N during legume symbiosis (SP). When compared with the commercial inoculant strain, the SP of soils ranged between 14 to 143% efficacy. The N-fixing ability of rhizobia populations varied more between samples collected from within a single hill country field (0.8 ha) than between 26 samples collected from diverse locations across New Zealand. Correlations between SP and calcium and aluminium content were found in all sites, except within a dairy farm field. Given the general lack of association between SP and MPN, and high spatial variability of SP at single field scale, provision of advice for treating legume seed with rhizobia based on field-average MPN counts needs to be carefully considered. PMID:29489845

  1. High Levels of Inflammatory Cytokines in the Reproductive Tract of Women with BV and Engaging in Intravaginal Douching: A Cross-Sectional Study of Participants in the Women Interagency HIV Study.

    PubMed

    Alcaide, Maria L; Rodriguez, Violeta J; Brown, Megan R; Pallikkuth, Suresh; Arheart, Kristopher; Martinez, Octavio; Roach, Margaret; Fichorova, Raina N; Jones, Deborah L; Pahwa, Savita; Fischl, Margaret A

    2017-04-01

    High levels of inflammatory cytokines in the genital tract suggest mucosal vulnerability and increased risk of HIV and sexually transmitted infection (STI) acquisition. Intravaginal douching is associated with bacterial vaginosis (BV) in women in the United States, and both douching and BV are linked to HIV and STI acquisition. This study evaluates inflammatory cytokines in the genital tract to increase understanding of the effects of both BV and intravaginal douching to the vaginal mucosa. A cross-sectional study of participants in the Miami WIHS investigated 72 reproductive age women (45 HIV + and 27 high-risk HIV - ) who completed intravaginal douching questionnaires and underwent collection of vaginal swabs and cervicovaginal lavages (CVLs). BV was assessed using the Nugent score. Inflammatory cytokines in the CVLs (interleukin [IL]-6, IL-8, IL-1α, IL-1β, soluble intracellular adhesion molecule-1 [sICAM-1], interferon [IFN]α2, chemokine C ligand 5 (CCL5), vascular endothelial growth factor (VEGF), monocyte chemotactic protein-1 (MCP1), tumor necrosis factor alpha (TNFα), and secretory leukocyte protease inhibitor [SLPI]) were measured. Fourteen (19%) women reported intravaginal douching; 24 (33%) had BV. BV, intravaginal douching, and HIV were associated with higher levels of inflammatory cytokines. After controlling for demographic and risk factors and HIV status, women who had BV and douched had higher levels of inflammatory cytokines than those without BV and who did not douche, or who only had BV or only douched. These findings suggest that BV and douching are associated with greater mucosal inflammation and may facilitate HIV acquisition and transmission. Although longitudinal studies are needed to determine temporal associations and causality, interventions to decrease rates of intravaginal douching and BV could significantly decrease women's risks of acquiring STIs and HIV and limit the spread of HIV.

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

    SciTech Connect

    Rahman, Mohammad Mubinur; Andberg, Martina; Koivula, Anu

    l-Arabinonate dehydratase and d-xylonate dehydratase from the IlvD/EDD family were crystallized by the vapour-diffusion method. Diffraction data sets were collected to resolutions of 2.40 and 2.66 Å from crystals of l-arabinonate dehydratase and d-xylonate dehydratase, respectively. 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 dehydratasemore » 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 P2{sub 1}, 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{sub M} value of 3.2 Å{sup 3} Da{sup −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

  3. Microarray and Pathway Analysis Reveal Distinct Mechanisms Underlying Cannabinoid-Mediated Modulation of LPS-Induced Activation of BV-2 Microglial Cells

    PubMed Central

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

    2013-01-01

    Cannabinoids are known to exert immunosuppressive activities. However, the mechanisms which contribute to these effects are unknown. Using lipopolysaccharide (LPS) to activate BV-2 microglial cells, we examined how Δ9-tetrahydrocannabinol (THC), the major psychoactive component of marijuana, and cannabidiol (CBD) the non-psychoactive component, modulate the inflammatory response. Microarray analysis of genome-wide mRNA levels was performed using Illumina platform and the resulting expression patterns analyzed using the Ingenuity Pathway Analysis to identify functional subsets of genes, and the Ingenuity System Database to denote the gene networks regulated by CBD and THC. From the 5338 transcripts that were differentially expressed across treatments, 400 transcripts were found to be upregulated by LPS, 502 by CBD+LPS and 424 by THC+LPS, while 145 were downregulated by LPS, 297 by CBD+LPS and 149 by THC+LPS, by 2-fold or more (p≤0.005). Results clearly link the effects of CBD and THC to inflammatory signaling pathways and identify new cannabinoid targets in the MAPK pathway (Dusp1, Dusp8, Dusp2), cell cycle related (Cdkn2b, Gadd45a) as well as JAK/STAT regulatory molecules (Socs3, Cish, Stat1). The impact of CBD on LPS-stimulated gene expression was greater than that of THC. We attribute this difference to the fact that CBD highly upregulated several genes encoding negative regulators of both NFκB and AP-1 transcriptional activities, such as Trib3 and Dusp1 known to be modulated through Nrf2 activation. The CBD-specific expression profile reflected changes associated with oxidative stress and glutathione depletion via Trib3 and expression of ATF4 target genes. Furthermore, the CBD affected genes were shown to be controlled by nuclear factors usually involved in regulation of stress response and inflammation, mainly via Nrf2/Hmox1 axis and the Nrf2/ATF4-Trib3 pathway. These observations indicate that CBD, and less so THC, induce a cellular stress response and

  4. 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

  5. Inhibition of AGEs/RAGE/Rho/ROCK pathway suppresses non-specific neuroinflammation by regulating BV2 microglial M1/M2 polarization through the NF-κB pathway.

    PubMed

    Chen, Jingkao; Sun, Zhaowei; Jin, Minghua; Tu, Yalin; Wang, Shengnan; Yang, Xiaohong; Chen, Qiuhe; Zhang, Xiao; Han, Yifan; Pi, Rongbiao

    2017-04-15

    The microglia-mediated neuroinflammation plays an important role in the pathogenesis of Alzheimer's disease (AD). Advanced glycation end products (AGEs)/receptor for advanced glycation end products (RAGE) or Rho/Rho kinase (ROCK) are both involved in the development of non-specific inflammation. However, there are few reports about their effects on neuroinflammation. Here, we explored the mechanism of AGEs/RAGE/Rho/ROCK pathway underlying the non-specific inflammation and microglial polarization in BV2 cells. AGEs could activate ROCK pathway in a concentration-dependent manner. ROCK inhibitor fasudil and RAGE-specific blocker FPS-ZM1 significantly inhibited AGEs-mediated activation of BV2 cells and induction of reactive oxygen species (ROS). FPS-ZM1 and fasudil exerted their anti-inflammatory effects by downregulating inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), NLRP3 and nuclear translocation of nuclear factor kappa B (NF-κB) p65. In addition, AGEs induced both M1 (CD16/32, M1 marker) and M2 (CD206, M2 marker) phenotype in BV2 cells. Fasudil and FPS-ZM1 led to a decreased M1 and increased M2 phenotype. Together, these results indicate that the AGEs/RAGE/Rho/ROCK pathway in BV2 cells could intensify the non-specific inflammation of AD, which will provide novel strategies for the development of anti-AD drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. The glycoprotein TRP36 of Ehrlichia sp. UFMG-EV and related cattle pathogen Ehrlichia sp. UFMT-BV evolved from a highly variable clade of E. canis under adaptive diversifying selection.

    PubMed

    Cabezas-Cruz, Alejandro; Valdés, James J; de la Fuente, José

    2014-12-10

    A new species of Ehrlichia, phylogenetically distant from E. ruminantium, was found in 2010 infecting cattle in Canada. In 2012 and 2013, we reported the in vitro propagation, molecular and ultrastructural characterization of Ehrlichia sp. UFMG-EV (E. mineirensis), a new species of Ehrlichia isolated from the haemolymph of Brazilian Rhipicephalus (Boophilus) microplus ticks. A new organism, named Ehrlichia sp. UFMT-BV, closely related to Ehrlichia sp. UFMG-EV, was recently described in Brazil and after experimental infection it was shown to be pathogenic for cattle. This new emerging clade of cattle Ehrlichia pathogens is closely related to E. canis. The major immunogenic Tandem Repeat Protein (TRP36; also known as gp36) is extensively used to characterize the genetic diversity of E. canis. Homologs of TRP36 were found in both Ehrlichia sp. UFMG-EV and Ehrlichia sp. UFMT-BV. Herein, we characterized the evolution of this new Ehrlichia clade using TRP36 sequences. Our working hypothesis is that Ehrlichia sp. UFMG-EV and related microorganisms evolved from a highly variable E. canis clade. In support of our hypothesis we found that Ehrlichia sp. UFMG-EV and Ehrlichia sp. UFMT-BV TRP36 evolved from a highly divergent and variable clade within E. canis and this clade evolved under episodic diversifying selection with a high proportion of sites under positive selection. Our results suggest that Ehrlichia sp. UFMG-EV and Ehrlichia sp. UFMT-BV evolved from a variable clade within E. canis.

  7. SU-E-T-795: Validations of Dose Calculation Accuracy of Acuros BV in High-Dose-Rate (HDR) Brachytherapy with a Shielded Cylinder Applicator Using Monte Carlo Simulation

    SciTech Connect

    Li, Y; Department of Engineering Physics, Tsinghua University, Beijing; Tian, Z

    Purpose: Acuros BV has become available to perform accurate dose calculations in high-dose-rate (HDR) brachytherapy with phantom heterogeneity considered by solving the Boltzmann transport equation. In this work, we performed validation studies regarding the dose calculation accuracy of Acuros BV in cases with a shielded cylinder applicator using Monte Carlo (MC) simulations. Methods: Fifteen cases were considered in our studies, covering five different diameters of the applicator and three different shielding degrees. For each case, a digital phantom was created in Varian BrachyVision with the cylinder applicator inserted in the middle of a large water phantom. A treatment plan withmore » eight dwell positions was generated for these fifteen cases. Dose calculations were performed with Acuros BV. We then generated a voxelized phantom of the same geometry, and the materials were modeled according to the vendor’s specifications. MC dose calculations were then performed using our in-house developed fast MC dose engine for HDR brachytherapy (gBMC) on a GPU platform, which is able to simulate both photon transport and electron transport in a voxelized geometry. A phase-space file for the Ir-192 HDR source was used as a source model for MC simulations. Results: Satisfactory agreements between the dose distributions calculated by Acuros BV and those calculated by gBMC were observed in all cases. Quantitatively, we computed point-wise dose difference within the region that receives a dose higher than 10% of the reference dose, defined to be the dose at 5mm outward away from the applicator surface. The mean dose difference was ∼0.45%–0.51% and the 95-percentile maximum difference was ∼1.24%–1.47%. Conclusion: Acuros BV is able to accurately perform dose calculations in HDR brachytherapy with a shielded cylinder applicator.« less

  8. Intracellular Ca2+ homeostasis and JAK1/STAT3 pathway are involved in the protective effect of propofol on BV2 microglia against hypoxia-induced inflammation and apoptosis

    PubMed Central

    Wang, Jiaqiang; Miao, Changhong

    2017-01-01

    Background Perioperative hypoxia may induce microglial inflammation and apoptosis, resulting in brain injury. The neuroprotective effect of propofol against hypoxia has been reported, but the underlying mechanisms are far from clear. In this study, we explored whether and how propofol could attenuate microglia BV2 cells from CoCl2-induced hypoxic injury. Methods Mouse microglia BV2 cells were pretreated with propofol, and then stimulated with CoCl2. TNF-α level in the culture medium was measured by ELISA kit. Cell apoptosis and intracellular calcium concentration were measured by flow cytometry analysis. The effect of propofol on CoCl2-modulated expression of Ca2+/Calmodulin (CaM)-dependent protein kinase II (CAMKIIα), phosphorylated CAMKIIα (pCAMKIIα), STAT3, pSTAT3Y705, pSTAT3S727, ERK1/2, pERK1/2, pNFκB(p65), pro-caspase3, cleaved caspase 3, JAK1, pJAK1, JAK2, pJAK2 were detected by Western blot. Results In BV2 cell, CoCl2 treatment time-dependently increased TNF-α release and induced apoptosis, which were alleviated by propofol. CoCl2 (500μmol/L, 8h) treatment increased intracellular Ca2+ level, and caused the phosphorylation of CAMKIIα, ERK1/2 and NFκB (p65), as well as the activation of caspase 3. More importantly, these effects could be modulated by 25μmol/L propofol via maintaining intracellular Ca2+ homeostasis and via up-regulating the phosphorylation of JAK1 and STAT3 at Tyr705. Conclusion Propofol could protect BV2 microglia from hypoxia-induced inflammation and apoptosis. The potential mechanisms may involve the maintaining of intracellular Ca2+ homeostasis and the activation of JAK1/STAT3 pathway. PMID:28542400

  9. Dietary supplementation with the polyphenol-rich açaí pulps (Euterpe oleracea Mart. and Euterpe precatoria Mart.) improves cognition in aged rats and attenuates inflammatory signaling in BV-2 microglial cells.

    PubMed

    Carey, Amanda N; Miller, Marshall G; Fisher, Derek R; Bielinski, Donna F; Gilman, Casey K; Poulose, Shibu M; Shukitt-Hale, Barbara

    2017-05-01

    The present study was carried out to determine if lyophilized açaí fruit pulp (genus, Euterpe), rich in polyphenols and other bioactive antioxidant and anti-inflammatory phytochemicals, is efficacious in reversing age-related cognitive deficits in aged rats. The diets of 19-month-old Fischer 344 rats were supplemented for 8 weeks with 2% Euterpe oleracea (EO), Euterpe precatoria (EP), or a control diet. Rats were tested in the Morris water maze and then blood serum from the rats was used to assess inflammatory responses of BV-2 microglial cells. After 8 weeks of dietary supplementation with 2% EO or EP, rats demonstrated improved working memory in the Morris water maze, relative to controls; however, only the EO diet improved reference memory. BV-2 microglial cells treated with blood serum collected from EO-fed rats produced less nitric oxide (NO) than control-fed rats. Serum from both EO- and EP-fed rats reduced tumor necrosis factor-alpha (TNF-α). There is a relationship between performance in the water maze and the production of NO and TNF-α by serum-treated BV-2 cells, such that serum from rats with better performance was more protective against inflammatory signaling. Protection of memory during aging by supplementation of lyophilized açaí fruit pulp added to the diet may result from its ability to influence antioxidant and anti-inflammatory signaling.

  10. Early Interactions of Rhizobium leguminosarum bv. phaseoli and Bean Roots: Specificity in the Process of Adsorption and Its Requirement of Ca(sup2+) and Mg(sup2+) Ions

    PubMed Central

    Lodeiro, A. R.; Lagares, A.; Martinez, E. N.; Favelukes, G.

    1995-01-01

    Roots of Phaseolus vulgaris L. were incubated with dilute suspensions (1 x 10(sup3) to 3 x 10(sup3) bacteria ml(sup-1)) of an antibiotic-resistant indicator strain of Rhizobium leguminosarum bv. phaseoli in mineral medium and washed four times by a standardized procedure prior to quantitation of adsorption (G. Caetano-Anolles and G. Favelukes, Appl. Environ. Microbiol. 52:371-376, 1986). The population of rhizobia remaining adsorbed on roots after washing was homogeneous, as indicated by the first-order course of its desorption by hydrodynamic shear. Rhizobia were maximally active for adsorption in the early stationary phase of growth. The process leading to adsorption was rapid, without an initial lag, and slowed down after 1 h. Adsorption of the indicator strain at 10(sup3) bacteria ml(sup-1) was inhibited to different extents in the presence of 10(sup3) to 10(sup8) antibiotic-sensitive competitor rhizobia ml(sup-1). After a steep rise above 10(sup4) bacteria ml(sup-1), inhibition by heterologous competitors in the concentration range of 10(sup5) to 10(sup7) bacteria ml(sup-1) was markedly less than by homologous strains, while at 10(sup8) bacteria ml(sup-1) it approached the high level of inhibition by the latter. At 10(sup7) bacteria ml(sup-1), all of the heterologous strains tested were consistently less inhibitory than homologous competitors (P < 0.001). These differences in competitive behavior indicate that in the process of adsorption of R. leguminosarum bv. phaseoli to its host bean roots, different modes of adsorption occur and that some of these modes are specific for the microsymbiont (as previously reported for the alfalfa system [G. Caetano-Anolles and G. Favelukes, Appl. Environ. Microbiol. 52:377-381, 1986]). Moreover, whereas the nonspecific process occurred either in the absence or in the presence of Ca(sup2+) and Mg(sup2+) ions, expression of specificity was totally dependent on the presence of those cations. R. leguminosarum bv. phaseoli

  11. The protective effect of fermented Curcuma longa L. on memory dysfunction in oxidative stress-induced C6 gliomal cells, proinflammatory-activated BV2 microglial cells, and scopolamine-induced amnesia model in mice.

    PubMed

    Eun, Cheong-Su; Lim, Jong-Soon; Lee, Jihye; Lee, Sam-Pin; Yang, Seun-Ah

    2017-07-17

    Curcuma longa L. is a well-known medicinal plant that has been used for its anti-cancer, neuroprotective, and hepatoprotective effects. However, the neuroprotective effect of fermented C. longa (FCL) has not been reported. Therefore, in this study, the effectiveness of FCL for the regulation of memory dysfunction was investigated in two brain cell lines (rat glioma C6 and murine microglia BV2) and scopolamine-treated mice. C. longa powder was fermented by 5% Lactobacillus plantarum K154 containing 2% (w/v) yeast extract at 30 °C for 72 h followed by sterilization at 121 °C for 15 min. The protective effects of fermented C. longa (FCL) on oxidative stress induced cell death were analyzed by MTT assay in C6 cells. The anti-inflammatory effects of FCL were investigated by measuring the production of nitric oxide (NO) and prostaglandin E 2 (PGE 2 ) as well as the expression levels of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) in LPS-stimulated BV2 cells. The step-through passive avoidance test, Morris water maze test, acetylcholinesterase (AChE) activity, and expression of cAMP response element-binding protein (CREB) and brain-derived neurotropic factor (BDNF) were employed to determine the effects of FCL on scopolamine-induced memory deficit in mice. The contents of curcuminoids were analyzed through LC/MS. Pretreatment with FCL effectively prevented the cell death induced by oxidative stress in C6 cells. Moreover, FCL inhibited the production NO and PGE 2 via the inhibition of iNOS and COX-2 expression in BV2 cells. FCL significantly attenuated scopolamine-induced memory impairment in mice and prevented scopolamine-induced AChE activity in the hippocampus. Additionally, FCL reversed the reduction of CREB and BDNF expression. The curcuminoids content in FCL was 1.44%. FCL pretreatment could alleviate scopolamine-induced memory impairment in mice, as well as oxidative stress and inflammation in C6 and BV2 cells, respectively. Thus, FCL might be a

  12. 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 Central

    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

  13. Anti-neuroinflammatory effects of grossamide from hemp seed via suppression of TLR-4-mediated NF-κB signaling pathways in lipopolysaccharide-stimulated BV2 microglia cells.

    PubMed

    Luo, Qian; Yan, Xiaoli; Bobrovskaya, Larisa; Ji, Mei; Yuan, Huiqing; Lou, Hongxiang; Fan, Peihong

    2017-04-01

    Grossamide, a representative lignanamide in hemp seed, has been reported to possess potential anti-inflammatory effects. However, the potential anti-neuroinflammatory effects and underlying mechanisms of action of grossamide are still unclear. Therefore, the present study investigated the possible effects and underlying mechanisms of grossamide against lipopolysaccharide (LPS)-induced inflammatory response in BV2 microglia cells. BV2 microglia cells were pre-treated with various concentrations of grossamide before being stimulated with LPS to induce inflammation. The levels of pro-inflammatory cytokines were determined using the enzyme-linked immunoassay (ELISA) and mRNA expression levels were measured by real-time PCR. The translocation of nuclear factor-kappa B (NF-κB) and contribution of TLR4-mediated NF-κB activation on inflammatory effects were evaluated by immunostaining and Western blot analysis. This study demonstrated that grossamide significantly inhibited the secretion of pro-inflammatory mediators such as interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α), and decreased the level of LPS-mediated IL-6 and TNF-α mRNA. In addition, it significantly reduced the phosphorylation levels of NF-κB subunit p65 in a concentration-dependent manner and suppressed translocation of NF-κB p65 into the nucleus. Furthermore, grossamide markedly attenuated the LPS-induced expression of Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88). Taken together, these data suggest that grossamide could be a potential therapeutic candidate for inhibiting neuroinflammation in neurodegenerative diseases.

  14. Pathways to cognitive design.

    PubMed

    Wertz, Annie E; Moya, Cristina

    2018-05-30

    Despite a shared recognition that the design of the human mind and the design of human culture are tightly linked, researchers in the evolutionary social sciences tend to specialize in understanding one at the expense of the other. The disciplinary boundaries roughly correspond to research traditions that focus more on natural selection and those that focus more on cultural evolution. In this paper, we articulate how two research traditions within the evolutionary social sciences-evolutionary psychology and cultural evolution-approach the study of design. We focus our analysis on the design of cognitive mechanisms that are the result of the interplay of genetic and cultural evolution. We aim to show how the approaches of these two research traditions can complement each other, and provide a framework for developing a wider range of testable hypotheses about cognitive design. To do so, we provide concrete illustrations of how this integrated approach can be used to interrogate cognitive design using examples from our own work on plant and symbolic group boundary cognition. We hope this recognition of different pathways to design will broaden the hypothesis space in the evolutionary social sciences and encourage methodological pluralism in the investigation of the mind. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. Isobutyrylshikonin inhibits lipopolysaccharide-induced nitric oxide and prostaglandin E2 production in BV2 microglial cells by suppressing the PI3K/Akt-mediated nuclear transcription factor-κB pathway.

    PubMed

    Jayasooriya, Rajapaksha Gedara Prasad Tharanga; Lee, Kyoung-Tae; Kang, Chang-Hee; Dilshara, Matharage Gayani; Lee, Hak-Ju; Choi, Yung Hyun; Choi, Il-Whan; Kim, Gi-Young

    2014-12-01

    Microglia are important macrophages to defend against pathogens in the central nervous system (CNS); however, persistent or acute inflammation of microglia lead to CNS disorders via neuronal cell death. Therefore, we theorized that a good strategy for the treatment of CNS disorders would be to target inflammatory mediators from microglia in disease. Consequently, we investigated whether isobutyrylshikonin (IBS) attenuates the production of proinflammatory mediators, such as nitric oxide (NO) and prostaglandin E2, in lipopolysaccharide (LPS)-stimulated BV2 microglial cells. Treatment with IBS inhibited the secretion of NO and prostaglandin E2 (as well as the expression of their key regulatory genes), inducible NO synthase (iNOS), and cyclooxygenase-2 (COX-2). Isobutyrylshikonin also suppressed LPS-induced DNA-binding activity of nuclear transcription factor-κB (NF-κB), by inhibiting the nuclear translocation of p50 and p65 in addition to blocking the phosphorylation and degradation of IκBα. Pretreatment with pyrrolidine dithiocarbamate, a specific NF-κB inhibitor, showed the down-regulation of LPS-induced iNOS and COX-2 messenger RNA by suppressing NF-κB activity. This indirectly suggests that IBS-mediated NF-κB inhibition is the main signaling pathway involved in the inhibition of iNOS and COX-2 expression. In addition, IBS attenuated LPS-induced phosphorylation of PI3K and Akt, which are upstream molecules of NF-κB, in LPS-stimulated BV2 microglial cells. The functional aspects of the PI3K/Akt signaling pathway were analyzed with LY294002, which is a specific PI3K/Akt inhibitor that attenuated LPS-induced iNOS and COX-2 expression by suppressing NF-κB activity. These data suggest that an IBS-mediated anti-inflammatory effect may be involved in suppressing the PI3K/Akt-mediated NF-κB signaling pathway. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. The sp2-iminosugar glycolipid 1-dodecylsulfonyl-5N,6O-oxomethylidenenojirimycin (DSO2-ONJ) as selective anti-inflammatory agent by modulation of hemeoxygenase-1 in Bv.2 microglial cells and retinal explants.

    PubMed

    Alcalde-Estévez, Elena; Arroba, Ana I; Sánchez-Fernández, Elena M; Mellet, Carmen Ortiz; García Fernández, Jose M; Masgrau, Laura; Valverde, Ángela M

    2018-01-01

    Neuroinflammation is an early event during diabetic retinopathy (DR) that impacts the dynamics of microglia polarization. Gliosis is a hallmark of DR and we have reported the beneficial effects of 1R-DSO-ONJ, a member of the sp 2 -iminosugar glycolipid (sp 2 -IGL) family, in targeting microglia and reducing gliosis in diabetic db/db mice. Herein, we analyzed the effect of DSO 2 -ONJ, another family compound incorporating a sulfone group that better mimics the phosphate group of phosphatidylinositol ether lipid analogues (PIAs), in Bv.2 microglial cells treated with bacterial lipopolysaccaride (LPS) and in retinal explants from db/db mice. In addition to decreasing iNOS and inflammasome activation, the anti-inflammatory effect of DSO 2 -ONJ was mediated by direct p38α MAPK activation. Computational docking experiments demonstrated that DSO 2 -ONJ binds to p38α MAPK at the same site where PIAs and the alkyl phospholipid perifosine activators do, suggesting similar mechanism of action. Moreover, treatment of microglial cells with DSO 2 -ONJ increased both heme-oxygenase (HO)-1 and Il10 expression regardless the presence of LPS. In retinal explants from db/db mice, DSO 2 -ONJ also induced HO-1 and reduced gliosis. Since IL-10-mediated induction of HO-1 expression is mediated by p38α MAPK activation, our results suggest that this molecular mechanism is involved in the anti-inflammatory effects of DSO 2 -ONJ in microglia. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. 5-Hydroxy-3,6,7,8,3'4'-hexamethoxyflavone inhibits nitric oxide production in lipopolysaccharide-stimulated BV2 microglia via NF-κB suppression and Nrf-2-dependent heme oxygenase-1 induction.

    PubMed

    Kang, Chang-Hee; Kim, Min Jeong; Seo, Min Jeong; Choi, Yung Hyun; Jo, Wol Soon; Lee, Kyung-Tae; Jeong, Yong Kee; Kim, Gi-Young

    2013-07-01

    In this study, we found that 5-hydroxy-3,6,7,8,3'4'-hexamethoxyflavone (5HHMF) from Hizikia fusiforme considerably inhibits lipopolysaccharide (LPS)-stimulated NO production by suppressing the expression of inducible NO synthase (iNOS) in BV2 microglia. In addition, 5HHMF blocked LPS-induced phosphorylation of IκB, resulting in suppression of the nuclear translocation of nuclear factor-κB (NF-κB) subunits, namely p65 and p50, which are important molecules involved in the regulation of iNOS expression. Pyrrolidine dithiocarbamate (PDTC), a specific NF-κB inhibitor, along with 20S proteasome inhibitor (PSI) significantly inhibited LPS-induced iNOS expression, which indirectly suggested that 5HHMF downregulated iNOS expression by suppressing NF-κB activity. Thus, we found that 5HHMF enhances heme oxygenase-1 (HO-1) expression via nuclear factor-erythroid 2-related factor 2 (Nrf2) activation. In addition, cobalt protoporphyrin (CoPP), a specific HO-1 inducer, predominantly suppressed LPS-induced NO production. In contrast, zinc protoporphyrin (ZnPP), a specific HO-1 inhibitor, showed a partial suppressive effect of 5HHMF on LPS-induced NO production. Further, 5HHMF increased specific DNA-binding activity of Nrf2, and transient knockdown with Nrf2 siRNA subsequently reversed 5HHMF-induced NO inhibition, which was followed by suppression of HO-1 activity. Taken together, our findings indicate that 5HHMF suppresses NO production through modulation of iNOS, consequently suppressing NF-κB activity and induction of Nrf2-dependent HO-1 activity. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. 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

  19. 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

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

    2011-09-01

    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. Copyright © 2011, American Society for Microbiology. All Rights Reserved.

  20. Protective Effects of α-Tocopherol, γ-Tocopherol and Oleic Acid, Three Compounds of Olive Oils, and No Effect of Trolox, on 7-Ketocholesterol-Induced Mitochondrial and Peroxisomal Dysfunction in Microglial BV-2 Cells.

    PubMed

    Debbabi, Meryam; Nury, Thomas; Zarrouk, Amira; Mekahli, Nadia; Bezine, Maryem; Sghaier, Randa; Grégoire, Stéphane; Martine, Lucy; Durand, Philippe; Camus, Emmanuelle; Vejux, Anne; Jabrane, Aymen; Bretillon, Lionel; Prost, Michel; Moreau, Thibault; Ammou, Sofien Ben; Hammami, Mohamed; Lizard, Gérard

    2016-11-25

    Lipid peroxidation products, such as 7-ketocholesterol (7KC), may be increased in the body fluids and tissues of patients with neurodegenerative diseases and trigger microglial dysfunction involved in neurodegeneration. It is therefore important to identify synthetic and natural molecules able to impair the toxic effects of 7KC. We determined the impact of 7KC on murine microglial BV-2 cells, especially its ability to trigger mitochondrial and peroxisomal dysfunction, and evaluated the protective effects of α- and γ-tocopherol, Trolox, and oleic acid (OA). Multiple complementary chemical assays, flow cytometric and biochemical methods were used to evaluate the antioxidant and cytoprotective properties of these molecules. According to various complementary assays to estimate antioxidant activity, only α-, and γ-tocopherol, and Trolox had antioxidant properties. However, only α-tocopherol, γ-tocopherol and OA were able to impair 7KC-induced loss of mitochondrial transmembrane potential, which is associated with increased permeability to propidium iodide, an indicator of cell death. In addition, α-and γ-tocopherol, and OA were able to prevent the decrease in Abcd3 protein levels, which allows the measurement of peroxisomal mass, and in mRNA levels of Abcd1 and Abcd2, which encode for two transporters involved in peroxisomal β-oxidation. Thus, 7KC-induced side effects are associated with mitochondrial and peroxisomal dysfunction which can be inversed by natural compounds, thus supporting the hypothesis that the composition of the diet can act on the function of organelles involved in neurodegenerative diseases.

  1. 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. Copyright © 2010 Elsevier Inc. All rights reserved.

  2. Protective Effects of α-Tocopherol, γ-Tocopherol and Oleic Acid, Three Compounds of Olive Oils, and No Effect of Trolox, on 7-Ketocholesterol-Induced Mitochondrial and Peroxisomal Dysfunction in Microglial BV-2 Cells

    PubMed Central

    Debbabi, Meryam; Nury, Thomas; Zarrouk, Amira; Mekahli, Nadia; Bezine, Maryem; Sghaier, Randa; Grégoire, Stéphane; Martine, Lucy; Durand, Philippe; Camus, Emmanuelle; Vejux, Anne; Jabrane, Aymen; Bretillon, Lionel; Prost, Michel; Moreau, Thibault; Ammou, Sofien Ben; Hammami, Mohamed; Lizard, Gérard

    2016-01-01

    Lipid peroxidation products, such as 7-ketocholesterol (7KC), may be increased in the body fluids and tissues of patients with neurodegenerative diseases and trigger microglial dysfunction involved in neurodegeneration. It is therefore important to identify synthetic and natural molecules able to impair the toxic effects of 7KC. We determined the impact of 7KC on murine microglial BV-2 cells, especially its ability to trigger mitochondrial and peroxisomal dysfunction, and evaluated the protective effects of α- and γ-tocopherol, Trolox, and oleic acid (OA). Multiple complementary chemical assays, flow cytometric and biochemical methods were used to evaluate the antioxidant and cytoprotective properties of these molecules. According to various complementary assays to estimate antioxidant activity, only α-, and γ-tocopherol, and Trolox had antioxidant properties. However, only α-tocopherol, γ-tocopherol and OA were able to impair 7KC-induced loss of mitochondrial transmembrane potential, which is associated with increased permeability to propidium iodide, an indicator of cell death. In addition, α-and γ-tocopherol, and OA were able to prevent the decrease in Abcd3 protein levels, which allows the measurement of peroxisomal mass, and in mRNA levels of Abcd1 and Abcd2, which encode for two transporters involved in peroxisomal β-oxidation. Thus, 7KC-induced side effects are associated with mitochondrial and peroxisomal dysfunction which can be inversed by natural compounds, thus supporting the hypothesis that the composition of the diet can act on the function of organelles involved in neurodegenerative diseases. PMID:27897980

  3. 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.

  4. Rotorcraft Design

    DTIC Science & Technology

    1978-01-01

    MOMENT GROWTH BV %tV • REDUCE BLADr. BENDING MOMENTS B’< 17* HUB VIBRATORV FORCES • REDUCE VIBRATORV LOADSBV W FLIGHTWOR THINE SS • FAIL SAM...standardization in future military helicopter development. 2.4 SOME TECHNICAL ASPECTS OF MILITARY HELICOPTER DEVELOPMENT ^- Ss In recent years, the...8217 - fT • SS 1 H Fig.2 The Lynx HAS MK 2 Fig.3 The Gazelle — — " - Fig.4 Wessex MK 2 Fig. 5 The Puma MteMA

  5. Design Studio.

    ERIC Educational Resources Information Center

    Draze, Dianne; Palouda, Annelise

    This book presents information about 10 areas of design, with the main emphasis on graphic design. One section presents the creative problem solving process and provides practice in using this process to solve design problems. Students are given a glimpse of other areas of design, including fashion, industrial, architectural, decorative,…

  6. 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.

  7. 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.

  8. Design Fixation

    ERIC Educational Resources Information Center

    Kelley, Todd R.; Sung, Euisuk

    2017-01-01

    The purpose of this article is to provide awareness of the danger of design fixation and promote the uses of brainstorming early in the design process--before fixation limits creative ideas. The authors challenged technology teachers to carefully limit the use of design examples too early in the process and provided suggestions for facilitating…

  9. Appraising design

    DTIC Science & Technology

    2016-05-26

    Appraising Design A Monograph by MAJ Donald J. Nunemaker United States Army School of...NUMBER Appraising Design Sb. GRANT NUMBER Sc. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Sd. PROJECT NUMBER MAJ Donald J. Nunemaker Se. TASK NUMBER Sf...Distribution is unlimited. 13. SUPPLEMENTARY NOTES 14. ABSTRACT In the context of military operations, ideas about design developed over the past fifteen

  10. Research design.

    PubMed

    Toledo-Pereyra, Luis H

    2012-10-01

    The development of a good research design permits us to obtain the best research data possible. From the experimental question to the research hypothesis and data collection variables, we can begin to consider the optimal research design. Details pertaining to the selection of the research design are considered within and very much in relation with the knowledge of the researcher and the support of his research group.

  11. Probe design

    NASA Technical Reports Server (NTRS)

    Cowan, W.

    1974-01-01

    Outer planetary probe designs consider mission characteristics, structural configuration, delivery mode, scientific payload, environmental extremes, mass properties, and the launch vehicle and spacecraft interface.

  12. Publication Design.

    ERIC Educational Resources Information Center

    Nelson, Roy Paul

    This book is designed to solve the problem of coordinating art and typography with content in publications. Through text and illustrations, this book suggests ways to make pages and spreads in magazines, newspapers, and books attractive and readable. As a book of techniques, it is directed at potential and practicing art directors, designers, and…

  13. 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,…

  14. Aircraft Design

    NASA Technical Reports Server (NTRS)

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

  15. 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…

  16. 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…

  17. Design tools

    Treesearch

    Anton TenWolde; Mark T. Bomberg

    2009-01-01

    Overall, despite the lack of exact input data, the use of design tools, including models, is much superior to the simple following of rules of thumbs, and a moisture analysis should be standard procedure for any building envelope design. Exceptions can only be made for buildings in the same climate, similar occupancy, and similar envelope construction. This chapter...

  18. 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)

  19. Scenario Design

    DTIC Science & Technology

    2006-09-01

    communities were bled for the well-intent Continuum’ to define other military missio designer is given much greater leeway wher Until now, you learned that...Design Continuum. as more sporting event than political struggle. Originating from lucrative diamond trade went underground (See Stewart and 89 to just...fulfilment, hoping some day to attain the higher elf -enrichment outright. Realizing that their presence in resource- rnment soldiers sold munitions to

  20. 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.

  1. 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.

  2. Pulsation Modes of sdBV Stars Observed with Kepler

    NASA Astrophysics Data System (ADS)

    Reed, M. D.; Baran, A. S.; Quint, A. C.; Telting, J. H.; Østensen, R. H.; O'Toole, S. J.

    2012-03-01

    During the Kepler satellite's first year of operation, its short cadence observations were obtained in a survey mode where targets received one month of nearly continuous observations. 48 subdwarf B stars were observed of which 14 were found to be pulsators, with only one of these having predominantly short periods. The other 13 were mostly long-period (g-mode) pulsators. With Kepler's exquisite duty cycle and data quality, an average of 23 periods per star were detected with ranges from 6 to 44. As the g-mode pulsations are high-overtone (typically n > 10), asymptotic period relations could apply and so we searched for evenly spaced periods. We found these for l =1 and 2 modes in all but one of the Kepler stars and that one outlier has a very complex temporal spectrum caused by a close companion. We were able to associate 204 of 299 measured periods with l = 1 and 2 modes. Those results should provide tight constraints on pulsation models. However, they also offer a surprise as current structure models predict significant mode trapping, which is inconsistent with the period spacings we have found.

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

    MedlinePlus

    ... YouTube follow us on Flickr follow us on Instagram Español NICHD Theme Browse AZTopics Browse A-Z ... Publications Sitemap Español facebook twitter pinterest youtube flickr Instagram NEWSROOM NICHD News Videos OUTREACH Safe to Sleep® ...

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

    MedlinePlus

    ... YouTube follow us on Flickr follow us on Instagram Español NICHD Theme Browse AZTopics Browse A-Z ... Publications Sitemap Español facebook twitter pinterest youtube flickr Instagram NEWSROOM NICHD News Videos OUTREACH Safe to Sleep® ...

  5. Hα spectroscopy and BV photometry of RT Lacertae

    NASA Astrophysics Data System (ADS)

    Frasca, A.; Çakırlı, Ö.; Catalano, S.; Ibanoǧlu, C.; Marilli, E.; Evren, S.; Taş, G.

    2002-06-01

    Contemporaneous spectroscopic and photometric B V observations of the RS CVn type eclipsing binary RT Lacertae were performed in summer 2000. The photometric observations were obtained at the Ege University Observatory, while the spectroscopic ones were carried out at Catania Astrophysical Observatory in the spectral range 5860-6700 Å. We obtained a high quality radial velocity curve of the system that allowed us to give more accurate values of the orbital parameters. A steady decrease of the barycentric velocity from 1920 to 2000 has been pointed out and has been discussed in the context of a third body hypothesis. Through the subtraction of a ``synthetic'' spectrum, built up with spectra of inactive standard stars, we detected Hα excess emission which fills in the photospheric absorption profiles of both components. With the exception of a few spectra, taken close to the eclipses, in which some extra absorption or a faint double-peaked broad emission appears, there is no further evidence of circumstellar matter in this system, as suggested in previous works. The hotter and more massive star appears also as the more active at a chromospheric level, since it has a Hα flux about ten times greater than the companion, on average. Rotational modulation of the Hα emission has been detected in both stars. The hemisphere of the more massive star facing the observer at phase 0fp75 appears brighter (in Hα ) than that seen at phase 0fp25 , while for the less massive G9 IV star the maximum Hα emission is seen around phase 0fp0-0fp1 . From the analysis of the contemporaneous light curve (Lanza et al. \\cite{Lanza2001}), the more massive G5 IV star results to be more active than the companion at a photospheric level, in agreement with the chromospheric behaviour observed in Hα . In addition, the starspots of the G5 IV star are mainly located in the Hα brighter hemisphere, suggesting a close spatial association of spots and plages in this star. The G9 IV star displays instead the maximum Hα emission at the phase of maximum visibility of the smaller spotted area found from the light-curve analysis. The minimum Hα emission occurs when the more heavily spotted region is visible. Based on observations collected at Catania Astrophysical Observatory, Italy, and at Ege University Observatory, Turkey. Table 1 only available at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or via http://cdsweb.u-strasbg.fr/cgi-bin/qcat?J/A+A/388/298

  6. 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.

  7. 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.

  8. 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…

  9. Experimental design

    NASA Technical Reports Server (NTRS)

    Lim, H. S.

    1983-01-01

    The design of long life, low weight nickel cadmium cells is studied. The status of a program to optimize nickel electrodes for the best performance is discussed. The pore size of the plaque, the mechanical strength and active material loading are considered in depth.

  10. Design Fragments

    DTIC Science & Technology

    2007-04-19

    define the patterns and are better at analyzing behavior. SPQR (System for Pattern Query and Recognition) [18, 58] can recognize pattern vari- ants...Stotts. SPQR : Flexible automated design pattern extraction from source code. ase, 00:215, 2003. ISSN 1527-1366. doi: http://doi.ieeecomputersociety. org

  11. 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…

  12. 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)…

  13. Experimental toxicology: Issues of statistics, experimental design, and replication.

    PubMed

    Briner, Wayne; Kirwan, Jeral

    2017-01-01

    The difficulty of replicating experiments has drawn considerable attention. Issues with replication occur for a variety of reasons ranging from experimental design to laboratory errors to inappropriate statistical analysis. Here we review a variety of guidelines for statistical analysis, design, and execution of experiments in toxicology. In general, replication can be improved by using hypothesis driven experiments with adequate sample sizes, randomization, and blind data collection techniques. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Environmental Design

    DTIC Science & Technology

    2015-04-13

    Emphasis within planning needs to shift away from reductionism and towards a holistic understanding of the operational environment. This paper addresses...the author (INTENTION..4UY BLANK) Environmental Design By Christopher D. Gardiner Lieutenant Colonel, Australian Army A paper submitted to the...and Strategy. The contents of this paper reOect my own personal views and are not necessarily endorsed by the Joint Forces Staff College or the

  15. 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.

  16. Robot Design

    NASA Technical Reports Server (NTRS)

    1988-01-01

    Martin Marietta Aero and Naval Systems has advanced the CAD art to a very high level at its Robotics Laboratory. One of the company's major projects is construction of a huge Field Material Handling Robot for the Army's Human Engineering Lab. Design of FMR, intended to move heavy and dangerous material such as ammunition, was a triumph in CAD Engineering. Separate computer problems modeled the robot's kinematics and dynamics, yielding such parameters as the strength of materials required for each component, the length of the arms, their degree of freedom and power of hydraulic system needed. The Robotics Lab went a step further and added data enabling computer simulation and animation of the robot's total operational capability under various loading and unloading conditions. NASA computer program (IAC), integrated Analysis Capability Engineering Database was used. Program contains a series of modules that can stand alone or be integrated with data from sensors or software tools.

  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,…

  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. Two Theories of Design and Instructional Design.

    ERIC Educational Resources Information Center

    Tripp, Steven D.

    This paper address three questions: (1) What is the nature of design? (2) How do skilled designers function? and (3) Can a theory of design be constructed which will allow novice and expert instructional designers to perform their tasks more efficiently and effectively? It begins by presenting two general theories of design: Simon's conception of…

  1. 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…

  2. 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.

  3. FAPA mass spectrometry of designer drugs.

    PubMed

    Smoluch, Marek; Gierczyk, Blazej; Reszke, Edward; Babij, Michal; Gotszalk, Teodor; Schroeder, Grzegorz; Silberring, Jerzy

    2016-01-01

    Application of a flowing atmospheric-pressure afterglow ion source for mass spectrometry (FAPA-MS) for the analysis of designer drugs is described. In this paper, we present application of FAPA MS for identification of exemplary psychotropic drugs: JWH-122, 4BMC, Pentedrone, 3,4-DNNC and ETH-CAT. We have utilized two approaches for introducing samples into the plasma stream; first in the form of a methanolic aerosol from the nebulizer, and the second based on a release of vapors from the electrically heated crucible by thermal desorption. The analytes were ionized by FAPA and identified in the mass analyzer. The order of release of the compounds depends on their volatility. These methods offer fast and reliable structural information, without pre-separation, and can be an alternative to the Electron Impact, GC/MS, and ESI for fast analysis of designer-, and other psychoactive drugs. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Enhancing biomedical design with design thinking.

    PubMed

    Kemnitzer, Ronald; Dorsa, Ed

    2009-01-01

    The development of biomedical equipment is justifiably focused on making products that "work." However, this approach leaves many of the people affected by these designs (operators, patients, etc.) with little or no representation when it comes to the design of these products. Industrial design is a "user focused" profession which takes into account the needs of diverse groups when making design decisions. The authors propose that biomedical equipment design can be enhanced, made more user and patient "friendly" by adopting the industrial design approach to researching, analyzing, and ultimately designing biomedical products.

  5. Designing research: ex post facto designs.

    PubMed

    Giuffre, M

    1997-06-01

    The research design is the overall plan or structure of the study. The goal of a good research design is to insure internal validity and answer the question being asked. The only clear rule in selecting a design is that the question dictates the design. Over the next few issues this column will cover types of research designs and their inherent strengths and weaknesses. This article discusses ex post facto research.

  6. 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;…

  7. Drafting the Outside Designer.

    ERIC Educational Resources Information Center

    Aldrich, Charles R.

    1981-01-01

    Areas discussed in selecting an outside designer include: how to find the right designer; dealing with a purchasing agent; the differences between studio and free-lance designers; how much freedom a designer should have; how to deal with the designer; and what advice designers can give. (LC)

  8. CEM-designer: design of custom expression microarrays in the post-ENCODE Era.

    PubMed

    Arnold, Christian; Externbrink, Fabian; Hackermüller, Jörg; Reiche, Kristin

    2014-11-10

    Microarrays are widely used in gene expression studies, and custom expression microarrays are popular to monitor expression changes of a customer-defined set of genes. However, the complexity of transcriptomes uncovered recently make custom expression microarray design a non-trivial task. Pervasive transcription and alternative processing of transcripts generate a wealth of interweaved transcripts that requires well-considered probe design strategies and is largely neglected in existing approaches. We developed the web server CEM-Designer that facilitates microarray platform independent design of custom expression microarrays for complex transcriptomes. CEM-Designer covers (i) the collection and generation of a set of unique target sequences from different sources and (ii) the selection of a set of sensitive and specific probes that optimally represents the target sequences. Probe design itself is left to third party software to ensure that probes meet provider-specific constraints. CEM-Designer is available at http://designpipeline.bioinf.uni-leipzig.de. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. 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.

  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. © 2015 Wiley Periodicals, Inc.

  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. Social Design Experiments: Toward Equity by Design

    ERIC Educational Resources Information Center

    Gutiérrez, Kris D.; Jurow, A. Susan

    2016-01-01

    In this article, we advance an approach to design research that is organized around a commitment to transforming the educational and social circumstances of members of non-dominant communities as a means of promoting social equity and learning. We refer to this approach as social design experimentation. The goals of social design experiments…

  13. Teaching Ethics as Design

    ERIC Educational Resources Information Center

    Kirkman, Robert; Fu, Katherine; Lee, Bumsoo

    2017-01-01

    This paper introduces an approach to teaching ethics as design in a new course entitled Design Ethics, team-taught by a philosopher and an engineer/designer. The course follows a problem-based learning model in which groups of students work through the phases of the design process on a project for a local client, considering the design values and…

  14. The Distributed Criterion Design

    ERIC Educational Resources Information Center

    McDougall, Dennis

    2006-01-01

    This article describes and illustrates a novel form of the changing criterion design called the distributed criterion design, which represents perhaps the first advance in the changing criterion design in four decades. The distributed criterion design incorporates elements of the multiple baseline and A-B-A-B designs and is well suited to applied…

  15. 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…

  16. Designing for Change.

    ERIC Educational Resources Information Center

    Loeffelman, Pamela

    2001-01-01

    Discusses how educational facility designers can design schools for greater building flexibility. Understanding how corridors and hidden spaces can be better utilized is highlighted, and better design of the scale and syntax of a school's parts is discussed. (GR)

  17. Antagonistic effects of acetylshikonin on LPS-induced NO and PGE2 production in BV2 microglial cells via inhibition of ROS/PI3K/Akt-mediated NF-κB signaling and activation of Nrf2-dependent HO-1.

    PubMed

    Jayasooriya, Rajapaksha Gedara Prasad Tharanga; Lee, Kyoung-Tae; Choi, Yung Hyun; Moon, Sung-Kwon; Kim, Wun-Jae; Kim, Gi-Young

    2015-10-01

    Although acetylshikonin (ACS) is known to have antioxidant and antitumor activities, whether ACS regulates the expression of proinflammatory mediators in lipopolysaccharide (LPS)-stimulated microglial cells remains unclear. In this study, it was found that ACS isolated from Lithospermum erythrorhizon inhibits LPS-induced nitric oxide (NO) and prostaglandin E2 (PGE2) release by suppressing the expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) in BV2 microglial cells. Furthermore, ACS reduced the LPS-induced DNA-binding activity of nuclear factor-κB (NF-κB) and subsequently suppressed iNOS and COX-2 expression. Consistent with these data, ACS attenuated the phosphorylation of PI3K and Akt and suppressed the DNA-binding activity of NF-κB by inducing the generation of reactive oxygen species (ROS) in LPS-stimulated cells. In addition, ACS enhanced heme oxygenase-1 (HO-1) expression via nuclear factor-erythroid 2-related factor 2 (Nrf2) activation. Zinc protoporphyrin, a specific HO-1 inhibitor, partially attenuated the antagonistic effects of ACS on LPS-induced NO and PGE2 production. By contrast, the presence of cobalt protoporphyrin, a specific HO-1 inducer, potently suppressed LPS-induced NO and PGE2 production. These data indicate that ACS downregulates proinflammatory mediators such as NO and PGE2 by suppressing PI3K/Akt-dependent NF-κB activity induced by ROS as well as inducing Nrf2-dependent HO-1 activity. Taken together, ACS might be a good candidate to regulate LPS-mediated inflammatory diseases.

  18. Applying the miniaturization technologies for biosensor design.

    PubMed

    Derkus, Burak

    2016-05-15

    Microengineering technologies give us some opportunities in developing high-tech sensing systems that operate with low volumes of samples, integrates one or more laboratory functions on a single substrate, and enables automation. These millimetric sized devices can be produced for only a few dollars, which makes them promising candidates for mass-production. Besides electron beam lithography, stencil lithography, nano-imprint lithography or dip pen lithography, basic photolithography is the technique which is extensively used for the design of microengineered sensing systems. This technique has some advantages such as easy-to-manufacture, do not require expensive instrumentation, and allow creation of lower micron-sized patterns. In this review, it has been focused on three different type of microengineered sensing devices which are developed using micro/nano-patterning techniques, microfluidic technology, and microelectromechanics system based technology. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Solar Design Workbook

    SciTech Connect

    Franta, G.; Baylin, F.; Crowther, R.

    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 themore » 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.« less

  20. Design Thinking Pedagogy: The Educational Design Ladder

    ERIC Educational Resources Information Center

    Wrigley, Cara; Straker, Kara

    2017-01-01

    As global industries change and technology advances, traditional education systems might no longer be able to supply companies with graduates who possess an appropriate mix of skills and experience. The recent increased interest in Design Thinking as an approach to innovation has resulted in its adoption by non-design-trained professionals. This…

  1. Designing Public Schools.

    ERIC Educational Resources Information Center

    Connections, 2002

    2002-01-01

    Presents an interview with Steven Bingler, an expert on community-based planning and design, about the design of public schools. Topics include the contribution of architecture to student learning, mega- versus small schools, the authentic economics of design decisions, and the role of the community in the design process. (EV)

  2. CBETA Design Report

    SciTech Connect

    Hoffstaetter, G.; Trbojevic, D.; Mayes, C.

    This Design Report describes the baseline design of the Cornell-BNL ERL Test Accelerator, as it exists on the date of its publication in June 2017. The Design Report will not change frequently in the future. In contrast, the parameter sheets that summarize the CBETA design will respond as quickly and as thoroughly as necessary to maintain con guration control.

  3. CBETA Design Report

    SciTech Connect

    Hoffstaetter, G.; Trbojevic, D.; Mayes, C.

    This Design Report describes the baseline design of the Cornell-BNL ERL Test Accelerator, as it exists on the date of its publication in June 2017. The Design Report will not change frequently in the future. In contrast, the parameter sheets that summarize the CBETA design will respond as quickly and as thoroughly as necessary to maintain configuration control.

  4. Rethinking Process through Design

    ERIC Educational Resources Information Center

    Newcomb, Matthew; Leshowitz, Allison

    2017-01-01

    We take a look at work on writing processes by examining design processes. Design processes offer a greater emphasis on empathy with users, feedback and critique during idea generation, and varied uses of materials. After considering work already done on design and composition, we explore a variety of design processes and develop our own…

  5. Design, Desire, and Difference

    ERIC Educational Resources Information Center

    Leander, Kevin M.; Boldt, Gail

    2018-01-01

    In response to the rise in popularity of concepts of "design" in education research, pedagogy, and curriculum design, in this article we consider how the New London Group conceived of the role of student design practices as an outcome of pedagogy, as well as the parallel role of design in teaching practices. In this descriptive analysis,…

  6. 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…

  7. Designing environmental research for impact.

    PubMed

    Campbell, C A; Lefroy, E C; Caddy-Retalic, S; Bax, N; Doherty, P J; Douglas, M M; Johnson, D; Possingham, H P; Specht, A; Tarte, D; West, J

    2015-11-15

    Transdisciplinary research, involving close collaboration between researchers and the users of research, has been a feature of environmental problem solving for several decades, often spurred by the need to find negotiated outcomes to intractable problems. In 2005, the Australian government allocated funding to its environment portfolio for public good research, which resulted in consecutive four-year programmes (Commonwealth Environmental Research Facilities, National Environmental Research Program). In April 2014, representatives of the funders, researchers and research users associated with these programmes met to reflect on eight years of experience with these collaborative research models. This structured reflection concluded that successful multi-institutional transdisciplinary research is necessarily a joint enterprise between funding agencies, researchers and the end users of research. The design and governance of research programmes need to explicitly recognise shared accountabilities among the participants, while respecting the different perspectives of each group. Experience shows that traditional incentive systems for academic researchers, current trends in public sector management, and loose organisation of many end users, work against sustained transdisciplinary research on intractable problems, which require continuity and adaptive learning by all three parties. The likelihood of research influencing and improving environmental policy and management is maximised when researchers, funders and research users have shared goals; there is sufficient continuity of personnel to build trust and sustain dialogue throughout the research process from issue scoping to application of findings; and there is sufficient flexibility in the funding, structure and operation of transdisciplinary research initiatives to enable the enterprise to assimilate and respond to new knowledge and situations. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. 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?

  9. Quality by Design: Multidimensional exploration of the design space in high performance liquid chromatography method development for better robustness before validation.

    PubMed

    Monks, K; Molnár, I; Rieger, H-J; Bogáti, B; Szabó, E

    2012-04-06

    Robust HPLC separations lead to fewer analysis failures and better method transfer as well as providing an assurance of quality. This work presents the systematic development of an optimal, robust, fast UHPLC method for the simultaneous assay of two APIs of an eye drop sample and their impurities, in accordance with Quality by Design principles. Chromatography software is employed to effectively generate design spaces (Method Operable Design Regions), which are subsequently employed to determine the final method conditions and to evaluate robustness prior to validation. Copyright © 2011 Elsevier B.V. All rights reserved.

  10. 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.

  11. 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.

  12. Designing the design at JPL'S innovation foundary

    NASA Astrophysics Data System (ADS)

    Balint, Tibor S.; Freeman, Anthony

    2017-08-01

    NASA is a dynamic and living organization. Looking at it through the optics of cybernetics, we can describe it as an autopoietic system. It has to sustain itself, and compete successfully to be viable. Its organizational elements have to interact with the broader environment by maintaining and improving its processes that generate the means for future sustainability. It also needs to bring up follow-on generations who are not simply aligning with the status quo, but also improve the system's viability. For government-run programs, organizational, programmatic and project management practices are often rigidly linear. They can be characterized as observed first-order cybernetic systems, where the paradigm is bound by well-established requirements. At the implementation level this does not readily accommodate flexibility and change. To address this, broadening the system's worldview is needed from the strategic level. This corresponds to an observing second-order cybernetic system, where strategic leadership can overwrite the rules of a first-order system. Changing the worldview of an organization can be complex and face much resistance. Still, with the appropriate strategic-level support, it can be achieved by introducing novel languages, new perspectives, and adding new disciplines to existing ones. In effect, this helps to broaden the organizational paradigm, and subsequently influence its mission, impact the culture, and open up its core processes. These changes can be effectively introduced through design conversations in the early formulation stages, when new ideas are conceived. Within NASA's Jet Propulsion Laboratory, early-stage concept developments are performed at a specially formulated environment, called the Innovation Foundry. Within this office, a continuous effort is being made on designing the design processes, which helps to broaden the variety of the option trades. It is achieved by an added focus on conversations and the inclusion of non

  13. Amino acids as promoieties in prodrug design and development.

    PubMed

    Vig, Balvinder S; Huttunen, Kristiina M; Laine, Krista; Rautio, Jarkko

    2013-10-01

    Prodrugs are biologically inactive agents that upon biotransformation in vivo result in active drug molecules. Since prodrugs might alter the tissue distribution, efficacy and the toxicity of the parent drug, prodrug design should be considered at the early stages of preclinical development. In this regard, natural and synthetic amino acids offer wide structural diversity and physicochemical properties. This review covers the use of amino acid prodrugs to improve poor solubility, poor permeability, sustained release, intravenous delivery, drug targeting, and metabolic stability of the parent drug. In addition, practical considerations and challenges associated with the development of amino acid prodrugs are also covered. Copyright © 2012 Elsevier B.V. All rights reserved.

  14. Designing Printed Instructional Materials.

    ERIC Educational Resources Information Center

    Burbank, Lucille; Pett, Dennis

    1986-01-01

    Discusses the importance of identifying the audience and determining specific objectives when designing printed instructional materials that will communicate effectively and provides detailed guidelines for dealing with such design factors as content, writing style, typography, illustrations, and page organization. (MBR)

  15. 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 ...

  16. 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 ...

  17. DMS message design workshops.

    DOT National Transportation Integrated Search

    2009-03-01

    This report summarizes the training conducted statewide regarding the design and display of messages on : dynamic message signs. The training is based on the Dynamic Message Sign Message Design and Display : Manual (0-4023-P3). Researchers developed ...

  18. Caltrans : highway design manual

    DOT National Transportation Integrated Search

    2008-07-01

    The Highway Design Manual establishes uniform policies and procedures to carry out the highway design functions of the California Department of Transportation (Caltrans). The policies established herein are for the information and guidance of the off...

  19. 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.

  20. Optimum study designs.

    PubMed

    Gu, C; Rao, D C

    2001-01-01

    Because simplistic designs will lead to prohibitively large sample sizes, the optimization of genetic study designs is critical for successfully mapping genes for complex diseases. Creative designs are necessary for detecting and amplifying the usually weak signals for complex traits. Two important outcomes of a study design--power and resolution--are implicitly tied together by the principle of uncertainty. Overemphasis on either one may lead to suboptimal designs. To achieve optimality for a particular study, therefore, practical measures such as cost-effectiveness must be used to strike a balance between power and resolution. In this light, the myriad of factors involved in study design can be checked for their effects on the ultimate outcomes, and the popular existing designs can be sorted into building blocks that may be useful for particular situations. It is hoped that imaginative construction of novel designs using such building blocks will lead to enhanced efficiency in finding genes for complex human traits.

  1. Rock Slope Design Criteria

    DOT National Transportation Integrated Search

    2010-06-01

    Based on the stratigraphy and the type of slope stability problems, the flat lying, Paleozoic age, sedimentary : rocks of Ohio were divided into three design units: 1) competent rock design unit consisting of sandstones, limestones, : and siltstones ...

  2. Escalator Design Features Evaluation

    DOT National Transportation Integrated Search

    1982-05-01

    This study provides an evaluation of the effectiveness of several special design features associated with escalators in rail transit systems. The objective of the study was to evaluate the effectiveness of three escalator design features: (1) mat ope...

  3. Architecture, Design, Implementatio

    DTIC Science & Technology

    2003-05-01

    The terms architecture , design , and implementation are typically used informally in partitioning software specifications into three coarse strata of...we formalize the Intension and the Locality criteria, which imply that the distinction between architecture , design , and implementation is

  4. ARDesigner: a web-based system for allosteric RNA design.

    PubMed

    Shu, Wenjie; Liu, Ming; Chen, Hebing; Bo, Xiaochen; Wang, Shengqi

    2010-12-01

    RNA molecules play vital informational, structural, and functional roles in molecular biology, making them ideal targets for synthetic biology. However, several challenges remain for engineering novel allosteric RNA molecules, and the development of efficient computational design techniques is vitally needed. Here we describe the development of Allosteric RNA Designer (ARDesigner), a user-friendly and freely available web-based system for allosteric RNA design that incorporates mutational robustness in the design process. The system output includes detailed design information in a graphical HTML format. We used ARDesigner to engineer a temperature-sensitive AR, and found that the resulting design satisfied the prescribed properties/input. ARDesigner provides a simple means for researchers to design allosteric RNAs with specific properties. With its versatile framework and possibilities for further enhancement, ARDesigner may serve as a useful tool for synthetic biologists and therapeutic design. ARDesigner and its executable version are freely available at http://biotech.bmi.ac.cn/ARDesigner. Crown Copyright © 2010. Published by Elsevier B.V. All rights reserved.

  5. Help Design Software Project

    DTIC Science & Technology

    1988-11-30

    discrete guidelines or rules to be used in the design. They pay little if any attention to how the developer can utilize the guidance. At best, they...designer’s attention on the critical design features and present ihe rationale for those features. It also describes alternative designs that were...more leading between lines, and careful attention to the selection of fonts (Rubens and Krull, 1985 ; Brockman, 1986). Bradford (1984) outlines the

  6. 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.

  7. 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.

  8. What Is Information Design?

    ERIC Educational Resources Information Center

    Redish, Janice C. (Ginny)

    2000-01-01

    Defines two meanings of information design: the overall process of developing a successful document; and the way the information is presented on the screen (layout, typography, color, and so forth). Discusses the future importance of both of these meanings of information design, in terms of design for the web and single-sources (planning…

  9. 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…

  10. 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…

  11. Rational Design Methodology.

    DTIC Science & Technology

    1978-09-01

    This report describes an effort to specify a software design methodology applicable to the Air Force software environment . Available methodologies...of techniques for proof of correctness, design specification, and performance assessment of static designs. The rational methodology selected is a

  12. 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.

  13. 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…

  14. 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…

  15. Bolted-connection design

    Treesearch

    Lawrence A. Soltis; Thomas Lee Wilkinson

    1987-01-01

    Recent failures of bolted connections have raised doubts about our knowledge of their design. Some of the design criteria are based on research conducted more than 50 years ago. This paper compares results found in the literature, using the European Yield Theory as a basis of comparison, to summarize what is known about bolted-connection design and what needs further...

  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. 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,…

  18. Educating Ethical Designers

    ERIC Educational Resources Information Center

    Haug, Anders

    2017-01-01

    In recent years, there has been an increased focus on bringing sustainability into design education. The focus of such education, however, mainly concerns providing design students with the knowledge and skills needed to create sustainable design, which, so this paper argues, may not be enough. Thus, with a basis in Aristotelian virtue ethics,…

  19. Designing Online Education Courses.

    ERIC Educational Resources Information Center

    Trentin, Guglielmo

    2001-01-01

    Focuses on the main elements that characterize online course design. Topics include design constraints; analysis of learning needs; defining objectives; course prerequisites; content structuring; course flexibility; learning strategies; evaluation criteria; course activities; course structure; communication architecture; and design evaluation.…

  20. 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…

  1. 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…

  2. Information Design Theories

    ERIC Educational Resources Information Center

    Pettersson, Rune

    2014-01-01

    Information design has practical and theoretical components. As an academic discipline we may view information design as a combined discipline, a practical theory, or as a theoretical practice. So far information design has incorporated facts, influences, methods, practices, principles, processes, strategies, and tools from a large number of…

  3. School Building Design Asia.

    ERIC Educational Resources Information Center

    Asian Regional Inst. for School Building Research, Colombo (Sri Lanka).

    Guidelines are presented for the design, costs, and use of primary and secondary general schools in the 18 countries comprising the Asian region served by UNESCO. Because of the great diversity in climate, building design and construction skills, and resources in these countries, the generalizations about school building design and furniture…

  4. Applied optimal shape design

    NASA Astrophysics Data System (ADS)

    Mohammadi, B.; Pironneau, O.

    2002-12-01

    This paper is a short survey of optimal shape design (OSD) for fluids. OSD is an interesting field both mathematically and for industrial applications. Existence, sensitivity, correct discretization are important theoretical issues. Practical implementation issues for airplane designs are critical too. The paper is also a summary of the material covered in our recent book, Applied Optimal Shape Design, Oxford University Press, 2001.

  5. 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…

  6. 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…

  7. 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.

  8. 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…

  9. 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…

  10. Alternative Fleet Architecture Design

    DTIC Science & Technology

    2005-08-01

    Alternative Fleet Architecture Design Stuart E. Johnson and Arthur K. Cebrowski Center...2005 4. TITLE AND SUBTITLE Alternative Fleet Architecture Design 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d...these principles in mind. An alternative fleet architecture design and three examples of future fleet platform architectures are presented in this

  11. Lyophilization process design space.

    PubMed

    Patel, Sajal Manubhai; Pikal, Michael J

    2013-11-01

    The application of key elements of quality by design (QbD), such as risk assessment, process analytical technology, and design space, is discussed widely as it relates to freeze-drying process design and development. However, this commentary focuses on constructing the Design and Control Space, particularly for the primary drying step of the freeze-drying process. Also, practical applications and considerations of claiming a process Design Space under the QbD paradigm have been discussed. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

  12. Interior design for dentistry.

    PubMed

    Unthank, M; True, G

    1999-11-01

    In the increasingly complex, competitive and stressful field of dentistry, effectively designed dental offices can offer significant benefits. Esthetic, functional and life-cycle cost issues to be considered when developing your interior design scheme include color, finishes, lighting, furnishings, art and accessories. An appropriately designed dental office serves as a valuable marketing tool for your practice, as well as a safe and enjoyable work environment. Qualified interior design professionals can help you make design decisions that can yield optimum results within your budget.

  13. Empathic design: Research strategies.

    PubMed

    Thomas, Joyce; McDonagh, Deana

    2013-01-01

    This paper explores the role of empathy within new product development from the perspective of human-centred design. The authors have developed a range of empathic design tools and strategies that help to identify authentic human needs.For products and services to be effective, they need to satisfy both functional and emotional needs of individuals. In addition, the individual user needs to feel that the product and/or service has been designed 'just for them', otherwise they may misuse, underuse or abandon the product/service. This becomes critical with a product such as a Zimmer frame (walker), when it fails to resonate with the patient due to any stigma the patient may perceive, and thus remains unused.When training young designers to consider the wider community (people unlike themselves) during the design process, it has proven extremely valuable to take them outside their comfort zones, by seeking to develop empathy with the end user for whom they are designing. Empathic modelling offers designers the opportunity to develop greater insight and understanding, in order to support more effective design outcomes. Sensitising designers to the different ways that individuals complete daily tasks has helped to diminish the gap between themselves and others (e.g. people with disabilities).The authors intend for this paper to resonate with health care providers. Human-centred design can help to refocus the designer, by placing the individual end user's needs at the heart of their decision-making.

  14. 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.

  15. 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.

  16. The meaning of "design".

    PubMed

    Leslie, J

    2001-12-01

    Our universe obeys elegant laws that permit living beings to evolve. This can suggest divine design. So can fine tuning of physical and cosmological parameters in ways that seem essential to life. Understanding the idea of design is, however, difficult for many reasons. For instance, could a designer be said to "fine tune" through choosing all-dictating laws very carefully? Again, would taking advantage of early quantum indeterminacies be a case of design, or would it be design-destroying interference? Can we speak of "design" if God is not a mind but an abstract Platonic principle? And what if, as Spinoza believed, the structure of our universe is just the structure of divine thinking? If such thinking extended to other universes which were lifeless, could those "exhibit design" simply through being orderly?

  17. 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.…

  18. 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).

  19. 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.

  20. 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).

  1. The constructal law and the evolution of design in nature.

    PubMed

    Bejan, Adrian; Lorente, Sylvie

    2011-10-01

    The constructal law accounts for the universal phenomenon of generation and evolution of design (configuration, shape, structure, pattern, rhythm). This phenomenon is observed across the board, in animate, inanimate and human systems. The constructal law states the time direction of the evolutionary design phenomenon. It defines the concept of design evolution in physics. Along with the first and second law, the constructal law elevates thermodynamics to a science of systems with configuration. In this article we review the more recent work of our group, with emphasis on the advances made with the constructal law in the natural sciences. Highlighted are the oneness of animate and inanimate designs, the origin of finite-size organs on animals and vehicles, the flow of stresses as the generator of design in solid structures (skeletons, vegetation), the universality and rigidity of hierarchy in all flow systems, and the global design of human flows. Noteworthy is the tapestry of distributed energy systems, which balances nodes of production with networks of distribution on the landscape, and serves as key to energy sustainability and empowerment. At the global level, the constructal law accounts for the geography and design of human movement, wealth and communications. Copyright © 2011 Elsevier B.V. All rights reserved.

  2. 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)

  3. Design of radar receivers

    NASA Astrophysics Data System (ADS)

    Sokolov, M. A.

    This handbook treats the design and analysis of of pulsed radar receivers, with emphasis on elements (especially IC elements) that implement optimal and suboptimal algorithms. The design methodology is developed from the viewpoint of statistical communications theory. Particular consideration is given to the synthesis of single-channel and multichannel detectors, the design of analog and digital signal-processing devices, and the analysis of IF amplifiers.

  4. STV engine design considerations

    NASA Technical Reports Server (NTRS)

    1991-01-01

    The topics covered include the following: (1) engine design criteria and issues; (2) design requirements for man rating; (3) test requirements for man rating; (4) design requirements for space basing; (5) engine operation requirements; (6) health monitoring; (7) lunar transfer vehicle (LTV) feed system; (8) lunar excursion vehicle (LEV) propellant system; (9) area ratio gimbal angle limits; (10) reaction control system; and (11) engine configuration and characteristics. This document is presented in viewgraph form.

  5. 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.

  6. Rectenna system design

    NASA Technical Reports Server (NTRS)

    Brown, W. C.; Dickinson, R. M.; Nalos, E. J.; Ott, J. H.

    1980-01-01

    The function of the rectenna in the solar power satellite system is described and the basic design choices based on the desired microwave field concentration and ground clearance requirements are given. One important area of concern, from the EMI point of view, harmonic reradiation and scattering from the rectenna is also designed. An optimization of a rectenna system design to minimize costs was performed. The rectenna cost breakdown for a 56 w installation is given as an example.

  7. Exploration Design Challenge 2014

    NASA Image and Video Library

    2014-04-25

    NASA Administrator, Charles Bolden and Lockheed Martin CEO, Marillyn Hewson announce the winner of the Exploration Design Challenge at the USA Science and Engineering Festival on April 25, 2014. The goal of the Exploration Design Challenge was for students to research and design ways to protect astronauts from space radiation.The USA Science and Engineering Festival is taking place at the Washington Convention Center in Washington, DC on April 26 and 27, 2014. Photo Credit: (NASA/Aubrey Gemignani)

  8. Exploration Design Challenge 2014

    NASA Image and Video Library

    2014-04-25

    Team Lore poses with NASA Administrator Charles Bolden and Lockheed Martin CEO, Marillyn Hewson. Team Lore was one of the semi-finalists in the Exploration Design Challenge. The goal of the Exploration Design Challenge is for students to research and design ways to protect astronauts from space radiation. The winner of the challenge was announced on April 25, 2014 at the USA Science and Engineering Festival at the Washington Convention Center in Washington, DC. Photo Credit: (NASA/Aubrey Gemignani)

  9. Exploration Design Challenge 2014

    NASA Image and Video Library

    2014-04-25

    Team Aegis poses with NASA Administrator Charles Bolden and Lockheed Martin CEO, Marillyn Hewson. Team Aegis was one of the semi-finalists in the Exploration Design Challenge. The goal of the Exploration Design Challenge is for students to research and design ways to protect astronauts from space radiation. The winner of the challenge was announced on April 25, 2014 at the USA Science and Engineering Festival at the Washington Convention Center in Washington, DC. Photo Credit: (NASA/Aubrey Gemignani)

  10. Exploration Design Challenge 2014

    NASA Image and Video Library

    2014-04-25

    Team ARES poses with NASA Administrator Charles Bolden and Lockheed Martin CEO, Marillyn Hewson. Team ARES was the winner of the Exploration Design Challenge. The goal of the Exploration Design Challenge is for students to research and design ways to protect astronauts from space radiation. The winning team was announced on April 25, 2014 at the USA Science and Engineering Festival at the Washington Convention Center in Washington, DC. Photo Credit: (NASA/Aubrey Gemignani)

  11. Transonic aerodynamic design experience

    NASA Technical Reports Server (NTRS)

    Bonner, E.

    1989-01-01

    Advancements have occurred in transonic numerical simulation that place aerodynamic performance design into a relatively well developed status. Efficient broad band operating characteristics can be reliably developed at the conceptual design level. Recent aeroelastic and separated flow simulation results indicate that systematic consideration of an increased range of design problems appears promising. This emerging capability addresses static and dynamic structural/aerodynamic coupling and nonlinearities associated with viscous dominated flows.

  12. Innovative Clinical Trial Designs

    PubMed Central

    Lavori, Philip W.

    2015-01-01

    Whereas the 20th-century health care system sometimes seemed to be inhospitable to and unmoved by experimental research, its inefficiency and unaffordability have led to reforms that foreshadow a new health care system. We point out certain opportunities and transformational needs for innovations in study design offered by the 21st-century health care system, and describe some innovative clinical trial designs and novel design methods to address these needs and challenges. PMID:26140056

  13. MINDS: Architecture & Design

    DTIC Science & Technology

    2006-07-14

    MINDS: Architecture & Design Technical Report Department of Computer Science and Engineering University of Minnesota 4-192 EECS Building 200 Union...Street SE Minneapolis, MN 55455-0159 USA TR 06-022 MINDS: Architecture & Design Varun Chandola, Eric Eilertson, Levent Ertoz, Gyorgy Simon, and Vipin...REPORT DATE 14 JUL 2006 2. REPORT TYPE 3. DATES COVERED 00-07-2006 to 00-07-2006 4. TITLE AND SUBTITLE MINDS: Architecture & Design 5a

  14. Management Design Theories

    NASA Astrophysics Data System (ADS)

    Pries-Heje, Jan; Baskerville, Richard L.

    This paper elaborates a design science approach for management planning anchored to the concept of a management design theory. Unlike the notions of design theories arising from information systems, management design theories can appear as a system of technological rules, much as a system of hypotheses or propositions can embody scientific theories. The paper illus trates this form of management design theories with three grounded cases. These grounded cases include a software process improvement study, a user involvement study, and an organizational change study. Collectively these studies demonstrate how design theories founded on technological rules can not only improve the design of information systems, but that these concepts have great practical value for improving the framing of strategic organi zational design decisions about such systems. Each case is either grounded in an empirical sense, that is to say, actual practice, or it is grounded to practices described extensively in the practical literature. Such design theories will help managers more easily approach complex, strategic decisions.

  15. Exploration Design Challenge 2014

    NASA Image and Video Library

    2014-04-25

    Pictured are all Semi-finalist teams in the Exploration Design Challenge. NASA Administrator, Charles Bolden and Lockheed Martin CEO, Marillyn Hewson announced the winner of the Exploration Design Challenge at the USA Science and Engineering Festival on April 25, 2014. The goal of the challenge was for students to research and design ways to protect astronauts from space radiation. The winning team's design will be built and flown aboard the Orion/EFT-1. The USA Science and Engineering Festival is taking place at the Washington Convention Center in Washington, DC on April 26 and 27, 2014. Photo Credit: (NASA/Aubrey Gemignani)

  16. Rock ramp design guidelines

    USGS Publications Warehouse

    Mooney, David M.; Holmquist-Johnson, Christopher L.; Broderick, Susan

    2007-01-01

    Rock ramps or roughened channels consist of steep reaches stabilized by large immobile material (riprap). Primary objectives for rock ramps include: Create adequate head for diversionMaintain fish passage during low-flow conditionsMaintain hydraulic conveyance during high-flow conditionsSecondary objectives for rock ramp design include:Emulate natural systemsMinimize costsThe rock ramp consists of a low-flow channel designed to maintain biologically adequate depth and velocity conditions during periods of small discharges. The remainder of the ramp is designed to withstand and pass large flows with minimal structural damage. The following chapters outline a process for designing rock ramps.

  17. 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.

  18. 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.

  19. The Experimental Design Assistant

    PubMed Central

    Bamsey, Ian; Bate, Simon T.; Berdoy, Manuel; Clark, Robin A.; Cuthill, Innes; Fry, Derek; Karp, Natasha A.; Macleod, Malcolm; Moon, Lawrence; Stanford, S. Clare; Lings, Brian

    2017-01-01

    Addressing the common problems that researchers encounter when designing and analysing animal experiments will improve the reliability of in vivo research. In this article, the Experimental Design Assistant (EDA) is introduced. The EDA is a web-based tool that guides the in vivo researcher through the experimental design and analysis process, providing automated feedback on the proposed design and generating a graphical summary that aids communication with colleagues, funders, regulatory authorities, and the wider scientific community. It will have an important role in addressing causes of irreproducibility. PMID:28957312

  20. Exploration Design Challenge 2014

    NASA Image and Video Library

    2014-04-25

    Astronaut Rex Walheim spoke at the USA Science and Engineering Festival on April 25, 2014. The event was held to announce the winner of the Exploration Design Challenge. The goal of the Exploration Design Challenge was for students to research and design ways to protect astronauts from space radiation.The winning team's design will be built and flown aboard the Orion/EFT-1. The USA Science and Engineering Festival takes place at the Washington Convention Center in Washington, DC on April 26 and 27, 2014. Photo Credit: (NASA/Aubrey Gemignani)

  1. Exploration Design Challenge 2014

    NASA Image and Video Library

    2014-04-25

    Mark Geyer, Orion Program Manager, spoke at the USA Science and Engineering Festival on April 25, 2014. The event was held to announce the winner of the Exploration Design Challenge. The goal of the Exploration Design Challenge was for students to research and design ways to protect astronauts from space radiation.The winning team's design will be built and flown aboard the Orion/EFT-1. The USA Science and Engineering Festival takes place at the Washington Convention Center in Washington, DC on April 26 and 27, 2014. Photo Credit: (NASA/Aubrey Gemignani)

  2. Exploration Design Challenge 2014

    NASA Image and Video Library

    2014-04-25

    After announcing that Team ARES won the Exploration Design Challenge, NASA Administrator, Charles Bolden and CEO, Marillyn Hewson invite the team up to the stage to receive their award. The goal of the Exploration Design Challenge was for students to research and design ways to protect astronauts from space radiation.Team ARES's design will be built and flown aboard the Orion/EFT-1. The USA Science and Engineering Festival is taking place at the Washington Convention Center in Washington, DC on April 26 and 27, 2014. Photo Credit: (NASA/Aubrey Gemignani)

  3. The Experimental Design Assistant.

    PubMed

    Percie du Sert, Nathalie; Bamsey, Ian; Bate, Simon T; Berdoy, Manuel; Clark, Robin A; Cuthill, Innes; Fry, Derek; Karp, Natasha A; Macleod, Malcolm; Moon, Lawrence; Stanford, S Clare; Lings, Brian

    2017-09-01

    Addressing the common problems that researchers encounter when designing and analysing animal experiments will improve the reliability of in vivo research. In this article, the Experimental Design Assistant (EDA) is introduced. The EDA is a web-based tool that guides the in vivo researcher through the experimental design and analysis process, providing automated feedback on the proposed design and generating a graphical summary that aids communication with colleagues, funders, regulatory authorities, and the wider scientific community. It will have an important role in addressing causes of irreproducibility.

  4. Designing Flightdeck Procedures

    NASA Technical Reports Server (NTRS)

    Barshi, Immanuel; Mauro, Robert; Degani, Asaf; Loukopoulou, Loukia

    2016-01-01

    The primary goal of this document is to provide guidance on how to design, implement, and evaluate flight deck procedures. It provides a process for developing procedures that meet clear and specific requirements. This document provides a brief overview of: 1) the requirements for procedures, 2) a process for the design of procedures, and 3) a process for the design of checklists. The brief overview is followed by amplified procedures that follow the above steps and provide details for the proper design, implementation and evaluation of good flight deck procedures and checklists.

  5. Design Producibility Assessment System

    DTIC Science & Technology

    1989-06-30

    Data Base Material Code 17 - 4PH Manufactu Description Precipitation-Handling, corrosion-resist steel Strategic? No Strip Sheet Bar Wire Tube Yes Yes Yes...planned production quantity: 10000 PRODUCTION FACILITIES 5 Select the design material: 17 - 4PH <PgUp> Page Up, <PgDn> Page Down, <Fl> Help, <Esc> Exit DPAS...vl.00 Saturday June 17 , 1989 11:06 am Design Producibility Assessment System Select the design material: 17 - 4PH Select the design material’s form

  6. 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.

  7. 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…

  8. Engineering Design Handbook. Breech Mechanism Design

    DTIC Science & Technology

    1979-02-01

    4-22 4-11.2 Tool and Gage Requirements ...................................... 4-22 R eferences...16 4-5 Total Cost per Piece---Sum of Tool Costs, Machining Cost, and Nonproductive Cost ....................................................... 4-20 4...practical design limits are end of the gun tube from which the projectile numerous as well as stringent Today, the multi- emerges and the breecb end is that

  9. Preliminary Structural Design - Defining the Design Space

    DTIC Science & Technology

    1993-02-01

    York, 1949 7. Rosenblatt, R., Prnciples of Neurodynamics , New York, Spartan Books, 1959 8. Swift, R.,"Structural Design Using Neural Networks," Ph.D...Explorations in the Microstructure of Cognition . Vol. 1 Foundations D. E. Rumelhart and J.L. McClelland Editors, MIT Press, 1986 40. Parker, D. B...Processing: Explorations in the Microstructure of Cognition , MIT Press 1986 45. Schittkowski, K., Nonlinear o a gmi codes Lecture Notes in Economics and

  10. Detection of the Helicobacter pylori dupA gene is strongly affected by the PCR design.

    PubMed

    Abadi, Amin Talebi Bezmin; Loffeld, Ruud J L F; Constancia, Ashandra C; Wagenaar, Jaap A; Kusters, Johannes G

    2014-11-01

    The Helicobacter pylori virulence gene dupA is usually detected by PCR, but the primer binding sites used are highly variable. Our newly designed qPCR against a conserved region of dupA was positive in 64.2% of 394 clinical isolates while the positivity rate of the commonly used PCRs ranged from 29.9% to 37.8%. Copyright © 2014. Published by Elsevier B.V.

  11. Expanding the term "Design Space" in high performance liquid chromatography (I).

    PubMed

    Monks, K E; Rieger, H-J; Molnár, I

    2011-12-15

    The current article presents a novel approach to applying Quality by Design (QbD) principles to the development of high pressure reversed phase liquid chromatography (HPLC) methods. Four common critical parameters in HPLC--gradient time, temperature, pH of the aqueous eluent, and stationary phase--are evaluated within the Quality by Design framework by the means of computer modeling software and a column database, to a satisfactory degree. This work proposes the establishment of two mutually complimentary Design Spaces to fully depict a chromatographic method; one Column Design Space (CDS) and one Eluent Design Space (EDS) to describe the influence of the stationary phase and of the mobile phase on the separation selectivity, respectively. The merge of both Design Spaces into one is founded on the continuous nature of the mobile phase influence on retention and the great variety of the stationary phases available. Copyright © 2011 Elsevier B.V. All rights reserved.

  12. 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…

  13. 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;…

  14. 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)

  15. 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:…

  16. 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.…

  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. Implementing Target Value Design.

    PubMed

    Alves, Thais da C L; Lichtig, Will; Rybkowski, Zofia K

    2017-04-01

    An alternative to the traditional way of designing projects is the process of target value design (TVD), which takes different departure points to start the design process. The TVD process starts with the client defining an allowable cost that needs to be met by the design and construction teams. An expected cost in the TVD process is defined through multiple interactions between multiple stakeholders who define wishes and others who define ways of achieving these wishes. Finally, a target cost is defined based on the expected profit the design and construction teams are expecting to make. TVD follows a series of continuous improvement efforts aimed at reaching the desired goals for the project and its associated target value cost. The process takes advantage of rapid cycles of suggestions, analyses, and implementation that starts with the definition of value for the client. In the traditional design process, the goal is to identify user preferences and find solutions that meet the needs of the client's expressed preferences. In the lean design process, the goal is to educate users about their values and advocate for a better facility over the long run; this way owners can help contractors and designers to identify better solutions. This article aims to inform the healthcare community about tools and techniques commonly used during the TVD process and how they can be used to educate and support project participants in developing better solutions to meet their needs now as well as in the future.

  19. Universal Playground Design.

    ERIC Educational Resources Information Center

    Ensign, Arselia, Ed.

    1993-01-01

    This publication presents principles of universal playgrounds, designed to maximize accessibility for all children, with and without disabilities. First, the rationale for the universal playground is given including the importance of play and the value of integration. Next current guidelines for playground design are discussed including safety,…

  20. 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…

  1. 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…

  2. STEAM by Design

    ERIC Educational Resources Information Center

    Keane, Linda; Keane, Mark

    2016-01-01

    We live in a designed world. STEAM by Design presents a transdisciplinary approach to learning that challenges young minds with the task of making a better world. Learning today, like life, is dynamic, connected and engaging. STEAM (Science, Technology, Environment, Engineering, Art, and Math) teaching and learning integrates information in…

  3. 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.

  4. 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…

  5. Designing Interactive Learning Systems.

    ERIC Educational Resources Information Center

    Barker, Philip

    1990-01-01

    Describes multimedia, computer-based interactive learning systems that support various forms of individualized study. Highlights include design models; user interfaces; design guidelines; media utilization paradigms, including hypermedia and learner-controlled models; metaphors and myths; authoring tools; optical media; workstations; four case…

  6. 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…

  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. 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...

  9. Design mentoring tool.

    DOT National Transportation Integrated Search

    2011-01-01

    In 2004 a design engineer on-line mentoring tool was developed and implemented The purpose of the tool was to assist senior engineers : mentoring new engineers to the INDOT design process and improve their technical competency. This approach saves se...

  10. EVA design: lessons learned.

    PubMed

    Ross, J L

    1994-01-01

    Extravehicular Activities (EVAs) are very demanding and specialized space flight activities. There are many aspects to consider in the design of hardware, tools, and procedures to be used on an EVA mission. To help minimize costs and optimize the EVA productivity, experience shows that astronauts should become involved early in the design process.

  11. 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…

  12. 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…

  13. 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…

  14. 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…

  15. 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.…

  16. 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…

  17. Optimization of digital designs

    NASA Technical Reports Server (NTRS)

    Miles, Lowell H. (Inventor); Whitaker, Sterling R. (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.

  18. A Design Selection Procedure.

    ERIC Educational Resources Information Center

    Kroeker, Leonard P.

    The problem of blocking on a status variable was investigated. The one-way fixed-effects analysis of variance, analysis of covariance, and generalized randomized block designs each treat the blocking problem in a different way. In order to compare these designs, it is necessary to restrict attention to experimental situations in which observations…

  19. Suspended Substrate Resonator Design

    DTIC Science & Technology

    1990-12-01

    1967. 10. Fred E. Gardiol, "Careful MIC Design Prevents Waveguide Modes", Microwaves, pp. 188-191, May 1977. 11. David Rubin and Alfred R. Hislop ...34Design Techniques for Sus- pended Substrate and Microstrip", Microwave Journal, October 1980 . 12. Robert Grover Brown, Robert A. Sharpe, William E. Post

  20. 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.

  1. 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…

  2. Designing using manufacturing features

    NASA Astrophysics Data System (ADS)

    Szecsi, T.; Hoque, A. S. M.

    2012-04-01

    This paper presents a design system that enables the composition of a part using manufacturing features. Features are selected from feature libraries. Upon insertion, the system ensures that the feature does not contradict the design-for-manufacture rules. This helps eliminating costly manufacturing problems. The system is developed as an extension to a commercial CAD/CAM system Pro/Engineer.

  3. 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…

  4. Training Interactive Videodisc Designers.

    ERIC Educational Resources Information Center

    Allen, Brockenbrough S.; Erickson, Debra M.

    1986-01-01

    Describes a model for training instructional designers who will work as members of videodisc development teams. This model develops and integrates competencies relating to instructional design, project management, interpersonal skills, storyboarding and flowcharting, programming, video production, and interactive video system knowledge. Three…

  5. 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.

  6. 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.

  7. Planning and Designing Schools.

    ERIC Educational Resources Information Center

    Brubaker, C. William

    This book offers and examines a number of suggestions for school architecture. The book consists of a review of 22 school projects from around the United States. The text opens with a brief history of school design in the nineteenth and twentieth centuries, but the focus throughout the book focuses on several distinct elements: designing schools…

  8. 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…

  9. Learning Space Service Design

    ERIC Educational Resources Information Center

    Felix, Elliot

    2011-01-01

    Much progress has been made in creating informal learning spaces that incorporate technology and flexibly support a variety of activities. This progress has been principally in designing the right combination of furniture, technology, and space. However, colleges and universities do not design services within learning spaces with nearly the same…

  10. NPR design basis

    SciTech Connect

    Locke, G.L.

    1958-09-08

    The design basis is composed of requirements and conditions for the design of the reactor plant (composed of the reactor and heat dissipation system). Its intent is to insure that the final product meets the economic, safety, and technical objectives of the project. The design basis is dependent on the ground rules, objectives, technical criteria, and practical design considerations. This document is being issued with the understanding that these items are not yet firmly established in all respects, and therefore, the numbers put down here are subject to change. Consideration of the spectrum of probable changes that might be mademore » leads to the conclusion that the numbers here are close to the final ones and are satisfactory as a basis for the initial stages of design. Some numbers are omitted because of insufficient data at this time.« less

  11. Connecting drug delivery reality to smart materials design.

    PubMed

    Grainger, David W

    2013-09-15

    Inflated claims to both design and mechanistic novelty in drug delivery and imaging systems, including most nanotechnologies, are not supported by the generally poor translation of these systems to clinical efficacy. The "form begets function" design paradigm is seductive but perhaps over-simplistic in translation to pharmaceutical efficacy. Most innovations show few clinically important distinctions in their therapeutic benefits in relevant preclinical disease and delivery models, despite frequent claims to the contrary. Long-standing challenges in drug delivery issues must enlist more realistic, back-to-basics approaches to address fundamental materials properties in complex biological systems, preclinical test beds, and analytical methods to more reliably determine fundamental pharmaceutical figures of merit, including drug carrier purity and batch-batch variability, agent biodistribution, therapeutic index (safety), and efficacy. Copyright © 2013 Elsevier B.V. All rights reserved.

  12. The case-control design in veterinary sciences: A survey.

    PubMed

    Cullen, Jonah N; Sargeant, Jan M; Makielski, Kelly M; O'Connor, Annette M

    2016-11-01

    The case-control study design is deceptively simple. However, many design considerations influence the estimated effect measure. An investigation of case-control studies in the human health literature suggested that some of these considerations are not described in reports of case-control studies. Our hypothesis was that the majority of veterinary studies labeled as case-controls would be incident density designs, and many would not interpret the effect measure obtained from those studies as the rate ratio rather than the odds ratio. Reference databases were searched for author-designated case-control studies. A survey of 100 randomly selected studies was conducted to examine the different design options described and estimated effect measures. Of the 100 author-identified case-control studies, 83 assessed an exposure-outcome association and, of those, only 54 (65.1%) sampled the study population based on an outcome and would thus be considered case-control designs. Twelve studies were incidence density designs but none used this terminology. Of the studies that reported an odds ratio as the effect measure, none reported on additional considerations that would have enabled a more interpretable result. This survey indicated many case-control-labeled studies were not case-control designs and among case-control studies, key design aspects were not often described. The absence of information about study design elements and underlying assumptions in case-control studies limits the ability to establish the effect measured by the study and the evidentiary value of the study might be underestimated. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. 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.

  14. 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

  15. 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.

  16. Aspheric design for manufacturability

    NASA Astrophysics Data System (ADS)

    Kreischer, Cody B.

    2007-05-01

    The experienced lens designer is well aware of the potential advantages aspherics can afford. Within the last few years, machines specifically designed for the CNC machining and polishing of glass aspheres have become commercially available through several manufacturers. This has brought down manufacturing cost to the point that designs incorporating aspheres can be used to reduce system cost compared to all spherical designs. (That is aspheres are no longer used just to save space and weight at the expense of cost.) Not all aspheres are equally manufacturable, however. Arbitrary choices at the beginning of a design can have major impact on manufacturing cost and limit final "as built" performance. This paper considers factors in designing ground and polished (as opposed to molded) glass aspheres which may not be obvious to even the experienced lens designer accustomed to using spherical surfaces or who has dealt with diamond turned aspheres. Factors considered include the surface shape, how the shape is specified, how the surface is to be tested and how it is toleranced. Emphasis will be placed on medium priced components where practical considerations are important.

  17. 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

  18. 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.

  19. 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.

  20. Exploration Design Challenge 2014

    NASA Image and Video Library

    2014-04-25

    Lockheed Martin CEO Marillyn Hewson spoke at the Orion exhibit at the USA Science and Engineering Festival on April 25, 2014. The event was held to announce the winner of the Exploration Design Challenge. The goal of the Exploration Design Challenge was for students to research and design ways to protect astronauts from space radiation.The USA Science and Engineering Festival is taking place at the Washington Convention Center in Washington, DC on April 26 and 27, 2014. Photo Credit: (NASA/Aubrey Gemignani)

  1. Exploration Design Challenge 2014

    NASA Image and Video Library

    2014-04-25

    NASA Administrator Charles Bolden spoke at the Orion exhibit at the USA Science and Engineering Festival on April 25, 2014. The event was held to announce the winner of the Exploration Design Challenge. The goal of the Exploration Design Challenge was for students to research and design ways to protect astronauts from space radiation.The USA Science and Engineering Festival is taking place at the Washington Convention Center in Washington, DC on April 26 and 27, 2014. Photo Credit: (NASA/Aubrey Gemignani)

  2. Recursive Deadbeat Controller Design

    NASA Technical Reports Server (NTRS)

    Juang, Jer-Nan; Phan, Minh Q.

    1997-01-01

    This paper presents a recursive algorithm for a deadbeat predictive controller design. The method combines together the concepts of system identification and deadbeat controller designs. It starts with the multi-step output prediction equation and derives the control force in terms of past input and output time histories. The formulation thus derived satisfies simultaneously system identification and deadbeat controller design requirements. As soon as the coefficient matrices are identified satisfying the output prediction equation, no further work is required to compute the deadbeat control gain matrices. The method can be implemented recursively just as any typical recursive system identification techniques.

  3. Exploration Design Challenge 2014

    NASA Image and Video Library

    2014-04-25

    Team Lore listens in the audience as NASA Administrator Charles Bolden speaks at the event to announce the winner of the Exploration Design Challenge. Team Lore was one of the semi-finalists in the challenge. The goal of the Exploration Design Challenge is for students to research and design ways to protect astronauts from space radiation. The winner of the challenge was announced on April 25, 2014 at the USA Science and Engineering Festival at the Washington Convention Center in Washington, DC. Photo Credit: (NASA/Aubrey Gemignani)

  4. Exploration Design Challenge 2014

    NASA Image and Video Library

    2014-04-25

    Team Titan Shielding Systems poses with NASA Administrator Charles Bolden and Lockheed Martin CEO, Marillyn Hewson. Team Titan Shielding Systems was one of the semi-finalists in the Exploration Design Challenge. The goal of the Exploration Design Challenge is for students to research and design ways to protect astronauts from space radiation. The winner of the challenge was announced on April 25, 2014 at the USA Science and Engineering Festival at the Washington Convention Center in Washington, DC. Photo Credit: (NASA/Aubrey Gemignani)

  5. Nonlinear aerodynamic wing design

    NASA Technical Reports Server (NTRS)

    Bonner, Ellwood

    1985-01-01

    The applicability of new nonlinear theoretical techniques is demonstrated for supersonic wing design. The new technology was utilized to define outboard panels for an existing advanced tactical fighter model. Mach 1.6 maneuver point design and multi-operating point compromise surfaces were developed and tested. High aerodynamic efficiency was achieved at the design conditions. A corollary result was that only modest supersonic penalties were incurred to meet multiple aerodynamic requirements. The nonlinear potential analysis of a practical configuration arrangement correlated well with experimental data.

  6. Principles of engineering design

    PubMed Central

    Penny, R. K.

    1970-01-01

    The paper sets out procedures used in engineering design by listing the various steps in a sequential pattern. This pattern is not universally applicable and the variants on it depend on the type of problem involved and the information available. Of critical importance is the way in which models—physical or mathematical—can be constructed and depending on these, three design methods are described. These types are illustrated by reference to a number of medical aids which have been designed. ImagesFig. 3 PMID:5476130

  7. 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.

  8. Advanced wind turbine design

    SciTech Connect

    Jamieson, P.M.; Jaffrey, A.

    1997-11-01

    Garrad Hassan have a project in progress funded by the U.K. 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.

  9. Designer Stories: A Commentary on the Community of Design Practice

    ERIC Educational Resources Information Center

    Mc Glashan, A. A.

    2011-01-01

    This research explores the design practice of three prominent New Zealand designers. It seeks to identify the key elements and methodologies they employ and to answer the research question: "How do designers design?" The need to gain understanding on how designers work, gave me occasion to visit and speak with designers about their…

  10. 40 CFR 130.9 - Designation and de-designation.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 22 2011-07-01 2011-07-01 false Designation and de-designation. 130.9... QUALITY PLANNING AND MANAGEMENT § 130.9 Designation and de-designation. (a) Designation. Areawide planning... approval in accordance with section 208(a)(7) of the Act. (b) De-designation. The Governor may modify or...

  11. 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…

  12. The frontal-anatomic specificity of design fluency repetitions and their diagnostic relevance for behavioral variant frontotemporal dementia.

    PubMed

    Possin, Katherine L; Chester, Serana K; Laluz, Victor; Bostrom, Alan; Rosen, Howard J; Miller, Bruce L; Kramer, Joel H

    2012-09-01

    On tests of design fluency, an examinee draws as many different designs as possible in a specified time limit while avoiding repetition. The neuroanatomical substrates and diagnostic group differences of design fluency repetition errors and total correct scores were examined in 110 individuals diagnosed with dementia, 53 with mild cognitive impairment (MCI), and 37 neurologically healthy controls. The errors correlated significantly with volumes in the right and left orbitofrontal cortex (OFC), the right and left superior frontal gyrus, the right inferior frontal gyrus, and the right striatum, but did not correlate with volumes in any parietal or temporal lobe regions. Regression analyses indicated that the lateral OFC may be particularly crucial for preventing these errors, even after excluding patients with behavioral variant frontotemporal dementia (bvFTD) from the analysis. Total correct correlated more diffusely with volumes in the right and left frontal and parietal cortex, the right temporal cortex, and the right striatum and thalamus. Patients diagnosed with bvFTD made significantly more repetition errors than patients diagnosed with MCI, Alzheimer's disease, semantic dementia, progressive supranuclear palsy, or corticobasal syndrome. In contrast, total correct design scores did not differentiate the dementia patients. These results highlight the frontal-anatomic specificity of design fluency repetitions. In addition, the results indicate that the propensity to make these errors supports the diagnosis of bvFTD. (JINS, 2012, 18, 1-11).

  13. Designer biomaterials for mechanobiology

    NASA Astrophysics Data System (ADS)

    Li, Linqing; Eyckmans, Jeroen; Chen, Christopher S.

    2017-12-01

    Biomaterials engineered with specific bioactive ligands, tunable mechanical properties and complex architecture have emerged as powerful tools to probe cell sensing and response to physical properties of their material surroundings, and ultimately provide designer approaches to control cell function.

  14. Cybernetics and Workshop Design.

    ERIC Educational Resources Information Center

    Eckstein, Daniel G.

    1979-01-01

    Cybernetic sessions allow for the investigation of several variables concurrently, resulting in a large volume of input compacted into a concise time frame. Three session questions are reproduced to illustrate the variety of ideas generated relative to workshop design. (Author)

  15. Aircraft Design Software

    NASA Technical Reports Server (NTRS)

    1997-01-01

    Successful commercialization of the AirCraft SYNThesis (ACSYNT) tool has resulted in the creation of Phoenix Integration, Inc. ACSYNT has been exclusively licensed to the company, an outcome of a seven year, $3 million effort to provide unique software technology to a focused design engineering market. Ames Research Center formulated ACSYNT and in working with the Virginia Polytechnic Institute CAD Laboratory, began to design and code a computer-aided design for ACSYNT. Using a Joint Sponsored Research Agreement, Ames formed an industry-government-university alliance to improve and foster research and development for the software. As a result of the ACSYNT Institute, the software is becoming a predominant tool for aircraft conceptual design. ACSYNT has been successfully applied to high- speed civil transport configuration, subsonic transports, and supersonic fighters.

  16. Highway subdrainage design

    DOT National Transportation Integrated Search

    1990-07-01

    This report contains five chapters relating to highway subdrainage design. Chapter 1 is devoted to a general discussion of the adverse effects of subsurface water, the types and sources of subsurface water and its movements, and the types of subsurfa...

  17. Computer aided airship design

    NASA Technical Reports Server (NTRS)

    Davis, S. J.; Rosenstein, H.

    1975-01-01

    The Comprehensive Airship Sizing and Performance Computer Program (CASCOMP) is described which was developed and used in the design and evaluation of advanced lighter-than-air (LTA) craft. The program defines design details such as engine size and number, component weight buildups, required power, and the physical dimensions of airships which are designed to meet specified mission requirements. The program is used in a comparative parametric evaluation of six advanced lighter-than-air concepts. The results indicate that fully buoyant conventional airships have the lightest gross lift required when designed for speeds less than 100 knots and the partially buoyant concepts are superior above 100 knots. When compared on the basis of specific productivity, which is a measure of the direct operating cost, the partially buoyant lifting body/tilting prop-rotor concept is optimum.

  18. 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)

  19. Probabilistic 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 components. 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% 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% cyclic-stress to static-strength ratios.

  20. LMSS communication network design

    NASA Technical Reports Server (NTRS)

    1982-01-01

    The architecture of the telecommunication network as the first step in the design of the LMSS system is described. A set of functional requirements including the total number of users to be served by the LMSS are hypothesized. The design parameters are then defined at length and are systematically selected such that the resultant system is capable of serving the hypothesized number of users. The design of the backhaul link is presented. The number of multiple backhaul beams required for communication to the base stations is determined. A conceptual procedure for call-routing and locating a mobile subscriber within the LMSS network is presented. The various steps in placing a call are explained, and the relationship between the two sets of UHF and S-band multiple beams is developed. A summary of the design parameters is presented.

  1. True Experimental Design.

    ERIC Educational Resources Information Center

    Huck, Schuyler W.

    1991-01-01

    This poem, with stanzas in limerick form, refers humorously to the many threats to validity posed by problems in research design, including problems of sample selection, data collection, and data analysis. (SLD)

  2. BIOREACTOR LANDFILL DESIGN

    EPA Science Inventory

    Modern landfill design entails many elements including foundations, liner systems, leachate collection systems, stormwater control systems, slope stability considerations, leachate management systems, gas extraction systems, and capping and closure. The use of bioreactor technolo...

  3. Particle Pollution Designations

    EPA Pesticide Factsheets

    This area provides information on the process EPA, the states, and the tribes follow to designate areas as attainment (meeting) or nonattainment (not meeting) the particle pollution air quality standards.

  4. Rock slope design guide.

    DOT National Transportation Integrated Search

    2011-04-01

    This Manual is intended to provide guidance for the design of rock cut slopes, rockfall catchment, and : rockfall controls. Recommendations presented in this manual are based on research presented in Shakoor : and Admassu (2010) entitled Rock Slop...

  5. Designated Airworthiness Representatives

    DOT National Transportation Integrated Search

    1985-10-01

    This advisory circular (AC) contains information and guidance concerning the : selection and appointment of Designated Airworthiness Representatives (DAR's) and identifies the specific functions which may be delegated to DAR's as authorized by the Fe...

  6. Roundabout geometric design guidance.

    DOT National Transportation Integrated Search

    2007-06-01

    This research report is intended to examine the geometric standards, guidelines, and practices used nationally and by other states to develop recommendations on roundabout design guidance for California. This research serves as a guidance tool in sup...

  7. Marshall mix design criteria.

    DOT National Transportation Integrated Search

    1980-01-01

    This report discusses the basis of the original Marshall design criteria established by the Waterways Experiment Station and criteria used by the Asphalt Institute and Virginia Department of Highways and Transportation. Marshall test properties are d...

  8. CVISN system design description

    DOT National Transportation Integrated Search

    1999-05-01

    This document focuses on the Commercial Vehicle Information Systems and Networks (CVISN) System Design and Architecture. It begins with a discussion on the relationships between the National ITS Architecture the CVISN Architecture, and the Internatio...

  9. Studies in Interior Design

    ERIC Educational Resources Information Center

    Environ Planning Design, 1970

    1970-01-01

    Floor plans and photographs illustrate a description of the Samuel C. Williams Library at Stevens Institute of Technology, Hoboken, N.J. The unusual interior design allows students to take full advantage of the library's resources. (JW)

  10. Design Review Improvement Recommendations

    DTIC Science & Technology

    2015-06-18

    Anne Ramsey, Harris Corporation Ronald H. Mandel, Lockheed Martin Mark King, Micropac Industries Melanie Berg, NASA Cindy Kohlmiller, Northrop...Donna Potter , SSL ii Executive Summary The aerospace industry continues to experience design escapes that significantly impact program

  11. Design Review Improvement Recommendations

    DTIC Science & Technology

    2015-06-18

    Worcester, Boeing Anne Ramsey, Harris Corporation Ronald H. Mandel, Lockheed Martin Mark King, Micropac Industries Melanie Berg, NASA Cindy...Peters, Raytheon Donna Potter , SSL ii Executive Summary The aerospace industry continues to experience design escapes that significantly impact

  12. LSST Camera Optics Design

    SciTech Connect

    Riot, V J; Olivier, S; Bauman, B

    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 willmore » meet their performance goals.« less

  13. 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 designmore » report, and the final report on the design and fabrication project. (LEW)« less

  14. Sulfur Dioxide Designations

    EPA Pesticide Factsheets

    This area provides information on the process EPA, the states, and the tribes follow to designate areas as attainment (meeting) or nonattainment (not meeting) the sulfur dioxide air quality standards.

  15. DESIGN MANUAL: PHOSPHORUS REMOVAL

    EPA Science Inventory

    This manual summarizes process design information for the best developed methods for removing phosphorus from wastewater. his manual discusses several proven phosphorus removal methods, including phosphorus removal obtainable through biological activity as well as chemical precip...

  16. Designing automatic resupply systems.

    PubMed

    Harding, M L

    1999-02-01

    This article outlines the process for designing and implementing autoresupply systems. The planning process includes determination of goals and appropriate participation. Different types of autoresupply mechanisms include kanban, breadman, consignment, systems contracts, and direct shipping from an MRP schedule.

  17. Cognitive Protocol Stack Design

    DTIC Science & Technology

    2015-12-30

    SECURITY CLASSIFICATION OF: In the ARO “ Cognitive Protocol Stack Design" project we proposed cognitive networking solutions published in international...areas related to cognitive networking, opening also new lines of research that was not possible to forecast at the beginning of the project. In a...Distribution Unlimited Final Report: Cognitive Protocol Stack Design The views, opinions and/or findings contained in this report are those of the author(s

  18. Exploration Design Challenge 2014

    NASA Image and Video Library

    2014-04-25

    Sponsors of all of the semi-finalist teams in the Exploration Design Challenge pose for a group photo with the teams. Team ARES from the Governors School for Science and Technology in Hampton, Va. won the challenge with their radiation shield design, which will be built and flown aboard the Orion/EFT-1. The award was announced at the USA Science and Engineering Festival on April 25, 2014 at the Washington Convention Center. Photo Credit: (NASA/Aubrey Gemignani)

  19. Multiparadigm Design Environments

    DTIC Science & Technology

    1992-01-01

    following results: 1. New methods for programming in terms of conceptual models 2. Design of object-oriented languages 3. Compiler optimization and...experimented with object-based methods for programming directly in terms of conceptual models, object-oriented language design, computer program...expect the3e results to have a strong influence on future ,,j :- ...... L ! . . • a mm ammmml ll Illlll • l I 1 Conceptual Programming Conceptual

  20. Adaptation as organism design

    PubMed Central

    Gardner, Andy

    2009-01-01

    The problem of adaptation is to explain the apparent design of organisms. Darwin solved this problem with the theory of natural selection. However, population geneticists, whose responsibility it is to formalize evolutionary theory, have long neglected the link between natural selection and organismal design. Here, I review the major historical developments in theory of organismal adaptation, clarifying what adaptation is and what it is not, and I point out future avenues for research. PMID:19793739

  1. Fastener Design Course [Workbook

    NASA Technical Reports Server (NTRS)

    Barrett, Richart T.

    1997-01-01

    Richard T. Barrett, Senior Aerospace Engineer of NASA Lewis Research Center presents a comprehensive course on fastener design. A recognized expert in the field of fastener technology Mr. Barrett combines lecture, charts, illustrations with real-world experiences. Topics covered include: materials, plantings and coatings, locking methods threads, joint stiffness, rivets, inserts, nut plates, thread lubricants, design criteria, etc. These presentation slides accompany the DVD.

  2. Induction launcher design considerations

    NASA Technical Reports Server (NTRS)

    Driga, M. D.; Weldon, W. F.

    1989-01-01

    New concepts in the design of induction accelerators and their power supplies for space and military applications are discussed. Particular attention is given to a piecewise-rising-frequency power supply in which each elementary generator (normal compulsator or rising frequency generator) has a different base frequency. A preliminary design of a coaxial induction accelerator for a hypersonic real gas facility is discussed to illustrate the concepts described.

  3. TPF coronagraph instrument design

    NASA Technical Reports Server (NTRS)

    Shaklan, S B.; Balasubramanian, K.; Ceperly, D.; Green, J.; Hoppe, D.; Lay, O. P.; Lisman, P. D.; Mouroulis, P. Z.

    2005-01-01

    For the past 2 years, NASA has invested substantial resources to study the design and performance of the Terrestrial Planet Finder Coronagraph (TPF-C). The work, led by the Jet Propulsion Laboratory with collaboration from Goddard Space Flight Center and several university and commercial entities, encompasses observatory design, performance modeling, materials characterization, primary mirror studies, and a significant technology development effort including a high-contrast imaging testbed that has achieved 1e-9 contrast in a laboratory experiment.

  4. Permanent magnet design methodology

    NASA Technical Reports Server (NTRS)

    Leupold, Herbert A.

    1991-01-01

    Design techniques developed for the exploitation of high energy magnetically rigid materials such as Sm-Co and Nd-Fe-B have resulted in a revolution in kind rather than in degree in the design of a variety of electron guidance structures for ballistic and aerospace applications. Salient examples are listed. Several prototype models were developed. These structures are discussed in some detail: permanent magnet solenoids, transverse field sources, periodic structures, and very high field structures.

  5. Designing Successful Proteomics Experiments.

    PubMed

    Ruderman, Daniel

    2017-01-01

    Because proteomics experiments are so complex they can readily fail, and do so without clear cause. Using standard experimental design techniques and incorporating quality control can greatly increase the chances of success. This chapter introduces the relevant concepts and provides examples specific to proteomic workflows. Applying these notions to design successful proteomics experiments is straightforward. It can help identify failure causes and greatly increase the likelihood of inter-laboratory reproducibility.

  6. Exploration Design Challenge 2014

    NASA Image and Video Library

    2014-04-25

    Sponsors of Team ARES pose for a group photo with the winning high school team in the Exploration Design Challenge. Team ARES from the Governors School for Science and Technology in Hampton, Va. won the challenge with their radiation shield design, which will be built and flown aboard the Orion/EFT-1. The award was announced at the USA Science and Engineering Festival on April 25, 2014 at the Washington Convention Center. Photo Credit: (NASA/Aubrey Gemignani)

  7. Exploration Design Challenge 2014

    NASA Image and Video Library

    2014-04-25

    NASA’s Administrator, Charles Bolden speaks with the winning high school team in the Exploration Design Challenge prior to the award ceremony. Team ARES from the Governors School for Science and Technology in Hampton, Va. won the challenge with their radiation shield design, which will be built and flown aboard the Orion/EFT-1. The award was announced at the USA Science and Engineering Festival on April 25, 2014 at the Washington Convention Center. Photo Credit: (NASA/Aubrey Gemignani)

  8. Vector Magnetograph Design

    NASA Technical Reports Server (NTRS)

    Chipman, Russell A.

    1996-01-01

    This report covers work performed during the period of November 1994 through March 1996 on the design of a Space-borne Solar Vector Magnetograph. This work has been performed as part of a design team under the supervision of Dr. Mona Hagyard and Dr. Alan Gary of the Space Science Laboratory. Many tasks were performed and this report documents the results from some of those tasks, each contained in the corresponding appendix. Appendices are organized in chronological order.

  9. 2002 Controls Design Challenge

    NASA Technical Reports Server (NTRS)

    Hess, Ronald A.; Vetter, T. K.; Wells, S. R.

    2002-01-01

    This document is intended to provide the specifications and requirements for a flight control system design challenge. The response to the challenge will involve documenting whether the particular design has met the stated requirements through analysis and computer simulation. The response should be written in the general format of a technical publication with corresponding length limits, e.g., an approximate maximum length of 45 units, with each full-size figure and double-spaced typewritten page constituting one unit.

  10. Space Station galley design

    NASA Technical Reports Server (NTRS)

    Trabanino, Rudy; Murphy, George L.; Yakut, M. M.

    1986-01-01

    An Advanced Food Hardware System galley for the initial operating capability (IOC) Space Station is discussed. Space Station will employ food hardware items that have never been flown in space, such as a dishwasher, microwave oven, blender/mixer, bulk food and beverage dispensers, automated food inventory management, a trash compactor, and an advanced technology refrigerator/freezer. These new technologies and designs are described and the trades, design, development, and testing associated with each are summarized.

  11. Design documentation: Krypton encapsulation preconceptual design

    SciTech Connect

    Knecht, D.A.

    1994-10-01

    US EPA regulations limit the release of Krypton-85 to the environment from commercial facilities after January 1, 1983. In order to comply with these regulations, Krypton-85, which would be released during reprocessing of commercial nuclear fuel, must be collected and stored. Technology currently exists for separation of krypton from other inert gases, and for its storage as a compressed gas in steel cylinders. The requirements, which would be imposed for 100-year storage of Krypton-85, have led to development of processes for encapsulation of krypton within a stable solid matrix. The objective of this effort was to provide preconceptual engineering designs,more » technical evaluations, and life cycle costing data for comparison of two alternate candidate processes for encapsulation of Krypton-85. This report has been prepared by The Ralph M. Parsons Company for the US Department of Energy.« less

  12. Adaptive clinical trial design.

    PubMed

    Chow, Shein-Chung

    2014-01-01

    In recent years, the use of adaptive design methods in clinical trials based on accumulated data at interim has received much attention because of its flexibility and efficiency in pharmaceutical/clinical development. In practice, adaptive design may provide the investigators a second chance to modify or redesign the trial while the study is still ongoing. However, it is a concern that a shift in target patient population may occur after significant adaptations are made. In addition, the overall type I error rate may not be preserved. Moreover, the results may not be reliable and hence are difficult to interpret. As indicated by the US Food and Drug Administration draft guidance on adaptive design clinical trials, the adaptive design has to be a prospectively planned opportunity and should be based on information collected within the study, with or without formal statistical hypothesis testing. This article reviews the relative advantages, limitations, and feasibility of commonly considered adaptive designs in clinical trials. Statistical concerns when implementing adaptive designs are also discussed.

  13. Maglev guideway design issues

    SciTech Connect

    Plotkin, D.; Kim, S.

    1997-05-01

    This paper reports results from guideway analyses conducted as part of the National Maglev Initiative (NMI), a government-industry effort from 1989 to 1994, formed to encourage the development of US maglev technology and to assess its potential application within the US transportation system. Covered here are some key guideway design issues that were common to the designs assessed for the NMI, and to maglev guideways in general. They represent aspects that will need additional attention in future efforts to produce structurally sound and economical maglev guideways. These recommendations come from the analyses conducted by a team from the US Armymore » Construction Engineering Research Laboratories, the Civil Engineering Department of the University of Illinois, and Alfred Benesch and Company. The recommendations focus on design philosophy and the development of general design criteria, guideway maintenance and the provision for future alignment adjustment in both the guideway and the magnets, foundation design, and the long-term performance of guideway materials and reinforcement. Generally, one of the main challenges to guideway designers is to produce a structure that will be easily maintainable to the narrow tolerances and precise alignment required for practical high-speed maglev operation.« less

  14. Stratospheric Airship Design Sensitivity

    NASA Astrophysics Data System (ADS)

    Smith, Ira Steve; Fortenberry, Michael; Noll, . James; Perry, William

    2012-07-01

    The concept of a stratospheric or high altitude powered platform has been around almost as long as stratospheric free balloons. Airships are defined as Lighter-Than-Air (LTA) vehicles with propulsion and steering systems. Over the past five (5) years there has been an increased interest by the U. S. Department of Defense as well as commercial enterprises in airships at all altitudes. One of these interests is in the area of stratospheric airships. Whereas DoD is primarily interested in things that look down, such platforms offer a platform for science applications, both downward and outward looking. Designing airships to operate in the stratosphere is very challenging due to the extreme high altitude environment. It is significantly different than low altitude airship designs such as observed in the familiar advertising or tourism airships or blimps. The stratospheric airship design is very dependent on the specific application and the particular requirements levied on the vehicle with mass and power limits. The design is a complex iterative process and is sensitive to many factors. In an effort to identify the key factors that have the greatest impacts on the design, a parametric analysis of a simplified airship design has been performed. The results of these studies will be presented.

  15. 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.…

  16. Computer-aided design for metabolic engineering.

    PubMed

    Fernández-Castané, Alfred; Fehér, Tamás; Carbonell, Pablo; Pauthenier, Cyrille; Faulon, Jean-Loup

    2014-12-20

    The development and application of biotechnology-based strategies has had a great socio-economical impact and is likely to play a crucial role in the foundation of more sustainable and efficient industrial processes. Within biotechnology, metabolic engineering aims at the directed improvement of cellular properties, often with the goal of synthesizing a target chemical compound. The use of computer-aided design (CAD) tools, along with the continuously emerging advanced genetic engineering techniques have allowed metabolic engineering to broaden and streamline the process of heterologous compound-production. In this work, we review the CAD tools available for metabolic engineering with an emphasis, on retrosynthesis methodologies. Recent advances in genetic engineering strategies for pathway implementation and optimization are also reviewed as well as a range of bionalytical tools to validate in silico predictions. A case study applying retrosynthesis is presented as an experimental verification of the output from Retropath, the first complete automated computational pipeline applicable to metabolic engineering. Applying this CAD pipeline, together with genetic reassembly and optimization of culture conditions led to improved production of the plant flavonoid pinocembrin. Coupling CAD tools with advanced genetic engineering strategies and bioprocess optimization is crucial for enhanced product yields and will be of great value for the development of non-natural products through sustainable biotechnological processes. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. 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.

  18. Application of Design Patterns in Refactoring Software Design

    NASA Technical Reports Server (NTRS)

    Baggs. Rjpda; 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.

  19. Towards Enhanced Affective Design: Rethinking the Notion of Design

    NASA Astrophysics Data System (ADS)

    Kim, SuKyoung; Cho, Youngil

    2017-09-01

    Design disciplines have been contributing to shaping the life of human beings, as well as fostering culture and heritage. Design disciplines and research have been rapidly transforming, and not only objects but also services are target of design. This paper reviews design disciplines towards enhanced affective design, which attributes to intuitive knowledge. It aims at rethinking the notion of design to propose a conceptual framework for integrating user experience into objects that strengthen the form and function based design with pleasing.

  20. Advanced solar panel designs

    NASA Technical Reports Server (NTRS)

    Ralph, E. L.; Linder, E.

    1995-01-01

    This paper describes solar cell panel designs that utilize new hgih efficiency solar cells along with lightweight rigid panel technology. The resulting designs push the W/kg and W/sq m parameters to new high levels. These new designs are well suited to meet the demand for higher performance small satellites. This paper reports on progress made on two SBIR Phase 1 contracts. One panel design involved the use of large area (5.5 cm x 6.5 cm) GaAs/Ge solar cells of 19% efficiency combined with a lightweight rigid graphite fiber epoxy isogrid substrate configuration. A coupon (38 cm x 38 cm) was fabricated and tested which demonstrated an array specific power level of 60 W/kg with a potential of reaching 80 W/kg. The second panel design involved the use of newly developed high efficiency (22%) dual junction GaInP2/GaAs/Ge solar cells combined with an advanced lightweight rigid substrate using aluminum honeycomb core with high strength graphite fiber mesh facesheets. A coupon (38 cm x 38 cm) was fabricated and tested which demonstrated an array specific power of 105 W/kg and 230 W/sq m. This paper will address the construction details of the panels and an a analysis of the component weights. A strawman array design suitable for a typical small-sat mission is described for each of the two panel design technologies being studied. Benefits in respect to weight reduction, area reduction, and system cost reduction are analyzed and compared to conventional arrays.

  1. Fault Management Design Strategies

    NASA Technical Reports Server (NTRS)

    Day, John C.; Johnson, Stephen B.

    2014-01-01

    Development of dependable systems relies on the ability of the system to determine and respond to off-nominal system behavior. Specification and development of these fault management capabilities must be done in a structured and principled manner to improve our understanding of these systems, and to make significant gains in dependability (safety, reliability and availability). Prior work has described a fundamental taxonomy and theory of System Health Management (SHM), and of its operational subset, Fault Management (FM). This conceptual foundation provides a basis to develop framework to design and implement FM design strategies that protect mission objectives and account for system design limitations. Selection of an SHM strategy has implications for the functions required to perform the strategy, and it places constraints on the set of possible design solutions. The framework developed in this paper provides a rigorous and principled approach to classifying SHM strategies, as well as methods for determination and implementation of SHM strategies. An illustrative example is used to describe the application of the framework and the resulting benefits to system and FM design and dependability.

  2. Crewbot Suspension Design

    NASA Technical Reports Server (NTRS)

    Wood, Nathan A.

    2005-01-01

    Planetary Surface Robot Work Crews (RWC) represent a new class of construction robots for future deployment in planetary exploration. Rovers currently being used for the RWC platform lack the load carrying capabilities required in regular work. Two new rovers, dubbed CrewBots, being designed in JPL's Planetary Robotics Lab specifically for RWC applications greatly increase the load carrying capabilities of the platform. A major component of the rover design was the design of the rocker type suspension, which increases rover mobility. The design of the suspension for the Crewbots departed from the design of recent rovers. While many previous rovers have used internal bevel gear differentials, the increased load requirements of the Crewbots calls for a more robust system. The solution presented is the use of an external modified three-bar, slider-linkage, rocker-style suspension that increases the moment arm of the differential. The final product is a suspension system capable of supporting the extreme loading cases the RWC platform presents, without consuming a large portion of the Crewbots' internal space.

  3. Considerations of study design.

    PubMed

    Koretz, Ronald L

    2007-12-01

    Research projects attempt to answer specific questions. The particular study design that is selected will depend in large measure on the nature of the question and the time and resources available. There are 5 common categories of clinical questions; they relate to etiology, prognosis, utility of diagnostic tests, efficacy of proposed interventions, and cost of treatment in specific disease states. A number of study designs can be used. Case reports serve to memorialize unusual or novel aspects of diseases. Retrospective case series are useful for defining natural history. Case-control studies are used by epidemiologists to elucidate potential etiologies of diseases. Prospective cohort studies can be used to assess natural history or to assess potential disease etiologies. Controlled trials are designed to assess the efficacy of therapeutic interventions. Studies that define the sensitivity and specificity of diagnostic tests can be used to assess the utility of those tests. Economic analyses estimate the costs that particular diseases or therapies will require. Each of these study designs has limitations; with the exception of high-quality randomized trials, none of these study designs can establish a causative relationship between putative etiologic (or therapeutic) factors and disease (outcomes).

  4. Design oriented structural analysis

    NASA Technical Reports Server (NTRS)

    Giles, Gary L.

    1994-01-01

    Desirable characteristics and benefits of design oriented analysis methods are described and illustrated by presenting a synoptic description of the development and uses of the Equivalent Laminated Plate Solution (ELAPS) computer code. ELAPS is a design oriented structural analysis method which is intended for use in the early design of aircraft wing structures. Model preparation is minimized by using a few large plate segments to model the wing box structure. Computational efficiency is achieved by using a limited number of global displacement functions that encompass all segments over the wing planform. Coupling with other codes is facilitated since the output quantities such as deflections and stresses are calculated as continuous functions over the plate segments. Various aspects of the ELAPS development are discussed including the analytical formulation, verification of results by comparison with finite element analysis results, coupling with other codes, and calculation of sensitivity derivatives. The effectiveness of ELAPS for multidisciplinary design application is illustrated by describing its use in design studies of high speed civil transport wing structures.

  5. Safeguards by Design Challenge

    SciTech Connect

    Alwin, Jennifer Louise

    The International Atomic Energy Agency (IAEA) defines Safeguards as a system of inspection and verification of the peaceful uses of nuclear materials as part of the Nuclear Nonproliferation Treaty. IAEA oversees safeguards worldwide. Safeguards by Design (SBD) involves incorporation of safeguards technologies, techniques, and instrumentation during the design phase of a facility, rather that after the fact. Design challenge goals are the following: Design a system of safeguards technologies, techniques, and instrumentation for inspection and verification of the peaceful uses of nuclear materials. Cost should be minimized to work with the IAEA’s limited budget. Dose to workers should always bemore » as low are reasonably achievable (ALARA). Time is of the essence in operating facilities and flow of material should not be interrupted significantly. Proprietary process information in facilities may need to be protected, thus the amount of information obtained by inspectors should be the minimum required to achieve the measurement goal. Then three different design challenges are detailed: Plutonium Waste Item Measurement System, Marine-based Modular Reactor, and Floating Nuclear Power Plant (FNPP).« less

  6. Mechanical Design of Spacecraft

    NASA Technical Reports Server (NTRS)

    1962-01-01

    In the spring of 1962, engineers from the Engineering Mechanics Division of the Jet Propulsion Laboratory gave a series of lectures on spacecraft design at the Engineering Design seminars conducted at the California Institute of Technology. Several of these lectures were subsequently given at Stanford University as part of the Space Technology seminar series sponsored by the Department of Aeronautics and Astronautics. Presented here are notes taken from these lectures. The lectures were conceived with the intent of providing the audience with a glimpse of the activities of a few mechanical engineers who are involved in designing, building, and testing spacecraft. Engineering courses generally consist of heavily idealized problems in order to allow the more efficient teaching of mathematical technique. Students, therefore, receive a somewhat limited exposure to actual engineering problems, which are typified by more unknowns than equations. For this reason it was considered valuable to demonstrate some of the problems faced by spacecraft designers, the processes used to arrive at solutions, and the interactions between the engineer and the remainder of the organization in which he is constrained to operate. These lecture notes are not so much a compilation of sophisticated techniques of analysis as they are a collection of examples of spacecraft hardware and associated problems. They will be of interest not so much to the experienced spacecraft designer as to those who wonder what part the mechanical engineer plays in an effort such as the exploration of space.

  7. Designing Inquiry Starters

    NASA Astrophysics Data System (ADS)

    Kluger-Bell, B.

    2010-12-01

    The term "Inquiry Starter" comes from the Institute for Inquiry's model for teaching and learning science through inquiry. It refers to the first phase of an inquiry activity where learners engage in actions that stimulate their curiosity and generate questions for further investigation. In the Professional Development Program, staff and participants have designed a wide variety of inquiry activities with a number of variations on the inquiry starter. This has provided a laboratory for examining inquiry starter design. In this paper, I describe and examine in detail the elements of this design and how the design of those elements is related to achieving learning objectives. There are a number of important common objectives in all inquiry starters. For example, all starters must define a domain for investigation and engage the learner's curiosity in that domain. There are also critical differences in learning objectives depending on the content area being studied, the learners' background knowledge and skills, and many other factors. In this paper I examine designs for both of these types of objectives.

  8. Designing Teaching--Teaching Designing: Teacher's Guidance in a Virtual Design Studio

    ERIC Educational Resources Information Center

    Lahti, Henna; Seitamaa-Hakkarainen, Pirita

    2014-01-01

    This study examined pedagogical aspects of virtual designing. It focused on how an industrial design teacher organised a university course in plastic product design and how the teacher guided student teams' design processes in a virtual design studio. The model of Learning by Collaborative Design was used as a pedagogical and analytical framework.…

  9. Food Design Thinking: A Branch of Design Thinking Specific to Food Design

    ERIC Educational Resources Information Center

    Zampollo, Francesca; Peacock, Matthew

    2016-01-01

    Is there a need for a set of methods within Design Thinking tailored specifically for the Food Design process? Is there a need for a branch of Design Thinking dedicated to Food Design alone? Chefs are not generally trained in Design or Design Thinking, and we are only just beginning to understand how they ideate and what recourses are available to…

  10. A quality by design approach to optimization of emulsions for electrospinning using factorial and D-optimal designs.

    PubMed

    Badawi, Mariam A; El-Khordagui, Labiba K

    2014-07-16

    Emulsion electrospinning is a multifactorial process used to generate nanofibers loaded with hydrophilic drugs or macromolecules for diverse biomedical applications. Emulsion electrospinnability is greatly impacted by the emulsion pharmaceutical attributes. The aim of this study was to apply a quality by design (QbD) approach based on design of experiments as a risk-based proactive approach to achieve predictable critical quality attributes (CQAs) in w/o emulsions for electrospinning. Polycaprolactone (PCL)-thickened w/o emulsions containing doxycycline HCl were formulated using a Span 60/sodium lauryl sulfate (SLS) emulsifier blend. The identified emulsion CQAs (stability, viscosity and conductivity) were linked with electrospinnability using a 3(3) factorial design to optimize emulsion composition for phase stability and a D-optimal design to optimize stable emulsions for viscosity and conductivity after shifting the design space. The three independent variables, emulsifier blend composition, organic:aqueous phase ratio and polymer concentration, had a significant effect (p<0.05) on emulsion CQAs, the emulsifier blend composition exerting prominent main and interaction effects. Scanning electron microscopy (SEM) of emulsion-electrospun NFs and desirability functions allowed modeling of emulsion CQAs to predict electrospinnable formulations. A QbD approach successfully built quality in electrospinnable emulsions, allowing development of hydrophilic drug-loaded nanofibers with desired morphological characteristics. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Modeling in the quality by design environment: Regulatory requirements and recommendations for design space and control strategy appointment.

    PubMed

    Djuris, Jelena; Djuric, Zorica

    2017-11-30

    Mathematical models can be used as an integral part of the quality by design (QbD) concept throughout the product lifecycle for variety of purposes, including appointment of the design space and control strategy, continual improvement and risk assessment. Examples of different mathematical modeling techniques (mechanistic, empirical and hybrid) in the pharmaceutical development and process monitoring or control are provided in the presented review. In the QbD context, mathematical models are predominantly used to support design space and/or control strategies. Considering their impact to the final product quality, models can be divided into the following categories: high, medium and low impact models. Although there are regulatory guidelines on the topic of modeling applications, review of QbD-based submission containing modeling elements revealed concerns regarding the scale-dependency of design spaces and verification of models predictions at commercial scale of manufacturing, especially regarding real-time release (RTR) models. Authors provide critical overview on the good modeling practices and introduce concepts of multiple-unit, adaptive and dynamic design space, multivariate specifications and methods for process uncertainty analysis. RTR specification with mathematical model and different approaches to multivariate statistical process control supporting process analytical technologies are also presented. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Designs for a quantum electron microscope.

    PubMed

    Kruit, P; Hobbs, R G; Kim, C-S; Yang, Y; Manfrinato, V R; Hammer, J; Thomas, S; Weber, P; Klopfer, B; Kohstall, C; Juffmann, T; Kasevich, M A; Hommelhoff, P; Berggren, K K

    2016-05-01

    One of the astounding consequences of quantum mechanics is that it allows the detection of a target using an incident probe, with only a low probability of interaction of the probe and the target. This 'quantum weirdness' could be applied in the field of electron microscopy to generate images of beam-sensitive specimens with substantially reduced damage to the specimen. A reduction of beam-induced damage to specimens is especially of great importance if it can enable imaging of biological specimens with atomic resolution. Following a recent suggestion that interaction-free measurements are possible with electrons, we now analyze the difficulties of actually building an atomic resolution interaction-free electron microscope, or "quantum electron microscope". A quantum electron microscope would require a number of unique components not found in conventional transmission electron microscopes. These components include a coherent electron beam-splitter or two-state-coupler, and a resonator structure to allow each electron to interrogate the specimen multiple times, thus supporting high success probabilities for interaction-free detection of the specimen. Different system designs are presented here, which are based on four different choices of two-state-couplers: a thin crystal, a grating mirror, a standing light wave and an electro-dynamical pseudopotential. Challenges for the detailed electron optical design are identified as future directions for development. While it is concluded that it should be possible to build an atomic resolution quantum electron microscope, we have also identified a number of hurdles to the development of such a microscope and further theoretical investigations that will be required to enable a complete interpretation of the images produced by such a microscope. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  13. Shuttle freezer conceptual design

    NASA Technical Reports Server (NTRS)

    Proctor, B. W.; Russell, D. J.

    1975-01-01

    A conceptual design for a kit freezer for operation onboard shuttle was developed. The freezer features a self-contained unit which can be mounted in the orbiter crew compartment and is capable of storing food at launch and returning with medical samples. Packaging schemes were investigated to provide the optimum storage capacity with a minimum weight and volume penalty. Several types of refrigeration systems were evaluated to select one which would offer the most efficient performance and lowest hazard of safety to the crew. Detailed performance data on the selected, Stirling cycle principled refrigeration unit were developed to validate the feasibility of its application to this freezer. Thermal analyses were performed to determine the adequacy of the thermal insulation to maintain the desired storage temperature with the design cooling capacity. Stress analyses were made to insure the design structure integrity could be maintained over the shuttle flight regime. A proposed prototype freezer development plan is presented.

  14. Biological materials by design.

    PubMed

    Qin, Zhao; Dimas, Leon; Adler, David; Bratzel, Graham; Buehler, Markus J

    2014-02-19

    In this topical review we discuss recent advances in the use of physical insight into the way biological materials function, to design novel engineered materials 'from scratch', or from the level of fundamental building blocks upwards and by using computational multiscale methods that link chemistry to material function. We present studies that connect advances in multiscale hierarchical material structuring with material synthesis and testing, review case studies of wood and other biological materials, and illustrate how engineered fiber composites and bulk materials are designed, modeled, and then synthesized and tested experimentally. The integration of experiment and simulation in multiscale design opens new avenues to explore the physics of materials from a fundamental perspective, and using complementary strengths from models and empirical techniques. Recent developments in this field illustrate a new paradigm by which complex material functionality is achieved through hierarchical structuring in spite of simple material constituents.

  15. Small FDIRC designs

    DOE PAGES

    Dey, B.; Ratcliff, B.; Va’vra, J.

    2017-02-16

    In this article, we explore the angular resolution limits attainable in small FDIRC designs taking advantage of the new highly pixelated detectors that are now available. Since the basic FDIRC design concept attains its particle separation performance mostly in the angular domain as measured by two-dimensional pixels, this paper relies primarily on a pixel-based analysis, with additional chromatic corrections using the time domain, requiring single photon timing resolution at a level of 100–200 ps only. This approach differs from other modern DIRC design concepts such as TOP or TORCH detectors, whose separation performances rely more strongly on time-dependent analyses. Inmore » conclusion, we find excellent single photon resolution with a geometry where individual bars are coupled to a single plate, which is coupled in turn to a cylindrical lens focusing camera.« less

  16. Bioreactor design concepts

    NASA Technical Reports Server (NTRS)

    Bowie, William

    1987-01-01

    Two parallel lines of work are underway in the bioreactor laboratory. One of the efforts is devoted to the continued development and utilization of a laboratory research system. That system's design is intended to be fluid and dynamic. The sole purpose of such a device is to allow testing and development of equipment concepts and procedures. Some of the results of those processes are discussed. A second effort is designed to produce a flight-like bioreactor contained in a double middeck locker. The result of that effort has been to freeze a particular bioreactor design in order to allow fabrication of the custom parts. The system is expected to be ready for flight in early 1988. However, continued use of the laboratory system will lead to improvements in the space bioreactor. Those improvements can only be integrated after the initial flight series.

  17. Battery Pack Thermal Design

    SciTech Connect

    Pesaran, Ahmad

    This presentation describes the thermal design of battery packs at the National Renewable Energy Laboratory. A battery thermal management system essential for xEVs for both normal operation during daily driving (achieving life and performance) and off-normal operation during abuse conditions (achieving safety). The battery thermal management system needs to be optimized with the right tools for the lowest cost. Experimental tools such as NREL's isothermal battery calorimeter, thermal imaging, and heat transfer setups are needed. Thermal models and computer-aided engineering tools are useful for robust designs. During abuse conditions, designs should prevent cell-to-cell propagation in a module/pack (i.e., keep themore » fire small and manageable). NREL's battery ISC device can be used for evaluating the robustness of a module/pack to cell-to-cell propagation.« less

  18. Simultaneous analysis and design

    NASA Technical Reports Server (NTRS)

    Haftka, R. T.

    1984-01-01

    Optimization techniques are increasingly being used for performing nonlinear structural analysis. The development of element by element (EBE) preconditioned conjugate gradient (CG) techniques is expected to extend this trend to linear analysis. Under these circumstances the structural design problem can be viewed as a nested optimization problem. There are computational benefits to treating this nested problem as a large single optimization problem. The response variables (such as displacements) and the structural parameters are all treated as design variables in a unified formulation which performs simultaneously the design and analysis. Two examples are used for demonstration. A seventy-two bar truss is optimized subject to linear stress constraints and a wing box structure is optimized subject to nonlinear collapse constraints. Both examples show substantial computational savings with the unified approach as compared to the traditional nested approach.

  19. Small FDIRC designs

    SciTech Connect

    Dey, B.; Ratcliff, B.; Va’vra, J.

    In this article, we explore the angular resolution limits attainable in small FDIRC designs taking advantage of the new highly pixelated detectors that are now available. Since the basic FDIRC design concept attains its particle separation performance mostly in the angular domain as measured by two-dimensional pixels, this paper relies primarily on a pixel-based analysis, with additional chromatic corrections using the time domain, requiring single photon timing resolution at a level of 100–200 ps only. This approach differs from other modern DIRC design concepts such as TOP or TORCH detectors, whose separation performances rely more strongly on time-dependent analyses. Inmore » conclusion, we find excellent single photon resolution with a geometry where individual bars are coupled to a single plate, which is coupled in turn to a cylindrical lens focusing camera.« less

  20. Telerobotic workstation design aid

    NASA Technical Reports Server (NTRS)

    Corker, K.; Hudlicka, E.; Young, D.; Cramer, N.

    1989-01-01

    Telerobot systems are being developed to support a number of space mission applications. In low earth orbit, telerobots and teleoperated manipulators will be used in shuttle operations and space station construction/maintenance. Free flying telerobotic service vehicles will be used at low and geosynchronous orbital operations. Rovers and autonomous vehicles will be equipped with telerobotic devices in planetary exploration. In all of these systems, human operators will interact with the robot system at varied levels during the scheduled operations. The human operators may be in either orbital or ground-based control systems. To assure integrated system development and maximum utility across these systems, designers must be sensitive to the constraints and capabilities that the human brings to system operation and must be assisted in applying these human factors to system development. The simulation and analysis system is intended to serve the needs of system analysis/designers as an integrated workstation in support of telerobotic design.

  1. Flexible weapons architecture design

    NASA Astrophysics Data System (ADS)

    Pyant, William C., III

    Present day air-delivered weapons are of a closed architecture, with little to no ability to tailor the weapon for the individual engagement. The closed architectures require weaponeers to make the target fit the weapon instead of fitting the individual weapons to a target. The concept of a flexible weapons aims to modularize weapons design using an open architecture shell into which different modules are inserted to achieve the desired target fractional damage while reducing cost and civilian casualties. This thesis shows that the architecture design factors of damage mechanism, fusing, weapons weight, guidance, and propulsion are significant in enhancing weapon performance objectives, and would benefit from modularization. Additionally, this thesis constructs an algorithm that can be used to design a weapon set for a particular target class based on these modular components.

  2. Patient Satisfaction by Design

    PubMed Central

    Jacobs, Karen

    2016-01-01

    The concept of the patient experience as it relates to patient satisfaction is a complex dynamic. It is a dynamic that is becoming increasingly more important as patients are faced with multiple choices for their hearing and balance care. As reimbursement and performance policies have become more normative within health care, patient satisfaction has become a metric to measure quality. Patient satisfaction is no longer contained to just the interaction with the audiologist. It extends to the entire experience—the staff, the service, the product, and other factors. Many practices fail to capitalize on one of the primary components of the patient experience—office design. This article discusses the role of evidence-based design in facility planning as it relates to patient satisfaction. It will illustrate how design principles and ideal attributes may be used to send conscious and subconscious cues that will motivate staff, facilitate patient-centered care, and ultimately increase patient satisfaction. PMID:28028324

  3. Patient Satisfaction by Design.

    PubMed

    Jacobs, Karen

    2016-11-01

    The concept of the patient experience as it relates to patient satisfaction is a complex dynamic. It is a dynamic that is becoming increasingly more important as patients are faced with multiple choices for their hearing and balance care. As reimbursement and performance policies have become more normative within health care, patient satisfaction has become a metric to measure quality. Patient satisfaction is no longer contained to just the interaction with the audiologist. It extends to the entire experience-the staff, the service, the product, and other factors. Many practices fail to capitalize on one of the primary components of the patient experience-office design. This article discusses the role of evidence-based design in facility planning as it relates to patient satisfaction. It will illustrate how design principles and ideal attributes may be used to send conscious and subconscious cues that will motivate staff, facilitate patient-centered care, and ultimately increase patient satisfaction.

  4. Sludge pipeline design.

    PubMed

    Slatter, P T

    2001-01-01

    The need for the design engineer to have a sound basis for designing sludge pumping and pipelining plant is becoming more critical. This paper examines both a traditional text-book approach and one of the latest approaches from the literature, and compares them with experimental data. The pipelining problem can be divided into the following main areas; rheological characterisation, laminar, transitional and turbulent flow and each is addressed in turn. Experimental data for a digested sludge tested in large pipes is analysed and compared with the two different theoretical approaches. Discussion is centred on the differences between the two methods and the degree of agreement with the data. It is concluded that the new approach has merit and can be used for practical design.

  5. Advances in Antibody Design

    PubMed Central

    Tiller, Kathryn E.; Tessier, Peter M.

    2017-01-01

    The use of monoclonal antibodies as therapeutics requires optimizing several of their key attributes. These include binding affinity and specificity, folding stability, solubility, pharmacokinetics, effector functions, and compatibility with the attachment of additional antibody domains (bispecific antibodies) and cytotoxic drugs (antibody–drug conjugates). Addressing these and other challenges requires the use of systematic design methods that complement powerful immunization and in vitro screening methods. We review advances in designing the binding loops, scaffolds, domain interfaces, constant regions, post-translational and chemical modifications, and bispecific architectures of antibodies and fragments thereof to improve their bioactivity. We also highlight unmet challenges in antibody design that must be overcome to generate potent antibody therapeutics. PMID:26274600

  6. Habitability design for spacecraft

    NASA Technical Reports Server (NTRS)

    Franklin, G. C.

    1978-01-01

    Habitability is understood to mean those spacecraft design elements that involve a degree of comfort, quality or necessities to support man in space. These elements are environment, architecture, mobility, clothing, housekeeping, food and drink, personal hygiene, off-duty activities, each of which plays a substantial part in the success of a mission. Habitability design for past space flights is discussed relative to the Mercury, Gemini, Apollo, and Skylab spacecraft, with special emphasis on an examination of the Shuttle Orbiter cabin design from a habitability standpoint. Future projects must consider the duration and mission objectives to meet their habitability requirements. Larger ward rooms, improved sleeping quarters and more complete hygiene facilities must be provided for future prolonged space flights

  7. Water Cooled Mirror Design

    SciTech Connect

    Dale, Gregory E.; Holloway, Michael Andrew; Pulliam, Elias Noel

    2015-03-30

    This design is intended to replace the current mirror setup being used for the NorthStar Moly 99 project in order to monitor the target coupon. The existing setup has limited movement for camera alignment and is difficult to align properly. This proposed conceptual design for a water cooled mirror will allow for greater thermal transfer between the mirror and the water block. It will also improve positioning of the mirror by using flexible vacuum hosing and a ball head joint capable of a wide range of motion. Incorporating this design into the target monitoring system will provide more efficient coolingmore » of the mirror which will improve the amount of diffraction caused by the heating of the mirror. The process of aligning the mirror for accurate position will be greatly improved by increasing the range of motion by offering six degrees of freedom.« less

  8. Parachute mortar design.

    NASA Technical Reports Server (NTRS)

    Pleasants, J. E.

    1973-01-01

    Mortars are used as one method for ejecting parachutes into the airstream to decelerate spacecraft and aircraft pilot escape modules and to effect spin recovery of the aircraft. An approach to design of mortars in the class that can accommodate parachutes in the 20- to 55-foot-diameter size is presented. Parachute deployment considerations are discussed. Comments are made on the design of a power unit, mortar tube, cover, and sabot. Propellant selection and breech characteristics and size are discussed. A method of estimating hardware weights and reaction load is presented. In addition, some aspects of erodible orifices are given as well as comments concerning ambient effects on performance. This paper collates data and experience from design and flight qualification of four mortar systems, and provides pertinent estimations that should be of interest on programs considering parachute deployment.

  9. The Iterative Design of a Virtual Design Studio

    ERIC Educational Resources Information Center

    Blevis, Eli; Lim, Youn-kyung; Stolterman, Erik; Makice, Kevin

    2008-01-01

    In this article, the authors explain how they implemented Design eXchange as a shared collaborative online and physical space for design for their students. Their notion for Design eXchange favors a complex mix of key elements namely: (1) a virtual online studio; (2) a forum for review of all things related to design, especially design with the…

  10. 40 CFR 130.9 - Designation and de-designation.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... QUALITY PLANNING AND MANAGEMENT § 130.9 Designation and de-designation. (a) Designation. Areawide planning... specified in Water Quality Management (WQM) plans. Areawide planning agencies shall monitor DMA activities... continue water quality planning activities within the designated boundaries. (c) Impact of de-designation...

  11. Visual Design Principles: An Empirical Study of Design Lore

    ERIC Educational Resources Information Center

    Kimball, Miles A.

    2013-01-01

    Many books, designers, and design educators talk about visual design principles such as balance, contrast, and alignment, but with little consistency. This study uses empirical methods to explore the lore surrounding design principles. The study took the form of two stages: a quantitative literature review to determine what design principles are…

  12. Design, Research, and Design Research: Synergies and Contradictions

    ERIC Educational Resources Information Center

    Nelson, Wayne A.

    2013-01-01

    Notions of design, research, and design research in the field of educational technology are quite different from conceptualizations held by other design fields. Examining the ways that research is conducted and used in educational technology in comparison to other design fields can provide novel insights into how research and design practice can…

  13. [Designer drugs in Finland].

    PubMed

    Tacke, Ulrich; den Hollander, Bjørnar; Simojoki, Kaarlo; Korpi, Esa R; Pihlainen, Katja; Alho, Hannu

    2011-01-01

    Designer drugs are synthetic psychotropic drugs which are marketed as "legal drugs". Their emergence, rapid spreading and unpredictable effects have challenged the health and substance abuse care. The slow process of classification of an abusable drug has provided too many possibilities for spreading the designer drugs. Once a certain substance receives an illegal drugs classification, dealers and users usually move to another, slightly different molecule that is still legal. In Finland, the Narcotics Act has been amended to the effect that the addition of a new substance to the illegal drug list does not require an amendment to the law.

  14. Optical design for SOFIA

    NASA Technical Reports Server (NTRS)

    Davis, Paul K.; Maa, Scott S.; Rajan, N.

    1989-01-01

    A preliminary first-order optical design for the Stratospheric Observatory for Infrared Astronomy (SOFIA) is presented. This is a Cassegrain design with a 3 meter diameter, approximately f/1 primary mirror. Phenomena limiting the image quality of the telescope are divided into 'seeing', optics, and guidance. An error budget is presented for these categories and specific effects contributing to each. The seeing effects from the shear layer between the telescope cavity and the external air are expected to be dominant. Results are presented on the necessary thermal, optical, structural and guidance requirements to maintain contributions of these phenomena below that of the shear-layer seeing.

  15. Integrated system design report

    SciTech Connect

    Not Available

    1989-07-01

    The primary objective of the integrated system test phase is to demonstrate the commercial potential of a coal fueled diesel engine in its actual operating environment. The integrated system in this project is defined as a coal fueled diesel locomotive. This locomotive, shown on drawing 41D715542, is described in the separate Concept Design Report. The test locomotive will be converted from an existing oil fueled diesel locomotive in three stages, until it nearly emulates the concept locomotive. Design drawings of locomotive components (diesel engine, locomotive, flatcar, etc.) are included.

  16. Exploration Design Challenge 2014

    NASA Image and Video Library

    2014-04-25

    NASA’s Administrator, Charles Bolden (left), President/CEO of Lockheed Martin, Marillyn Hewson (right), and astronaut Rex Walheim (back row) pose for a group photo with the winning high school team in the Exploration Design Challenge. Team ARES from the Governors School for Science and Technology in Hampton, Va. won the challenge with their radiation shield design, which will be built and flown aboard the Orion/EFT-1. The award was announced at the USA Science and Engineering Festival on April 25, 2014 at the Washington Convention Center. Photo Credit: (NASA/Aubrey Gemignani)

  17. Excavator Design Validation

    NASA Technical Reports Server (NTRS)

    Pholsiri, Chalongrath; English, James; Seberino, Charles; Lim, Yi-Je

    2010-01-01

    The Excavator Design Validation tool verifies excavator designs by automatically generating control systems and modeling their performance in an accurate simulation of their expected environment. Part of this software design includes interfacing with human operations that can be included in simulation-based studies and validation. This is essential for assessing productivity, versatility, and reliability. This software combines automatic control system generation from CAD (computer-aided design) models, rapid validation of complex mechanism designs, and detailed models of the environment including soil, dust, temperature, remote supervision, and communication latency to create a system of high value. Unique algorithms have been created for controlling and simulating complex robotic mechanisms automatically from just a CAD description. These algorithms are implemented as a commercial cross-platform C++ software toolkit that is configurable using the Extensible Markup Language (XML). The algorithms work with virtually any mobile robotic mechanisms using module descriptions that adhere to the XML standard. In addition, high-fidelity, real-time physics-based simulation algorithms have also been developed that include models of internal forces and the forces produced when a mechanism interacts with the outside world. This capability is combined with an innovative organization for simulation algorithms, new regolith simulation methods, and a unique control and study architecture to make powerful tools with the potential to transform the way NASA verifies and compares excavator designs. Energid's Actin software has been leveraged for this design validation. The architecture includes parametric and Monte Carlo studies tailored for validation of excavator designs and their control by remote human operators. It also includes the ability to interface with third-party software and human-input devices. Two types of simulation models have been adapted: high-fidelity discrete

  18. Escalator design features evaluation

    NASA Technical Reports Server (NTRS)

    Zimmerman, W. F.; Deshpande, G. K.

    1982-01-01

    Escalators are available with design features such as dual speed (90 and 120 fpm), mat operation and flat steps. These design features were evaluated based on the impact of each on capital and operating costs, traffic flow, and safety. A human factors engineering model was developed to analyze the need for flat steps at various speeds. Mat operation of escalators was found to be cost effective in terms of energy savings. Dual speed operation of escalators with the higher speed used during peak hours allows for efficient operation. A minimum number of flat steps required as a function of escalator speed was developed to ensure safety for the elderly.

  19. Remote Systems Design & Deployment

    SciTech Connect

    Bailey, Sharon A.; Baker, Carl P.; Valdez, Patrick LJ

    2009-08-28

    The Pacific Northwest National Laboratory (PNNL) was tasked by Washington River Protection Solutions, LLC (WRPS) to provide information and lessons learned relating to the design, development and deployment of remote systems, particularly remote arm/manipulator systems. This report reflects PNNL’s experience with remote systems and lays out the most important activities that need to be completed to successfully design, build, deploy and operate remote systems in radioactive and chemically contaminated environments. It also contains lessons learned from PNNL’s work experiences, and the work of others in the national laboratory complex.

  20. Designing Flight Deck Procedures

    NASA Technical Reports Server (NTRS)

    Degani, Asaf; Wiener, Earl

    2005-01-01

    Three reports address the design of flight-deck procedures and various aspects of human interaction with cockpit systems that have direct impact on flight safety. One report, On the Typography of Flight- Deck Documentation, discusses basic research about typography and the kind of information needed by designers of flight deck documentation. Flight crews reading poorly designed documentation may easily overlook a crucial item on the checklist. The report surveys and summarizes the available literature regarding the design and typographical aspects of printed material. It focuses on typographical factors such as proper typefaces, character height, use of lower- and upper-case characters, line length, and spacing. Graphical aspects such as layout, color coding, fonts, and character contrast are discussed; and several cockpit conditions such as lighting levels and glare are addressed, as well as usage factors such as angular alignment, paper quality, and colors. Most of the insights and recommendations discussed in this report are transferable to paperless cockpit systems of the future and computer-based procedure displays (e.g., "electronic flight bag") in aerospace systems and similar systems that are used in other industries such as medical, nuclear systems, maritime operations, and military systems.

  1. Guidelines for Document Designers.

    ERIC Educational Resources Information Center

    Felker, Daniel B.; And Others

    Intended to improve the quality of public documents by making them clearer to the people who use them, this book contains document design principles concerned with writing documents that are visually distinct, attractive, and easily understood. Following an introduction, the major portion of the book presents the 25 principles, each of which…

  2. Vintage Vinyl Record Design

    ERIC Educational Resources Information Center

    Sacco, Michael

    2008-01-01

    In this article, the author describes a project in which his ninth-grade art students utilized a vinyl record as an unusual medium to create a work that exhibited solid design, great creativity, and strong craftsmanship. Students presented their pieces to the class for critique, explained the process, the media, and their feelings about their…

  3. Accelerated test design

    NASA Technical Reports Server (NTRS)

    Mcdermott, P. P.

    1980-01-01

    The design of an accelerated life test program for electric batteries is discussed. A number of observations and suggestions on the procedures and objectives for conducting an accelerated life test program are presented. Equations based on nonlinear regression analysis for predicting the accelerated life test parameters are discussed.

  4. Web Page Design.

    ERIC Educational Resources Information Center

    Lindsay, Lorin

    Designing a web home page involves many decisions that affect how the page will look, the kind of technology required to use the page, the links the page will provide, and kinds of patrons who can use the page. The theme of information literacy needs to be built into every web page; users need to be taught the skills of sorting and applying…

  5. Athermal laser design.

    PubMed

    Bovington, Jock; Srinivasan, Sudharsanan; Bowers, John E

    2014-08-11

    This paper discusses circuit based and waveguide based athermalization schemes and provides some design examples of athermalized lasers utilizing fully integrated athermal components as an alternative to power hungry thermo-electric controllers (TECs), off-chip wavelength lockers or monitors with lookup tables for tunable lasers. This class of solutions is important for uncooled transmitters on silicon.

  6. Locker Room Design Trends.

    ERIC Educational Resources Information Center

    Wiens, Janet

    2001-01-01

    Examines how today's college and university athletic locker rooms have become sophisticated recruiting tools that rival many professional facilities. Locker room design and location and their level of furniture, finishes, and equipment are discussed as is the trend for more environmentally friendly locker rooms. (GR)

  7. Tool and Fixture Design

    SciTech Connect

    Graham, Mark W.

    2015-07-28

    In a manufacturing process, a need is identified and a product is created to fill this need. While design and engineering of the final product is important, the tools and fixtures that aid in the creation of the final product are just as important, if not more so. Power supplies assembled at the TA-55 PF-5 have been designed by an excellent engineering team. The task in PF-5 now is to ensure that all steps of the assembly and manufacturing process can be completed safely, reliably, and in a quality repeatable manner. One of these process steps involves soldering fine wiresmore » to an electrical connector. During the process development phase, the method of soldering included placing the power supply in a vice in order to manipulate it into a position conducive to soldering. This method is unacceptable from a reliability, repeatability, and ergonomic standpoint. To combat these issues, a fixture was designed to replace the current method. To do so, a twelve step engineering design process was used to create the fixture that would provide a solution to a multitude of problems, and increase the safety and efficiency of production.« less

  8. An Arsenal Ship Design

    DTIC Science & Technology

    1996-12-01

    151 B. PROPULSION PLANT SELECTION....................................................................... 152 ix C. PROPULSION PLANT LAYOUT...155 D. ELECTRICAL PLANT SELECTION...designed into the hull and power plant and once finalized is only a function of how many miles the ship is to be driven. Decision trade- offs are to

  9. Balloon Design Software

    NASA Technical Reports Server (NTRS)

    Farley, Rodger

    2007-01-01

    PlanetaryBalloon Version 5.0 is a software package for the design of meridionally lobed planetary balloons. It operates in a Windows environment, and programming was done in Visual Basic 6. By including the effects of circular lobes with load tapes, skin mass, hoop and meridional stress, and elasticity in the structural elements, a more accurate balloon shape of practical construction can be determined as well as the room-temperature cut pattern for the gore shapes. The computer algorithm is formulated for sizing meridionally lobed balloons for any generalized atmosphere or planet. This also covers zero-pressure, over-pressure, and super-pressure balloons. Low circumferential loads with meridionally reinforced load tapes will produce shapes close to what are known as the "natural shape." The software allows for the design of constant angle, constant radius, or constant hoop stress balloons. It uses the desired payload capacity for given atmospheric conditions and determines the required volume, allowing users to design exactly to their requirements. The formulations are generalized to use any lift gas (or mixture of gases), any atmosphere, or any planet as described by the local acceleration of gravity. PlanetaryBalloon software has a comprehensive user manual that covers features ranging from, but not limited to, buoyancy and super-pressure, convenient design equations, shape formulation, and orthotropic stress/strain.

  10. Designing the molecular future.

    PubMed

    Schneider, Gisbert

    2012-01-01

    Approximately 25 years ago the first computer applications were conceived for the purpose of automated 'de novo' drug design, prominent pioneering tools being ALADDIN, CAVEAT, GENOA, and DYLOMMS. Many of these early concepts were enabled by innovative techniques for ligand-receptor interaction modeling like GRID, MCSS, DOCK, and CoMFA, which still provide the theoretical framework for several more recently developed molecular design algorithms. After a first wave of software tools and groundbreaking applications in the 1990s--expressly GROW, GrowMol, LEGEND, and LUDI representing some of the key players--we are currently witnessing a renewed strong interest in this field. Innovative ideas for both receptor and ligand-based drug design have recently been published. We here provide a personal perspective on the evolution of de novo design, highlighting some of the historic achievements as well as possible future developments of this exciting field of research, which combines multiple scientific disciplines and is, like few other areas in chemistry, subject to continuous enthusiastic discussion and compassionate dispute.

  11. Kayak Design Challenge

    ERIC Educational Resources Information Center

    Wood, Anson

    2011-01-01

    Living in the Adirondack Park and being an avid outdoorsman has often resulted in the author's love of the outdoors working its way into class projects. In 2010, the author gave a group of 25 students in grades 9-12 a challenge that required them to design and construct a prototype inexpensive, lightweight kayak for backpackers and fisherman. In…

  12. Simplex turbopump design

    NASA Technical Reports Server (NTRS)

    Marsh, Matt; Cowan, Penny

    1994-01-01

    Turbomachinery used in liquid rocket engines typically are composed of complex geometries made from high strength-to-weight super alloys and have long design and fabrication cycle times (3 to 5 years). A simple, low-cost turbopump is being designed in-house to demonstrate the ability to reduce the overall cost to $500K and compress life cycle time to 18 months. The simplex turbopump was designed to provide a discharge pressure of 1500 psia of liquid oxygen at 90 lbm/s. The turbine will be powered by gaseous oxygen. This eliminates the need for an inter-propellant seal typically required to separate the fuel-rich turbine gases from the liquid oxygen pump components. Materials used in the turbine flow paths will utilize existing characterized metals at 800 deg R that are compatible with a warm oxygen environment. This turbopump design would be suitable for integration with a 40 K pound thrust hybrid motor that provides warm oxygen from a tapped-off location to power the turbine. The preliminary and detailed analysis was completed in a year by a multiple discipline, concurrent engineering team. Manpower, schedule, and cost data were tracked during the process for a comparison to the initial goal. The Simplex hardware is the procurement cycle with the expectation of the first test to occur approximately 1.5 months behind the original schedule goal.

  13. Designing Places for Learning.

    ERIC Educational Resources Information Center

    Meek, Anne, Ed.

    This book presents information about the condition of schools around the United States. It also describes the link between architecture and academic success and offers suggestions for improving the design of existing and future school buildings. Eleven articles look at schools as places of deep meaning and show how that view can alter approaches…

  14. Mechanical Drawing and Design.

    ERIC Educational Resources Information Center

    Mikulsky, Marilyn; McEnaney, Walter K.

    A syllabus is provided for a comprehensive foundation course in mechanical drawing and design for grades 9, 10, 11, or 12 that is prerequisite to advanced elective courses. Introductory materials include course objectives, an overview of basic concepts, and guidelines for implementation. Brief discussions of and suggestions for the areas of design…

  15. SMS engineering design report

    NASA Technical Reports Server (NTRS)

    1976-01-01

    The engineering design for the Shuttle Missions Simulator is presented in sections, with each section representing a subsystem development activity. Subsystems covered include: electrical power system; mechanical power system; main propellant and external tank; solid rocket booster; reaction control system; orbital maneuvering system; guidance, navigation, and control; data processing system; mission control center interface; and image display system.

  16. WATERSHED BASED SURVEY DESIGNS

    EPA Science Inventory

    The development of watershed-based design and assessment tools will help to serve the multiple goals for water quality monitoring required under the Clean Water Act, including assessment of regional condition to meet Section 305(b), identification of impaired water bodies or wate...

  17. Advanced Solar Panel Designs

    NASA Technical Reports Server (NTRS)

    Ralph, E. L.; Linder, E. B.

    1995-01-01

    Solar panel designs that utilize new high-efficiency solar cells and lightweight rigid panel technologies are described. The resulting designs increase the specific power (W/kg) achievable in the near-term and are well suited to meet the demands of higher performance small satellites (smallsats). Advanced solar panel designs have been developed and demonstrated on two NASA SBIR contracts at Applied Solar. The first used 19% efficient, large area (5.5 cm x 6.5 cm) GaAs/Ge solar cells with a lightweight rigid graphite epoxy isogrid substrate configuration. A 1,445 sq cm coupon was fabricated and tested to demonstrate 60 W/kg with a high potential of achieving 80 W/kg. The second panel design used new 22% efficiency, dual-junction GaInP2/GaAs/Ge solar cells combined with a lightweight aluminum core/graphite fiber mesh facesheet substrate. A 1,445 sq cm coupon was fabricated and tested to demonstrate 105 W/kg with the potential of achieving 115 W/kg.

  18. Designing shear-thinning

    NASA Astrophysics Data System (ADS)

    Nelson, Arif Z.; Ewoldt, Randy H.

    2017-11-01

    Design in fluid mechanics often focuses on optimizing geometry (airfoils, surface textures, microfluid channels), but here we focus on designing fluids themselves. The dramatically shear-thinning ``yield-stress fluid'' is currently the most utilized non-Newtonian fluid phenomenon. These rheologically complex materials, which undergo a reversible transition from solid-like to liquid-like fluid flow, are utilized in pedestrian products such as paint and toothpaste, but also in emerging applications like direct-write 3D printing. We present a paradigm for yield-stress fluid design that considers constitutive model representation, material property databases, available predictive scaling laws, and the many ways to achieve a yield stress fluid, flipping the typical structure-to-rheology analysis to become the inverse: rheology-to-structure with multiple possible materials as solutions. We describe case studies of 3D printing inks and other flow scenarios where designed shear-thinning enables performance remarkably beyond that of Newtonian fluids. This work was supported by Wm. Wrigley Jr. Company and the National Science Foundation under Grant No. CMMI-1463203.

  19. Innovation in Course Design

    ERIC Educational Resources Information Center

    Knipe, Sally

    2016-01-01

    Initial teacher education programs offered at Australian universities tend to qualify graduates to teach in the age-related contexts of early childhood/primary or secondary, a model that has reflected the organisational evolution of schools. Greater flexibility is required in the design of teacher preparation courses in order to produce graduates…

  20. Architecture as Design Study.

    ERIC Educational Resources Information Center

    Kauppinen, Heta

    1989-01-01

    Explores the use of analogies in architectural design, the importance of Gestalt theory and aesthetic cannons in understanding and being sensitive to architecture. Emphasizes the variation between public and professional appreciation of architecture. Notes that an understanding of architectural process enables students to improve the aesthetic…

  1. Designing a Language Study.

    ERIC Educational Resources Information Center

    Brown, James Dean

    Some issues in the design of classroom research on second language teaching are discussed, with the intention of helping the researcher avoid conceptual pitfalls that may cripple the study later in the process. This begins with an examination of concerns in sampling, including definition of a population to be studied, alternative sampling…

  2. Genetic circuit design automation.

    PubMed

    Nielsen, Alec A K; Der, Bryan S; Shin, Jonghyeon; Vaidyanathan, Prashant; Paralanov, Vanya; Strychalski, Elizabeth A; Ross, David; Densmore, Douglas; Voigt, Christopher A

    2016-04-01

    Computation can be performed in living cells by DNA-encoded circuits that process sensory information and control biological functions. Their construction is time-intensive, requiring manual part assembly and balancing of regulator expression. We describe a design environment, Cello, in which a user writes Verilog code that is automatically transformed into a DNA sequence. Algorithms build a circuit diagram, assign and connect gates, and simulate performance. Reliable circuit design requires the insulation of gates from genetic context, so that they function identically when used in different circuits. We used Cello to design 60 circuits forEscherichia coli(880,000 base pairs of DNA), for which each DNA sequence was built as predicted by the software with no additional tuning. Of these, 45 circuits performed correctly in every output state (up to 10 regulators and 55 parts), and across all circuits 92% of the output states functioned as predicted. Design automation simplifies the incorporation of genetic circuits into biotechnology projects that require decision-making, control, sensing, or spatial organization. Copyright © 2016, American Association for the Advancement of Science.

  3. Designing "Educationally Effective" Discussion

    ERIC Educational Resources Information Center

    Swann, Joan

    2007-01-01

    This paper analyses data from a curriculum intervention project designed to introduce new forms of discussion, seen as educationally effective, into the primary classroom. While the introduction of talk as an aid to learning is premised on a social approach to learning, such interventions are often evaluated in terms of cognitive benefits and…

  4. Space Tethers Design Criteria

    NASA Technical Reports Server (NTRS)

    Tomlin, Donald D.; Faile, Gwyn C.; Hayashida, Kazuo B.; Frost, Cynthia L.; Wagner, Carole Y.; Mitchell, Michael L.; Vaughn, Jason A.; Galuska, Michael J.

    1998-01-01

    The small expendable deployable system and tether satellite system programs did not have a uniform written criteria for tethers. The JSC safety panel asked what criteria was used to design the tethers. Since none existed, a criteria was written based on past experience for future tether programs.

  5. Designing sustainable acute hospitals.

    PubMed

    Cory, Alistair

    2008-01-01

    The need to provide sustainable hospitals lies in the fact that we have an obligation to act responsibly towards good stewardship of our environment and the world's precious resources, ensuring a healthy future for coming generations. As such, a sustainable hospital must sit squarely in a sustainable society, and the global and local context should be considered when designing a sustainable health facility.

  6. Designing the Campaign.

    ERIC Educational Resources Information Center

    Cheney, Carol

    1995-01-01

    For colleges and schools concerned with the image they project to the public, guidelines for creating and presenting a graphic identity, particularly for fund raising, are offered. Design principles include creating a unified communications program, accurately reflecting the institution's mission and spirit, inspiring confidence in workers and…

  7. Designing the Reading Curriculum.

    ERIC Educational Resources Information Center

    Ediger, Marlow

    The design of the reading curriculum presents a vision of what will be stressed in reading instruction. A first ingredient to discuss in developing the reading curriculum emphasizes the degree to which different curriculum areas should be related in teaching and learning. Reading then could be taught as a separate subject matter area from the…

  8. Graphic Design for Researchers

    ERIC Educational Resources Information Center

    Regional Educational Laboratory, 2014

    2014-01-01

    Technology continues to radically change how we create and consume information. Today, news, reports, and other material are often delivered quickly through pictures, colors, or other eye-catching visual elements. Words still matter, but they may be tweeted, viewed on a smartphone, or placed in a call-out box in a report. The design of these items…

  9. Designing Networks for Innovation

    ERIC Educational Resources Information Center

    Laskowski, Paul Luke

    2009-01-01

    The last decades have seen tremendous growth and transformation in the Internet's commercial landscape. Underneath this success, however, the underlying network architecture has shown a marked resistance to change; it is now described as stagnant and ossified. Numerous design proposals have been developed by researchers, implemented in code, and…

  10. Designing for Specific Learners

    ERIC Educational Resources Information Center

    Cutting, Hal

    2009-01-01

    Today's primary schools are being designed in a totally different way from those of only a few years ago. In Australia, both the Victorian Government and the Catholic education authorities have changed their notion of schooling. The most significant change has been the linking of curriculum, pedagogy and the types of spaces in which children…

  11. Camp Unit Design Guidelines.

    ERIC Educational Resources Information Center

    Hultsman, John T.; Cottrell, Richard L.

    This document provides a set of generalized guidelines for the design of units in large family campgrounds. Managers of recreational lands have two responsibilities and goals: to protect the natural resources, and to provide an enjoyable experience for users. With these goals in mind, unique variables to each unit such as shade, site aesthetics,…

  12. Digital systems design language

    NASA Technical Reports Server (NTRS)

    Shiva, S. G.

    1979-01-01

    Digital Systems Design Language (DDL) is implemented on the SEL-32 Computer Systems. The detaileds of the language, the translator, and the simulator, and the smulator programs are given. Several example descriptions and a tutorial on hardware description languages are provided, to guide the user.

  13. Designing and Assessing Learning

    ERIC Educational Resources Information Center

    Quan, Hong; Liu, Dandan; Cun, Xiangqin; Lu, Yingchun

    2009-01-01

    This paper analyses the design, implementation and assessment of a level 2 module for non-English major students in higher vocational and professional education. 1132001 is a code of module that uses active methods to teach college English in China. It specifically reflects on the module's advantage and defect for developing and improving learning…

  14. Designing the Electronic Classroom.

    ERIC Educational Resources Information Center

    Adams, Laural L.

    In an increasingly technological environment, traditional teaching presentation methods such as the podium, overhead, and transparencies are no longer sufficient. This document serves as a guide to designing and planning an electronic classroom for "bidirectional" communication between teacher and student. Topics include: (1) determining…

  15. Designing for Decision Making

    ERIC Educational Resources Information Center

    Jonassen, David H.

    2012-01-01

    Decision making is the most common kind of problem solving. It is also an important component skill in other more ill-structured and complex kinds of problem solving, including policy problems and design problems. There are different kinds of decisions, including choices, acceptances, evaluations, and constructions. After describing the centrality…

  16. Data System Design.

    ERIC Educational Resources Information Center

    Thomas, Charles R.

    Some of the major elements of administrative information systems design as applied to higher education are described. Differences between the application of computer technology in the commercial environment and the educational environment are discussed. The major steps in systems development from problem definition through implementation are…

  17. Designing for International Teletraining.

    ERIC Educational Resources Information Center

    Chute, Alan G.; Shatzer, Linda S.

    The ability to bridge together geographically-distant populations for training is made possible through teletraining, a human performance system which integrates telecommunications into the planning, design, and delivery of training programs. Typically, teletraining uses standard telephone lines or digital communication services to provide…

  18. CAD: Designs on Business.

    ERIC Educational Resources Information Center

    Milburn, Ken

    1988-01-01

    Provides a general review of the field of Computer-Aided Design Software including specific reviews of "Autosketch,""Generic CADD,""Drafix 1 Plus,""FastCAD," and "Autocad Release 9." Brief articles include "Blueprint for Generation,""CAD for Every Department,""Ideas…

  19. Design verification of SIFT

    NASA Technical Reports Server (NTRS)

    Moser, Louise; Melliar-Smith, Michael; Schwartz, Richard

    1987-01-01

    A SIFT reliable aircraft control computer system, designed to meet the ultrahigh reliability required for safety critical flight control applications by use of processor replications and voting, was constructed for SRI, and delivered to NASA Langley for evaluation in the AIRLAB. To increase confidence in the reliability projections for SIFT, produced by a Markov reliability model, SRI constructed a formal specification, defining the meaning of reliability in the context of flight control. A further series of specifications defined, in increasing detail, the design of SIFT down to pre- and post-conditions on Pascal code procedures. Mechanically checked mathematical proofs were constructed to demonstrate that the more detailed design specifications for SIFT do indeed imply the formal reliability requirement. An additional specification defined some of the assumptions made about SIFT by the Markov model, and further proofs were constructed to show that these assumptions, as expressed by that specification, did indeed follow from the more detailed design specifications for SIFT. This report provides an outline of the methodology used for this hierarchical specification and proof, and describes the various specifications and proofs performed.

  20. Dover Schools' Unintelligent Design

    ERIC Educational Resources Information Center

    Barlow, Dudley

    2006-01-01

    The author of this article was surprised to read in the December 21, 2005, Ann Arbor News that "The Ann Arbor-based Thomas More Law Center, which represented the Dover [Pennsylvania] School District in its federal case for the teaching of intelligent design, has threatened to sue Gull Lake [Michigan] Community Schools over its policy that…