2016-01-01
Understanding the electrostatic interactions between bacterial membranes and exogenous proteins is crucial to designing effective antimicrobial agents against Gram-negative bacteria. Here we study, using neutron reflecometry under multiple isotopic contrast conditions, the role of the uncharged sugar groups in the outer core region of lipopolysaccharide (LPS) in protecting the phosphate-rich inner core region from electrostatic interactions with antimicrobial proteins. Models of the asymmetric Gram negative outer membrane on silicon were prepared with phopshatidylcholine (PC) in the inner leaflet (closest to the silicon), whereas rough LPS was used to form the outer leaflet (facing the bulk solution). We show how salt concentration can be used to reversibly alter the binding affinity of a protein antibiotic colicin N (ColN) to the anionic LPS confirming that the interaction is electrostatic in nature. By examining the interaction of ColN with two rough LPS types with different-sized core oligosaccharide regions we demonstrate the role of uncharged sugars in blocking short-range electrostatic interactions between the cationic antibiotics and the vulnerable anionic phosphate groups. PMID:27003358
Effect of Divalent Cation Removal on the Structure of Gram-Negative Bacterial Outer Membrane Models
DOE Office of Scientific and Technical Information (OSTI.GOV)
Clifton, Luke A.; Skoda, Maximilian W. A.; Le Brun, Anton P.
The Gram-negative bacterial outer membrane (GNB-OM) is asymmetric in its lipid composition with a phospholipid-rich inner leaflet and an outer leaflet predominantly composed of lipopolysaccharides (LPS). LPS are polyanionic molecules, with numerous phosphate groups present in the lipid A and core oligosaccharide regions. The repulsive forces due to accumulation of the negative charges are screened and bridged by the divalent cations (Mg 2+ and Ca 2+) that are known to be crucial for the integrity of the bacterial OM. Indeed, chelation of divalent cations is a well-established method to permeabilize Gram-negative bacteria such as Escherichia coli. Here, we use X-raymore » and neutron reflectivity (XRR and NR, respectively) techniques to examine the role of calcium ions in the stability of a model GNB-OM. Using XRR we show that Ca 2+ binds to the core region of the rough mutant LPS (RaLPS) films, producing more ordered structures in comparison to divalent cation free monolayers. Using recently developed solid-supported models of the GNB-OM, we study the effect of calcium removal on the asymmetry of DPPC:RaLPS bilayers. We show that without the charge screening effect of divalent cations, the LPS is forced to overcome the thermodynamically unfavorable energy barrier and flip across the hydrophobic bilayer to minimize the repulsive electrostatic forces, resulting in about 20% mixing of LPS and DPPC between the inner and outer bilayer leaflets. These results reveal for the first time the molecular details behind the well-known mechanism of outer membrane stabilization by divalent cations. This confirms the relevance of the asymmetric models for future studies of outer membrane stability and antibiotic penetration.« less
Effect of Divalent Cation Removal on the Structure of Gram-Negative Bacterial Outer Membrane Models
Clifton, Luke A.; Skoda, Maximilian W. A.; Le Brun, Anton P.; ...
2014-12-09
The Gram-negative bacterial outer membrane (GNB-OM) is asymmetric in its lipid composition with a phospholipid-rich inner leaflet and an outer leaflet predominantly composed of lipopolysaccharides (LPS). LPS are polyanionic molecules, with numerous phosphate groups present in the lipid A and core oligosaccharide regions. The repulsive forces due to accumulation of the negative charges are screened and bridged by the divalent cations (Mg 2+ and Ca 2+) that are known to be crucial for the integrity of the bacterial OM. Indeed, chelation of divalent cations is a well-established method to permeabilize Gram-negative bacteria such as Escherichia coli. Here, we use X-raymore » and neutron reflectivity (XRR and NR, respectively) techniques to examine the role of calcium ions in the stability of a model GNB-OM. Using XRR we show that Ca 2+ binds to the core region of the rough mutant LPS (RaLPS) films, producing more ordered structures in comparison to divalent cation free monolayers. Using recently developed solid-supported models of the GNB-OM, we study the effect of calcium removal on the asymmetry of DPPC:RaLPS bilayers. We show that without the charge screening effect of divalent cations, the LPS is forced to overcome the thermodynamically unfavorable energy barrier and flip across the hydrophobic bilayer to minimize the repulsive electrostatic forces, resulting in about 20% mixing of LPS and DPPC between the inner and outer bilayer leaflets. These results reveal for the first time the molecular details behind the well-known mechanism of outer membrane stabilization by divalent cations. This confirms the relevance of the asymmetric models for future studies of outer membrane stability and antibiotic penetration.« less
Effect of Divalent Cation Removal on the Structure of Gram-Negative Bacterial Outer Membrane Models
2014-01-01
The Gram-negative bacterial outer membrane (GNB-OM) is asymmetric in its lipid composition with a phospholipid-rich inner leaflet and an outer leaflet predominantly composed of lipopolysaccharides (LPS). LPS are polyanionic molecules, with numerous phosphate groups present in the lipid A and core oligosaccharide regions. The repulsive forces due to accumulation of the negative charges are screened and bridged by the divalent cations (Mg2+ and Ca2+) that are known to be crucial for the integrity of the bacterial OM. Indeed, chelation of divalent cations is a well-established method to permeabilize Gram-negative bacteria such as Escherichia coli. Here, we use X-ray and neutron reflectivity (XRR and NR, respectively) techniques to examine the role of calcium ions in the stability of a model GNB-OM. Using XRR we show that Ca2+ binds to the core region of the rough mutant LPS (RaLPS) films, producing more ordered structures in comparison to divalent cation free monolayers. Using recently developed solid-supported models of the GNB-OM, we study the effect of calcium removal on the asymmetry of DPPC:RaLPS bilayers. We show that without the charge screening effect of divalent cations, the LPS is forced to overcome the thermodynamically unfavorable energy barrier and flip across the hydrophobic bilayer to minimize the repulsive electrostatic forces, resulting in about 20% mixing of LPS and DPPC between the inner and outer bilayer leaflets. These results reveal for the first time the molecular details behind the well-known mechanism of outer membrane stabilization by divalent cations. This confirms the relevance of the asymmetric models for future studies of outer membrane stability and antibiotic penetration. PMID:25489959
Corsaro, M Michela; Parrilli, Ermenegilda; Lanzetta, Rosa; Naldi, Teresa; Pieretti, Giuseppina; Lindner, Buko; Carpentieri, Andrea; Parrilli, Michelangelo; Tutino, M Luisa
2009-08-01
The role of lipopolysaccharides (LPSs) in the biogenesis of outer membrane proteins have been investigated in several studies. Some of these analyses showed that LPS is required for correct and efficient folding of outer membrane proteins; other studies support the idea of independence of outer membrane proteins biogenesis from LPS structure. In this article, we investigated the involvement of LPS structure in the anomalous aggregation of outer membrane proteins in a E. coli mutant strain (S17-1(lambdapir)). To achieve this aim, the LPS structure of the mutant strain was carefully determined and compared with the E. coli K-12 one. It turned out that LPS of these two strains differs in the inner core for the absence of a heptose residue (HepIII). We demonstrated that this difference is due to a mutation in waaQ, a gene encoding the transferase for the branch heptose HepIII residue. The mutation was complemented to find out if the restoration of LPS structure influenced the observed outer membrane proteins aggregation. Data reported in this work demonstrated that, in E. coli S17-1(lambdapir) there is no influence of LPS structure on the outer membrane proteins inclusion bodies formation.
Periplasmic orientation of nascent lipid A in the inner membrane of an Escherichia coli LptA mutant
Ma, Bing; Reynolds, C. Michael; Raetz, Christian R. H.
2008-01-01
The core-lipid A domain of Escherichia coli lipopolysaccharide (LPS) is synthesized on the inner surface of the inner membrane (IM) and flipped to its outer surface by the ABC transporter MsbA. Recent studies with deletion mutants implicate the periplasmic protein LptA, the cytosolic protein LptB, and the IM proteins LptC, LptF, and LptG in the subsequent transport of nascent LPS to the outer membrane (OM), where the LptD/LptE complex flips LPS to the outer surface. We have isolated a temperature-sensitive mutant (MB1) harboring the S22C and Q111P substitutions in LptA. MB1 stops growing after 30 min at 42°C. 32Pi and [35S]methionine labeling show that export of newly synthesized phospholipids and proteins is not severely impaired, but export of LPS is defective. Using the lipid A 1-phosphatase LpxE as a periplasmic IM marker and the lipid A 3-O-deacylase PagL as an OM marker, we show that core-lipid A reaches the periplasmic side of the IM at 42°C in MB1 but not the outer surface of the OM. Electron microscopy of MB1 reveals dense periplasmic material and a smooth OM at 42°C, consistent with a role for LptA in shuttling LPS across the periplasm. PMID:18768814
Periplasmic orientation of nascent lipid A in the inner membrane of an Escherichia coli LptA mutant.
Ma, Bing; Reynolds, C Michael; Raetz, Christian R H
2008-09-16
The core-lipid A domain of Escherichia coli lipopolysaccharide (LPS) is synthesized on the inner surface of the inner membrane (IM) and flipped to its outer surface by the ABC transporter MsbA. Recent studies with deletion mutants implicate the periplasmic protein LptA, the cytosolic protein LptB, and the IM proteins LptC, LptF, and LptG in the subsequent transport of nascent LPS to the outer membrane (OM), where the LptD/LptE complex flips LPS to the outer surface. We have isolated a temperature-sensitive mutant (MB1) harboring the S22C and Q111P substitutions in LptA. MB1 stops growing after 30 min at 42 degrees C. (32)P(i) and [(35)S]methionine labeling show that export of newly synthesized phospholipids and proteins is not severely impaired, but export of LPS is defective. Using the lipid A 1-phosphatase LpxE as a periplasmic IM marker and the lipid A 3-O-deacylase PagL as an OM marker, we show that core-lipid A reaches the periplasmic side of the IM at 42 degrees C in MB1 but not the outer surface of the OM. Electron microscopy of MB1 reveals dense periplasmic material and a smooth OM at 42 degrees C, consistent with a role for LptA in shuttling LPS across the periplasm.
Steeghs, Liana; van Vliet, Sandra J; Uronen-Hansson, Heli; van Mourik, Andries; Engering, Anneke; Sanchez-Hernandez, Martha; Klein, Nigel; Callard, Robin; van Putten, Jos P M; van der Ley, Peter; van Kooyk, Yvette; van de Winkel, Jan G J
2006-02-01
Neisseria meningitidis lipopolysaccharide (LPS) has been identified as a major determinant of dendritic cell (DC) function. Here we report that one of a series of meningococcal mutants with defined truncations in the lacto-N-neotetraose outer core of the LPS exhibited unique strong adhesion and internalization properties towards DC. These properties were mediated by interaction of the GlcNAc(beta1-3)-Gal(beta1-4)-Glc-R oligosaccharide outer core of lgtB LPS with the dendritic-cell-specific ICAM-3 grabbing non-integrin (DC-SIGN) lectin receptor. Activation of DC-SIGN with this novel oligosaccharide ligand skewed T-cell responses driven by DC towards T helper type 1 activity. Thus, the use of lgtB LPS may provide a powerful instrument to selectively induce the desired arm of the immune response and potentially increase vaccine efficacy.
Structural Characterization of Core Region in Erwinia amylovora Lipopolysaccharide.
Casillo, Angela; Ziaco, Marcello; Lindner, Buko; Merino, Susana; Mendoza-Barberá, Elena; Tomás, Juan M; Corsaro, Maria Michela
2017-03-04
Erwinia amylovora ( E. amylovora ) is the first bacterial plant pathogen described and demonstrated to cause fire blight, a devastating plant disease affecting a wide range of species including a wide variety of Rosaceae . In this study, we reported the lipopolysaccharide (LPS) core structure from E. amylovora strain CFBP1430, the first one for an E. amylovora highly pathogenic strain. The chemical characterization was performed on the mutants waaL (lacking only the O-antigen LPS with a complete LPS-core), wabH and wabG (outer-LPS core mutants). The LPSs were isolated from dry cells and analyzed by means of chemical and spectroscopic methods. In particular, they were subjected to a mild acid hydrolysis and/or a hydrazinolysis and investigated in detail by one and two dimensional Nuclear Magnetic Resonance (NMR) spectroscopy and ElectroSpray Ionization Fourier Transform-Ion Cyclotron Resonance (ESI FT-ICR) mass spectrometry.
USDA-ARS?s Scientific Manuscript database
This project aims to elucidate molecular mechanisms of Xylella fastidiosa (Xf) pathogenicity. Work is focused on the lipopolysaccharide (LPS) component of the outer membrane, which consists of lipid A, core oligosaccharides, and a variable O-antigen moiety. Specifically, the O-antigen portion of LPS...
Lipopolysaccharide Structure and Biosynthesis in Helicobacter pylori.
Li, Hong; Liao, Tingting; Debowski, Aleksandra W; Tang, Hong; Nilsson, Hans-Olof; Stubbs, Keith A; Marshall, Barry J; Benghezal, Mohammed
2016-12-01
This review covers the current knowledge and gaps in Helicobacter pylori lipopolysaccharide (LPS) structure and biosynthesis. H. pylori is a Gram-negative bacterium which colonizes the luminal surface of the human gastric epithelium. Both a constitutive alteration of the lipid A preventing TLR4 elicitation and host mimicry of the Lewis antigen decorated O-antigen of H. pylori LPS promote immune escape and chronic infection. To date, the complete structure of H. pylori LPS is not available, and the proposed model is a linear arrangement composed of the inner core defined as the hexa-saccharide (Kdo-LD-Hep-LD-Hep-DD-Hep-Gal-Glc), the outer core composed of a conserved trisaccharide (-GlcNAc-Fuc-DD-Hep-) linked to the third heptose of the inner core, the glucan, the heptan and a variable O-antigen, generally consisting of a poly-LacNAc decorated with Lewis antigens. Although the glycosyltransferases (GTs) responsible for the biosynthesis of the H. pylori O-antigen chains have been identified and characterized, there are many gaps in regard to the biosynthesis of the core LPS. These limitations warrant additional mutagenesis and structural studies to obtain the complete LPS structure and corresponding biosynthetic pathway of this important gastric bacterium. © 2016 John Wiley & Sons Ltd.
Cross, Alan S; Karreman, Hubert J; Zhang, Lei; Rosenberg, Zeil; Opal, Steven M; Lees, Andrew
2014-10-21
Translocation of gut-derived Gram-negative bacterial (GNB) lipopolysaccharide (LPS, or endotoxin) is a source of systemic inflammation that exacerbates HIV, cardiovascular and gastrointestinal diseases and malnutrition. The oral administration of bovine colostrum (BC) reduces endotoxemia in patients with impaired gut barrier function. Consequently, BC enriched in antibodies to LPS may ameliorate endotoxemia-related morbidities. We developed a detoxified J5 LPS/group B meningococcal outer membrane protein (J5dLPS/OMP) vaccine that induces antibodies against a highly conserved core region of LPS and protects against heterologous GNB infection. We now examine the ability of this vaccine to elicit anti-core endotoxin antibodies in BC. Two cohorts of pregnant cows were immunized with this vaccine in combination with FICA (Cohort 1) or Emulsigen-D (Cohort 2) adjuvants. Antibody responses to the J5 core LPS antigen were measured in both serum and colostrum and compared to antibody levels elicited by a commercially available veterinary vaccine (J5 Bacterin) comprised of heat-killed Escherichia coli O111, J5 mutant bacteria, from which the J5 LPS was purified. The J5dLPS/OMP vaccine induced high titers of serum IgG antibody to J5 LPS in all seven cows. Both IgG and to a lesser extent IgA anti-J5 LPS antibodies were generated in the colostrum. The J5dLPS/OMP vaccine was significantly more immunogenic in mice than was the J5 Bacterin. BC enriched in anti-J5 LPS antibody reduced circulating endotoxin levels in neutropenic rats, a model of "leaky gut". The J5dLPS/OMP vaccine elicits high titers of serum anti-endotoxin antibodies in cows that is passed to the colostrum. This BC enriched in anti-core LPS antibodies has the potential to reduce endotoxemia and ameliorate endotoxin-related systemic inflammation in patients with impaired gut barrier function. Since this vaccine is significantly more immunogenic than the J5 Bacterin vaccine, this J5dLPS/OMP vaccine might prove to be more useful for veterinary indications as well. Copyright © 2014 Elsevier Ltd. All rights reserved.
Palermo, D A; Evans, T M; Clark, V L
1987-01-01
A gonococcal gene bank maintained in Escherichia coli K-12 was screened by colony immunoblotting, and a transformant expressing a surface antigen reactive to anti-gonococcal outer membrane antiserum was isolated. The isolate carried a recombinant plasmid, pTME6, consisting of approximately 9 kilobases of Neisseria gonorrhoeae DNA inserted into the BamHI site of pBR322. Surface labeling of E. coli HB101(pTME6) confirmed that the antigen was expressed on the E. coli cell surface. The antigenic material was resistant to proteinase K digestion and sensitive to periodate oxidation, indicating that the material was carbohydrate. Purified lipopolysaccharide (LPS) from HB101(pTME6) produced a unique band on silver-stained polyacrylamide gels that contained immunoreactive material as seen on Western blots of LPS samples. Only two of three E. coli LPS mutant strains carrying pTME6 reacted with the antigonococcal antiserum, suggesting that a certain E. coli core structure is necessary for antigen expression. We conclude that pTME6 contains one or more gonococcal genes encoding an LPS core biosynthetic enzyme(s) which can modify E. coli core LPS to produce a gonococcuslike epitope(s). Images PMID:3117695
Nakagawa, Tetsuto; Shimada, Yoshimi; Pavlova, Nadejda V; Li, Su-Chen; Li, Yu-Teh
2015-01-01
We have previously reported that oyster hepatopancreas contained three unusual α-ketoside hydrolases: (i) a 3-deoxy-d-manno-oct-2-ulosonic acid α-ketoside hydrolase (α-Kdo-ase), (ii) a 3-deoxy-d-glycero-d-galacto-non-2-ulosonic acid α-ketoside hydrolase and (iii) a bifunctional ketoside hydrolase capable of cleaving both the α-ketosides of Kdn and Neu5Ac (Kdn-sialidase). After completing the purification of Kdn-sialidase, we proceeded to clone the gene encoding this enzyme. Unexpectedly, we found that instead of expressing Kdn-sialidase, our cloned gene expressed α-Kdo-ase activity. The full-length gene, consisting of 1176-bp (392 amino acids, Mr 44,604), expressed an active recombinant α-Kdo-ase (R-α-Kdo-ase) in yeast and CHO-S cells, but not in various Escherichia coli strains. The deduced amino acid sequence contains two Asp boxes (S277PDDGKTW and S328TDQGKTW) commonly found in sialidases, but is devoid of the signature FRIP-motif of sialidase. The R-α-Kdo-ase effectively hydrolyzed the Kdo in the core-oligosaccharide of the structurally defined lipopolysaccharide (LPS), Re-LPS (Kdo2-Lipid A) from Salmonella minnesota R595 and E. coli D31m4. However, Rd-LPS from S. minnesota R7 that contained an extra outer core phosphorylated heptose was only slowly hydrolyzed. The complex type LPS from Neisseria meningitides A1 and M992 that contained extra 5–6 sugar units at the outer core were refractory to R-α-Kdo-ase. This R-α-Kdo-ase should become useful for studying the structure and function of Kdo-containing glycans. PMID:26362869
Gregory, Stephen H.; Chen, Wilbur H.; Mott, Stephanie; Palardy, John E.; Parejo, Nicholas A.; Heninger, Sara; Anderson, Christine A.; Artenstein, Andrew W.; Opal, Steven M.; Cross, Alan S.
2010-01-01
Francisella tularensis is a category A select agent. J5dLPS/OMP is a novel vaccine construct consisting of detoxified, O-polysaccharide side chain-deficient, lipopolysaccharide non-covalently complexed with the outer membrane protein of N. meningitidis group B. Immunization elicits hightiter polyclonal antibodies specific for the highly-conserved epitopes expressed within the glycolipid core that constitutes gram-negative bacteria (e.g., F. tularensis). Mice immunized intranasally with J5dLPS/OMP exhibited protective immunity to intratracheal challenge with the live vaccine strain, as well as the highly-virulent SchuS4 strain, of F. tularensis. The efficacy of J5dLPS/OMP vaccine suggests its potential utility in immunizing the general population against several different gram-negative select agents concurrently. PMID:20170768
Arunmanee, Wanatchaporn; Pathania, Monisha; Solovyova, Alexandra S.; Le Brun, Anton P.; Ridley, Helen; Baslé, Arnaud; van den Berg, Bert; Lakey, Jeremy H.
2016-01-01
The outer membrane (OM) of gram-negative bacteria is an unusual asymmetric bilayer with an external monolayer of lipopolysaccharide (LPS) and an inner layer of phospholipids. The LPS layer is rigid and stabilized by divalent cation cross-links between phosphate groups on the core oligosaccharide regions. This means that the OM is robust and highly impermeable to toxins and antibiotics. During their biogenesis, OM proteins (OMPs), which function as transporters and receptors, must integrate into this ordered monolayer while preserving its impermeability. Here we reveal the specific interactions between the trimeric porins of Enterobacteriaceae and LPS. Isolated porins form complexes with variable numbers of LPS molecules, which are stabilized by calcium ions. In earlier studies, two high-affinity sites were predicted to contain groups of positively charged side chains. Mutation of these residues led to the loss of LPS binding and, in one site, also prevented trimerization of the porin, explaining the previously observed effect of LPS mutants on porin folding. The high-resolution X-ray crystal structure of a trimeric porin–LPS complex not only helps to explain the mutagenesis results but also reveals more complex, subtle porin–LPS interactions and a bridging calcium ion. PMID:27493217
Resurrecting Inactive Antimicrobial Peptides from the Lipopolysaccharide Trap
Mohanram, Harini
2014-01-01
Host defense antimicrobial peptides (AMPs) are a promising source of antibiotics for the treatment of multiple-drug-resistant pathogens. Lipopolysaccharide (LPS), the major component of the outer leaflet of the outer membrane of Gram-negative bacteria, functions as a permeability barrier against a variety of molecules, including AMPs. Further, LPS or endotoxin is the causative agent of sepsis killing 100,000 people per year in the United States alone. LPS can restrict the activity of AMPs inducing aggregations at the outer membrane, as observed for frog AMPs, temporins, and also in model AMPs. Aggregated AMPs, “trapped” by the outer membrane, are unable to traverse the cell wall, causing their inactivation. In this work, we show that these inactive AMPs can overcome LPS-induced aggregations while conjugated with a short LPS binding β-boomerang peptide motif and become highly bactericidal. The generated hybrid peptides exhibit activity against Gram-negative and Gram-positive bacteria in high-salt conditions and detoxify endotoxin. Structural and biophysical studies establish the mechanism of action of these peptides in LPS outer membrane. Most importantly, this study provides a new concept for the development of a potent broad-spectrum antibiotic with efficient outer membrane disruption as the mode of action. PMID:24419338
Izquierdo, Luis; Coderch, Núria; Piqué, Nuria; Bedini, Emiliano; Michela Corsaro, Maria; Merino, Susana; Fresno, Sandra; Tomás, Juan M.; Regué, Miguel
2003-01-01
To determine the function of the wabG gene in the biosynthesis of the core lipopolysaccharide (LPS) of Klebsiella pneumoniae, we constructed wabG nonpolar mutants. Data obtained from the comparative chemical and structural analysis of LPS samples obtained from the wild type, the mutant strain, and the complemented mutant demonstrated that the wabG gene is involved in attachment to α-l-glycero-d-manno-heptopyranose II (l,d-HeppII) at the O-3 position of an α-d-galactopyranosyluronic acid (α-d-GalAp) residue. K. pneumoniae nonpolar wabG mutants were devoid of the cell-attached capsular polysaccharide but were still able to produce capsular polysaccharide. Similar results were obtained with K. pneumoniae nonpolar waaC and waaF mutants, which produce shorter LPS core molecules than do wabG mutants. Other outer core K. pneumoniae nonpolar mutants in the waa gene cluster were encapsulated. K. pneumoniae waaC, waaF, and wabG mutants were avirulent when tested in different animal models. Furthermore, these mutants were more sensitive to some hydrophobic compounds than the wild-type strains. All these characteristics were rescued by reintroduction of the waaC, waaF, and wabG genes from K. pneumoniae. PMID:14645282
Filippov, Andrey A; Sergueev, Kirill V; He, Yunxiu; Huang, Xiao-Zhe; Gnade, Bryan T; Mueller, Allen J; Fernandez-Prada, Carmen M; Nikolich, Mikeljon P
2011-01-01
Bacteriophages specific for Yersinia pestis are routinely used for plague diagnostics and could be an alternative to antibiotics in case of drug-resistant plague. A major concern of bacteriophage therapy is the emergence of phage-resistant mutants. The use of phage cocktails can overcome this problem but only if the phages exploit different receptors. Some phage-resistant mutants lose virulence and therefore should not complicate bacteriophage therapy. The purpose of this work was to identify Y. pestis phage receptors using site-directed mutagenesis and trans-complementation and to determine potential attenuation of phage-resistant mutants for mice. Six receptors for eight phages were found in different parts of the lipopolysaccharide (LPS) inner and outer core. The receptor for R phage was localized beyond the LPS core. Most spontaneous and defined phage-resistant mutants of Y. pestis were attenuated, showing increase in LD₅₀ and time to death. The loss of different LPS core biosynthesis enzymes resulted in the reduction of Y. pestis virulence and there was a correlation between the degree of core truncation and the impact on virulence. The yrbH and waaA mutants completely lost their virulence. We identified Y. pestis receptors for eight bacteriophages. Nine phages together use at least seven different Y. pestis receptors that makes some of them promising for formulation of plague therapeutic cocktails. Most phage-resistant Y. pestis mutants become attenuated and thus should not pose a serious problem for bacteriophage therapy of plague. LPS is a critical virulence factor of Y. pestis.
Filippov, Andrey A.; Sergueev, Kirill V.; He, Yunxiu; Huang, Xiao-Zhe; Gnade, Bryan T.; Mueller, Allen J.; Fernandez-Prada, Carmen M.; Nikolich, Mikeljon P.
2011-01-01
Background Bacteriophages specific for Yersinia pestis are routinely used for plague diagnostics and could be an alternative to antibiotics in case of drug-resistant plague. A major concern of bacteriophage therapy is the emergence of phage-resistant mutants. The use of phage cocktails can overcome this problem but only if the phages exploit different receptors. Some phage-resistant mutants lose virulence and therefore should not complicate bacteriophage therapy. Methodology/Principal Findings The purpose of this work was to identify Y. pestis phage receptors using site-directed mutagenesis and trans-complementation and to determine potential attenuation of phage-resistant mutants for mice. Six receptors for eight phages were found in different parts of the lipopolysaccharide (LPS) inner and outer core. The receptor for R phage was localized beyond the LPS core. Most spontaneous and defined phage-resistant mutants of Y. pestis were attenuated, showing increase in LD50 and time to death. The loss of different LPS core biosynthesis enzymes resulted in the reduction of Y. pestis virulence and there was a correlation between the degree of core truncation and the impact on virulence. The yrbH and waaA mutants completely lost their virulence. Conclusions/Significance We identified Y. pestis receptors for eight bacteriophages. Nine phages together use at least seven different Y. pestis receptors that makes some of them promising for formulation of plague therapeutic cocktails. Most phage-resistant Y. pestis mutants become attenuated and thus should not pose a serious problem for bacteriophage therapy of plague. LPS is a critical virulence factor of Y. pestis. PMID:21980477
Benforte, Florencia C; Colonnella, Maria A; Ricardi, Martiniano M; Solar Venero, Esmeralda C; Lizarraga, Leonardo; López, Nancy I; Tribelli, Paula M
2018-01-01
Psychrotroph microorganisms have developed cellular mechanisms to cope with cold stress. Cell envelopes are key components for bacterial survival. Outer membrane is a constituent of Gram negative bacterial envelopes, consisting of several components, such as lipopolysaccharides (LPS). In this work we investigated the relevance of envelope characteristics for cold adaptation in the Antarctic bacterium Pseudomonas extremaustralis by analyzing a mini Tn5 wapH mutant strain, encoding a core LPS glycosyltransferase. Our results showed that wapH strain is impaired to grow under low temperature but not for cold survival. The mutation in wapH, provoked a strong aggregative phenotype and modifications of envelope nanomechanical properties such as lower flexibility and higher turgor pressure, cell permeability and surface area to volume ratio (S/V). Changes in these characteristics were also observed in the wild type strain grown at different temperatures, showing higher cell flexibility but lower turgor pressure under cold conditions. Cold shock experiments indicated that an acclimation period in the wild type is necessary for cell flexibility and S/V ratio adjustments. Alteration in cell-cell interaction capabilities was observed in wapH strain. Mixed cells of wild type and wapH strains, as well as those of the wild type strain grown at different temperatures, showed a mosaic pattern of aggregation. These results indicate that wapH mutation provoked marked envelope alterations showing that LPS core conservation appears as a novel essential feature for active growth under cold conditions.
Proteins required for lipopolysaccharide assembly in Escherichia coli form a transenvelope complex.
Chng, Shu-Sin; Gronenberg, Luisa S; Kahne, Daniel
2010-06-08
The viability of Gram-negative organisms is dependent on the proper placement of lipopolysaccharide (LPS) in the outer leaflet of its outer membrane. LPS is synthesized inside the cell and transported to the surface by seven essential lipopolysaccharide transport (Lpt) proteins. How these proteins cooperate to transport LPS is unknown. We show that these Lpt proteins can be found in a membrane fraction that contains inner and outer membranes and that they copurify. This constitutes the first evidence that the Lpt proteins form a transenvelope complex. We suggest that this protein bridge provides a route for LPS transport across the cell envelope.
Proteins required for lipopolysaccharide assembly in Escherichia coli form a trans-envelope complex†
Chng, Shu-Sin; Gronenberg, Luisa S.; Kahne, Daniel
2010-01-01
The viability of Gram-negative organisms is dependent on the proper placement of lipopolysaccharide (LPS) in the outer leaflet of its outer membrane. LPS is synthesized inside the cell and transported to the surface by seven essential Lpt proteins. How these proteins cooperate to transport LPS is unknown. We show that these Lpt proteins can be found in a membrane fraction that contains inner and outer membranes, and that they co-purify. This constitutes the first evidence that the Lpt proteins form a trans-envelope complex. We suggest that this protein bridge provides a route for LPS transport across the cell envelope. PMID:20446753
Agrawal, Anurag; Weisshaar, James C
2018-04-22
The outermost layer of Gram negative bacteria is composed of a lipopolysaccharide (LPS) network that forms a dense protective hydrophilic barrier against entry of hydrophobic drugs. At low μM concentrations, a large family of cationic polypeptides known as antimicrobial peptides (AMPs) are able to penetrate the LPS layer and permeabilize the outer membrane (OM) and the cytoplasmic membrane (CM), causing cell death. Cecropin A is a well-studied cationic AMP from moth. Here a battery of time-resolved, single-cell microscopy experiments explores how deletion of sugar layers and/or phosphoryl negative charges from the core oligosaccharide layer (core OS) of K12 E. coli alters the timing of OM and CM permeabilization induced by Cecropin A. Deletion of sugar layers, or phosphoryl charges, or both from the core OS shortens the time to the onset of OM permeabilization to periplasmic GFP and also the lag time between OM permeabilization and CM permeabilization. Meanwhile, the 12-h minimum inhibitory concentration (MIC) changes only twofold with core OS alterations. The results suggest a two-step model in which the core oligosaccharide layers act as a kinetic barrier to penetration of Cecropin A to the lipid A outer leaflet of the OM. Once a threshold concentration has built up at the lipid A leaflet, nucleation occurs and the OM is locally permeabilized to GFP and, by inference, to Cecropin A. Whenever Cecropin A permeabilizes the OM, CM permeabilization always follows, and cell growth subsequently halts and never recovers on the 45 min observation timescale. Copyright © 2018 Elsevier B.V. All rights reserved.
Genetic and Functional Diversity of Pseudomonas aeruginosa Lipopolysaccharide
Lam, Joseph S.; Taylor, Véronique L.; Islam, Salim T.; Hao, Youai; Kocíncová, Dana
2011-01-01
Lipopolysccharide (LPS) is an integral component of the Pseudomonas aeruginosa cell envelope, occupying the outer leaflet of the outer membrane in this Gram-negative opportunistic pathogen. It is important for bacterium–host interactions and has been shown to be a major virulence factor for this organism. Structurally, P. aeruginosa LPS is composed of three domains, namely, lipid A, core oligosaccharide, and the distal O antigen (O-Ag). Most P. aeruginosa strains produce two distinct forms of O-Ag, one a homopolymer of D-rhamnose that is a common polysaccharide antigen (CPA, formerly termed A band), and the other a heteropolymer of three to five distinct (and often unique dideoxy) sugars in its repeat units, known as O-specific antigen (OSA, formerly termed B band). Compositional differences in the O units among the OSA from different strains form the basis of the International Antigenic Typing Scheme for classification via serotyping of different strains of P. aeruginosa. The focus of this review is to provide state-of-the-art knowledge on the genetic and resultant functional diversity of LPS produced by P. aeruginosa. The underlying factors contributing to this diversity will be thoroughly discussed and presented in the context of its contributions to host–pathogen interactions and the control/prevention of infection. PMID:21687428
Designed β-Boomerang Antiendotoxic and Antimicrobial Peptides
Bhunia, Anirban; Mohanram, Harini; Domadia, Prerna N.; Torres, Jaume; Bhattacharjya, Surajit
2009-01-01
Lipopolysaccharide (LPS), an integral part of the outer membrane of Gram-negative bacteria, is involved in a variety of biological processes including inflammation, septic shock, and resistance to host-defense molecules. LPS also provides an environment for folding of outer membrane proteins. In this work, we describe the structure-activity correlation of a series of 12-residue peptides in LPS. NMR structures of the peptides derived in complex with LPS reveal boomerang-like β-strand conformations that are stabilized by intimate packing between the two aromatic residues located at the 4 and 9 positions. This structural feature renders these peptides with a high ability to neutralize endotoxicity, >80% at 10 nm concentration, of LPS. Replacements of these aromatic residues either with Ala or with Leu destabilizes the boomerang structure with the concomitant loss of antiendotoxic and antimicrobial activities. Furthermore, the aromatic packing stabilizing the β-boomerang structure in LPS is found to be maintained even in a truncated octapeptide, defining a structured LPS binding motif. The mode of action of the active designed peptides correlates well with their ability to perturb LPS micelle structures. Fourier transform infrared spectroscopy studies of the peptides delineate β-type conformations and immobilization of phosphate head groups of LPS. Trp fluorescence studies demonstrated selective interactions with LPS and the depth of insertion into the LPS bilayer. Our results demonstrate the requirement of LPS-specific structures of peptides for endotoxin neutralizations. In addition, we propose that structures of these peptides may be employed to design proteins for the outer membrane. PMID:19520860
Bhunia, Anirban; Mohanram, Harini; Domadia, Prerna N; Torres, Jaume; Bhattacharjya, Surajit
2009-08-14
Lipopolysaccharide (LPS), an integral part of the outer membrane of Gram-negative bacteria, is involved in a variety of biological processes including inflammation, septic shock, and resistance to host-defense molecules. LPS also provides an environment for folding of outer membrane proteins. In this work, we describe the structure-activity correlation of a series of 12-residue peptides in LPS. NMR structures of the peptides derived in complex with LPS reveal boomerang-like beta-strand conformations that are stabilized by intimate packing between the two aromatic residues located at the 4 and 9 positions. This structural feature renders these peptides with a high ability to neutralize endotoxicity, >80% at 10 nM concentration, of LPS. Replacements of these aromatic residues either with Ala or with Leu destabilizes the boomerang structure with the concomitant loss of antiendotoxic and antimicrobial activities. Furthermore, the aromatic packing stabilizing the beta-boomerang structure in LPS is found to be maintained even in a truncated octapeptide, defining a structured LPS binding motif. The mode of action of the active designed peptides correlates well with their ability to perturb LPS micelle structures. Fourier transform infrared spectroscopy studies of the peptides delineate beta-type conformations and immobilization of phosphate head groups of LPS. Trp fluorescence studies demonstrated selective interactions with LPS and the depth of insertion into the LPS bilayer. Our results demonstrate the requirement of LPS-specific structures of peptides for endotoxin neutralizations. In addition, we propose that structures of these peptides may be employed to design proteins for the outer membrane.
Dong, Haohao; Tang, Xiaodi; Zhang, Zhengyu; Dong, Changjiang
2017-11-01
Lipopolysaccharide (LPS) is an important component of the outer membrane (OM) of Gram-negative bacteria, playing essential roles in protecting bacteria from harsh environments, in drug resistance and in pathogenesis. LPS is synthesized in the cytoplasm and translocated to the periplasmic side of the inner membrane (IM), where it matures. Seven lipopolysaccharide transport proteins, LptA-G, form a trans‑envelope complex that is responsible for LPS extraction from the IM and transporting it across the periplasm to the OM. The LptD/E of the complex transports LPS across the OM and inserts it into the outer leaflet of the OM. In this review we focus upon structural and mechanistic studies of LPS transport proteins, with a particular focus upon the LPS ABC transporter LptB 2 FG. This ATP binding cassette transporter complex consists of twelve transmembrane segments and has a unique mechanism whereby it extracts LPS from the periplasmic face of the IM through a pair of lateral gates and then powers trans‑periplasmic transport to the OM through a slide formed by either of the periplasmic domains of LptF or LptG, LptC, LptA and the N-terminal domain of LptD. The structural and functional studies of the seven lipopolysaccharide transport proteins provide a platform to explore the unusual mechanisms of LPS extraction, transport and insertion from the inner membrane to the outer membrane. This article is part of a Special Issue entitled: Bacterial Lipids edited by Russell E. Bishop. Copyright © 2017 Elsevier B.V. All rights reserved.
Manterola, Lorea; Moriyón, Ignacio; Moreno, Edgardo; Sola-Landa, Alberto; Weiss, David S.; Koch, Michel H. J.; Howe, Jörg; Brandenburg, Klaus; López-Goñi, Ignacio
2005-01-01
The two-component BvrS/BvrR system is essential for Brucella abortus virulence. It was shown previously that its dysfunction abrogates expression of some major outer membrane proteins and increases bactericidal peptide sensitivity. Here, we report that BvrS/BvrR mutants have increased surface hydrophobicity and susceptibility to killing by nonimmune serum. The bvrS and bvrR mutant lipopolysaccharides (LPSs) bound more polymyxin B, chimeras constructed with bvrS mutant cells and parental LPS showed augmented polymyxin B resistance, and, conversely, parental cells and bvrS mutant LPS chimeras were more sensitive and displayed polymyxin B-characteristic outer membrane lesions, implicating LPS as being responsible for the phenotype of the BvrS/BvrR mutants. No qualitative or quantitative changes were detected in other envelope and outer membrane components examined: periplasmic β(1-2) glucans, native hapten polysaccharide, and phospholipids. The LPS of the mutants was similar to parental LPS in O-polysaccharide polymerization and fine structure but showed both increased underacylated lipid A species and higher acyl-chain fluidity that correlated with polymyxin B binding. These lipid A changes did not alter LPS cytokine induction, showing that in contrast to other gram-negative pathogens, recognition by innate immune receptors is not decreased by these changes in LPS structure. Transcription of Brucella genes required for incorporating long acyl chains into lipid A (acpXL and lpxXL) or implicated in lipid A acylation control (bacA) was not affected. We propose that in Brucella the outer membrane homeostasis depends on the functioning of BvrS/BvrR. Accordingly, disruption of BvrS/BvrR damages the outer membrane, thus contributing to the severe attenuation manifested by bvrS and bvrR mutants. PMID:16077108
Detoxifying Escherichia coli for endotoxin-free production of recombinant proteins.
Mamat, Uwe; Wilke, Kathleen; Bramhill, David; Schromm, Andra Beate; Lindner, Buko; Kohl, Thomas Andreas; Corchero, José Luis; Villaverde, Antonio; Schaffer, Lana; Head, Steven Robert; Souvignier, Chad; Meredith, Timothy Charles; Woodard, Ronald Wesley
2015-04-16
Lipopolysaccharide (LPS), also referred to as endotoxin, is the major constituent of the outer leaflet of the outer membrane of virtually all Gram-negative bacteria. The lipid A moiety, which anchors the LPS molecule to the outer membrane, acts as a potent agonist for Toll-like receptor 4/myeloid differentiation factor 2-mediated pro-inflammatory activity in mammals and, thus, represents the endotoxic principle of LPS. Recombinant proteins, commonly manufactured in Escherichia coli, are generally contaminated with endotoxin. Removal of bacterial endotoxin from recombinant therapeutic proteins is a challenging and expensive process that has been necessary to ensure the safety of the final product. As an alternative strategy for common endotoxin removal methods, we have developed a series of E. coli strains that are able to grow and express recombinant proteins with the endotoxin precursor lipid IVA as the only LPS-related molecule in their outer membranes. Lipid IVA does not trigger an endotoxic response in humans typical of bacterial LPS chemotypes. Hence the engineered cells themselves, and the purified proteins expressed within these cells display extremely low endotoxin levels. This paper describes the preparation and characterization of endotoxin-free E. coli strains, and demonstrates the direct production of recombinant proteins with negligible endotoxin contamination.
Sautrey, Guillaume; Zimmermann, Louis; Deleu, Magali; Delbar, Alicia; Souza Machado, Luiza; Jeannot, Katy; Van Bambeke, Françoise; Buyck, Julien M.; Decout, Jean-Luc
2014-01-01
The development of novel antimicrobial agents is urgently required to curb the widespread emergence of multidrug-resistant bacteria like colistin-resistant Pseudomonas aeruginosa. We previously synthesized a series of amphiphilic neamine derivatives active against bacterial membranes, among which 3′,6-di-O-[(2″-naphthyl)propyl]neamine (3′,6-di2NP), 3′,6-di-O-[(2″-naphthyl)butyl]neamine (3′,6-di2NB), and 3′,6-di-O-nonylneamine (3′,6-diNn) showed high levels of activity and low levels of cytotoxicity (L. Zimmermann et al., J. Med. Chem. 56:7691–7705, 2013). We have now further characterized the activity of these derivatives against colistin-resistant P. aeruginosa and studied their mode of action; specifically, we characterized their ability to interact with lipopolysaccharide (LPS) and to alter the bacterial outer membrane (OM). The three amphiphilic neamine derivatives were active against clinical colistin-resistant strains (MICs, about 2 to 8 μg/ml), The most active one (3′,6-diNn) was bactericidal at its MIC and inhibited biofilm formation at 2-fold its MIC. They cooperatively bound to LPSs, increasing the outer membrane permeability. Grafting long and linear alkyl chains (nonyl) optimized binding to LPS and outer membrane permeabilization. The effects of amphiphilic neamine derivatives on LPS micelles suggest changes in the cross-bridging of lipopolysaccharides and disordering in the hydrophobic core of the micelles. The molecular shape of the 3′,6-dialkyl neamine derivatives induced by the nature of the grafted hydrophobic moieties (naphthylalkyl instead of alkyl) and the flexibility of the hydrophobic moiety are critical for their fluidifying effect and their ability to displace cations bridging LPS. Results from this work could be exploited for the development of new amphiphilic neamine derivatives active against colistin-resistant P. aeruginosa. PMID:24867965
Freinkman, Elizaveta; Chng, Shu-Sin; Kahne, Daniel
2011-02-08
The cell surfaces of Gram-negative bacteria are composed of lipopolysaccharide (LPS). This glycolipid is found exclusively in the outer leaflet of the asymmetric outer membrane (OM), where it forms a barrier to the entry of toxic hydrophobic molecules into the cell. LPS typically contains six fatty acyl chains and up to several hundred sugar residues. It is biosynthesized in the cytosol and must then be transported across two membranes and an aqueous intermembrane space to the cell surface. These processes are required for the viability of most Gram-negative organisms. The integral membrane β-barrel LptD and the lipoprotein LptE form an essential complex in the OM, which is necessary for LPS assembly. It is not known how this complex translocates large, amphipathic LPS molecules across the OM to the outer leaflet. Here, we show that LptE resides within the LptD β-barrel both in vitro and in vivo. LptD/E associate via an extensive interface; in one specific interaction, LptE contacts a predicted extracellular loop of LptD through the lumen of the β-barrel. Disrupting this interaction site compromises the biogenesis of LptD. This unprecedented two-protein plug-and-barrel architecture suggests how LptD/E can insert LPS from the periplasm directly into the outer leaflet of the OM to establish the asymmetry of the bilayer.
Ruiz, Natividad; Gronenberg, Luisa S.; Kahne, Daniel; Silhavy, Thomas J.
2008-01-01
The outer membrane (OM) of most Gram-negative bacteria contains lipopolysaccharide (LPS) in the outer leaflet. LPS, or endotoxin, is a molecule of important biological activities. In the host, LPS elicits a potent immune response, while in the bacterium, it plays a crucial role by establishing a barrier to limit entry of hydrophobic molecules. Before LPS is assembled at the OM, it must be synthesized at the inner membrane (IM) and transported across the aqueous periplasmic compartment. Much is known about the biosynthesis of LPS but, until recently, little was known about its transport and assembly. We applied a reductionist bioinformatic approach that takes advantage of the small size of the proteome of the Gram-negative endosymbiont Blochmannia floridanus to search for novel factors involved in OM biogenesis. This led to the discovery of two essential Escherichia coli IM proteins of unknown function, YjgP and YjgQ, which are required for the transport of LPS to the cell surface. We propose that these two proteins, which we have renamed LptF and LptG, respectively, are the missing transmembrane components of the ABC transporter that, together with LptB, functions to extract LPS from the IM en route to the OM. PMID:18375759
Ruiz, Natividad; Gronenberg, Luisa S; Kahne, Daniel; Silhavy, Thomas J
2008-04-08
The outer membrane (OM) of most Gram-negative bacteria contains lipopolysaccharide (LPS) in the outer leaflet. LPS, or endotoxin, is a molecule of important biological activities. In the host, LPS elicits a potent immune response, while in the bacterium, it plays a crucial role by establishing a barrier to limit entry of hydrophobic molecules. Before LPS is assembled at the OM, it must be synthesized at the inner membrane (IM) and transported across the aqueous periplasmic compartment. Much is known about the biosynthesis of LPS but, until recently, little was known about its transport and assembly. We applied a reductionist bioinformatic approach that takes advantage of the small size of the proteome of the Gram-negative endosymbiont Blochmannia floridanus to search for novel factors involved in OM biogenesis. This led to the discovery of two essential Escherichia coli IM proteins of unknown function, YjgP and YjgQ, which are required for the transport of LPS to the cell surface. We propose that these two proteins, which we have renamed LptF and LptG, respectively, are the missing transmembrane components of the ABC transporter that, together with LptB, functions to extract LPS from the IM en route to the OM.
High rates of recombination in otitis media isolates of non-typeable Haemophilus influenzae✩
Cody, Alison J.; Field, Dawn; Feil, Edward J.; Stringer, Suzanna; Deadman, Mary E.; Tsolaki, Anthony G.; Gratz, Brett; Bouchet, Valérie; Goldstein, Richard; Hood, Derek W.; Moxon, E. Richard
2008-01-01
Non-typeable (NT) or capsule-deficient, Haemophilus influenzae (Hi) is a common commensal of the upper respiratory tract of humans and can be pathogenic resulting in diseases such as otitis media, sinusitis and pneumonia. The lipopolysaccharide (LPS) of NTHi is a major virulence factor that displays substantial intra-strain and inter-strain variation of its oligosaccharide structures. To investigate the genetic basis of LPS variation we sequenced internal regions of each of seven genes required for the biosynthesis of either the inner or the outer core oligosaccharide structures. These sequences were obtained from 25 representative NTHi isolates from episodes of otitis media. We found abundant evidence of recombination among LPS genes of NTHi, a finding in marked contrast to previous analyses of biosynthetic genes for capsular polysaccharide, a well-documented virulence factor of Hi. We found mosaic sequences, linkage equilibrium between loci and a lack of congruence between gene trees. These high rates were not confined to LPS genes since evidence for similar amounts of recombination was also found in eight housekeeping genes in a subset of the same 25 isolates. These findings provide a population based foundation for a better understanding of the role of NTHi LPS as a virulence factor and its potential as a candidate vaccine. PMID:12797973
Lins, Roberto D; Vorpagel, Erich R; Guglielmi, Matteo; Straatsma, T P
2008-01-01
Heavy metal environmental contaminants cannot be destroyed but require containment, preferably in concentrated form, in a solid or immobile form for recycling or final disposal. Microorganisms are able to take up and deposit high levels of contaminant metals, including radioactive metals such as uranium and plutonium, into their cell wall. Consequently, these microbial systems are of great interest as the basis for potential environmental bioremediation technologies. The outer membranes of Gram-negative microbes are highly nonsymmetric and exhibit a significant electrostatic potential gradient across the membrane. This gradient has a significant effect on the uptake and transport of charged and dipolar compounds. However, the effectiveness of microbial systems for environmental remediation will depend strongly on specific properties that determine the uptake of targeted contaminants by a particular cell wall. To aid in the design of microbial remediation technologies, knowledge of the factors that determine the affinity of a particular bacterial outer membrane for the most common ionic species found in contaminated soils and groundwater is of great importance. Using our previously developed model for the lipopolysaccharide (LPS) membrane of Pseudomonas aeruginosa, this work presents the potentials of mean force as the estimate of the free energy profile for uptake of sodium, calcium, chloride, uranyl ions, and a water molecule by the bacterial LPS membrane. A compatible classical parameter set for uranyl has been developed and validated. Results show that the uptake of uranyl is energetically a favorable process relative to the other ions studied. At neutral pH, this nuclide is shown to be retained on the surface of the LPS membrane through chelation with the carboxyl and hydroxyl groups located in the outer core.
Visualization and analysis of lipopolysaccharide distribution in binary phospholipid bilayers
DOE Office of Scientific and Technical Information (OSTI.GOV)
Henning, Maria Florencia; Sanchez, Susana; Bakas, Laura, E-mail: lbakas@biol.unlp.edu.ar
2009-05-22
Lipopolysaccharide (LPS) is an endotoxin released from the outer membrane of Gram-negative bacteria during infections. It have been reported that LPS may play a role in the outer membrane of bacteria similar to that of cholesterol in eukaryotic plasma membranes. In this article we compare the effect of introducing LPS or cholesterol in liposomes made of dipalmitoylphosphatidylcholine/dioleoylphosphatidylcholine on the solubilization process by Triton X-100. The results show that liposomes containing LPS or cholesterol are more resistant to solubilization by Triton X-100 than the binary phospholipid mixtures at 4 {sup o}C. The LPS distribution was analyzed on GUVs of DPPC:DOPC usingmore » FITC-LPS. Solid and liquid-crystalline domains were visualized labeling the GUVs with LAURDAN and GP images were acquired using a two-photon microscope. The images show a selective distribution of LPS in gel domains. Our results support the hypothesis that LPS could aggregate and concentrate selectively in biological membranes providing a mechanism to bring together several components of the LPS-sensing machinery.« less
Dysregulated humoral immunity to nontyphoidal Salmonella in HIV-infected African adults
MacLennan, Calman A.; Gilchrist, James J.; Gordon, Melita A.; Cunningham, Adam F.; Cobbold, Mark; Goodall, Margaret; Kingsley, Robert A.; van Oosterhout, Joep J. G.; Msefula, Chisomo L.; Mandala, Wilson L.; Leyton, Denisse L.; Marshall, Jennifer L.; Gondwe, Esther N.; Bobat, Saeeda; López-Macías, Constantino; Doffinger, Rainer; Henderson, Ian R.; Zijlstra, Eduard E.; Dougan, Gordon; Drayson, Mark T.; MacLennan, Ian C. M.; Molyneux, Malcolm E.
2013-01-01
Nontyphoidal Salmonellae are a major cause of life-threatening bacteremia among HIV-infected individuals. Although cell-mediated immunity controls intracellular infection, antibody protects against Salmonella bacteremia. We report that high titer antibodies specific for Salmonella lipopolysaccharide (LPS) associate with absent Salmonella-killing in HIV-infected African adults. Killing was restored by genetically shortening LPS from target Salmonella, or removing LPS-specific antibodies from serum. Complement-mediated killing of Salmonella by healthy serum is shown to be induced specifically by antibodies against outer membrane proteins. This killing is lost when excess antibody against Salmonella LPS is added. Thus our study indicates impaired immunity against nontyphoidal Salmonella bacteremia in HIV infection results from excess inhibitory antibodies against Salmonella LPS, whilst serum killing of Salmonella is induced by antibodies against outer membrane proteins. PMID:20413503
Reinhardt, Anika; Yang, You; Claus, Heike; Pereira, Claney L; Cox, Andrew D; Vogel, Ulrich; Anish, Chakkumkal; Seeberger, Peter H
2015-01-22
Neisseria meningitidis is a leading cause of bacterial meningitis worldwide. We studied the potential of synthetic lipopolysaccharide (LPS) inner core structures as broadly protective antigens against N. meningitidis. Based on the specific reactivity of human serum antibodies to synthetic LPS cores, we selected a highly conserved LPS core tetrasaccharide as a promising antigen. This LPS inner core tetrasaccharide induced a robust IgG response in mice when formulated as an immunogenic glycoconjugate. Binding of raised mouse serum to a broad collection of N. meningitidis strains demonstrated the accessibility of the LPS core on viable bacteria. The distal trisaccharide was identified as the crucial epitope, whereas the proximal Kdo moiety was immunodominant and induced mainly nonprotective antibodies that are responsible for lack of functional protection in polyclonal serum. Our results identified key antigenic determinants of LPS core glycan and, hence, may aid the design of a broadly protective immunization against N. meningitidis. Copyright © 2015 Elsevier Ltd. All rights reserved.
The Antibiotic Novobiocin Binds and Activates the ATPase That Powers Lipopolysaccharide Transport.
May, Janine M; Owens, Tristan W; Mandler, Michael D; Simpson, Brent W; Lazarus, Michael B; Sherman, David J; Davis, Rebecca M; Okuda, Suguru; Massefski, Walter; Ruiz, Natividad; Kahne, Daniel
2017-12-06
Novobiocin is an orally active antibiotic that inhibits DNA gyrase by binding the ATP-binding site in the ATPase subunit. Although effective against Gram-positive pathogens, novobiocin has limited activity against Gram-negative organisms due to the presence of the lipopolysaccharide-containing outer membrane, which acts as a permeability barrier. Using a novobiocin-sensitive Escherichia coli strain with a leaky outer membrane, we identified a mutant with increased resistance to novobiocin. Unexpectedly, the mutation that increases novobiocin resistance was not found to alter gyrase, but the ATPase that powers lipopolysaccharide (LPS) transport. Co-crystal structures, biochemical, and genetic evidence show novobiocin directly binds this ATPase. Novobiocin does not bind the ATP binding site but rather the interface between the ATPase subunits and the transmembrane subunits of the LPS transporter. This interaction increases the activity of the LPS transporter, which in turn alters the permeability of the outer membrane. We propose that novobiocin will be a useful tool for understanding how ATP hydrolysis is coupled to LPS transport.
Clifford, Jennifer C; Rapicavoli, Jeannette N; Roper, M Caroline
2013-06-01
Xylella fastidiosa is a gram-negative, xylem-limited bacterium that causes a lethal disease of grapevine called Pierce's disease. Lipopolysaccharide (LPS) composes approximately 75% of the outer membrane of gram-negative bacteria and, because it is largely displayed on the cell surface, it mediates interactions between the bacterial cell and its surrounding environment. LPS is composed of a conserved lipid A-core oligosaccharide component and a variable O-antigen portion. By targeting a key O-antigen biosynthetic gene, we demonstrate the contribution of the rhamnose-rich O-antigen to surface attachment, cell-cell aggregation, and biofilm maturation: critical steps for successful infection of the host xylem tissue. Moreover, we have demonstrated that a fully formed O-antigen moiety is an important virulence factor for Pierce's disease development in grape and that depletion of the O-antigen compromises its ability to colonize the host. It has long been speculated that cell-surface polysaccharides play a role in X. fastidiosa virulence and this study confirms that LPS is a major virulence factor for this important agricultural pathogen.
Lipopolysaccharide induces amyloid formation of antimicrobial peptide HAL-2.
Wang, Jiarong; Li, Yan; Wang, Xiaoming; Chen, Wei; Sun, Hongbin; Wang, Junfeng
2014-11-01
Lipopolysaccharide (LPS), the important component of the outer membrane of Gram-negative bacteria, contributes to the integrity of the outer membrane and protects the cell against bactericidal agents, including antimicrobial peptides. However, the mechanisms of interaction between antimicrobial peptides and LPS are not clearly understood. Halictines-2 (HAL-2), one of the novel antimicrobial peptides, was isolated from the venom of the eusocial bee Halictus sexcinctus. HAL-2 has exhibited potent antimicrobial activity against Gram-positive and Gram-negative bacteria and even against cancer cells. Here, we studied the interactions between HAL-2 and LPS to elucidate the antibacterial mechanism of HAL-2 in vitro. Our results show that HAL-2 adopts a significant degree of β-strand structure in the presence of LPS. LPS is capable of inducing HAL-2 amyloid formation, which may play a vital role in its antimicrobial activity. Copyright © 2014 Elsevier B.V. All rights reserved.
Oh, Yoo Jin; Plochberger, Birgit; Rechberger, Markus; Hinterdorfer, Peter
2017-06-01
Lipopolysaccharide (LPS) on gram-negative bacterial outer membranes is the first target for antimicrobial agents, due to their spatial proximity to outer environments of microorganisms. To develop antibacterial compounds with high specificity for LPS binding, the understanding of the molecular nature and their mode of recognition is of key importance. In this study, atomic force microscopy (AFM) and single molecular force spectroscopy were used to characterize the effects of antibiotic polymyxin B (PMB) to the bacterial membrane at the nanoscale. Isolated LPS layer and the intact bacterial membrane were examined with respect to morphological changes at different concentrations of PMB. Our results revealed that 3 hours of 10 μg/mL of PMB exposure caused the highest roughness changes on intact bacterial surfaces, arising from the direct binding of PMB to LPS on the bacterial membrane. Single molecular force spectroscopy was used to probe specific interaction forces between the isolated LPS layer and PMB coupled to the AFM tip. A short range interaction regime mediated by electrostatic forces was visible. Unbinding forces between isolated LPS and PMB were about 30 pN at a retraction velocity of 500 nm/s. We further investigated the effects of the polycationic peptide PMB on bacterial outer membranes and monitored its influences on the deterioration of the bacterial membrane structure. Polymyxin B binding led to rougher appearances and wrinkles on the outer membranes surface, which may finally lead to lethal membrane damage of bacteria. Our studies indicate the potential of AFM for applications in pathogen recognition and nano-resolution approaches in microbiology. Copyright © 2017 John Wiley & Sons, Ltd.
Ivanov, Ivan E; Kintz, Erica N; Porter, Laura A; Goldberg, Joanna B; Burnham, Nancy A; Camesano, Terri A
2011-03-01
Lipopolysaccharides (LPS) are an important class of macromolecules that are components of the outer membrane of Gram-negative bacteria such as Pseudomonas aeruginosa. P. aeruginosa contains two different sugar chains, the homopolymer common antigen (A band) and the heteropolymer O antigen (B band), which impart serospecificity. The characteristics of LPS are generally assessed after isolation rather than in the context of whole bacteria. Here we used atomic force microscopy (AFM) to probe the physical properties of the LPS of P. aeruginosa strain PA103 (serogroup O11) in situ. This strain contains a mixture of long and very long polymers of O antigen, regulated by two different genes. For this analysis, we studied the wild-type strain and four mutants, ΔWzz1 (producing only very long LPS), ΔWzz2 (producing only long LPS), DΔM (with both the wzz1 and wzz2 genes deleted), and Wzy::GM (producing an LPS core oligosaccharide plus one unit of O antigen). Forces of adhesion between the LPS on these strains and the silicon nitride AFM tip were measured, and the Alexander and de Gennes model of steric repulsion between a flat surface and a polymer brush was used to calculate the LPS layer thickness (which we refer to as length), compressibility, and spacing between the individual molecules. LPS chains were longest for the wild-type strain and ΔWzz1, at 170.6 and 212.4 nm, respectively, and these values were not statistically significantly different from one another. Wzy::GM and DΔM have reduced LPS lengths, at 34.6 and 37.7 nm, respectively. Adhesion forces were not correlated with LPS length, but a relationship between adhesion force and bacterial pathogenicity was found in a mouse acute pneumonia model of infection. The adhesion forces with the AFM probe were lower for strains with LPS mutations, suggesting that the wild-type strain is optimized for maximal adhesion. Our research contributes to further understanding of the role of LPS in the adhesion and virulence of P. aeruginosa.
The Escherichia coli Phospholipase PldA Regulates Outer Membrane Homeostasis via Lipid Signaling.
May, Kerrie L; Silhavy, Thomas J
2018-03-20
The outer membrane (OM) bilayer of Gram-negative bacteria is biologically unique in its asymmetrical organization of lipids, with an inner leaflet composed of glycerophospholipids (PLs) and a surface-exposed outer leaflet composed of lipopolysaccharide (LPS). This lipid organization is integral to the OM's barrier properties. Perturbations of the outer leaflet by antimicrobial peptides or defects in LPS biosynthesis or transport to the OM cause a compensatory flipping of PLs to the outer leaflet. As a result, lipid asymmetry is disrupted and OM integrity is compromised. Recently, we identified an Escherichia coli mutant that exhibits aberrant accumulation of surface PLs accompanied by a cellular increase in LPS production. Remarkably, the observed hyperproduction of LPS is PldA dependent. Here we provide evidence that the fatty acids generated by PldA at the OM are transported into the cytoplasm and simultaneously activated by thioesterification to coenzyme A (CoA) by FadD. The acyl-CoAs produced ultimately inhibit LpxC degradation by FtsH. The increased levels of LpxC, the enzyme that catalyzes the first committed step in LPS biosynthesis, increases the amount of LPS produced. Our data suggest that PldA acts as a sensor for lipid asymmetry in the OM. PldA protects the OM barrier by both degrading mislocalized PLs and generating lipid second messengers that enable long-distance signaling that prompts the cell to restore homeostasis at a distant organelle. IMPORTANCE The outer membrane of Gram-negative bacteria is an effective permeability barrier that protects the cell from toxic agents, including antibiotics. Barrier defects are often manifested by phospholipids present in the outer leaflet of this membrane that take up space normally occupied by lipopolysaccharide. We have discovered a signaling mechanism that operates across the entire cell envelope used by the cell to detect these outer membrane defects. A phospholipase, PldA, that functions to degrade these mislocalized phospholipids has a second, equally important function as a sensor. The fatty acids produced by hydrolysis of the phospholipids act as second messengers to signal the cell that more lipopolysaccharide is needed. These fatty acids diffuse across the periplasm and are transported into the cytoplasm by a process that attaches coenzyme A. The acyl-CoA molecule produces signals to inhibit the degradation of the critical enzyme LpxC by the ATP-dependent protease FtsH, increasing lipopolysaccharide production. Copyright © 2018 May and Silhavy.
Roberts, James M D; Graham, Lori L; Quinn, Bonnie; Pink, David A
2013-03-01
Campylobacter fetus is a Gram negative bacterium recognized for its virulence in animals and humans. This bacterium possesses a paracrystalline array of high molecular weight proteins known as surface-layer proteins covering its cell surface. A mathematical model has been made of the outer membrane of this bacterium, both with its surface-layer proteins (S+) and without (S-). Monte Carlo computer simulation was used to understand the stability of the surface-layer protein structure as a function of ionic concentration. The interactions of an electrically-charged antimicrobial agent, the cationic antimicrobial peptide protamine, with surface-layer proteins and with the lipopolysaccharides of the outer membrane were modeled and analyzed. We found that (1) divalent ions stabilize the surface-layer protein array by reducing the fluctuations perpendicular and parallel to the membrane plane thereby promoting adhesion to the LPS region. This was achieved via (2) divalent ions bridging the negatively-charged LPS Core. The effect of this bridging is to bring individual Core regions closer together so that the O-antigens can (3) increase their attractive van der Waals interactions and "collapse" to form a surface with reduced perpendicular fluctuations. These findings provide support for the proposal of Yang et al. [1]. (4) No evidence for a significant increase in Ca(2+) concentration in the region of the surface-layer protein subunits was observed in S+ simulations compared to S- simulations. (5) We predicted the trends of protamine MIC tests performed on C. fetus and these were in good agreement with our experimental results. Copyright © 2012 Elsevier B.V. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Taylor, P.; Sugiman-Marangos, S; Zhang, K
2010-01-01
Lipopolysaccharide is a major component of the outer membrane of Gram-negative bacteria and provides a permeability barrier to many commonly used antibiotics. ADP-heptose residues are an integral part of the LPS inner core, and mutants deficient in heptose biosynthesis demonstrate increased membrane permeability. The heptose biosynthesis pathway involves phosphorylation and dephosphorylation steps not found in other pathways for the synthesis of nucleotide sugar precursors. Consequently, the heptose biosynthetic pathway has been marked as a novel target for antibiotic adjuvants, which are compounds that facilitate and potentiate antibiotic activity. D-{alpha},{beta}-D-Heptose-1,7-bisphosphate phosphatase (GmhB) catalyzes the third essential step of LPS heptose biosynthesis.more » This study describes the first crystal structure of GmhB and enzymatic analysis of the protein. Structure-guided mutations followed by steady state kinetic analysis, together with established precedent for HAD phosphatases, suggest that GmhB functions through a phosphoaspartate intermediate. This study provides insight into the structure-function relationship of GmhB, a new target for combatting Gram-negative bacterial infection.« less
Valguarnera, Ezequiel; Spera, Juan M; Czibener, Cecilia; Fulgenzi, Fabiana R; Casabuono, Adriana C; Altabe, Silvia G; Pasquevich, Karina A; Guaimas, Francisco; Cassataro, Juliana; Couto, Alicia S; Ugalde, Juan E
2018-03-28
Brucellaceae are stealthy pathogens with the ability to survive and replicate in the host in the context of a strong immune response. This capacity relies on several virulence factors that are able to modulate the immune system and in their structural components that have low proinflammatory activities. Lipopolysaccharide (LPS), the main component of the outer membrane, is a central virulence factor of Brucella, and it has been well established that it induces a low inflammatory response. We describe here the identification and characterization of a novel periplasmic protein (RomA) conserved in alpha-proteobacteria, which is involved in the homeostasis of the outer membrane. A mutant in this gene showed several phenotypes, such as membrane defects, altered LPS composition, reduced adhesion, and increased virulence and inflammation. We show that RomA is involved in the synthesis of LPS, probably coordinating part of the biosynthetic complex in the periplasm. Its absence alters the normal synthesis of this macromolecule and affects the homeostasis of the outer membrane, resulting in a strain with a hyperinflammatory phenotype. Our results suggest that the proper synthesis of LPS is central to maximize virulence and minimize inflammation.
Sperandeo, Paola; Cescutti, Rachele; Villa, Riccardo; Di Benedetto, Cristiano; Candia, Daniela; Dehò, Gianni; Polissi, Alessandra
2007-01-01
The outer membrane (OM) of gram-negative bacteria is an asymmetric lipid bilayer that protects the cell from toxic molecules. Lipopolysaccharide (LPS) is an essential component of the OM in most gram-negative bacteria, and its structure and biosynthesis are well known. Nevertheless, the mechanisms of transport and assembly of this molecule in the OM are poorly understood. To date, the only proteins implicated in LPS transport are MsbA, responsible for LPS flipping across the inner membrane, and the Imp/RlpB complex, involved in LPS targeting to the OM. Here, we present evidence that two Escherichia coli essential genes, yhbN and yhbG, now renamed lptA and lptB, respectively, participate in LPS biogenesis. We show that mutants depleted of LptA and/or LptB not only produce an anomalous LPS form, but also are defective in LPS transport to the OM and accumulate de novo-synthesized LPS in a novel membrane fraction of intermediate density between the inner membrane (IM) and the OM. In addition, we show that LptA is located in the periplasm and that expression of the lptA-lptB operon is controlled by the extracytoplasmic sigma factor RpoE. Based on these data, we propose that LptA and LptB are implicated in the transport of LPS from the IM to the OM of E. coli.
Sperandeo, Paola; Cescutti, Rachele; Villa, Riccardo; Di Benedetto, Cristiano; Candia, Daniela; Dehò, Gianni; Polissi, Alessandra
2007-01-01
The outer membrane (OM) of gram-negative bacteria is an asymmetric lipid bilayer that protects the cell from toxic molecules. Lipopolysaccharide (LPS) is an essential component of the OM in most gram-negative bacteria, and its structure and biosynthesis are well known. Nevertheless, the mechanisms of transport and assembly of this molecule in the OM are poorly understood. To date, the only proteins implicated in LPS transport are MsbA, responsible for LPS flipping across the inner membrane, and the Imp/RlpB complex, involved in LPS targeting to the OM. Here, we present evidence that two Escherichia coli essential genes, yhbN and yhbG, now renamed lptA and lptB, respectively, participate in LPS biogenesis. We show that mutants depleted of LptA and/or LptB not only produce an anomalous LPS form, but also are defective in LPS transport to the OM and accumulate de novo-synthesized LPS in a novel membrane fraction of intermediate density between the inner membrane (IM) and the OM. In addition, we show that LptA is located in the periplasm and that expression of the lptA-lptB operon is controlled by the extracytoplasmic σ factor RpoE. Based on these data, we propose that LptA and LptB are implicated in the transport of LPS from the IM to the OM of E. coli. PMID:17056748
Surface changes and polymyxin interactions with a resistant strain of Klebsiella pneumoniae.
Velkov, Tony; Deris, Zakuan Z; Huang, Johnny X; Azad, Mohammad A K; Butler, Mark; Sivanesan, Sivashangarie; Kaminskas, Lisa M; Dong, Yao-Da; Boyd, Ben; Baker, Mark A; Cooper, Matthew A; Nation, Roger L; Li, Jian
2014-05-01
This study examines the interaction of polymyxin B and colistin with the surface and outer membrane components of a susceptible and resistant strain of Klebsiella pneumoniae. The interaction between polymyxins and bacterial membrane and isolated LPS from paired wild type and polymyxin-resistant strains of K. pneumoniae were examined with N-phenyl-1-naphthylamine (NPN) uptake, fluorometric binding and thermal shift assays, lysozyme and deoxycholate sensitivity assays, and by (1)H NMR. LPS from the polymyxin-resistant strain displayed a reduced binding affinity for polymyxins B and colistin in comparison with the wild type LPS. The outer membrane NPN permeability of the resistant strain was greater compared with the susceptible strain. Polymyxin exposure enhanced the permeability of the outer membrane of the wild type strain to lysozyme and deoxycholate, whereas polymyxin concentrations up to 32 mg/ml failed to permeabilize the outer membrane of the resistant strain. Zeta potential measurements revealed that mid-logarithmic phase wild type cells exhibited a greater negative charge than the mid-logarithmic phase-resistant cells. Taken together, our findings suggest that the resistant derivative of K. pneumoniae can block the electrostatically driven first stage of polymyxin action, which thereby renders the hydrophobically driven second tier of polymyxin action on the outer membrane inconsequential.
Bos, Martine P; Tommassen, Jan
2011-08-19
The biosynthesis of lipopolysaccharide (LPS) in gram-negative bacteria is well understood, in contrast to the transport to its destination, the outer leaflet of the outer membrane. In Escherichia coli, synthesis and transport of LPS are essential processes. Neisseria meningitidis, conversely, can survive without LPS and tolerates inactivation of genes involved in LPS synthesis and transport. Here, we analyzed whether the LptA, LptB, LptC, LptE, LptF, and LptG proteins, recently implicated in LPS transport in E. coli, function similarly in N. meningitidis. None of the analyzed proteins was essential in N. meningitidis, consistent with their expected roles in LPS transport and additionally demonstrating that they are not required for an essential process such as phospholipid transport. As expected, the absence of most of the Lpt proteins resulted in a severe defect in LPS transport. However, the absence of LptE did not disturb transport of LPS to the cell surface. LptE was found to be associated with LptD, and its absence affected total levels of LptD, suggesting a chaperone-like role for LptE in LptD biogenesis. The absence of a direct role of LptE in LPS transport was substantiated by bioinformatic analyses showing a low conservation of LptE in LPS-producing bacteria. Apparently, the role of LptE in N. meningitidis deviates from that in E. coli, suggesting that the Lpt system does not function in a completely conserved manner in all gram-negative bacteria.
Bos, Martine P.; Tommassen, Jan
2011-01-01
The biosynthesis of lipopolysaccharide (LPS) in Gram-negative bacteria is well understood, in contrast to the transport to its destination, the outer leaflet of the outer membrane. In Escherichia coli, synthesis and transport of LPS are essential processes. Neisseria meningitidis, conversely, can survive without LPS and tolerates inactivation of genes involved in LPS synthesis and transport. Here, we analyzed whether the LptA, LptB, LptC, LptE, LptF, and LptG proteins, recently implicated in LPS transport in E. coli, function similarly in N. meningitidis. None of the analyzed proteins was essential in N. meningitidis, consistent with their expected roles in LPS transport and additionally demonstrating that they are not required for an essential process such as phospholipid transport. As expected, the absence of most of the Lpt proteins resulted in a severe defect in LPS transport. However, the absence of LptE did not disturb transport of LPS to the cell surface. LptE was found to be associated with LptD, and its absence affected total levels of LptD, suggesting a chaperone-like role for LptE in LptD biogenesis. The absence of a direct role of LptE in LPS transport was substantiated by bioinformatic analyses showing a low conservation of LptE in LPS-producing bacteria. Apparently, the role of LptE in N. meningitidis deviates from that in E. coli, suggesting that the Lpt system does not function in a completely conserved manner in all Gram-negative bacteria. PMID:21705335
Jiménez, Natalia; Senchenkova, Sofya N; Knirel, Yuriy A; Pieretti, Giuseppina; Corsaro, Maria M; Aquilini, Eleonora; Regué, Miguel; Merino, Susana; Tomás, Juan M
2012-07-01
The presence of cell-bound K1 capsule and K1 polysaccharide in culture supernatants was determined in a series of in-frame nonpolar core biosynthetic mutants from Escherichia coli KT1094 (K1, R1 core lipopolysaccharide [LPS] type) for which the major core oligosaccharide structures were determined. Cell-bound K1 capsule was absent from mutants devoid of phosphoryl modifications on L-glycero-D-manno-heptose residues (HepI and HepII) of the inner-core LPS and reduced in mutants devoid of phosphoryl modification on HepII or devoid of HepIII. In contrast, in all of the mutants, K1 polysaccharide was found in culture supernatants. These results were confirmed by using a mutant with a deletion spanning from the hldD to waaQ genes of the waa gene cluster to which individual genes were reintroduced. A nuclear magnetic resonance (NMR) analysis of core LPS from HepIII-deficient mutants showed an alteration in the pattern of phosphoryl modifications. A cell extract containing both K1 capsule polysaccharide and LPS obtained from an O-antigen-deficient mutant could be resolved into K1 polysaccharide and core LPS by column chromatography only when EDTA and deoxycholate (DOC) buffer were used. These results suggest that the K1 polysaccharide remains cell associated by ionically interacting with the phosphate-negative charges of the core LPS.
Jiménez, Natalia; Senchenkova, Sofya N.; Knirel, Yuriy A.; Pieretti, Giuseppina; Corsaro, Maria M.; Aquilini, Eleonora; Regué, Miguel; Merino, Susana
2012-01-01
The presence of cell-bound K1 capsule and K1 polysaccharide in culture supernatants was determined in a series of in-frame nonpolar core biosynthetic mutants from Escherichia coli KT1094 (K1, R1 core lipopolysaccharide [LPS] type) for which the major core oligosaccharide structures were determined. Cell-bound K1 capsule was absent from mutants devoid of phosphoryl modifications on l-glycero-d-manno-heptose residues (HepI and HepII) of the inner-core LPS and reduced in mutants devoid of phosphoryl modification on HepII or devoid of HepIII. In contrast, in all of the mutants, K1 polysaccharide was found in culture supernatants. These results were confirmed by using a mutant with a deletion spanning from the hldD to waaQ genes of the waa gene cluster to which individual genes were reintroduced. A nuclear magnetic resonance (NMR) analysis of core LPS from HepIII-deficient mutants showed an alteration in the pattern of phosphoryl modifications. A cell extract containing both K1 capsule polysaccharide and LPS obtained from an O-antigen-deficient mutant could be resolved into K1 polysaccharide and core LPS by column chromatography only when EDTA and deoxycholate (DOC) buffer were used. These results suggest that the K1 polysaccharide remains cell associated by ionically interacting with the phosphate-negative charges of the core LPS. PMID:22522903
Wang, L; Hu, X; Tao, G; Wang, X
2012-05-01
To investigate the role of lipopolysaccharide (LPS) structure in the stability of outer membrane and the ability of biofilm formation in Cronobacter sakazakii. A C. sakazakii mutant strain LWW02 was constructed by inactivating the gene ESA_04107 encoding for heptosyltransferase I. LPS were purified from LWW02, and changes in their structure were confirmed by thin-layer chromatography and electrospray ionization mass spectrometry. Comparing with the wild-type strain BAA-894, slower growth, higher membrane permeability, higher surface hydrophobicity, stronger ability of autoaggregation and biofilm formation were observed for the mutant strain LWW02. The gene ESA_04107 encodes heptosyltransferase I in C. sakazakii ATCC BAA-894. The cleavage of LPS in C. sakazakii could cause its outer membrane defects and increase its ability to form biofilms. The study is important for understanding the pathogenic mechanism and efficient control of C. sakazakii. © 2012 The Authors. Journal of Applied Microbiology © 2012 The Society for Applied Microbiology.
Sherman, David J.; Lazarus, Michael B.; Murphy, Lea; Liu, Charles; Walker, Suzanne; Ruiz, Natividad; Kahne, Daniel
2014-01-01
The cell surface of Gram-negative bacteria contains lipopolysaccharides (LPS), which provide a barrier against the entry of many antibiotics. LPS assembly involves a multiprotein LPS transport (Lpt) complex that spans from the cytoplasm to the outer membrane. In this complex, an unusual ATP-binding cassette transporter is thought to power the extraction of LPS from the outer leaflet of the cytoplasmic membrane and its transport across the cell envelope. We introduce changes into the nucleotide-binding domain, LptB, that inactivate transporter function in vivo. We characterize these residues using biochemical experiments combined with high-resolution crystal structures of LptB pre- and post-ATP hydrolysis and suggest a role for an active site residue in phosphate exit. We also identify a conserved residue that is not required for ATPase activity but is essential for interaction with the transmembrane components. Our studies establish the essentiality of ATP hydrolysis by LptB to power LPS transport in cells and suggest strategies to inhibit transporter function away from the LptB active site. PMID:24639492
NASA Astrophysics Data System (ADS)
Smart, Matthew; Rajagopal, Aruna; Liu, Wing-Ki; Ha, Bae-Yeun
2017-10-01
The permeability of the bacterial outer membrane, enclosing Gram-negative bacteria, depends on the interactions of the outer, lipopolysaccharide (LPS) layer, with surrounding ions and molecules. We present a coarse-grained model for describing how cationic amphiphilic molecules (e.g., antimicrobial peptides) interact with and perturb the LPS layer in a biologically relevant medium, containing monovalent and divalent salt ions (e.g., Mg2+). In our approach, peptide binding is driven by electrostatic and hydrophobic interactions and is assumed to expand the LPS layer, eventually priming it for disruption. Our results suggest that in parameter ranges of biological relevance (e.g., at micromolar concentrations) the antimicrobial peptide magainin 2 effectively disrupts the LPS layer, even though it has to compete with Mg2+ for the layer. They also show how the integrity of LPS is restored with an increasing concentration of Mg2+. Using the approach, we make a number of predictions relevant for optimizing peptide parameters against Gram-negative bacteria and for understanding bacterial strategies to develop resistance against cationic peptides.
Asymmetric phospholipid: lipopolysaccharide bilayers; a Gram-negative bacterial outer membrane mimic
Clifton, Luke A.; Skoda, Maximilian W. A.; Daulton, Emma L.; Hughes, Arwel V.; Le Brun, Anton P.; Lakey, Jeremy H.; Holt, Stephen A.
2013-01-01
The Gram-negative bacterial outer membrane (OM) is a complex and highly asymmetric biological barrier but the small size of bacteria has hindered advances in in vivo examination of membrane dynamics. Thus, model OMs, amenable to physical study, are important sources of data. Here, we present data from asymmetric bilayers which emulate the OM and are formed by a simple two-step approach. The bilayers were deposited on an SiO2 surface by Langmuir–Blodgett deposition of phosphatidylcholine as the inner leaflet and, via Langmuir–Schaefer deposition, an outer leaflet of either Lipid A or Escherichia coli rough lipopolysaccharides (LPS). The membranes were examined using neutron reflectometry (NR) to examine the coverage and mixing of lipids between the bilayer leaflets. NR data showed that in all cases, the initial deposition asymmetry was mostly maintained for more than 16 h. This stability enabled the sizes of the headgroups and bilayer roughness of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine and Lipid A, Rc-LPS and Ra-LPS to be clearly resolved. The results show that rough LPS can be manipulated like phospholipids and used to fabricate advanced asymmetric bacterial membrane models using well-known bilayer deposition techniques. Such models will enable OM dynamics and interactions to be studied under in vivo-like conditions. PMID:24132206
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wang, Zhongshan; College of Life Sciences, Sichuan University, Chengdu 610065; Biomedical Sciences Research Complex, School of Chemistry, University of St Andrews, North Haugh, St Andrews KY16 9ST
2014-09-26
Highlights: • Determination of the structure of the wild-type LptB in complex with ATP and Mg{sup 2+}. • Demonstrated that ATP binding residues are essential for LptB’s ATPase activity and LPS transport. • Dimerization is required for the LptB’s function and LPS transport. • Revealed relationship between activity of the LptB and the vitality of E. coli cells. - Abstract: Lipopolysaccharide (LPS) is the main component of the outer membrane of Gram-negative bacteria, which plays an essential role in protecting the bacteria from harsh conditions and antibiotics. LPS molecules are transported from the inner membrane to the outer membrane bymore » seven LPS transport proteins. LptB is vital in hydrolyzing ATP to provide energy for LPS transport, however this mechanism is not very clear. Here we report wild-type LptB crystal structure in complex with ATP and Mg{sup 2+}, which reveals that its structure is conserved with other nucleotide-binding proteins (NBD). Structural, functional and electron microscopic studies demonstrated that the ATP binding residues, including K42 and T43, are crucial for LptB’s ATPase activity, LPS transport and the vitality of Escherichia coli cells with the exceptions of H195A and Q85A; the H195A mutation does not lower its ATPase activity but impairs LPS transport, and Q85A does not alter ATPase activity but causes cell death. Our data also suggest that two protomers of LptB have to work together for ATP hydrolysis and LPS transport. These results have significant impacts in understanding the LPS transport mechanism and developing new antibiotics.« less
Futoma-Kołoch, Bożena; Godlewska, Urszula; Guz-Regner, Katarzyna; Dorotkiewicz-Jach, Agata; Klausa, Elżbieta; Rybka, Jacek; Bugla-Płoskońska, Gabriela
2015-01-01
The O48 group comprises Salmonella bacteria containing sialic acid in the lipopolysaccharide (LPS). Bacteria with sialylated surface structures are described as pathogens that avoid immunological response of the host by making similar their surface antigens to the host's tissues (molecular mimicry). It is known that the smooth-type LPS of Salmonella enterica and outer membrane proteins (OMP) PgtE, PagC and Rck mediate serum resistant phenotype by affecting complement system (C). The aim of this study was to investigate C3 component activation by Salmonella O48 LPS and OMP. In the present study, we examined C3 component deposition on the three Salmonella O48 strains: S. enterica subspecies enterica serovar Ngozi, S. enterica subsp. enterica sv. Isaszeg, and S. enterica subsp. arizonae containing sialic acid in the O-specific part of LPS. The greatest C3 deposition occurred on Salmonella sv. Isaszeg cells (p < 0.005) as well as on their LPS (low content of sialic acid in LPS) (p < 0.05) after 45 min of incubation in 50% human serum. Weaker C3 deposition ratio on the Salmonella sv. Ngozi (high content of sialic acid in LPS) and Salmonella subsp. arizonae (high content of sialic acid in LPS) cells correlated with the lower C3 activation on their LPS. Immunoblotting revealed that OMP isolated from the tested strains also bound C3 protein fragments. We suggest that activation of C3 serum protein is dependent on the sialic acid contents in the LPS as well as on the presence of OMP in the range of molecular masses of 35-48 kDa.
Mohanram, Harini; Bhattacharjya, Surajit
2014-04-21
Drug-resistant Gram-negative bacterial pathogens and endotoxin- or lipopolysaccharide (LPS)-mediated inflammations are among some of the most prominent health issues globally. Antimicrobial peptides (AMPs) are eminent molecules that can kill drug-resistant strains and neutralize LPS toxicity. LPS, the outer layer of the outer membrane of Gram-negative bacteria safeguards cell integrity against hydrophobic compounds, including antibiotics and AMPs. Apart from maintaining structural integrity, LPS, when released into the blood stream, also induces inflammatory pathways leading to septic shock. In previous works, we have reported the de novo design of a set of 12-amino acid long cationic/hydrophobic peptides for LPS binding and activity. These peptides adopt β-boomerang like conformations in complex with LPS. Structure-activity studies demonstrated some critical features of the β-boomerang scaffold that may be utilized for the further development of potent analogs. In this work, β-boomerang lipopeptides were designed and structure-activity correlation studies were carried out. These lipopeptides were homo-dimerized through a disulfide bridge to stabilize conformations and for improved activity. The designed peptides exhibited potent antibacterial activity and efficiently neutralized LPS toxicity under in vitro assays. NMR structure of C4YI13C in aqueous solution demonstrated the conserved folding of the lipopeptide with a boomerang aromatic lock stabilized with disulfide bond at the C-terminus and acylation at the N-terminus. These lipo-peptides displaying bacterial sterilization and low hemolytic activity may be useful for future applications as antimicrobial and antiendotoxin molecules.
Palusiak, Agata; Dzieciatkowska, Monika; Sidorczyk, Zygmunt
2008-01-01
Proteus penneri lipopolysaccharide (LPS) core regions are characterized by a greater structural variability than that observed in other Enterobacteriaceae. This fact and the small amount of published data concerning the serological activity of this part of P. penneri LPS prompted an examination of which fragment might determine cross-reactions with antibodies. To date, such epitopes have been found in the LPS core regions of P. mirabilis and P. vulgaris strains. Proteus sp. LPSs were tested with unabsorbed rabbit antisera by enzyme-linked immunosorbent assay (ELISA), sodium dodecyl sulfate polyacrylamide gel electrophoresis and Western blot, and once again by ELISA or passive immunohemolysis after the absorption of these antisera with selected LPSs. The serological studies of P. penneri 8 LPS demonstrated antibodies in the tested antisera recognizing a common epitope located in the core regions of six of the LPSs, i.e. P. penneri 8, 34, 133, 7, 14, and 15. Additionally, another type of antibody directed against some fragment of P. penneri 13 and the core regions of other LPSs investigated was observed in one antiserum. A distal, trisaccharide fragment of the P. penneri 8 LPS core region is suggested to determine the cross-reactions of the tested antisera with the six P. penneri LPSs.
Structural basis for lipopolysaccharide extraction by ABC transporter LptB2FG.
Luo, Qingshan; Yang, Xu; Yu, Shan; Shi, Huigang; Wang, Kun; Xiao, Le; Zhu, Guangyu; Sun, Chuanqi; Li, Tingting; Li, Dianfan; Zhang, Xinzheng; Zhou, Min; Huang, Yihua
2017-05-01
After biosynthesis, bacterial lipopolysaccharides (LPS) are transiently anchored to the outer leaflet of the inner membrane (IM). The ATP-binding cassette (ABC) transporter LptB 2 FG extracts LPS molecules from the IM and transports them to the outer membrane. Here we report the crystal structure of nucleotide-free LptB 2 FG from Pseudomonas aeruginosa. The structure reveals that lipopolysaccharide transport proteins LptF and LptG each contain a transmembrane domain (TMD), a periplasmic β-jellyroll-like domain and a coupling helix that interacts with LptB on the cytoplasmic side. The LptF and LptG TMDs form a large outward-facing V-shaped cavity in the IM. Mutational analyses suggest that LPS may enter the central cavity laterally, via the interface of the TMD domains of LptF and LptG, and is expelled into the β-jellyroll-like domains upon ATP binding and hydrolysis by LptB. These studies suggest a mechanism for LPS extraction by LptB 2 FG that is distinct from those of classical ABC transporters that transport substrates across the IM.
O-antigen and Core Carbohydrate of Vibrio fischeri Lipopolysaccharide
Post, Deborah M. B.; Yu, Liping; Krasity, Benjamin C.; Choudhury, Biswa; Mandel, Mark J.; Brennan, Caitlin A.; Ruby, Edward G.; McFall-Ngai, Margaret J.; Gibson, Bradford W.; Apicella, Michael A.
2012-01-01
Vibrio fischeri exists in a symbiotic relationship with the Hawaiian bobtail squid, Euprymna scolopes, where the squid provides a home for the bacteria, and the bacteria in turn provide camouflage that helps protect the squid from night-time predators. Like other Gram-negative organisms, V. fischeri expresses lipopolysaccharide (LPS) on its cell surface. The structure of the O-antigen and the core components of the LPS and their possible role in colonization of the squid have not previously been determined. In these studies, an O-antigen ligase mutant, waaL, was utilized to determine the structures of these LPS components and their roles in colonization of the squid. WaaL ligates the O-antigen to the core of the LPS; thus, LPS from waaL mutants lacks O-antigen. Our results show that the V. fischeri waaL mutant has a motility defect, is significantly delayed in colonization, and is unable to compete with the wild-type strain in co-colonization assays. Comparative analyses of the LPS from the wild-type and waaL strains showed that the V. fischeri LPS has a single O-antigen repeat composed of yersiniose, 8-epi-legionaminic acid, and N-acetylfucosamine. In addition, the LPS from the waaL strain showed that the core structure consists of l-glycero-d-manno-heptose, d-glycero-d-manno-heptose, glucose, 3-deoxy-d-manno-octulosonic acid, N-acetylgalactosamine, 8-epi-legionaminic acid, phosphate, and phosphoethanolamine. These studies indicate that the unusual V. fischeri O-antigen sugars play a role in the early phases of bacterial colonization of the squid. PMID:22247546
Autodisplay of the La/SSB protein on LPS-free E. coli for the diagnosis of Sjögren's syndrome.
Yoo, Gu; Dilkaute, Carina; Bong, Ji-Hong; Song, Hyun-Woo; Lee, Misu; Kang, Min-Jung; Jose, Joachim; Pyun, Jae-Chul
2017-05-01
The objective of this study was to present an immunoassay for the diagnosis of Sjögren's syndrome based on the autodisplayed La/SSB protein on the outer membrane of intact E. coli (strain UT-5600) and LPS-free E. coli (ClearColi™). As the first step, an autodisplay vector (pCK002) was transfected into intact E. coli and LPS-free E. coli for comparison of efficiency of autdisplay of La/SSB. The maximal level of La/SSB expression was estimated to be similar for LPS-free E. coli and intact E. coli at different optimal induction periods. Intact E. coli was found to grow twofold faster than LPS-free E. coli, and the maximal level of expression for LPS-free E. coli was obtained with a longer induction period. When the zeta potential was measured, both intact E. coli and LPS-free E. coli showed negative values, and the autodisplay of negatively charged La/SSB protein (pI<7) on the outer membrane of intact E. coli and LPS-free E. coli resulted in a slight change in zeta potential values. E. coli with autodisplayed La/SSB protein was used for an immunoassay of anti-La/SSB antibodies for the diagnosis of Sjögren's syndrome. The surface of E. coli with the autodisplayed antigen was modified with rabbit serum and papain to prevent false positive signals because of nonspecific binding of unrelated antibodies from human serum. LPS-free E. coli with autodisplayed La/SSB protein yielded sensitivity and selectivity of 81.6% and 78.6%, respectively. The Bland-Altman test showed that the immunoassays based on LPS-free E. coli and intact E. coli with autodisplayed La/SSB protein were statistically equivalent to a clinical immunoassay for detection of anti-La/SSB antibodies (confidence coefficient 95%). Copyright © 2017 Elsevier Inc. All rights reserved.
Mohanram, Harini; Bhattacharjya, Surajit
2014-01-01
Drug-resistant Gram-negative bacterial pathogens and endotoxin- or lipopolysaccharide (LPS)-mediated inflammations are among some of the most prominent health issues globally. Antimicrobial peptides (AMPs) are eminent molecules that can kill drug-resistant strains and neutralize LPS toxicity. LPS, the outer layer of the outer membrane of Gram-negative bacteria safeguards cell integrity against hydrophobic compounds, including antibiotics and AMPs. Apart from maintaining structural integrity, LPS, when released into the blood stream, also induces inflammatory pathways leading to septic shock. In previous works, we have reported the de novo design of a set of 12-amino acid long cationic/hydrophobic peptides for LPS binding and activity. These peptides adopt β-boomerang like conformations in complex with LPS. Structure-activity studies demonstrated some critical features of the β-boomerang scaffold that may be utilized for the further development of potent analogs. In this work, β-boomerang lipopeptides were designed and structure-activity correlation studies were carried out. These lipopeptides were homo-dimerized through a disulfide bridge to stabilize conformations and for improved activity. The designed peptides exhibited potent antibacterial activity and efficiently neutralized LPS toxicity under in vitro assays. NMR structure of C4YI13C in aqueous solution demonstrated the conserved folding of the lipopeptide with a boomerang aromatic lock stabilized with disulfide bond at the C-terminus and acylation at the N-terminus. These lipo-peptides displaying bacterial sterilization and low hemolytic activity may be useful for future applications as antimicrobial and antiendotoxin molecules. PMID:24756162
Simpson, Brent W; Owens, Tristan W; Orabella, Matthew J; Davis, Rebecca M; May, Janine M; Trauger, Sunia A; Kahne, Daniel; Ruiz, Natividad
2016-10-18
The surface of most Gram-negative bacteria is covered with lipopolysaccharide (LPS), creating a permeability barrier against toxic molecules, including many antimicrobials. To assemble LPS on their surface, Gram-negative bacteria must extract newly synthesized LPS from the inner membrane, transport it across the aqueous periplasm, and translocate it across the outer membrane. The LptA to -G proteins assemble into a transenvelope complex that transports LPS from the inner membrane to the cell surface. The Lpt system powers LPS transport from the inner membrane by using a poorly characterized ATP-binding cassette system composed of the ATPase LptB and the transmembrane domains LptFG. Here, we characterize a cluster of residues in the groove region of LptB that is important for controlling LPS transport. We also provide the first functional characterization of LptFG and identify their coupling helices that interact with the LptB groove. Substitutions at conserved residues in these coupling helices compromise both the assembly and function of the LptB 2 FG complex. Defects in LPS transport conferred by alterations in the LptFG coupling helices can be rescued by changing a residue in LptB that is adjacent to functionally important residues in the groove region. This suppression is achieved by increasing the ATPase activity of the LptB 2 FG complex. Taken together, these data identify a specific binding site in LptB for the coupling helices of LptFG that is responsible for coupling of ATP hydrolysis by LptB with LptFG function to achieve LPS extraction. Lipopolysaccharide (LPS) is synthesized at the cytoplasmic membrane of Gram-negative bacteria and transported across several compartments to the cell surface, where it forms a barrier that protects these organisms from antibiotics. The LptB 2 FG proteins form an ATP-binding cassette (ABC) transporter that uses energy from ATP hydrolysis in the cytoplasm to facilitate extraction of LPS from the outer face of the cytoplasmic membrane prior to transport to the cell surface. How ATP hydrolysis is coupled with LPS release from the membrane is not understood. We have identified residues at the interface between the ATPase and the transmembrane domains of this heteromeric ABC complex that are important for LPS transport, some of which coordinate ATPase activity with LPS release. Copyright © 2016 Simpson et al.
Energetics of Endotoxin Recognition in the Toll-Like Receptor 4 Innate Immune Response.
Paramo, Teresa; Tomasio, Susana M; Irvine, Kate L; Bryant, Clare E; Bond, Peter J
2015-12-09
Bacterial outer membrane lipopolysaccharide (LPS) potently stimulates the mammalian innate immune system, and can lead to sepsis, the primary cause of death from infections. LPS is sensed by Toll-like receptor 4 (TLR4) in complex with its lipid-binding coreceptor MD-2, but subtle structural variations in LPS can profoundly modulate the response. To better understand the mechanism of LPS-induced stimulation and bacterial evasion, we have calculated the binding affinity to MD-2 of agonistic and antagonistic LPS variants including lipid A, lipid IVa, and synthetic antagonist Eritoran, and provide evidence that the coreceptor is a molecular switch that undergoes ligand-induced conformational changes to appropriately activate or inhibit the receptor complex. The plasticity of the coreceptor binding cavity is shown to be essential for distinguishing between ligands, whilst similar calculations for a model bacterial LPS bilayer reveal the "membrane-like" nature of the protein cavity. The ability to predict the activity of LPS variants should facilitate the rational design of TLR4 therapeutics.
Energetics of Endotoxin Recognition in the Toll-Like Receptor 4 Innate Immune Response
Paramo, Teresa; Tomasio, Susana M.; Irvine, Kate L.; Bryant, Clare E.; Bond, Peter J.
2015-01-01
Bacterial outer membrane lipopolysaccharide (LPS) potently stimulates the mammalian innate immune system, and can lead to sepsis, the primary cause of death from infections. LPS is sensed by Toll-like receptor 4 (TLR4) in complex with its lipid-binding coreceptor MD-2, but subtle structural variations in LPS can profoundly modulate the response. To better understand the mechanism of LPS-induced stimulation and bacterial evasion, we have calculated the binding affinity to MD-2 of agonistic and antagonistic LPS variants including lipid A, lipid IVa, and synthetic antagonist Eritoran, and provide evidence that the coreceptor is a molecular switch that undergoes ligand-induced conformational changes to appropriately activate or inhibit the receptor complex. The plasticity of the coreceptor binding cavity is shown to be essential for distinguishing between ligands, whilst similar calculations for a model bacterial LPS bilayer reveal the “membrane-like” nature of the protein cavity. The ability to predict the activity of LPS variants should facilitate the rational design of TLR4 therapeutics. PMID:26647780
Lagares, Antonio; Hozbor, Daniela F.; Niehaus, Karsten; Otero, Augusto J. L. Pich; Lorenzen, Jens; Arnold, Walter; Pühler, Alfred
2001-01-01
The genetic characterization of a 5.5-kb chromosomal region of Sinorhizobium meliloti 2011 that contains lpsB, a gene required for the normal development of symbiosis with Medicago spp., is presented. The nucleotide sequence of this DNA fragment revealed the presence of six genes: greA and lpsB, transcribed in the forward direction; and lpsE, lpsD, lpsC, and lrp, transcribed in the reverse direction. Except for lpsB, none of the lps genes were relevant for nodulation and nitrogen fixation. Analysis of the transcriptional organization of lpsB showed that greA and lpsB are part of separate transcriptional units, which is in agreement with the finding of a DNA stretch homologous to a “nonnitrogen” promoter consensus sequence between greA and lpsB. The opposite orientation of lpsB with respect to its first downstream coding sequence, lpsE, indicated that the altered LPS and the defective symbiosis of lpsB mutants are both consequences of a primary nonpolar defect in a single gene. Global sequence comparisons revealed that the greA-lpsB and lrp genes of S. meliloti have a genetic organization similar to that of their homologous loci in R. leguminosarum bv. viciae. In particular, high sequence similarity was found between the translation product of lpsB and a core-related biosynthetic mannosyltransferase of R. leguminosarum bv. viciae encoded by the lpcC gene. The functional relationship between these two genes was demonstrated in genetic complementation experiments in which the S. meliloti lpsB gene restored the wild-type LPS phenotype when introduced into lpcC mutants of R. leguminosarum. These results support the view that S. meliloti lpsB also encodes a mannosyltransferase that participates in the biosynthesis of the LPS core. Evidence is provided for the presence of other lpsB-homologous sequences in several members of the family Rhizobiaceae. PMID:11157937
Tattawasart, U; Maillard, J Y; Furr, J R; Russell, A D
2000-11-01
Changes in outer membrane proteins (OMP) and lipopolysaccharide (LPS) in cells of strains of Pseudomonas stutzeri sensitive and resistant to chlorhexidine diacetate (CHA) or cetylpyridinium chloride (CPC) have been examined. Four of five CHA-resistant strains had alterations in OMP profiles, including the expression of two additional protein bands. All the CPC-resistant strains had altered OMP profiles but the changes varied from strain to strain. Loss of the fastest-migrating bands was observed in the LPS from CHX-resistant strains. In strain JM 302R with high-level CHX resistance (minimal inhibitory concentration 100 mg/l as opposed to 2.5 mg/l in the parent-strain, JM 302), all the fast-migrating bands were lost and the strain showed 'cross-resistance' to polymyxin, gentamicin and ethylenediamine tetraacetic acid. It is however, possible that the altered LPS patterns reflect a response to alterations in other components rather than being directly associated per se with the enhanced resistance.
Flow Analysis of a Gas Turbine Low- Pressure Subsystem
NASA Technical Reports Server (NTRS)
Veres, Joseph P.
1997-01-01
The NASA Lewis Research Center is coordinating a project to numerically simulate aerodynamic flow in the complete low-pressure subsystem (LPS) of a gas turbine engine. The numerical model solves the three-dimensional Navier-Stokes flow equations through all components within the low-pressure subsystem as well as the external flow around the engine nacelle. The Advanced Ducted Propfan Analysis Code (ADPAC), which is being developed jointly by Allison Engine Company and NASA, is the Navier-Stokes flow code being used for LPS simulation. The majority of the LPS project is being done under a NASA Lewis contract with Allison. Other contributors to the project are NYMA and the University of Toledo. For this project, the Energy Efficient Engine designed by GE Aircraft Engines is being modeled. This engine includes a low-pressure system and a high-pressure system. An inlet, a fan, a booster stage, a bypass duct, a lobed mixer, a low-pressure turbine, and a jet nozzle comprise the low-pressure subsystem within this engine. The tightly coupled flow analysis evaluates aerodynamic interactions between all components of the LPS. The high-pressure core engine of this engine is simulated with a one-dimensional thermodynamic cycle code in order to provide boundary conditions to the detailed LPS model. This core engine consists of a high-pressure compressor, a combustor, and a high-pressure turbine. The three-dimensional LPS flow model is coupled to the one-dimensional core engine model to provide a "hybrid" flow model of the complete gas turbine Energy Efficient Engine. The resulting hybrid engine model evaluates the detailed interaction between the LPS components at design and off-design engine operating conditions while considering the lumped-parameter performance of the core engine.
Pei, Dong; Jiang, Jinjin; Yu, Wanqin; Kukutla, Phanidhar; Uentillie, Alejandro; Xu, Jiannong
2015-08-27
The mosquito gut harbors a variety of bacteria that are dynamically associated with mosquitoes in various contexts. However, little is known about bacterial factors that affect bacterial inhabitation in the gut microbial community. Enterobacter sp. Ag1 is a predominant Gram negative bacterium in the mosquito midgut. In a mutant library that was generated using transposon Tn5-mediated mutagenesis, a mutant was identified, in which the gene waaL was disrupted by the Tn5 insertion. The waaL encodes O antigen ligase, which is required for the attachment of O antigen to the outer core oligosaccharide of the lipopolysaccharide (LPS). The waaL(-) mutation caused the O antigen repeat missing in the LPS. The normal LPS structure was restored when the mutant was complemented with a plasmid containing waaL gene. The waaL(-) mutation did not affect bacterial proliferation in LB culture, the mutant cells grew at a rate the same as the wildtype (wt) cells. However, when waaL(-) strain were co-cultured with the wt strain or complemented strain, the mutant cells proliferated with a slower rate, indicating that the mutants were less competitive than wt cells in a community setting. Similarly, in a co-feeding assay, when fluorescently tagged wt strain and waaL(-) strain were orally co-introduced into the gut of Anopheles stephensi mosquitoes, the mutant cells were less prevalent in both sugar-fed and blood-fed guts. The data suggest that the mutation compromised the bacterial inhabitation in the gut community. Besides, the mutant was more sensitive to oxidative stress, demonstrated by lower survival rate upon exposure to 20 mM H₂O₂. Lack of the O antigen structure in LPS of Enterobacter compromised the effective growth in co-culture and co-feeding assays. In addition, O-antigen was involved in protection against oxidative stress. The findings suggest that intact LPS is crucial for the bacteria to steadily stay in the gut microbial community.
Carpenter, Timothy S.; Parkin, Jamie; Khalid, Syma
2016-08-12
Permeation of small molecules across cell membranes is a ubiquitous process in biology and is dependent on the principles of physical chemistry at the molecular level. Here we use atomistic molecular dynamics simulations to calculate the free energy of permeation of a range of small molecules through a model of the outer membrane of Escherichia coli, an archetypical Gram-negative bacterium. The model membrane contains lipopolysaccharide (LPS) molecules in the outer leaflet and phospholipids in the inner leaflet. Our results show that the energetic barriers to permeation through the two leaflets of the membrane are distinctly asymmetric; the LPS headgroups providemore » a less energetically favorable environment for organic compounds than do phospholipids. In summary, we provide the first reported estimates of the relative free energies associated with the different chemical environments experienced by solutes as they attempt to cross the outer membrane of a Gram-negative bacterium. Furthermore, these results provide key insights for the development of novel antibiotics that target these bacteria.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Carpenter, Timothy S.; Parkin, Jamie; Khalid, Syma
Permeation of small molecules across cell membranes is a ubiquitous process in biology and is dependent on the principles of physical chemistry at the molecular level. Here we use atomistic molecular dynamics simulations to calculate the free energy of permeation of a range of small molecules through a model of the outer membrane of Escherichia coli, an archetypical Gram-negative bacterium. The model membrane contains lipopolysaccharide (LPS) molecules in the outer leaflet and phospholipids in the inner leaflet. Our results show that the energetic barriers to permeation through the two leaflets of the membrane are distinctly asymmetric; the LPS headgroups providemore » a less energetically favorable environment for organic compounds than do phospholipids. In summary, we provide the first reported estimates of the relative free energies associated with the different chemical environments experienced by solutes as they attempt to cross the outer membrane of a Gram-negative bacterium. Furthermore, these results provide key insights for the development of novel antibiotics that target these bacteria.« less
Molecular Characterization of Lipopolysaccharide Binding to Human α-1-Acid Glycoprotein
Huang, Johnny X.; Azad, Mohammad A. K.; Yuriev, Elizabeth; Baker, Mark A.; Nation, Roger L.; Li, Jian; Cooper, Matthew A.; Velkov, Tony
2012-01-01
The ability of AGP to bind circulating lipopolysaccharide (LPS) in plasma is believed to help reduce the proinflammatory effect of bacterial lipid A molecules. Here, for the first time we have characterized human AGP binding characteristics of the LPS from a number of pathogenic Gram-negative bacteria: Escherichia coli, Salmonella typhimurium, Klebsiella pneumonia, Pseudomonas aeruginosa, and Serratia marcescens. The binding affinity and structure activity relationships (SAR) of the AGP-LPS interactions were characterized by surface plasma resonance (SPR). In order to dissect the contribution of the lipid A, core oligosaccharide and O-antigen polysaccharide components of LPS, the AGP binding affinity of LPS from smooth strains, were compared to lipid A, Kdo2-lipid A, Ra, Rd, and Re rough LPS mutants. The SAR analysis enabled by the binding data suggested that, in addition to the important role played by the lipid A and core components of LPS, it is predominately the unique species- and strain-specific carbohydrate structure of the O-antigen polysaccharide that largely determines the binding affinity for AGP. Together, these data are consistent with the role of AGP in the binding and transport of LPS in plasma during acute-phase inflammatory responses to invading Gram-negative bacteria. PMID:23316371
Martorana, Alessandra M.; Benedet, Mattia; Maccagni, Elisa A.; Sperandeo, Paola; Villa, Riccardo; Dehò, Gianni
2016-01-01
ABSTRACT The assembly of lipopolysaccharide (LPS) in the outer leaflet of the outer membrane (OM) requires the transenvelope Lpt (lipopolysaccharide transport) complex, made in Escherichia coli of seven essential proteins located in the inner membrane (IM) (LptBCFG), periplasm (LptA), and OM (LptDE). At the IM, LptBFG constitute an unusual ATP binding cassette (ABC) transporter, composed by the transmembrane LptFG proteins and the cytoplasmic LptB ATPase, which is thought to extract LPS from the IM and to provide the energy for its export across the periplasm to the cell surface. LptC is a small IM bitopic protein that binds to LptBFG and recruits LptA via its N- and C-terminal regions, and its role in LPS export is not completely understood. Here, we show that the expression level of lptB is a critical factor for suppressing lethality of deletions in the C-terminal region of LptC and the functioning of a hybrid Lpt machinery that carries Pa-LptC, the highly divergent LptC orthologue from Pseudomonas aeruginosa. We found that LptB overexpression stabilizes C-terminally truncated LptC mutant proteins, thereby allowing the formation of a sufficient amount of stable IM complexes to support growth. Moreover, the LptB level seems also critical for the assembly of IM complexes carrying Pa-LptC which is otherwise defective in interactions with the E. coli LptFG components. Overall, our data suggest that LptB and LptC functionally interact and support a model whereby LptB plays a key role in the assembly of the Lpt machinery. IMPORTANCE The asymmetric outer membrane (OM) of Gram-negative bacteria contains in its outer leaflet an unusual glycolipid, the lipopolysaccharide (LPS). LPS largely contributes to the peculiar permeability barrier properties of the OM that prevent the entry of many antibiotics, thus making Gram-negative pathogens difficult to treat. In Escherichia coli the LPS transporter (the Lpt machine) is made of seven essential proteins (LptABCDEFG) that form a transenvelope complex. Here, we show that increased expression of the membrane-associated ABC protein LptB can suppress defects of LptC, which participates in the formation of the periplasmic bridge. This reveals functional interactions between these two components and supports a role of LptB in the assembly of the Lpt machine. PMID:27246575
Accumulation of phosphatidic acid increases vancomycin resistance in Escherichia coli.
Sutterlin, Holly A; Zhang, Sisi; Silhavy, Thomas J
2014-09-01
In Gram-negative bacteria, lipopolysaccharide (LPS) contributes to the robust permeability barrier of the outer membrane, preventing entry of toxic molecules such as antibiotics. Mutations in lptD, the beta-barrel component of the LPS transport and assembly machinery, compromise LPS assembly and result in increased antibiotic sensitivity. Here, we report rare vancomycin-resistant suppressors that improve barrier function of a subset of lptD mutations. We find that all seven suppressors analyzed mapped to the essential gene cdsA, which is responsible for the conversion of phosphatidic acid to CDP-diacylglycerol in phospholipid biosynthesis. These cdsA mutations cause a partial loss of function and, as expected, accumulate phosphatidic acid. We show that this suppression is not confined to mutations that cause defects in outer membrane biogenesis but rather that these cdsA mutations confer a general increase in vancomycin resistance, even in a wild-type cell. We use genetics and quadrupole time of flight (Q-TOF) liquid chromatography-mass spectrometry (LC-MS) to show that accumulation of phosphatidic acid by means other than cdsA mutations also increases resistance to vancomycin. We suggest that increased levels of phosphatidic acid change the physical properties of the outer membrane to impede entry of vancomycin into the periplasm, hindering access to its target, an intermediate required for the synthesis of the peptidoglycan cell wall. Copyright © 2014, American Society for Microbiology. All Rights Reserved.
Normal Mode Derived Models of the Physical Properties of Earth's Outer Core
NASA Astrophysics Data System (ADS)
Irving, J. C. E.; Cottaar, S.; Lekic, V.; Wu, W.
2017-12-01
Earth's outer core, the largest reservoir of metal in our planet, is comprised of an iron alloy of an uncertain composition. Its dynamical behaviour is responsible for the generation of Earth's magnetic field, with convection driven both by thermal and chemical buoyancy fluxes. Existing models of the seismic velocity and density of the outer core exhibit some variation, and there are only a small number of models which aim to represent the outer core's density.It is therefore important that we develop a better understanding of the physical properties of the outer core. Though most of the outer core is likely to be well mixed, it is possible that the uppermost outer core is stably stratified: it may be enriched in light elements released during the growth of the solid, iron enriched, inner core; by elements dissolved from the mantle into the outer core; or by exsolution of compounds previously dissolved in the liquid metal which will eventually be swept into the mantle. The stratified layer may host MAC or Rossby waves and it could impede communication between the chemically differentiated mantle and outer core, including screening out some of the geodynamo's signal. We use normal mode center frequencies to estimate the physical properties of the outer core in a Bayesian framework. We estimate the mineral physical parameters needed to best produce velocity and density models of the outer core which are consistent with the normal mode observations. We require that our models satisfy realistic physical constraints. We create models of the outer core with and without a distinct uppermost layer and assess the importance of this region.Our normal mode-derived models are compared with observations of body waves which travel through the outer core. In particular, we consider SmKS waves which are especially sensitive to the uppermost outer core and are therefore an important way to understand the robustness of our models.
Cross, Alan S; Greenberg, Nancy; Billington, Melissa; Zhang, Lei; DeFilippi, Christopher; May, Ryan C; Bajwa, Kanwaldeep K
2015-11-27
Gram-negative bacteria (GNB) are a leading cause of nosocomial infection and sepsis. Increasing multi-antibiotic resistance has left clinicians with fewer therapeutic options. Antibodies to GNB lipopolysaccharide (LPS, or endotoxin) have reduced morbidity and mortality as a result of infection and are not subject to the resistance mechanisms deployed by bacteria against antibiotics. In this phase 1 study, we administered a vaccine that elicits antibodies against a highly conserved portion of LPS with and without a CpG oligodeoxynucleotide (ODN) TLR9 agonist as adjuvant. A vaccine composed of the detoxified LPS (dLPS) from E. coli O111:B4 (J5 mutant) non-covalently complexed to group B meningococcal outer membrane protein (OMP). Twenty healthy adult subjects received three doses at 0, 29 and 59 days of antigen (10 μg dLPS) with or without CPG 7909 (250 or 500 μg). Subjects were evaluated for local and systemic adverse effects and laboratory findings. Anti-J5 LPS IgG and IgM antibody levels were measured by electrochemiluminesence. Due to premature study termination, not all subjects received all three doses. All vaccine formulations were well-tolerated with no local or systemic events of greater than moderate severity. The vaccine alone group achieved a ≥ 4-fold "responder" response in IgG and IgM antibody in only one of 6 subjects. In contrast, the vaccine plus CPG 7909 groups appeared to have earlier and more sustained (to 180 days) responses, greater mean-fold increases, and a higher proportion of "responders" achieving ≥ 4-fold increases over baseline. Although the study was halted before all enrolled subjects received all three doses, the J5dLPS/OMP vaccine, with or without CpG adjuvant, was safe and well-tolerated. The inclusion of CpG increased the number of subjects with a ≥ 4-fold antibody response, evident even after the second of three planned doses. A vaccine comprising J5dLPS/OMP antigen with CpG adjuvant merits further investigation. ClinicalTrials.gov Identifier: NCT01164514. Copyright © 2015 Elsevier Ltd. All rights reserved.
Ren, Xiuyan; Huang, Chang; Duan, Lijie; Liu, Baijun; Bu, Lvjun; Guan, Shuang; Hou, Jiliang; Zhang, Huixuan; Gao, Guanghui
2017-05-14
Toughness, strechability and compressibility for hydrogels were ordinarily balanced for their use as mechanically responsive materials. For example, macromolecular microsphere composite hydrogels with chemical crosslinking exhibited excellent compression strength and strechability, but poor tensile stress. Here, a novel strategy for the preparation of a super-tough, ultra-stretchable and strongly compressive hydrogel was proposed by introducing core-shell latex particles (LPs) as crosslinking centers for inducing efficient aggregation of hydrophobic chains. The core-shell LPs always maintained a spherical shape due to the presence of a hard core even by an external force and the soft shell could interact with hydrophobic chains due to hydrophobic interactions. As a result, the hydrogels reinforced by core-shell LPs exhibited not only a high tensile strength of 1.8 MPa and dramatic elongation of over 20 times, but also an excellent compressive performance of 13.5 MPa at a strain of 90%. The Mullins effect was verified for the validity of core-shell LP-reinforced hydrogels by inducing aggregation of hydrophobic chains. The novel strategy strives to provide a better avenue for designing and developing a new generation of hydrophobic association tough hydrogels with excellent mechanical properties.
Piek, Susannah; Kahler, Charlene M.
2012-01-01
The Gram-negative bacterial cell envelope consists of an inner membrane (IM) that surrounds the cytoplasm and an asymmetrical outer-membrane (OM) that forms a protective barrier to the external environment. The OM consists of lipopolysaccahride (LPS), phospholipids, outer membrane proteins (OMPs), and lipoproteins. Oxidative protein folding mediated by periplasmic oxidoreductases is required for the biogenesis of the protein components, mainly constituents of virulence determinants such as pili, flagella, and toxins, of the Gram-negative OM. Recently, periplasmic oxidoreductases have been implicated in LPS biogenesis of Escherichia coli and Neisseria meningitidis. Differences in OM biogenesis, in particular the transport pathways for endotoxin to the OM, the composition and role of the protein oxidation, and isomerization pathways and the regulatory networks that control them have been found in these two Gram-negative species suggesting that although form and function of the OM is conserved, the pathways required for the biosynthesis of the OM and the regulatory circuits that control them have evolved to suit the lifestyle of each organism. PMID:23267440
Mehta, Ojas H.; Norheim, Gunnstein; Hoe, J . Claire; Rollier, Christine S.; Nagaputra, Jerry C.; Makepeace, Katherine; Saleem, Muhammad; Chan, Hannah; Ferguson, David J. P.; Jones, Claire; Sadarangani, Manish; Hood, Derek W.; Feavers, Ian; Derrick, Jeremy P.; Pollard, Andrew J.; Moxon, E . Richard
2014-01-01
Neisseria meningitidis lipopolysaccharide (LPS) has adjuvant properties that can be exploited to assist vaccine immunogenicity. The modified penta-acylated LPS retains the adjuvant properties of hexa-acylated LPS but has a reduced toxicity profile. In this study we investigated whether two modified glycoform structures (LgtE and IcsB) of detoxified penta-acylated LPS exhibited differential adjuvant properties when formulated as native outer membrane vesicles (nOMVs) as compared to the previously described LgtB variant. Detoxified penta-acylated LPS was obtained by disruption of the lpxL1 gene (LpxL1 LPS), and three different glycoforms were obtained by disruption of the lgtB, lgtE or icsB genes respectively. Mice (mus musculus) were immunized with a recombinant PorA P1.7-2,4 (rPorA) protein co-administered with different nOMVs (containing a different PorA serosubtype P1.7,16), each of which expressed one of the three penta-acylated LPS glycoforms. All nOMVs induced IgG responses against the rPorA, but the nOMVs containing the penta-acylated LgtB-LpxL1 LPS glycoform induced significantly greater bactericidal activity compared to the other nOMVs or when the adjuvant was Alhydrogel. Compared to LgtE or IcsB LPS glycoforms, these data support the use of nOMVs containing detoxified, modified LgtB-LpxL1 LPS as a potential adjuvant for future meningococcal protein vaccines. PMID:25545241
Earth's Outer Core Properties Estimated Using Bayesian Inversion of Normal Mode Eigenfrequencies
NASA Astrophysics Data System (ADS)
Irving, J. C. E.; Cottaar, S.; Lekic, V.
2016-12-01
The outer core is arguably Earth's most dynamic region, and consists of an iron-nickel liquid with an unknown combination of lighter alloying elements. Frequencies of Earth's normal modes provide the strongest constraints on the radial profiles of compressional wavespeed, VΦ, and density, ρ, in the outer core. Recent great earthquakes have yielded new normal mode measurements; however, mineral physics experiments and calculations are often compared to the Preliminary reference Earth model (PREM), which is 35 years old and does not provide uncertainties. Here we investigate the thermo-elastic properties of the outer core using Earth's free oscillations and a Bayesian framework. To estimate radial structure of the outer core and its uncertainties, we choose to exploit recent datasets of normal mode centre frequencies. Under the self-coupling approximation, centre frequencies are unaffected by lateral heterogeneities in the Earth, for example in the mantle. Normal modes are sensitive to both VΦ and ρ in the outer core, with each mode's specific sensitivity depending on its eigenfunctions. We include a priori bounds on outer core models that ensure compatibility with measurements of mass and moment of inertia. We use Bayesian Monte Carlo Markov Chain techniques to explore different choices in parameterizing the outer core, each of which represents different a priori constraints. We test how results vary (1) assuming a smooth polynomial parametrization, (2) allowing for structure close to the outer core's boundaries, (3) assuming an Equation-of-State and adiabaticity and inverting directly for thermo-elastic parameters. In the second approach we recognize that the outer core may have distinct regions close to the core-mantle and inner core boundaries and investigate models which parameterize the well mixed outer core separately from these two layers. In the last approach we seek to map the uncertainties directly into thermo-elastic parameters including the bulk modulus, its pressure derivative, and molar mass and volume, with particular attention paid to the (inherent) trade-offs between the different coefficients. We discuss our results in terms of added uncertainty to the light element composition of the outer core and the potential existence of anomalous structure near the outer core's boundaries.
Pawlak, Aleksandra; Rybka, Jacek; Dudek, Bartłomiej; Krzyżewska, Eva; Rybka, Wojciech; Kędziora, Anna; Klausa, Elżbieta; Bugla-Płoskońska, Gabriela
2017-01-01
Complement is one of the most important parts of the innate immune system. Some bacteria can gain resistance against the bactericidal action of complement by decorating their outer cell surface with lipopolysaccharides (LPSs) containing a very long O-antigen or with specific outer membrane proteins. Additionally, the presence of sialic acid in the LPS molecules can provide a level of protection for bacteria, likening them to human cells, a phenomenon known as molecular mimicry. Salmonella O48, which contains sialic acid in the O-antigen, is the major cause of reptile-associated salmonellosis, a worldwide public health problem. In this study, we tested the effect of prolonged exposure to human serum on strains from Salmonella serogroup O48, specifically on the O-antigen length. After multiple passages in serum, three out of four tested strains became resistant to serum action. The gas-liquid chromatography/tandem mass spectrometry analysis showed that, for most of the strains, the average length of the LPS O-antigen increased. Thus, we have discovered a link between the resistance of bacterial cells to serum and the elongation of the LPS O-antigen. PMID:28934165
Pawlak, Aleksandra; Rybka, Jacek; Dudek, Bartłomiej; Krzyżewska, Eva; Rybka, Wojciech; Kędziora, Anna; Klausa, Elżbieta; Bugla-Płoskońska, Gabriela
2017-09-21
Complement is one of the most important parts of the innate immune system. Some bacteria can gain resistance against the bactericidal action of complement by decorating their outer cell surface with lipopolysaccharides (LPSs) containing a very long O-antigen or with specific outer membrane proteins. Additionally, the presence of sialic acid in the LPS molecules can provide a level of protection for bacteria, likening them to human cells, a phenomenon known as molecular mimicry. Salmonella O48, which contains sialic acid in the O-antigen, is the major cause of reptile-associated salmonellosis, a worldwide public health problem. In this study, we tested the effect of prolonged exposure to human serum on strains from Salmonella serogroup O48, specifically on the O-antigen length. After multiple passages in serum, three out of four tested strains became resistant to serum action. The gas-liquid chromatography/tandem mass spectrometry analysis showed that, for most of the strains, the average length of the LPS O-antigen increased. Thus, we have discovered a link between the resistance of bacterial cells to serum and the elongation of the LPS O-antigen.
Benedet, Mattia; Falchi, Federica A.; Puccio, Simone; Di Benedetto, Cristiano; Peano, Clelia; Polissi, Alessandra
2016-01-01
The lipopolysaccharide (LPS) transport (Lpt) system is responsible for transferring LPS from the periplasmic surface of the inner membrane (IM) to the outer leaflet of the outer membrane (OM), where it plays a crucial role in OM selective permeability. In E. coli seven essential proteins are assembled in an Lpt trans-envelope complex, which is conserved in γ-Proteobacteria. LptBFG constitute the IM ABC transporter, LptDE form the OM translocon for final LPS delivery, whereas LptC, an IM-anchored protein with a periplasmic domain, interacts with the IM ABC transporter, the periplasmic protein LptA, and LPS. Although essential, LptC can tolerate several mutations and its role in LPS transport is unclear. To get insights into the functional role of LptC in the Lpt machine we searched for viable mutants lacking LptC by applying a strong double selection for lptC deletion mutants. Genome sequencing of viable ΔlptC mutants revealed single amino acid substitutions at a unique position in the predicted large periplasmic domain of the IM component LptF (LptFSupC). In complementation tests, lptFSupC mutants suppress lethality of both ΔlptC and lptC conditional expression mutants. Our data show that mutations in a specific residue of the predicted LptF periplasmic domain can compensate the lack of the essential protein LptC, implicate such LptF domain in the formation of the periplasmic bridge between the IM and OM complexes, and suggest that LptC may have evolved to improve the performance of an ancestral six-component Lpt machine. PMID:27529623
Benedet, Mattia; Falchi, Federica A; Puccio, Simone; Di Benedetto, Cristiano; Peano, Clelia; Polissi, Alessandra; Dehò, Gianni
2016-01-01
The lipopolysaccharide (LPS) transport (Lpt) system is responsible for transferring LPS from the periplasmic surface of the inner membrane (IM) to the outer leaflet of the outer membrane (OM), where it plays a crucial role in OM selective permeability. In E. coli seven essential proteins are assembled in an Lpt trans-envelope complex, which is conserved in γ-Proteobacteria. LptBFG constitute the IM ABC transporter, LptDE form the OM translocon for final LPS delivery, whereas LptC, an IM-anchored protein with a periplasmic domain, interacts with the IM ABC transporter, the periplasmic protein LptA, and LPS. Although essential, LptC can tolerate several mutations and its role in LPS transport is unclear. To get insights into the functional role of LptC in the Lpt machine we searched for viable mutants lacking LptC by applying a strong double selection for lptC deletion mutants. Genome sequencing of viable ΔlptC mutants revealed single amino acid substitutions at a unique position in the predicted large periplasmic domain of the IM component LptF (LptFSupC). In complementation tests, lptFSupC mutants suppress lethality of both ΔlptC and lptC conditional expression mutants. Our data show that mutations in a specific residue of the predicted LptF periplasmic domain can compensate the lack of the essential protein LptC, implicate such LptF domain in the formation of the periplasmic bridge between the IM and OM complexes, and suggest that LptC may have evolved to improve the performance of an ancestral six-component Lpt machine.
Wang, Hua-Qin; Meng, Xin; Liu, Bao-Qin; Li, Chao; Gao, Yan-Yan; Niu, Xiao-Fang; Li, Ning; Guan, Yifu; Du, Zhen-Xian
2012-01-01
Lipopolysaccharide (LPS) is an outer-membrane glycolipid component of Gram-negative bacteria known for its fervent ability to activate monocytic cells and for its potent proinflammatory capabilities. Bcl-2-associated athanogene 3 (BAG3) is a survival protein that has been shown to be stimulated during cell response to stressful conditions, such as exposure to high temperature, heavy metals, proteasome inhibition, and human immunodeficiency virus 1 (HIV-1) infection. In addition, BAG3 regulates replication of Varicella-Zoster Virus (VZV) and Herpes Simplex Virus (HSV) replication, suggesting that BAG3 could participate in the host response to infection. In the current study, we found that LPS increased the expression of BAG3 in a dose- and time-dependent manner. Actinomycin D completely blocked the LPS-induced BAG3 accumulation, as well as LPS activated the proximal promoter of BAG3 gene, supported that the induction by LPS occurred at the level of gene transcription. LPS-induced BAG3 expression was blocked by JNK or NF-κB inhibition, suggesting that JNK and NF-κB pathways participated in BAG3 induction by LPS. In addition, we also found that induction of BAG3 was implicated in monocytic cell adhesion to extracellular matrix induced by LPS. Overall, the data support that BAG3 is induced by LPS via JNK and NF-κB-dependent signals, and involved in monocytic cell-extracellular matrix interaction, suggesting that BAG3 may have a role in the host response to LPS stimulation. Copyright © 2011 Elsevier Inc. All rights reserved.
Genetic Determinants of Intrinsic Colistin Tolerance in Acinetobacter baumannii
Hood, M. Indriati; Becker, Kyle W.; Roux, Christelle M.; Dunman, Paul M.
2013-01-01
Acinetobacter baumannii is a leading cause of multidrug-resistant infections worldwide. This organism poses a particular challenge due to its ability to acquire resistance to new antibiotics through adaptation or mutation. This study was undertaken to determine the mechanisms governing the adaptability of A. baumannii to the antibiotic colistin. Screening of a transposon mutant library identified over 30 genes involved in inducible colistin resistance in A. baumannii. One of the genes identified was lpsB, which encodes a glycosyltransferase involved in lipopolysaccharide (LPS) synthesis. We demonstrate that loss of LpsB function results in increased sensitivity to both colistin and cationic antimicrobial peptides of the innate immune system. Moreover, LpsB is critical for pathogenesis in a pulmonary model of infection. Taken together, these data define bacterial processes required for intrinsic colistin tolerance in A. baumannii and underscore the importance of outer membrane structure in both antibiotic resistance and the pathogenesis of A. baumannii. PMID:23230287
Usefulness of ELISA Methods for Assessing LPS Interactions with Proteins and Peptides
Martínez-Sernández, Victoria; Orbegozo-Medina, Ricardo A.; Romarís, Fernanda; Paniagua, Esperanza; Ubeira, Florencio M.
2016-01-01
Lipopolysaccharide (LPS), the major constituent of the outer membrane of Gram-negative bacteria, can trigger severe inflammatory responses during bacterial infections, possibly leading to septic shock. One approach to combatting endotoxic shock is to neutralize the most conserved part and major mediator of LPS activity (lipid A) with LPS-binding proteins or peptides. Although several available assays evaluate the biological activity of these molecules on LPS (e.g. inhibition of LPS-induced TNF-α production in macrophages), the development of simple and cost-effective methods that would enable preliminary screening of large numbers of potential candidate molecules is of great interest. Moreover, it would be also desirable that such methods could provide information about the possible biological relevance of the interactions between proteins and LPS, which may enhance or neutralize LPS-induced inflammatory responses. In this study, we designed and evaluated different types of ELISA that could be used to study possible interactions between LPS and any protein or peptide. We also analysed the usefulness and limitations of the different ELISAs. Specifically, we tested the capacity of several proteins and peptides to bind FITC-labeled LPSs from Escherichia coli serotypes O111:B4 and O55:B5 in an indirect ELISA and in two competitive ELISAs including casein hydrolysate (hCAS) and biotinylated polymyxin B (captured by deglycosylated avidin; PMX) as LPS-binding agents in the solid phase. We also examined the influence of pH, detergents and different blocking agents on LPS binding. Our results showed that the competitive hCAS-ELISA performed under mildly acidic conditions can be used as a general method for studying LPS interactions, while the more restrictive PMX-ELISA may help to identify proteins/peptides that are likely to have neutralizing properties in vitro or in vivo. PMID:27249227
Pulido, David; Moussaoui, Mohammed; Andreu, David; Nogués, M. Victòria
2012-01-01
Antimicrobial proteins and peptides (AMPs) are essential effectors of innate immunity, acting as a first line of defense against bacterial infections. Many AMPs exhibit high affinity for cell wall structures such as lipopolysaccharide (LPS), a potent endotoxin able to induce sepsis. Hence, understanding how AMPs can interact with and neutralize LPS endotoxin is of special relevance for human health. Eosinophil cationic protein (ECP) is an eosinophil secreted protein with high activity against both Gram-negative and Gram-positive bacteria. ECP has a remarkable affinity for LPS and a distinctive agglutinating activity. By using a battery of LPS-truncated E. coli mutant strains, we demonstrate that the polysaccharide moiety of LPS is essential for ECP-mediated bacterial agglutination, thereby modulating its antimicrobial action. The mechanism of action of ECP at the bacterial surface is drastically affected by the LPS structure and in particular by its polysaccharide moiety. We have also analyzed an N-terminal fragment that retains the whole protein activity and displays similar cell agglutination behavior. Conversely, a fragment with further minimization of the antimicrobial domain, though retaining the antimicrobial capacity, significantly loses its agglutinating activity, exhibiting a different mechanism of action which is not dependent on the LPS composition. The results highlight the correlation between the protein's antimicrobial activity and its ability to interact with the LPS outer layer and promote bacterial agglutination. PMID:22330910
Pulido, David; Moussaoui, Mohammed; Andreu, David; Nogués, M Victòria; Torrent, Marc; Boix, Ester
2012-05-01
Antimicrobial proteins and peptides (AMPs) are essential effectors of innate immunity, acting as a first line of defense against bacterial infections. Many AMPs exhibit high affinity for cell wall structures such as lipopolysaccharide (LPS), a potent endotoxin able to induce sepsis. Hence, understanding how AMPs can interact with and neutralize LPS endotoxin is of special relevance for human health. Eosinophil cationic protein (ECP) is an eosinophil secreted protein with high activity against both Gram-negative and Gram-positive bacteria. ECP has a remarkable affinity for LPS and a distinctive agglutinating activity. By using a battery of LPS-truncated E. coli mutant strains, we demonstrate that the polysaccharide moiety of LPS is essential for ECP-mediated bacterial agglutination, thereby modulating its antimicrobial action. The mechanism of action of ECP at the bacterial surface is drastically affected by the LPS structure and in particular by its polysaccharide moiety. We have also analyzed an N-terminal fragment that retains the whole protein activity and displays similar cell agglutination behavior. Conversely, a fragment with further minimization of the antimicrobial domain, though retaining the antimicrobial capacity, significantly loses its agglutinating activity, exhibiting a different mechanism of action which is not dependent on the LPS composition. The results highlight the correlation between the protein's antimicrobial activity and its ability to interact with the LPS outer layer and promote bacterial agglutination.
Material with core-shell structure
Luhrs, Claudia [Rio Rancho, NM; Richard, Monique N [Ann Arbor, MI; Dehne, Aaron [Maumee, OH; Phillips, Jonathan [Rio Rancho, NM; Stamm, Kimber L [Ann Arbor, MI; Fanson, Paul T [Brighton, MI
2011-11-15
Disclosed is a material having a composite particle, the composite particle including an outer shell and a core. The core is made from a lithium alloying material and the outer shell has an inner volume that is greater in size than the core of the lithium alloying material. In some instances, the outer mean diameter of the outer shell is less than 500 nanometers and the core occupies between 5 and 99% of the inner volume. In addition, the outer shell can have an average wall thickness of less than 100 nanometers.
Salles, M F; Mandine, E; Zalisz, R; Guenounou, M; Smets, P
1989-04-01
Murine monoclonal antibodies that bind outer membrane antigens of the J5 mutant of Escherichia coli O111:B4 were derived from spleen cells of BALB/c mice immunized with killed whole cells and boosted with lipopolysaccharide (LPS) and LPS-associated proteins. Seven hybridomas were selected for their reactivity against the J5 LPS; they cross-reacted with O111, O55, O127, and O128 E. coli LPS. One (B7B3) also reacted with the Serratia marcescens LPS and Klebsiella pneumoniae lipid A. A protective effect was obtained with D6B4 antibody in a lethal endotoxemia model induced by LPS from O111, O127, and O128 E. coli serotypes in D-galactosamine-sensitized mice. D6B4 and D6B3 antibodies protected mice infected with E. coli O111:B4, when administered before infection. The D6B4 antibody was also protective when administered after infection. The antibodies D6B3 and D4B5 were protective in heterologous infection induced by E. coli O2:K1.
Annexin A5 Binds to Lipopolysaccharide and Reduces Its Endotoxin Activity
Rand, Jacob H.; Wu, Xiao-Xuan; Lin, Elaine Y.; Griffel, Alexander; Gialanella, Philip; McKitrick, John C.
2012-01-01
ABSTRACT Annexin A5 (AnxA5) has a high affinity for phosphatidylserine. The protein is widely used to detect apoptotic cells because phosphatidylserine, a phospholipid that is normally present in the inner leaflets of cytoplasmic membranes, becomes translocated to the outer leaflets during programmed cell death. Here we report the novel observation that AnxA5 binds to Gram-negative bacteria via the lipid A domain of lipopolysaccharide (LPS). Binding of AnxA5 to bacteria was measured quantitatively, confirmed by fluorescence microscopy, and found to be inhibited by antibodies against lipid A. AnxA5 also bound to purified dot-blotted LPS and lipid A. Through ellipsometry, we found that the binding of AnxA5 to purified LPS was calcium dependent and rapid and showed a high affinity—characteristics similar to those of AnxA5 binding to phosphatidylserine. Initial functional studies indicated that AnxA5 can affect LPS activities. AnxA5 inhibited LPS-mediated gelation in the Limulus amebocyte lysate assay. Incubation of LPS with the protein reduced the quantity of tumor necrosis factor alpha (TNF-α) released by cultured monocytes compared to that released upon incubation with LPS alone. Initial in vivo experiments indicated that injection of mice with LPS preincubated with AnxA5 produced serum TNF-α levels lower than those seen after injection of LPS alone. These data demonstrate that AnxA5 binds to LPS and open paths to investigation of the potential biological and therapeutic implications of this interaction. PMID:22415004
Norris, Michael H.; Schweizer, Herbert P.
2017-01-01
Burkholderia pseudomallei (Bp) causes the disease melioidosis. The main cause of mortality in this disease is septic shock triggered by the host responding to lipopolysaccharide (LPS) components of the Gram-negative outer membrane. Bp LPS is thought to be a weak inducer of the host immune system. LPS from several strains of Bp were purified and their ability to induce the inflammatory mediators TNF-α and iNOS in murine macrophages at low concentrations was investigated. Innate and adaptive immunity qPCR arrays were used to profile expression patterns of 84 gene targets in response to the different LPS types. Additional qPCR validation confirmed large differences in macrophage response. LPS from a high-virulence serotype B strain 576a and a virulent rough central nervous system tropic strain MSHR435 greatly induced the innate immune response indicating that the immunopathogenesis of these strains is different than in infections with strains similar to the prototype strain 1026b. The accumulation of autophagic vesicles was also increased in macrophages challenged with highly immunogenic Bp LPS. Gene induction and concomitant cytokine secretion profiles of human PBMCs in response to the various LPS were also investigated. MALDI-TOF/TOF was used to probe the lipid A portions of the LPS, indicating substantial structural differences that likely play a role in host response to LPS. These findings add to the evolving knowledge of host-response to bacterial LPS, which can be used to better understand septic shock in melioidosis patients and in the rational design of vaccines. PMID:28453531
Tryptophan 375 stabilizes the outer-domain core of gp120 for HIV vaccine immunogen design.
Hu, Duoyi; Bowder, Dane; Wei, Wenzhong; Thompson, Jesse; Wilson, Mark A; Xiang, Shi-Hua
2017-05-25
The outer-domain core of gp120 may serve as a better HIV vaccine immunogen than the full-length gp120 because of its greater stability and immunogenicity. In our previous report, we introduced two disulfide bonds to the outer-domain core of gp120 to fix its conformation into a CD4-bound state, which resulted in a significant increase in its immunogenicity when compared to the wild-type outer-domain core. In this report, to further improve the immunogenicity of the outer-domain core based immunogen, we have introduced a Tryptophan residue at gp120 amino acid sequence position 375 (375S/W). Our data from immunized guinea pigs indeed shows a striking increase in the immune response due to this stabilized core outer-domain. Therefore, we conclude that the addition of 375W to the outer-domain core of gp120 further stabilizes the structure of immunogen and increases the immunogenicity. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.
Structural and functional insights into the lipopolysaccharide ABC transporter LptB2FG.
Dong, Haohao; Zhang, Zhengyu; Tang, Xiaodi; Paterson, Neil G; Dong, Changjiang
2017-08-09
The cell surface of most Gram-negative bacteria contains lipopolysaccharide that is essential for their viability and drug resistance. A 134-kDa protein complex LptB 2 FG is unique among ATP-binding cassette transporters because it extracts lipopolysaccharide from the external leaflet of the inner membrane and propels it along a filament that extends across the periplasm to directly deliver lipopolysaccharide into the external leaflet of the outer membrane. Here we report the crystal structure of the lipopolysaccharide transporter LptB 2 FG from Klebsiella pneumoniae, in which both LptF and LptG are composed of a β-jellyroll-like periplasmic domain and six α-helical segments in the transmembrane domain. LptF and LptG form a central cavity containing highly conserved hydrophobic residues. Structural and functional studies suggest that LptB 2 FG uses an alternating lateral access mechanism to extract lipopolysaccharide and traffic it along the hydrophobic cavity toward the transporter's periplasmic domains.Lipopolysaccharides (LPS) are synthesized at the periplasmic side of the inner membrane of Gram-negative bacteria and are then extracted by the LptB 2 FG complex during the first step of LPS transport to the outer membrane. Here the authors present the LptB 2 FG structure, which supports an alternating lateral access mechanism for LPS extraction.
Naito, Tomoaki; Mulet, Céline; De Castro, Cristina; Molinaro, Antonio; Saffarian, Azadeh; Nigro, Giulia; Bérard, Marion; Clerc, Mélanie; Pedersen, Amy B; Sansonetti, Philippe J; Pédron, Thierry
2017-10-17
We identified a crypt-specific core microbiota (CSCM) dominated by strictly aerobic, nonfermentative bacteria in murine cecal and proximal colonic (PC) crypts and hypothesized that, among its possible functions, it may affect epithelial regeneration. In the present work, we isolated representative CSCM strains using selective media based upon our initial 16S rRNA-based molecular identification (i.e., Acinetobacter , Delftia , and Stenotrophomonas ). Their tropism for the crypt was confirmed, and their influence on epithelial regeneration was demonstrated in vivo by monocolonization of germfree mice. We also showed that lipopolysaccharide (LPS), through its endotoxin activity, was the dominant bacterial agonist controlling proliferation. The relevant molecular mechanisms were analyzed using colonic crypt-derived organoids exposed to bacterial sonicates or highly purified LPS as agonists. We identified a Toll-like receptor 4 (TLR4)-dependent program affecting crypts at different stages of epithelial differentiation. LPS played a dual role: it repressed cell proliferation through RIPK3-mediated necroptosis of stem cells and cells of the transit-amplifying compartment and concurrently enhanced cell differentiation, particularly the goblet cell lineage. IMPORTANCE The LPS from crypt-specific core microbiota controls intestinal epithelium proliferation through necroptosis of stem cells and enhances cell differentiation, mainly the goblet cell lineage. Copyright © 2017 Naito et al.
Khan, Mohd M; Ernst, Orna; Sun, Jing; Fraser, Iain D C; Ernst, Robert K; Goodlett, David R; Nita-Lazar, Aleksandra
2018-06-24
One cause of sepsis is systemic maladaptive immune response of the host to bacteria and specifically, to Gram-negative bacterial outer membrane glycolipid lipopolysaccharide (LPS). On the host myeloid cell surface, proinflammatory LPS activates the innate immune system via Toll-like receptor-4 (TLR4)/myeloid differentiation factor-2 (MD2) complex. Intracellularly, LPS is also sensed by the noncanonical inflammasome through caspase-11 in mice and 4/5 in humans. The minimal functional determinant for innate immune activation is the membrane anchor of LPS called lipid A. Even subtle modifications to the lipid A scaffold can enable, diminish, or abolish immune activation. Bacteria are known to modify their LPS structure during environmental stress, and infection of hosts to alter cellular immune phenotypes. In this review, we describe how mass spectrometry (MS)-based structural analysis of endotoxin helped uncover major determinations of molecular pathogenesis. Through characterization of LPS modifications, we now better understand resistance to antibiotics and cationic antimicrobial peptides, as well as how the environment impacts overall endotoxin structure. In addition, MS-based systems immunoproteomics approaches can assist in elucidating the immune response against LPS. Many regulatory proteins have been characterized through proteomics and global/targeted analysis of protein modifications, enabling the discovery and characterization of novel endotoxin-mediated protein translational modifications (PTMs). Copyright © 2018. Published by Elsevier Ltd.
Mesophilic Aeromonas sp. serogroup O:11 resistance to complement-mediated killing.
Merino, S; Rubires, X; Aguilar, A; Albertí, S; Hernandez-Allés, S; Benedí, V J; Tomas, J M
1996-01-01
The complement activation by and resistance to complement-mediated killing of Aeromonas sp. strains from serogroup O:11 were investigated by using different wild-type strains (with an S-layer characteristic of this serogroup) and their isogenic mutants characterized for their surface components (S-layer and lipopolysaccharide [LPS]). All of the Aeromonas sp. serogroup O:11 wild-type strains are unable to activate complement, which suggested that the S-layer completely covered the LPS molecules. We found that the classical complement pathway is involved in serum killing of susceptible Aeromonas sp. mutant strains of serogroup O11, while the alternative complement pathway seems not to be involved, and that the complement activation seems to be independent of antibody. The smooth mutant strains devoid of the S-layer (S-layer isogenic mutants) or isogenic LPS mutant strains with a complete or rather complete LPS core (also without the S-layer) are able to activate complement but are resistant to complement-mediated killing. The reasons for this resistance are that C3b is rapidly degraded, and therefore the lytic membrane attack complex (C5b-9) is not formed. Isogenic LPS rough mutants with an incomplete LPS core are serum sensitive because they bind more C3b than the resistant strains, the C3b is not completely degraded, and therefore the lytic complex (C5b-9) is formed. PMID:8945581
Conservation and Accessibility of an Inner Core Lipopolysaccharide Epitope of Neisseria meningitidis
Plested, Joyce S.; Makepeace, Katherine; Jennings, Michael P.; Gidney, Margaret Anne J.; Lacelle, Suzanne; Brisson, J.-R.; Cox, Andrew D.; Martin, Adele; Bird, A. Graham; Tang, Christoph M.; Mackinnon, Fiona M.; Richards, James C.; Moxon, E. Richard
1999-01-01
We investigated the conservation and antibody accessibility of inner core epitopes of Neisseria meningitidis lipopolysaccharide (LPS) because of their potential as vaccine candidates. An immunoglobulin G3 murine monoclonal antibody (MAb), designated MAb B5, was obtained by immunizing mice with a galE mutant of N. meningitidis H44/76 (B.15.P1.7,16 immunotype L3). We have shown that MAb B5 can bind to the core LPS of wild-type encapsulated MC58 (B.15.P1.7,16 immunotype L3) organisms in vitro and ex vivo. An inner core structure recognized by MAb B5 is conserved and accessible in 26 of 34 (76%) of group B and 78 of 112 (70%) of groups A, C, W, X, Y, and Z strains. N. meningitidis strains which possess this epitope are immunotypes in which phosphoethanolamine (PEtn) is linked to the 3-position of the β-chain heptose (HepII) of the inner core. In contrast, N. meningitidis strains lacking reactivity with MAb B5 have an alternative core structure in which PEtn is linked to an exocyclic position (i.e., position 6 or 7) of HepII (immunotypes L2, L4, and L6) or is absent (immunotype L5). We conclude that MAb B5 defines one or more of the major inner core glycoforms of N. meningitidis LPS. These findings support the possibility that immunogens capable of eliciting functional antibodies specific to inner core structures could be the basis of a vaccine against invasive infections caused by N. meningitidis. PMID:10496924
Liechti, George; Goldberg, Joanna B.
2012-01-01
The bacterial pathogen Helicobacter pylori is capable of colonizing the gastric mucosa of the human stomach using a variety of factors associated with or secreted from its outer membrane (OM). Lipopolysaccharide (LPS) and numerous OM proteins have been shown to be involved in adhesion and immune stimulation/evasion. Many of these factors are essential for colonization and/or pathogenesis in a variety of animal models. Despite this wide array of potential targets present on the bacterial surface, the ability of H. pylori to vary its OM profile limits the effectiveness of vaccines or therapeutics that target any single one of these components. However, it has become evident that the proteins comprising the complexes that transport the majority of these molecules to the OM are highly conserved and often essential. The field of membrane biogenesis has progressed remarkably in the last few years, and the possibility now exists for targeting the mechanisms by which β-barrel proteins, lipoproteins, and LPS are transported to the OM, resulting in loss of bacterial fitness and significant altering of membrane permeability. In this review, the OM transport machinery for LPS, lipoproteins, and outer membrane proteins (OMPs) are discussed. While the principal investigations of these transport mechanisms have been conducted in Escherichia coli and Neisseria meningitidis, here these systems will be presented in the genetic context of ε proteobacteria. Bioinformatic analysis reveals that minimalist genomes, such as that of Helicobacter pylori, offer insight into the smallest number of components required for these essential pathways to function. Interestingly, in the majority of ε proteobacteria, while the inner and OM associated apparatus of LPS, lipoprotein, and OMP transport pathways appear to all be intact, most of the components associated with the periplasmic compartment are either missing or are almost unrecognizable when compared to their E. coli counterparts. Eventual targeting of these pathways would have the net effect of severely limiting the delivery/transport of components to the OM and preventing the bacterium's ability to infect its human host. PMID:22919621
Jones, Randall T.; Koeltzow, Donald E.; Stocker, B. A. D.
1972-01-01
Escherichia coli K-12 ϰ971 was crossed with a smooth Salmonella typhimurium donor, HfrK6, which transfers early the ilv-linked rfa region determining lipopolysaccharide (LPS) core structure. Two ilv+ hybrids differing in their response to the LPS-specific phages FO and C21 were then crossed with S. typhimurium HfrK9, which transfers early the rfb gene cluster determining O repeat unit structure. Most recombinants selected for his+ (near rfb) were agglutinated by Salmonella factor 4 antiserum. Transfer of an F′ factor (FS400) carrying the rfb–his region of S. typhimurium to the same two ilv+ hybrids gave similar results. LPS extracted from two ilv+,his+, factor 4-positive hybrids contained abequose, the immunodominant sugar for factor 4 specificity. By contrast, his+ hybrids obtained from ϰ971 itself by similar HfrK9 and F′FS400 crosses were not agglutinated by factor 4 antiserum, indicating that the parental E. coli ϰ971 does not have the capacity to attach Salmonella O repeat units to its LPS core. It is concluded that the Salmonella rfb genes are expressed only in E. coli ϰ971 hybrids which have also acquired ilv-linked genes (presumably rfa genes affecting core structure or O-translocase ability, or both) from a S. typhimurium donor. When E. coli ϰ971 was crossed with a smooth E. coli donor, Hfr59, of serotype O8, which transfers his early, most his+ recombinants were agglutinated by E. coli O8 antiserum and lysed by the O8-specific phage, Ω8. This suggests that, although the parental E. coli K-12 strain ϰ971 cannot attach Salmonella-specific repeat units to its LPS core, it does have the capacity to attach E. coli O8-specific repeat units. PMID:4559827
Noonin, Chadanat; Jiravanichpaisal, Pikul; Söderhäll, Irene; Merino, Susana; Tomás, Juan M.; Söderhäll, Kenneth
2010-01-01
Aeromonas hydrophila is the most common Aeromonas species causing infections in human and other animals such as amphibians, reptiles, fish and crustaceans. Pathogenesis of Aeromonas species have been reported to be associated with virulence factors such as lipopolysaccharides (LPS), bacterial toxins, bacterial secretion systems, flagella, and other surface molecules. Several mutant strains of A. hydrophila AH-3 were initially used to study their virulence in two animal species, Pacifastacus leniusculus (crayfish) and Tenebrio molitor larvae (mealworm). The AH-3 strains used in this study have mutations in genes involving the synthesis of flagella, LPS structures, secretion systems, and some other factors, which have been reported to be involved in A. hydrophila pathogenicity. Our study shows that the LPS (O-antigen and external core) is the most determinant A. hydrophila AH-3 virulence factor in both animals. Furthermore, we studied the immune responses of these hosts to infection of virulent or non-virulent strains of A. hydrophila AH-3. The AH-3 wild type (WT) containing the complete LPS core is highly virulent and this bacterium strongly stimulated the prophenoloxidase activating system resulting in melanization in both crayfish and mealworm. In contrast, the ΔwaaE mutant which has LPS without O-antigen and external core was non-virulent and lost ability to stimulate this system and melanization in these two animals. The high phenoloxidase activity found in WT infected crayfish appears to result from a low expression of pacifastin, a prophenoloxidase activating enzyme inhibitor, and this gene expression was not changed in the ΔwaaE mutant infected animal and consequently phenoloxidase activity was not altered as compared to non-infected animals. Therefore we show that the virulence factors of A. hydrophila are the same regardless whether an insect or a crustacean is infected and the O-antigen and external core is essential for activation of the proPO system and as virulence factors for this bacterium. PMID:21206752
Lu, Shuo; Zgurskaya, Helen I
2013-11-01
The Escherichia coli MacAB-TolC transporter has been implicated in efflux of macrolide antibiotics and secretion of enterotoxin STII. In this study, we found that purified MacA, a periplasmic membrane fusion protein, contains one tightly bound rough core lipopolysaccharide (R-LPS) molecule per MacA molecule. R-LPS was bound specifically to MacA protein with affinity exceeding that of polymyxin B. Sequence analyses showed that MacA contains two high-density clusters of positively charged amino acid residues located in the cytoplasmic N-terminal domain and the periplasmic C-terminal domain. Substitutions in the C-terminal cluster reducing the positive-charge density completely abolished binding of R-LPS. At the same time, these substitutions significantly reduced the functionality of MacA in the protection of E. coli against macrolides in vivo and in the in vitro MacB ATPase stimulation assays. Taken together, our results suggest that R-LPS or a similar glycolipid is a physiological substrate of MacAB-TolC.
Lu, Shuo
2013-01-01
The Escherichia coli MacAB-TolC transporter has been implicated in efflux of macrolide antibiotics and secretion of enterotoxin STII. In this study, we found that purified MacA, a periplasmic membrane fusion protein, contains one tightly bound rough core lipopolysaccharide (R-LPS) molecule per MacA molecule. R-LPS was bound specifically to MacA protein with affinity exceeding that of polymyxin B. Sequence analyses showed that MacA contains two high-density clusters of positively charged amino acid residues located in the cytoplasmic N-terminal domain and the periplasmic C-terminal domain. Substitutions in the C-terminal cluster reducing the positive-charge density completely abolished binding of R-LPS. At the same time, these substitutions significantly reduced the functionality of MacA in the protection of E. coli against macrolides in vivo and in the in vitro MacB ATPase stimulation assays. Taken together, our results suggest that R-LPS or a similar glycolipid is a physiological substrate of MacAB-TolC. PMID:23974027
Associations of Escherichia coli K-12 OmpF trimers with rough and smooth lipopolysaccharides
DOE Office of Scientific and Technical Information (OSTI.GOV)
Diedrich, D.L.; Stein, M.A.; Schnaitman, C.A.
1990-09-01
The associations of both rough and smooth lipopolysaccharides (LPS) with the OmpF porin of Escherichia coli K-12 were examined in galE strains deleted for ompC. Transformation with pSS37 and growth with galactose conferred the ability to assemble a Shigella dysenteriae O antigen onto the core oligosaccharide of E. coli K-12 LPS. The association of LPS with OmpF trimers was assessed by staining, autoradiography of LPS specifically labeled with (1-14C)galactose, and Western immunoblotting with a monoclonal antibody specific for OmpF trimers. These techniques revealed that the migration distances and multiple banding patterns of OmpF porin trimers in sodium dodecyl sulfate-polyacrylamide gelsmore » were dictated by the chemotype of associated LPS. Expression of smooth LPS caused almost all of the trimeric OmpF to run in gels with a slower mobility than trimers from rough strains. The LPS associated with trimers from a smooth strain differed from the bulk-phase LPS by consisting almost exclusively of molecules with O antigen.« less
Simpson, Brent W.; Owens, Tristan W.; Orabella, Matthew J.; Davis, Rebecca M.; May, Janine M.; Trauger, Sunia A.
2016-01-01
ABSTRACT The surface of most Gram-negative bacteria is covered with lipopolysaccharide (LPS), creating a permeability barrier against toxic molecules, including many antimicrobials. To assemble LPS on their surface, Gram-negative bacteria must extract newly synthesized LPS from the inner membrane, transport it across the aqueous periplasm, and translocate it across the outer membrane. The LptA to -G proteins assemble into a transenvelope complex that transports LPS from the inner membrane to the cell surface. The Lpt system powers LPS transport from the inner membrane by using a poorly characterized ATP-binding cassette system composed of the ATPase LptB and the transmembrane domains LptFG. Here, we characterize a cluster of residues in the groove region of LptB that is important for controlling LPS transport. We also provide the first functional characterization of LptFG and identify their coupling helices that interact with the LptB groove. Substitutions at conserved residues in these coupling helices compromise both the assembly and function of the LptB2FG complex. Defects in LPS transport conferred by alterations in the LptFG coupling helices can be rescued by changing a residue in LptB that is adjacent to functionally important residues in the groove region. This suppression is achieved by increasing the ATPase activity of the LptB2FG complex. Taken together, these data identify a specific binding site in LptB for the coupling helices of LptFG that is responsible for coupling of ATP hydrolysis by LptB with LptFG function to achieve LPS extraction. PMID:27795402
Hoffman, Jared M; Sullivan, Shea; Wu, Erin; Wilson, Eric; Erickson, David L
2017-09-07
RfaH enhances transcription of a select group of operons controlling bacterial surface features such as lipopolysaccharide (LPS). Previous studies have suggested that rfaH may be required for Yersinia pseudotuberculosis resistance to antimicrobial chemokines and survival during mouse infections. In order to further investigate the role of RfaH in LPS synthesis, resistance to host defense peptides, and virulence of Yersinia, we constructed ΔrfaH mutants of Y. pseudotuberculosis IP32953 and Y. pestis KIM6+. Loss of rfaH affected LPS synthesis in both species, resulting in a shorter core oligosaccharide. Susceptibility to polymyxin and the antimicrobial chemokine CCL28 was increased by loss of rfaH in Y. pseudotuberculosis but not in Y. pestis. Transcription of genes in the ddhD-wzz O-antigen gene cluster, but not core oligosaccharide genes, was reduced in ΔrfaH mutants. In addition, mutants with disruptions in specific ddhD-wzz O-antigen cluster genes produced LPS that was indistinguishable from the ΔrfaH mutant. This suggests that both Y. pseudotuberculosis and Y. pestis produce an oligosaccharide core with a single O-antigen unit attached in an RfaH-dependent fashion. Despite enhanced sensitivity to host defense peptides, the Y. pseudotuberculosis ΔrfaH strain was not attenuated in mice, suggesting that rfaH is not required for acute infection.
Shamsi, Mohammad Bagher; Rezaei, Mandana; Zamanlou, Mehdi; Sadeghi, Mehdi; Pourahmadi, Mohammad Reza
2016-01-01
The aim was to compare core stability and general exercises (GEs) in chronic low back pain (LBP) patients based on lumbopelvic stability (LPS) assessment through three endurance core stability tests. There is a controversy about preference of core stability exercise (CSE) over other types of exercise for chronic LBP. Studies which have compared these exercises used other outcomes than those related to LPS. As it is claimed that CSE enhances back stability, endurance tests for LPS were used. A 16-session CSE program and a GE program with the same duration were conducted for two groups of participants. Frequency of interventions for both groups was three times a week. Forty-three people (aged 18-60 years) with chronic non-specific LBP were alternately allocated to core stability (n = 22) or GE group (n = 21) when admitted. The primary outcomes were three endurance core stability tests including: (1) trunk flexor; (2) trunk extensor; and (3) side bridge tests. Secondary outcomes were disability and pain. Measurements were taken at baseline and the end of the intervention. After the intervention, test times increased and disability and pain decreased within groups. There was no significant difference between two groups in increasing test times (p = 0.23 to p = 0.36) or decreasing disability (p = 0.16) and pain (p = 0.73). CSE is not more effective than GE for improving endurance core stability tests and reducing disability and pain in chronic non-specific LBP patients.
Merino, S; Camprubí, S; Tomás, J M
1992-01-01
Growth of Aeromonas hydrophila strains from serotype O:34 at 20 and 37 degrees C in tryptic soy broth resulted in changes in the lipids, lipopolysaccharide (LPS), and virulence of the strains tested. Cells grown at 20 degrees C contained, relative to those cultured at 37 degrees C, increased levels of the phospholipid fatty acids hexadecanoate and octadecanoate and reduced levels of the corresponding saturated fatty acids. Furthermore, the lipid A fatty acids also showed thermoadaptation. In addition, LPS extracted from cells cultivated at 20 degrees C was smooth, while the LPS extracted from the same cells cultivated at 37 degrees C was rough. Finally, the strains were more virulent for fish and mice when they were grown at 20 degrees C than when they were grown at 37 degrees C and also showed increased different extracellular activities when they were grown at 20 degrees C. Images PMID:1398945
Merino, Susana; Knirel, Yuriy A.; Regué, Miguel; Tomás, Juan M.
2013-01-01
We experimentally identified the activities of six predicted heptosyltransferases in Actinobacillus pleuropneumoniae genome serotype 5b strain L20 and serotype 3 strain JL03. The initial identification was based on a bioinformatic analysis of the amino acid similarity between these putative heptosyltrasferases with others of known function from enteric bacteria and Aeromonas. The putative functions of all the Actinobacillus pleuropneumoniae heptosyltrasferases were determined by using surrogate LPS acceptor molecules from well-defined A. hydrophyla AH-3 and A. salmonicida A450 mutants. Our results show that heptosyltransferases APL_0981 and APJL_1001 are responsible for the transfer of the terminal outer core D-glycero-D-manno-heptose (D,D-Hep) residue although they are not currently included in the CAZY glycosyltransferase 9 family. The WahF heptosyltransferase group signature sequence [S(T/S)(GA)XXH] differs from the heptosyltransferases consensus signature sequence [D(TS)(GA)XXH], because of the substitution of D261 for S261, being unique. PMID:23383222
Sprayed skin turbine component
Allen, David B
2013-06-04
Fabricating a turbine component (50) by casting a core structure (30), forming an array of pits (24) in an outer surface (32) of the core structure, depositing a transient liquid phase (TLP) material (40) on the outer surface of the core structure, the TLP containing a melting-point depressant, depositing a skin (42) on the outer surface of the core structure over the TLP material, and heating the assembly, thus forming both a diffusion bond and a mechanical interlock between the skin and the core structure. The heating diffuses the melting-point depressant away from the interface. Subsurface cooling channels (35) may be formed by forming grooves (34) in the outer surface of the core structure, filling the grooves with a fugitive filler (36), depositing and bonding the skin (42), then removing the fugitive material.
Liquid Iron Alloys with Hydrogen at Outer Core Conditions by First Principles
NASA Astrophysics Data System (ADS)
Umemoto, K.; Hirose, K.
2015-12-01
Since the density of the outer core deduced from seismic data is about 10% lower than that of pure iron at core pressures and temperatures (P-T), it is widely believed that the outer core includes one or more light elements. Although intensive experimental and theoretical studies have been performed so far, the light element in the core has not yet been identified. Comparison of the density and sound velocity of liquid iron alloys with observations, such as the PREM, is a promising way to determine the species and quantity of light alloying component(s) in the outer core. Here we report the results of a first-principles molecular dynamics study on liquid iron alloyed with hydrogen, one of candidates of the light elements. Hydrogen had been much less studied than other candidates. However, hydrogen has been known to reduce the melting temperature of Fe-H solid [1]. Furthermore, very recently, Nomura et al. argued that the outer core may include 24 at.% H in order to be molten under relatively low temperature (< 3600 K) [2]. Since then hydrogen has attracted strong interests. We clarify the effects of hydrogen on density and sound velocity of liquid iron alloys under outer core P-T conditions. It is shown that ~1 wt% hydrogen can reproduce PREM density and sound velocity simultaneously very well. In addition, we show the presence of hydrogen rather reduces Gruneisen parameters. It indicates that, if hydrogen exists in the outer core, temperature profile of the outer core could be changed considerably from one estimated so far. [1] Sakamaki, K., E. Takahashi, Y. Nakajima, Y. Nishihara, K. Funakoshi, T. Suzuki, and Y. Fukai, Phys. Earth Planet. Inter., 174, 192-201 (2009). [2] Nomura, R., K. Hirose, K. Uesugi, Y. Ohishi, A. Tsuchiyama, A. Miyake, and Y. Ueno, Science 31, 522-525 (2014).
Praying Mantis Bending Core Breakoff and Retention Mechanism
NASA Technical Reports Server (NTRS)
Badescu, Mircea; Sherrit, Stewart; Bar-Cohen, Yoseph; Bao, Xiaoqi; Lindermann, Randel A.
2011-01-01
Sampling cores requires the controlled breakoff of the core at a known location with respect to the drill end. An additional problem is designing a mechanism that can be implemented at a small scale, yet is robust and versatile enough to be used for a variety of core samples. The new design consists of a set of tubes (a drill tube, an outer tube, and an inner tube) and means of sliding the inner and outer tubes axially relative to each other. Additionally, a sample tube can be housed inside the inner tube for storing the sample. The inner tube fits inside the outer tube, which fits inside the drill tube. The inner and outer tubes can move axially relative to each other. The inner tube presents two lamellae with two opposing grabbing teeth and one pushing tooth. The pushing tooth is offset axially from the grabbing teeth. The teeth can move radially and their motion is controlled by the outer tube. The outer tube presents two lamellae with radial extrusions to control the inner tube lamellae motion. In breaking the core, the mechanism creates two support points (the grabbing teeth and the bit tip) and one push point. The core is broken in bending. The grabbing teeth can also act as a core retention mechanism. The praying mantis that is disclosed herein is an active core breaking/retention mechanism that requires only one additional actuator other than the drilling actuator. It can break cores that are attached to the borehole bottom as
Gidney, Margaret Anne J.; Plested, Joyce S.; Lacelle, Suzanne; Coull, Philip A.; Wright, J. Claire; Makepeace, Katherine; Brisson, Jean-Robert; Cox, Andrew D.; Moxon, E. Richard; Richards, James C.
2004-01-01
A panel of six murine monoclonal antibodies (MAbs) recognizing inner core lipopolysaccharide (LPS) epitopes of Neisseria meningitidis was prepared and characterized in order to determine the diversity of inner core LPS glycoforms among disease and carrier isolates. Two of these MAbs, L2-16 (immunoglobulin G2b [IgG2b]) and LPT3-1 (IgG2a), together with a third, previously described MAb, L3B5 (IgG3), showed reactivity, either individually or in combination, with all except 3 of 143 disease and carriage isolates (125 of 126 strains from blood, cerebrospinal fluid, or skin biopsy samples and 15 of 17 from nasopharyngeal cultures). MAbs L3B5, L2-16, and LPT3-1 were further characterized in an indirect immunofluorescence assay. All three MAbs bound to the bacterial cell surface, findings that correlated strongly with whole-cell enzyme-linked immunosorbent assay and immunodot blots. However, in contrast to our findings with L3B5, cell surface binding of L2-16 or LPT 3-1 did not correlate with functional activity as determined by bactericidal or infant rat passive protection assays against wild-type N. meningitidis strains. These findings are provocative with respect to the requirements for protective activity of antibodies and the development of inner core LPS vaccines against invasive meningococcal disease. PMID:14688137
Professor Krystyna Kotełko and her contribution to the study of Proteus endotoxin.
Różalski, Antoni W
2018-04-01
Professor Krystyna Kotełko was working as a microbiologist at the University of Łódź (Poland). Her main object of study was the LPS (endotoxin) of opportunistic urinary pathogens from the genus Proteus. She demonstrated, for the first time, the presence of uronic acids and amino acids, as well as two heptoses (L- glycero-D- manno-heptose and D- glycero-D- manno-heptose) and hexosamines in Proteus LPS, and developed a classification scheme of the Proteus LPS into chemotypes. Prof Kotełko also initiated studies on the chemical structure of Proteus O-specific polysaccharide and investigations on the serological specificity of this part of LPS, as well its core region. She also analysed the virulence factors of these bacteria, such as haemolysin and invasiveness.
USDA-ARS?s Scientific Manuscript database
Rhizobium bacteria live in soil and plant environments, are capable of inducing symbiotic nodules on legumes, invade these nodules, and develop into bacteroids that fix atmospheric nitrogen into ammonium. Lipopolysaccharide (LPS) is anchored in the bacterial outer membrane through a specialized lipi...
Warshakoon, Hemamali J.; Burns, Mark R.; David, Sunil A.
2009-01-01
We have recently confirmed that lipoteichoic acid (LTA), a major constituent of the gram-positive bacterial surface, is the endotoxin of gram-positive bacteria that induces proinflammatory molecules in a Toll-like receptor 2 (TLR2)-dependent manner. LTA is an anionic amphipath whose physicochemical properties are similar to those of lipopolysaccharide (LPS), which is found on the outer leaflet of the outer membranes of gram-negative organisms. Hypothesizing that compounds that sequester LPS could also bind to and inhibit LTA-induced cellular activation, we screened congeneric series of polyamine sulfonamides which we had previously shown effectively neutralized LPS both in vitro and in animal models of endotoxemia. We observed that these compounds do bind to and neutralize LTA, as reflected by the inhibition of TLR2-mediated NF-κB induction in reporter gene assays. Structure-activity studies showed a clear dependence of the acyl chain length on activity against LTA in compounds with spermine and homospermine scaffolds. We then sought to examine possible correlations between the neutralizing potency toward LTA and antimicrobial activity in Staphylococcus aureus. A linear relationship between LTA sequestration activity and antimicrobial activity for compounds with a spermine backbone was observed, while all compounds with a homospermine backbone were equally active against S. aureus, regardless of their neutralizing potency toward LTA. These results suggest that the number of protonatable charges is a key determinant of the activity toward the membranes of gram-positive bacteria. The development of resistance to membrane-active antibiotics has been relatively slower than that to conventional antibiotics, and it is possible that compounds such as the acylpolyamines may be useful clinically, provided that they have an acceptable safety profile and margin of safety. A more detailed understanding of the mechanisms of interactions of these compounds with LPS and LTA, as well as the gram-negative and -positive bacterial cell surfaces, will be instructive and should allow the rational design of analogues which combine antisepsis and antibacterial properties. PMID:18955537
DOE Office of Scientific and Technical Information (OSTI.GOV)
Shi, Jia; Yu, Jian-bo, E-mail: yujianbo11@126.com; Liu, Wei
Acute respiratory distress syndrome (ARDS) is one of the most devastating complications of sepsis lacking of effective therapy. Mitochondrial dynamics undergoing continuous fusion and fission play a crucial role in mitochondrial structure and function. Fis1, as a small protein located on the outer membrane of mitochondria, has been thought to be an important protein mediated mitochondrial fission. During ARDS, alveolar macrophages suffer from increased oxidative stress and apoptosis, and also accompanied by disrupted mitochondrial dynamics. In addition, as one of the products of heme degradation catalyzed by heme oxygenase, carbon monoxide (CO) possesses powerful protective properties in vivo or inmore » vitro models, such as anti-inflammatory, antioxidant and anti-apoptosis function. However, there is little evidence that CO alleviates oxidative stress damage through altering mitochondrial fission in alveolar macrophages. In the present study, our results showed that CO increased cell vitality, improved mitochondrial SOD activity, reduced reactive oxygen species (ROS) production and inhibited cell apoptosis in NR8383 exposed to LPS. Meanwhile, CO decreased the expression of Fis1, increased mitochondrial membrane potential and sustained elongation of mitochondria in LPS-incubated NR8383. Overall, our study underscored a critical role of CO in suppressing the expression of Fis1 and alleviating LPS- induced oxidative stress damage in alveolar macrophages. - Highlights: • LPS exposure triggered cell injury in NR8383. • CO alleviated LPS-induced oxidative stress damage in alveolar macrophages. • CO inhibited Fis1 levels and improved mitochondrial function in LPS-induced NR8383.« less
The melting curve of iron to 250 gigapascals - A constraint on the temperature at earth's center
NASA Technical Reports Server (NTRS)
Williams, Quentin; Jeanloz, Raymond; Bass, Jay; Svendsen, Bob; Ahrens, Thomas J.
1987-01-01
The melting curve of iron, the primary constituent of earth's core, has been measured to pressures of 250 gigapascals with a combination of static and dynamic techniques. The melting temperature of iron at the pressure of the core-mantle boundary (136 GPa) is 4800 + or - 200 K, whereas at the inner core-outer core boundary (330 GPa), it is 7600 + or - 500 K. A melting temperature for iron-rich alloy of 6600 K at the inner core-outer core boundary and a maximum temperature of 6900 K at earth's center are inferred. This latter value is the first experimental upper bound on the temperature at earth's center, and these results imply that the temperature of the lower mantle is significantly less than that of the outer core.
Brandenburg, Klaus; Heinbockel, Lena; Correa, Wilmar; Fukuoka, Satoshi; Gutsmann, Thomas; Zähringer, Ulrich; Koch, Michel H J
2016-04-01
Lipopolysaccharides (LPS) belong to the strongest immune-modulating compounds known in nature, and are often described as pathogen-associated molecular patterns (PAMPs). In particular, at higher concentrations they are responsible for sepsis and the septic shock syndrome associated with high lethality. Since most data are indicative that LPS aggregates are the bioactive units, their supramolecular structures are considered to be of outmost relevance for deciphering the molecular mechanisms of its bioactivity. So far, however, most of the data available addressing this issue, were published only for the lipid part (lipid A) and the core-oligosaccharide containing rough LPS, representing the bioactive unit. By contrast, it is well known that most of the LPS specimen identified in natural habitats contain the smooth-form (S-form) LPS, which carry additionally a high-molecular polysaccharide (O-chain). To fill this lacuna and going into a more natural system, here various wild-type (smooth form) LPS including also some LPS fractions were investigated by small-angle X-ray scattering with synchrotron radiation to analyze their aggregate structure. Furthermore, the influence of a recently designed synthetic anti-LPS peptide (SALP) Pep19-2.5 on the aggregate structure, on the binding thermodynamics, and on the cytokine-inducing activity of LPS were characterized, showing defined aggregate changes, high affinity binding and inhibition of cytokine secretion. The data obtained are suitable to refine our view on the preferences of LPS for non-lamellar structures, representing the highest bioactive forms which can be significantly influenced by the binding with neutralizing peptides such as Pep19-2.5. Copyright © 2016 Elsevier Inc. All rights reserved.
The thermal evolution of Mercury's Fe-Si core
NASA Astrophysics Data System (ADS)
Knibbe, Jurriën Sebastiaan; van Westrenen, Wim
2018-01-01
We have studied the thermal and magnetic field evolution of planet Mercury with a core of Fe-Si alloy to assess whether an Fe-Si core matches its present-day partially molten state, Mercury's magnetic field strength, and the observed ancient crustal magnetization. The main advantages of an Fe-Si core, opposed to a previously assumed Fe-S core, are that a Si-bearing core is consistent with the highly reduced nature of Mercury and that no compositional convection is generated upon core solidification, in agreement with magnetic field indications of a stable layer at the top of Mercury's core. This study also present the first implementation of a conductive temperature profile in the core where heat fluxes are sub-adiabatic in a global thermal evolution model. We show that heat migrates from the deep core to the outer part of the core as soon as heat fluxes at the outer core become sub-adiabatic. As a result, the deep core cools throughout Mercury's evolution independent of the temperature evolution at the core-mantle boundary, causing an early start of inner core solidification and magnetic field generation. The conductive layer at the outer core suppresses the rate of core growth after temperature differences between the deep and shallow core are relaxed, such that a magnetic field can be generated until the present. Also, the outer core and mantle operate at higher temperatures than previously thought, which prolongs mantle melting and mantle convection. The results indicate that S is not a necessary ingredient of Mercury's core, bringing bulk compositional models of Mercury more in line with reduced meteorite analogues.
Experimental constraints on light elements in the Earth’s outer core
Zhang, Youjun; Sekine, Toshimori; He, Hongliang; Yu, Yin; Liu, Fusheng; Zhang, Mingjian
2016-01-01
Earth’s outer core is liquid and dominantly composed of iron and nickel (~5–10 wt%). Its density, however, is ~8% lower than that of liquid iron, and requires the presence of a significant amount of light element(s). A good way to specify the light element(s) is a direct comparison of density and sound velocity measurements between seismological data and those of possible candidate compositions at the core conditions. We report the sound velocity measurements of a model core composition in the Fe-Ni-Si system at the outer core conditions by shock-wave experiments. Combining with the previous studies, we found that the best estimate for the outer core’s light elements is ~6 wt% Si, ~2 wt% S, and possible ~1–2.5 wt% O. This composition satisfies the requirements imposed by seismology, geochemistry, and some models of the early core formation. This finding may help us to further constrain the thermal structure of the Earth and the models of Earth’s core formation. PMID:26932596
NASA Astrophysics Data System (ADS)
Zhang, Youjun; Sekine, Toshimori; Lin, Jung-Fu; He, Hongliang; Liu, Fusheng; Zhang, Mingjian; Sato, Tomoko; Zhu, Wenjun; Yu, Yin
2018-02-01
Understanding the melting behavior and the thermal equation of state of Fe-Ni alloyed with candidate light elements at conditions of the Earth's core is critical for our knowledge of the region's thermal structure and chemical composition and the heat flow across the liquid outer core into the lowermost mantle. Here we studied the shock equation of state and melting curve of an Fe-8 wt% Ni-10 wt% Si alloy up to 250 GPa by hypervelocity impacts with direct velocity and reliable temperature measurements. Our results show that the addition of 10 wt% Si to Fe-8 wt% Ni alloy slightly depresses the melting temperature of iron by 200-300 (±200) K at the core-mantle boundary ( 136 GPa) and by 600-800 (±500) K at the inner core-outer core boundary ( 330 GPa), respectively. Our results indicate that Si has a relatively mild effect on the melting temperature of iron compared with S and O. Our thermodynamic modeling shows that Fe-5 wt% Ni alloyed with 6 wt% Si and 2 wt% S (which has a density-velocity profile that matches the outer core's seismic profile well) exhibits an adiabatic profile with temperatures of 3900 K and 5300 K at the top and bottom of the outer core, respectively. If Si is a major light element in the core, a geotherm modeled for the outer core indicates a thermal gradient of 5.8-6.8 (±1.6) K/km in the D″ region and a high heat flow of 13-19 TW across the core-mantle boundary.
Naito, Tomoaki; Mulet, Céline; De Castro, Cristina; Molinaro, Antonio; Saffarian, Azadeh; Nigro, Giulia; Bérard, Marion; Clerc, Mélanie; Pedersen, Amy B.; Pédron, Thierry
2017-01-01
ABSTRACT We identified a crypt-specific core microbiota (CSCM) dominated by strictly aerobic, nonfermentative bacteria in murine cecal and proximal colonic (PC) crypts and hypothesized that, among its possible functions, it may affect epithelial regeneration. In the present work, we isolated representative CSCM strains using selective media based upon our initial 16S rRNA-based molecular identification (i.e., Acinetobacter, Delftia, and Stenotrophomonas). Their tropism for the crypt was confirmed, and their influence on epithelial regeneration was demonstrated in vivo by monocolonization of germfree mice. We also showed that lipopolysaccharide (LPS), through its endotoxin activity, was the dominant bacterial agonist controlling proliferation. The relevant molecular mechanisms were analyzed using colonic crypt-derived organoids exposed to bacterial sonicates or highly purified LPS as agonists. We identified a Toll-like receptor 4 (TLR4)-dependent program affecting crypts at different stages of epithelial differentiation. LPS played a dual role: it repressed cell proliferation through RIPK3-mediated necroptosis of stem cells and cells of the transit-amplifying compartment and concurrently enhanced cell differentiation, particularly the goblet cell lineage. PMID:29042502
Zhao, Peng; Turdi, Subat; Dong, Feng; Xiao, Xiaoyan; Su, Guohai; Zhu, Xinglei; Scott, Glenda I; Ren, Jun
2009-07-01
Lipopolysaccharide (LPS), a component of the outer membrane of Gram-negative bacteria, plays a key role in cardiac dysfunction in sepsis. Low circulating levels of insulin-like growth factor 1 (IGF-1) are found in sepsis, although the influence of IGF-1 on septic cardiac defect is unknown. This study was designed to examine the impact of IGF-1 on LPS-induced cardiac contractile and intracellular Ca2+ dysfunction, activation of stress signal and endoplasmic reticulum (ER) stress. Mechanical and intracellular Ca2+ properties were examined in cardiomyocytes from Fast Violet B and cardiac-specific IGF-1 overexpression mice treated with or without LPS (4 mg kg(-1), 6 h). Reactive oxygen species (ROS), protein carbonyl formation and apoptosis were measured. Activation of mitogen-activated protein kinase pathways (p38, c-jun N-terminal kinase [JNK] and extracellular signal-related kinase [ERK]), ER stress and apoptotic markers were evaluated using Western blot analysis. Our results revealed decreased peak shortening and maximal velocity of shortening/relengthening and prolonged duration of relengthening in LPS-treated Fast Violet B cardiomyocytes associated with reduced intracellular Ca2+ decay. Accumulation of ROS protein carbonyl and apoptosis were elevated after LPS treatment. Western blot analysis revealed activated p38 and JNK, up-regulated Bax, and the ER stress markers GRP78 and Gadd153 in LPS-treated mouse hearts without any change in ERK and Bcl-2. Total protein expression of p38, JNK, and ERK was unaffected by either LPS or IGF-1. Interestingly, these LPS-induced changes in mechanical and intracellular Ca2+ properties, ROS, protein carbonyl, apoptosis, stress signal activation, and ER stress markers were effectively ablated by IGF-1. In vitro LPS exposure (1 microg mL(-1)) produced cardiomyocyte mechanical dysfunction reminiscent of the in vivo setting, which was alleviated by exogenous IGF-1 (50 nM). These data collectively suggested a beneficial of IGF-1 in the management of cardiac dysfunction under sepsis.
Osmium-187 enrichment in some plumes: Evidence for core-mantle interaction?
Walker, R.J.; Morgan, J.W.; Horan, M.F.
1995-01-01
Calculations with data for asteroidal cores indicate that Earth's outer core may have a rhenium/osmium ratio at least 20 percent greater than that of the chondritic upper mantle, potentially leading to an outer core with an osmium-187/osmium-188 ratio at least 8 percent greater than that of chondrites. Because of the much greater abundance of osmium in the outer core relative to the mantle, even a small addition of metal to a plume ascending from the D??? layer would transfer the enriched isotopic signature to the mixture. Sources of certain plume-derived systems seem to have osmium-187/osmium-188 ratios 5 to 20 percent greater than that for chondrites, consistent with the ascent of a plume from the core-mantle boundary.
Physicochemical properties of kiwifruit starch.
Li, Dongxing; Zhu, Fan
2017-04-01
Three varieties of golden kiwifruit (Actinidia chinensis) (Gold3, Gold9 and Hort16A) were collected at the commercial harvesting time, and physicochemical properties of starches from core and outer pericarp were studied. Starch contents (dry weight basis) in outer pericarp and core tissues ranged from 38.6 to 51.8% and 34.6 to 40.7%, respectively. All the kiwifruit starches showed B-type polymorph. Compared to the outer pericarp starches, amylose content and enzyme susceptibility of core starches were higher, and the degree of crystallinity, granule size and gelatinization parameters of core starches were somewhat lower. This suggests different biosynthetic properties between these two starches. The enthalpy changes of gelatinization of outer pericarp starches were high (∼21J/g). Rheological properties of outer pericarp starches were compared with normal maize and potato starches showed high yield stress of flow properties. This study revealed the unique properties of kiwifruit starch among various types of starches. Copyright © 2016 Elsevier Ltd. All rights reserved.
Jiang, Lili; Lu, Yili; Jin, Jiahui; Dong, Lili; Xu, Fengli; Chen, Shuangshuang; Wang, Zhanyue; Liang, Guang; Shan, Xiaoou
2015-01-01
Sepsis, which is caused by severe infection, is an important cause of mortality, but effective clinical treatment against sepsis is extremely limited. As the main component of the outer membrane of Gram-negative bacteria, lipopolysaccharide (LPS) plays a major role in inflammatory responses. Studies have shown beneficial pharmacological effects for Folium isatidis. The present study further illuminated the effects of n-butanol extract from Folium isatidis in LPS-induced septic shock and identified the main active chemical components. Our study showed that pretreatment with n-butanol extract from Folium isatidis not only significantly inhibited LPS-induced tumor necrosis factor-α and interleukin-6 production but also markedly and dose dependently enhanced the recruitment of MyD88, the phosphorylation of extracellular signal-regulated kinase, and the degradation of IκB-α. Additionally, the extract exhibited dramatic protective effects against lung injury and death in mice with septic shock. Eight main active compounds were identified, including organic acids, glycoside, indolinones, and flavonoids. These findings provide a perspective on the respiratory protection offered by n-butanol extract from Folium isatidis in LPS-induced sepsis and outline a novel therapeutic strategy for the treatment of sepsis. PMID:26491261
Freer, E; Moreno, E; Moriyón, I; Pizarro-Cerdá, J; Weintraub, A; Gorvel, J P
1996-01-01
A rough (R) Brucella abortus 45/20 mutant was more sensitive to the bactericidal activity of polymyxin B and lactoferricin B than was its smooth (S) counterpart but considerably more resistant than Salmonella montevideo. The outer membrane (OM) and isolated lipopolysaccharide (LPS) of S. montevideo showed a higher affinity for these cationic peptides than did the corresponding B. abortus OM and LPS. We took advantage of the moderate sensitivity of R B. abortus to cationic peptides to construct live R B. abortus-S-LPS chimeras to test the activities of polymyxin B, lactoferricin B, and EDTA. Homogeneous and abundant peripheral distribution of the heterologous S-LPS was observed on the surface of the chimeras, and this coating had no effect on the viability or morphology of the cells. When the heterologous LPS corresponded to the less sensitive bacterium S B. abortus S19, the chimeras were more resistant to cationic peptides; in contrast, when the S-LPS was from the more sensitive bacterium S. montevideo, the chimeras were more susceptible to the action of peptides and EDTA. A direct correlation between the amount of heterologous S-LPS on the surface of chimeric Brucella cells and peptide sensitivity was observed. Whereas the damage produced by polymyxin B in S. montevideo and B. abortus-S. montevideo S-LPS chimeras was manifested mainly as OM blebbing and inner membrane rolling, lactoferricin B caused inner membrane detachment, vacuolization, and the formation of internal electron-dense granules in these cells. Native S and R B. abortus strains were permeable to the hydrophobic probe N-phenyl-1-naphthylamine (NPN). In contrast, only reduced amounts of NPN partitioned into the OMs of the S. montevideo and B. abortus-S. montevideo S-LPS chimeras. Following peptide exposure, accelerated NPN uptake similar to that observed for S. montevideo was detected for the B. abortus-S. montevideo LPS chimeras. The partition of NPN into native or EDTA-, polymyxin B-, or lactoferricin B-treated LPS micelles of S. montevideo or B. abortus mimicked the effects observed with intact cells, and this was confirmed by using micelle hybrids of B. abortus and S. montevideo LPSs. The results showed that LPS is the main cause of B. abortus' resistance to bactericidal cationic peptides, the OM-disturbing action of divalent cationic chelants, and OM permeability to hydrophobic substances. It is proposed that these three features are related to the ability of Brucella bacteria to multiply within phagocytes. PMID:8830680
Freer, E; Moreno, E; Moriyón, I; Pizarro-Cerdá, J; Weintraub, A; Gorvel, J P
1996-10-01
A rough (R) Brucella abortus 45/20 mutant was more sensitive to the bactericidal activity of polymyxin B and lactoferricin B than was its smooth (S) counterpart but considerably more resistant than Salmonella montevideo. The outer membrane (OM) and isolated lipopolysaccharide (LPS) of S. montevideo showed a higher affinity for these cationic peptides than did the corresponding B. abortus OM and LPS. We took advantage of the moderate sensitivity of R B. abortus to cationic peptides to construct live R B. abortus-S-LPS chimeras to test the activities of polymyxin B, lactoferricin B, and EDTA. Homogeneous and abundant peripheral distribution of the heterologous S-LPS was observed on the surface of the chimeras, and this coating had no effect on the viability or morphology of the cells. When the heterologous LPS corresponded to the less sensitive bacterium S B. abortus S19, the chimeras were more resistant to cationic peptides; in contrast, when the S-LPS was from the more sensitive bacterium S. montevideo, the chimeras were more susceptible to the action of peptides and EDTA. A direct correlation between the amount of heterologous S-LPS on the surface of chimeric Brucella cells and peptide sensitivity was observed. Whereas the damage produced by polymyxin B in S. montevideo and B. abortus-S. montevideo S-LPS chimeras was manifested mainly as OM blebbing and inner membrane rolling, lactoferricin B caused inner membrane detachment, vacuolization, and the formation of internal electron-dense granules in these cells. Native S and R B. abortus strains were permeable to the hydrophobic probe N-phenyl-1-naphthylamine (NPN). In contrast, only reduced amounts of NPN partitioned into the OMs of the S. montevideo and B. abortus-S. montevideo S-LPS chimeras. Following peptide exposure, accelerated NPN uptake similar to that observed for S. montevideo was detected for the B. abortus-S. montevideo LPS chimeras. The partition of NPN into native or EDTA-, polymyxin B-, or lactoferricin B-treated LPS micelles of S. montevideo or B. abortus mimicked the effects observed with intact cells, and this was confirmed by using micelle hybrids of B. abortus and S. montevideo LPSs. The results showed that LPS is the main cause of B. abortus' resistance to bactericidal cationic peptides, the OM-disturbing action of divalent cationic chelants, and OM permeability to hydrophobic substances. It is proposed that these three features are related to the ability of Brucella bacteria to multiply within phagocytes.
Si-depleted outer core inferred from sound velocity measurements of liquid Fe-Si alloys
NASA Astrophysics Data System (ADS)
Nakajima, Y.; Imada, S.; Hirose, K.; Kuwayama, Y.; Sinmyo, R.; Tateno, S.; Ozawa, H.; Tsutsui, S.; Uchiyama, H.; Baron, A. Q. R.
2016-12-01
Recent core formation models [1,2] suggested that a large amount of Si could have been incorporated into the core forming metals in the early stage of the Earth. These studies gave estimates for the Si content in the core, from 2 to 9 wt.%. In order to constrain the Si content of the outer core, we have determined the sound wave velocity of liquid Fe-Si alloys under high pressures and high temperatures. Starting materials of Fe-Si alloys with 6.5 and 9 wt.% Si were melted in a laser-heated diamond-anvil cell. The longitudinal acoustic phonon excitation of a liquid metal was measured up to 52 GPa and 3200 K by using high resolution inelastic X-ray scattering spectroscopy at beamline BL35XU [3] of the SPring-8 synchrotron facility. Our results show that silicon significantly increases the P-wave velocity of liquid Fe. Seismological observation shows that the P-wave velocity in the outer core is 3-4% faster than in pure iron. Comparing the present results with seismological observations, the silicon content of the outer core should be limited to be <2 wt.%, significantly lower than previous estimates based on the element partitioning between core forming mental and silicate magma ocean during core formation processes. This indicates that the present-day core is depleted in Si relative to the ancient core just after core formation, which agrees with the recent proposal [4] that the Si content in the outer core has been diminished by SiO2 crystallization through the core cooling history. [1] Rubie et al. (2011) Earth Planet. Sci. Lett. 301, 31-42. [2] Siebert et al. (2013) Science 339, 1194-1197. [3] Baron et al. (2000) J. Phys. Chem. Solids 61, 461-465 [4] Hirose et al. (2015) Abstract presented at AGU Fall Meeting 2015.
Gravitational Core-Mantle Coupling and the Acceleration of the Earth
NASA Technical Reports Server (NTRS)
Rubincam, David Parry; Smith, David E. (Technical Monitor)
2001-01-01
Gravitational core-mantle coupling may be the cause of the observed variable acceleration of the Earth's rotation on the 1000 year timescale. The idea is that density inhomogeneities which randomly come and go in the liquid outer core gravitationally attract density inhomogeneities in the mantle and crust, torquing the mantle and changing its rotation state. The corresponding torque by the mantle on the core may also explain the westward drift of the magnetic field of 0.2 deg per year. Gravitational core-mantle coupling would stochastically affect the rate of change of the Earth's obliquity by just a few per cent. Its contribution to polar wander would only be about 0.5% the presently observed rate. Tidal friction is slowing down the rotation of the Earth, overwhelming a smaller positive acceleration from postglacial rebound. Coupling between the liquid outer core of the Earth and the mantle has long been a suspected reason for changes in the length-of-day. The present investigation focuses on the gravitational coupling between the density anomalies in the convecting liquid outer core and those in the mantle and crust as a possible cause for the observed nonsecular acceleration on the millenial timescale. The basic idea is as follows. There are density inhomogeneities caused by blobs circulating in the outer core like the blobs in a lava lamp; thus the outer core's gravitational field is not featureless. Moreover, these blobs will form and dissipate somewhat randomly. Thus there will be a time variability to the fields. These density inhomogeneities will gravitationally attract the density anomalies in the mantle.
Chowdhury, Amrita A; Gawali, Nitin B; Shinde, Prashant; Munshi, Renuka; Juvekar, Archana R
2018-04-26
Lipopolysaccharide (LPS), an endotoxin from the outer membrane of Gram negative bacteria has been reported to cause neuroinflammation and learning and memory deficits. There are reports describing the beneficial effects of Imperatorin (IMP), a naturally occurring furanocoumarin in central nervous system (CNS) disorders such as anxiety and epilepsy. In the current study, we investigated whether IMP protects against LPS mediated memory deficits and neuroinflammation. Mice pretreated with IMP (5, 10 mg/kg po) were administered LPS (250 μg/kg ip) for 7 days. Memory was evaluated in the Morris water maze (MWM) and Y maze. The mice were euthanised and different biochemical assessments were carried out to measure oxidative stress and acetyl choline esterase (AChE). Further, evaluation of proinflammatory cytokines such as tumor necrosis factor (TNF-α) and interleukin-6 (IL-6) levels and brain derived neurotrophic factor (BDNF) in hippocampus and cortex of brain were performed. LPS administration caused poor memory retention in both, MWM and Y maze, and caused distinct oxidative stress since decrease in superoxide dismutase (SOD), reduced glutathione (GSH) levels and increased lipid peroxidation were observed. Also, a significant rise was observed in the levels of AChE. Moreover, a rise in TNF-α and IL-6 levels and depleted levels of BDNF were noted. IMP pretreatment reversed LPS induced behavioral and memory disturbances and significantly decreased the oxidative stress and AChE levels. It also reduced TNF-α and IL-6 levels and caused a significant upregulation of BDNF levels. Present study highlights the potential neuroprotective role of IMP against LPS mediated cognitive impairment and neuroinflammation. Copyright © 2018 Elsevier Ltd. All rights reserved.
Azuma, Masahiro; Matsuo, Aya; Fujimoto, Yukari; Fukase, Koichi; Hazeki, Kaoru; Hazeki, Osamu; Matsumoto, Misako; Seya, Tsukasa
2007-03-09
Lipopolysaccharide (LPS), a major constituent of the outer membrane of gram-negative bacteria, consists of polysaccharides and a lipid structure named lipid A. Lipid A is a typical microbial pattern molecule that serves as a ligand for Toll-like receptor 4 (TLR4). TLR4 signals the presence of lipid A to recruit adaptor molecules and induces cytokines and type I interferon (IFN) by activating transcription factor, NF-kappaB or IRF-3. Here we showed that chemically synthesized TLR4-agonistic lipid A analogues but not antagonistic lipid A activate IFN-beta promoter in TLR4-expressing HEK293 cells. The amplitude of IFN-beta promoter activation was in parallel with that of NF-kappaB. LPS-binding protein (LBP) was required for efficient IFN-beta induction in this system, and this LBP activity was antagonized by bactericidal/permeability-increasing protein (BPI). Thus, we first show that BPI blocks the TLR4 responses by exogenous administration of BPI to lipid A-sensitive cells. Although the functional mechanism whereby extra-cellular BPI modulates the intra-cellular signal pathways selected by the TLR adaptors, MyD88 and TICAM-1 (TRIF), remains unknown, we infer that the lipid A portion of LPS participates in LBP-amplified IFN-beta induction and that BPI binding to LPS leads to inhibition of the activation of NF-kappaB and IFN-beta by LPS or agonistic lipid A via TLR4 in an extrinsic mode. BPI may serve as a therapeutic potential against endotoxin shock by acting as a regulator for the MyD88- and TICAM-1 pathways in the LPS-TLR4 signaling.
Bigot-Astruc, Marianne; Molin, Denis; Sillard, Pierre
2014-11-04
A depressed graded-index multimode optical fiber includes a central core, an inner depressed cladding, a depressed trench, an outer depressed cladding, and an outer cladding. The central core has an alpha-index profile. The depressed claddings limit the impact of leaky modes on optical-fiber performance characteristics (e.g., bandwidth, core size, and/or numerical aperture).
Annexin A5 binds to lipopolysaccharide and reduces its endotoxin activity.
Rand, Jacob H; Wu, Xiao-Xuan; Lin, Elaine Y; Griffel, Alexander; Gialanella, Philip; McKitrick, John C
2012-01-01
Annexin A5 (AnxA5) has a high affinity for phosphatidylserine. The protein is widely used to detect apoptotic cells because phosphatidylserine, a phospholipid that is normally present in the inner leaflets of cytoplasmic membranes, becomes translocated to the outer leaflets during programmed cell death. Here we report the novel observation that AnxA5 binds to Gram-negative bacteria via the lipid A domain of lipopolysaccharide (LPS). Binding of AnxA5 to bacteria was measured quantitatively, confirmed by fluorescence microscopy, and found to be inhibited by antibodies against lipid A. AnxA5 also bound to purified dot-blotted LPS and lipid A. Through ellipsometry, we found that the binding of AnxA5 to purified LPS was calcium dependent and rapid and showed a high affinity-characteristics similar to those of AnxA5 binding to phosphatidylserine. Initial functional studies indicated that AnxA5 can affect LPS activities. AnxA5 inhibited LPS-mediated gelation in the Limulus amebocyte lysate assay. Incubation of LPS with the protein reduced the quantity of tumor necrosis factor alpha (TNF-α) released by cultured monocytes compared to that released upon incubation with LPS alone. Initial in vivo experiments indicated that injection of mice with LPS preincubated with AnxA5 produced serum TNF-α levels lower than those seen after injection of LPS alone. These data demonstrate that AnxA5 binds to LPS and open paths to investigation of the potential biological and therapeutic implications of this interaction. AnxA5 is highly expressed in cells that have a barrier function-including, among others, vascular endothelium, placental trophoblasts, and epithelial cells lining bile ducts, renal tubules, mammary ducts, and nasal epithelium. The protein has been well characterized for its binding to phospholipid bilayers that contain phosphatidylserine. This report of a previously unrecognized activity of AnxA5 opens the door to investigation of the possibility that this binding may have biological and therapeutic ramifications. In view of the tissue expression of the protein, the present results suggest the possibility that AnxA5 plays a role in modulating the host defense against lipopolysaccharide at these anatomic sites, where cells may interface with microorganisms. These results also raise the intriguing possibility that AnxA5 or analogous proteins or peptides could provide novel approaches to addressing the difficult clinical problem of Gram-negative sepsis.
Laminated electromagnetic pump stator core
Fanning, Alan W.
1995-01-01
A stator core for an electromagnetic pump includes a plurality of circumferentially abutting tapered laminations extending radially outwardly from a centerline axis to collectively define a radially inner bore and a radially outer circumference. Each of the laminations includes radially inner and outer edges and has a thickness increasing from the inner edge toward the outer edge to provide a substantially continuous path adjacent the circumference.
Qian, Jinghua; Garrett, Teresa A; Raetz, Christian R H
2014-03-04
There are five distinct core structures in the lipopolysaccharides of Escherichia coli and at least two in Salmonella isolates, which vary principally in the outer core oligosaccharide. Six outer core glycosyltransferases, E. coli K-12 WaaG, WaaB, and WaaO and Salmonella typhimurium WaaI, WaaJ, and WaaK, were cloned, overexpressed, and purified. A novel substrate for WaaG was isolated from ΔwaaG E. coli overexpressing the lipid A phosphatase lpxE and the lipid A late acyltransferase lpxM. The action of lpxE and lpxM in the ΔwaaG background yielded heptose2-1-dephospho Kdo2-lipid A, a 1-dephosphorylated hexa-acylated lipid A with the inner core sugars that is easily isolated by organic extraction. Using this structurally defined acceptor and commercially available sugar nucleotides, each outer core glycosyltransferases was assayed in vitro. We show that WaaG and WaaB add a glucose and galactose sequentially to heptose2-1-dephospho Kdo2-lipid A. E. coli K-12 WaaO and S. typhimurium WaaI add a galactose to the WaaG/WaaB product but can also add a galactose to the WaaG product directly without the branched core sugar added by WaaB. Both WaaI and WaaO require divalent metal ions for optimal activity; however, WaaO, unlike WaaI, can add several glucose residues to its lipid acceptor. Using the product of WaaG, WaaB, and WaaI, we show that S. typhimurium WaaJ and WaaK transfer a glucose and N-acetylglucosamine, respectively, to yield the full outer core. This is the first demonstration of the in vitro assembly of the outer core of the lipopolysaccharide using defined lipid A-oligosaccharide acceptors and sugar donors.
2015-01-01
There are five distinct core structures in the lipopolysaccharides of Escherichia coli and at least two in Salmonella isolates, which vary principally in the outer core oligosaccharide. Six outer core glycosyltransferases, E. coli K-12 WaaG, WaaB, and WaaO and Salmonella typhimurium WaaI, WaaJ, and WaaK, were cloned, overexpressed, and purified. A novel substrate for WaaG was isolated from ΔwaaG E. coli overexpressing the lipid A phosphatase lpxE and the lipid A late acyltransferase lpxM. The action of lpxE and lpxM in the ΔwaaG background yielded heptose2-1-dephospho Kdo2-lipid A, a 1-dephosphorylated hexa-acylated lipid A with the inner core sugars that is easily isolated by organic extraction. Using this structurally defined acceptor and commercially available sugar nucleotides, each outer core glycosyltransferases was assayed in vitro. We show that WaaG and WaaB add a glucose and galactose sequentially to heptose2-1-dephospho Kdo2-lipid A. E. coli K-12 WaaO and S. typhimurium WaaI add a galactose to the WaaG/WaaB product but can also add a galactose to the WaaG product directly without the branched core sugar added by WaaB. Both WaaI and WaaO require divalent metal ions for optimal activity; however, WaaO, unlike WaaI, can add several glucose residues to its lipid acceptor. Using the product of WaaG, WaaB, and WaaI, we show that S. typhimurium WaaJ and WaaK transfer a glucose and N-acetylglucosamine, respectively, to yield the full outer core. This is the first demonstration of the in vitro assembly of the outer core of the lipopolysaccharide using defined lipid A-oligosaccharide acceptors and sugar donors. PMID:24479701
Wireline-rotary air coring of the Bandelier Tuff, Los Alamos, New Mexico
Teasdale, W.E.; Pemberton, R.R.
1984-01-01
This paper describes experiments using wireline-rotary air-coring techniques conducted in the Bandelier Tuff using a modified standard wireline core-barrel system. The modified equipment was used to collect uncontaminated cores of unconsolidated ash and indurated tuff at Los Alamos, New Mexico. Core recovery obtained from the 210-foot deep test hole was about 92 percent. A standard HQ-size, triple-tube wireline core barrel (designed for the passage of liquid drilling fluids) was modified for air coring as follows: (1) Air passages were milled in the latch body part of the head assembly; (2) the inside dimension of the outer core barrel tube was machined and honed to provide greater clearance between the inner and outer barrels; (3) oversized reaming devices were added to the outer core barrel and the coring bit to allow more clearance for air and cuttings return; (4) the eight discharge ports in the coring bit were enlarged. To control airborne-dust pollution, a dust-and-cuttings discharge subassembly, designed and built by project personnel, was used. (USGS)
Characterization of polymer chain fractions of kiwifruit starch.
Li, Dongxing; Zhu, Fan
2018-02-01
In this report, the amylose composition and molecular structure of starches from the core and outer pericarp of 3 golden kiwifruit varieties were characterised, using enzymatic and chromatographic techniques. Starches from the core tissues of kiwifruit tend to have higher amylose contents (by ∼3-5%) and longer unit chains of both amylopectins and their φ, β-limit dextrins (LDs) than those of the outer pericarp starches. The contents of short B-chains of the φ, β-LDs of amylopectins from the outer pericarp were higher (by ∼3%) than those of φ, β-LDs of the core amylopectins. Overall, the composition and structure of starches from the outer pericarp and core tissues of a golden kiwifruit were different. This study provides a structural basis to further investigate the starch degradation in kiwifruit, which may be of importance for the storage and eating quality of the fruit. Copyright © 2017 Elsevier Ltd. All rights reserved.
Lv, Qi; Yin, Xiaofeng; Song, Jianqi; Landén, Ning Xu; Fan, Haojun
2014-01-01
Acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome (ARDS) are the leading causes of death in critical care. Despite extensive efforts in research and clinical medicine, mortality remains high in these diseases. Perfluorocarbon (PFC), a chemical compound known as liquid ventilation medium, is capable of dissolving large amounts of physiologically important gases (mainly oxygen and carbon dioxide). In this study we aimed to investigate the effect of intravenous infusion of PFC emulsion on lipopolysaccharide (LPS) induced ALI in rats and elucidate its mechanism of action. Forty two Wistar rats were randomly divided into three groups: 6 rats were treated with saline solution by intratracheal instillation (control group), 18 rats were treated with LPS by intratracheal instillation (LPS group) and the other 18 rats received PFC through femoral vein prior to LPS instillation (LPS+PFC group). The rats in the control group were sacrificed 6 hours later after saline instillation. At 2, 4 and 6 hours of exposure to LPS, 6 rats in the LPS group and 6 rats in LPS+PFC group were sacrificed at each time point. By analyzing pulmonary pathology, partial pressure of oxygen in the blood (PaO2) and lung wet-dry weight ratio (W/D) of each rat, we found that intravenous infusion of PFC significantly alleviated acute lung injury induced by LPS. Moreover, we showed that the expression of pulmonary myeloperoxidase (MPO), intercellular adhesion molecule-1 (ICAM-1) of endothelial cells and CD11b of polymorphonuclear neutrophils (PMN) induced by LPS were significantly decreased by PFC treatment in vivo. Our results indicate that intravenous infusion of PFC inhibits the infiltration of PMNs into lung tissue, which has been shown as the core pathogenesis of ALI/ARDS. Thus, our study provides a theoretical foundation for using intravenous infusion of PFC to prevent and treat ALI/ARDS in clinical practice. PMID:24489970
Release of outer membrane vesicles from Bordetella pertussis.
Hozbor, D; Rodriguez, M E; Fernández, J; Lagares, A; Guiso, N; Yantorno, O
1999-05-01
The aim of the study reported here was to investigate the production of Bordetella pertussis outer membrane vesicles (OMVs). Numerous vesicles released from cells grown in Stainer-Scholte liquid medium were observed. The formation of similar vesicle-like structures could also be artificially induced by sonication of concentrated bacterial suspensions. Immunoblot analysis showed that OMVs contain adenylate cyclase-hemolysin (AC-Hly), among other polypeptides, as well as the lipopolysaccharide (LPS). Experiments carried out employing purified AC-Hly and OMVs isolated from B. pertussis AC-Hly- showed that AC-Hly is an integral component of the vesicles. OMVs reported here contain several protective immunogens and might be considered a possible basic material for the development of acellular pertussis vaccines.
Strunk, R C; Whitehead, A S; Cole, F S
1985-01-01
The third component of complement (C3) is a plasma glycoprotein with a variety of biologic functions in the initiation and maintenance of host response to infectious agents. While the hepatocyte is the primary source of plasma C3, mononuclear phagocytes contribute to the regulation of tissue availability of C3. Lipopolysaccharide (LPS), a constituent of cell walls of gram-negative bacteria, consists of a polysaccharide moiety (core polysaccharide and O antigen) covalently linked to a lipid portion (lipid A). Using metabolic labeling with [35S]methionine, immunoprecipitation, and SDS-polyacrylamide gel electrophoresis, we examined the effects of LPS on synthesis of C3 by human mononuclear phagocytes as well as synthesis of the second component of complement (C2), factor B, lysozyme, and total protein. LPS increased C3 synthesis 5-30-fold without affecting the kinetics of secretion of C3 or the synthesis of C2, lysozyme, or total protein. Factor B synthesis was consistently increased by LPS. Experiments with lipid A-inactivated LPS (alkaline treated), LPS from a polysaccharide mutant strain, and lipid X (a lipid A precursor) indicated that the lipid A portion is the structural element required for this effect. Northern blot analysis demonstrated at least a fivefold increase in C3 mRNA in LPS-treated monolayers, which suggests that the regulation of the increase in C3 synthesis is pretranslational. C2 mRNA and factor B mRNA were increased approximately twofold. The availability of specific gene products in human mononuclear phagocytes that respond to LPS should permit understanding of the molecular regulation of more complex functions of these cells elicited by LPS in which multiple gene products are coordinately expressed. Images PMID:3900137
NASA Technical Reports Server (NTRS)
Kennedy, G. C.; Higgins, G. H.
1973-01-01
Rebuttal of suggestions from various critics attempting to provide an escape from the seeming paradox originated by Higgins and Kennedy's (1971) proposed possibility that the liquid in the outer core was thermally stably stratified and that this stratification might prove a powerful inhibitor to circulation of the outer core fluid of the kind postulated for the generation of the earth's magnetic field. These suggestions are examined and shown to provide no reasonable escape from the core paradox.
NASA Technical Reports Server (NTRS)
Voorhies, Coerte V.
1998-01-01
The idea that geomagnetic westward drift indicates convective leveling of the planetary momentum gradient within Earth's core is pursued in search of a differentially rotating mean state, upon which various oscillations and secular effects might be superimposed. The desired state conforms to roughly spherical boundary conditions, minimizes dissipative interference with convective cooling in the bulk of the core, yet may aid core cooling by depositing heat in the uppermost core and lower mantle. The variational calculus of stationary dissipation applied to a spherical vortex within the core yields an interesting differential rotation profile, akin to spherical Couette flow bounded by thin Hartmann layers. Four boundary conditions are required. To concentrate shear induced dissipation near the core-mantle boundary, these are taken to be: (i) no-slip at the core-mantle interface; (ii) geomagnetically estimated bulk westward flow at the base of the core-mantle boundary layer; (iii) no-slip at the inner-outer core interface; and, to describe magnetic locking of the inner core to the deep outer core; (iv) hydrodynamically stress-free at the inner-outer core boundary. By boldly assuming the axial core angular momentum anomaly to be zero, the super-rotation of the inner core relative to the mantle is calculated to be at most 1.5 deg./yr.
NASA Technical Reports Server (NTRS)
Voorhies, C. V.
1999-01-01
The idea that geomagnetic westward drift indicates convective leveling of the planetary momentum gradient within Earth's core is pursued in search of a differentially rotating mean state, upon which various oscillations and secular effects might be superimposed. The desired state conforms to roughly spherical boundary conditions, minimizes dissipative interference with convective cooling in the bulk of the core, yet may aide core cooling by depositing heat in the uppermost core and lower mantle. The variational calculus of stationary dissipation applied to a spherical vortex within the core yields an interesting differential rotation profile akin to spherical Couette flow bounded by thin Hartmann layers. Four boundary conditions are required. To concentrate shear induced dissipation near the core-mantle boundary, these are taken to be: (i) no-slip at the core-mantle interface; (ii) geomagnetically estimated bulk westward flow at the base of the core-mantle boundary layer; (iii) no-slip at the inner-outer core interface; and, to describe magnetic locking of the inner core to the deep outer core, (iv) hydrodynamically stress-free at the inner-outer core boundary. By boldly assuming the axial core angular momentum anomaly to be zero, the super-rotation of the inner core is calculated to be at most 1.5 degrees per year.
NASA Astrophysics Data System (ADS)
Lassiter, J. C.
2005-12-01
Thermal and chemical interaction between the core and mantle has played a critical role in the thermal and chemical evolution of the Earth's interior. Outer core convection is driven by core cooling and inner core crystallization. Core/mantle heat transfer also buffers mantle potential temperature, resulting in slower rates of mantle cooling (~50-100 K/Ga) than would be predicted from the discrepancy between current rates of surface heat loss (~44 TW) and internal radioactive heat production (~20 TW). Core/mantle heat transfer may also generate thermal mantle plumes responsible for ocean island volcanic chains such as the Hawaiian Islands. Several studies suggest that mantle plumes, in addition to transporting heat from the core/mantle boundary, also carry a chemical signature of core/mantle interaction. Elevated 186Os/188Os ratios in lavas from Hawaii, Gorgona, and in the 2.8 Ga Kostomuksha komatiites have been interpreted as reflecting incorporation of an outer core component with high time-integrated Pt/Os and Re/Os ( Brandon et al., 1999, 2003; Puchtel et al., 2005). Preferential partitioning of Os relative to Re and Pt into the inner core during inner core growth may generate elevated Re/Os and Pt/Os ratios in the residual outer core. Because of the long half-life of 190Pt (the parent of 186Os, t1/2 = 489 Ga), an elevated 186Os/188Os outer core signature in plume lavas requires that inner core crystallization began early in Earth history, most likely prior to 3.5 Ga. This in turn requires low time-averaged core/mantle heat flow (<~2.5 TW) or large quantities of heat-producing elements in the core. Core/mantle heat flow may be estimated using boundary-layer theory, by measuring the heat transported in mantle plumes, by estimating the heat transported along the outer core adiabat, or by comparing the rates of heat production, surface heat loss, and secular cooling of the mantle. All of these independent methods suggest time-averaged core/mantle heat flow of ~5-14 TW. In the absence of heat-producing elements in the core, such high heat flow rates require an inner core younger than ~1 Ga and preclude the development of significant 186Os enrichment in the outer core. Experimental studies suggest that potassium may partition into Fe-S-O liquids during core formation. Radioactive decay of potassium in the core could provide an additional heat source and reconcile geophysical evidence for high core/mantle heat flow with apparent geochemical evidence for an ancient inner core. However, high concentrations of chalcophile elements such as Cu in the mantle are inconsistent with significant segregation of a S-rich liquid during core formation, precluding K partitioning into the core by this mechanism. Furthermore, core formation scenarios that would lead to high K content in the core (e.g., core formation prior to terrestrial volatile depletion) also result in high core Pb concentrations. Core/mantle interaction would then produce strong negative correlations between 186Os/188Os and 207Pb/204Pb ratios, but such correlations are not observed. In summary, elevated 186Os/188Os ratios in some plume-derived lavas are unlikely to reflect core/mantle interaction because the inner core is too young for this isotopic signature to have developed in the outer core. Melt generation from pyroxenite or fractionation of PGEs between sulfide melts and monosulfide solid solutions provide alternative mechanisms for generating ancient mantle reservoirs with elevated Pt/Os and 186Os/188Os.
Gleńska-Olender, J; Durlik, K; Konieczna, I; Kowalska, P; Gawęda, J; Kaca, W
2017-11-01
Bacteria of the genus Proteus of the family Enterobacteriaceae are facultative human pathogens responsible mainly for urinary tract and wound infections, bacteremia and the development of rheumatoid arthritis (RA). We have analyzed and compared by ELISA the titer of antibodies in plasmas of healthy individuals and in sera of rheumatoid arthritis patients recognizing a potential host cross-reactive epitope (lysine-galacturonic acid epitopes) present in Proteus lipopolysaccharide (LPS). In our experiments LPSs isolated from two mutants of smooth Proteus mirabilis 1959 (O3), i.e. strains R110 and R45, were used. R110 (Ra type mutant) is lacking the O-specific polysaccharide, but possesses a complete core oligosaccharide, while R45 (Re type) has a reduced core oligosaccharide and contains two 3-deoxy-D-manno-oct-2-ulosonic acid residues and one of 4-amino-4-deoxy-L-arabinopyranose residues. Titer of P. mirabilis S1959 LPS-specific-antibodies increased with the age of blood donors. RA and blood donors' sera contained antibodies against S and Ra and Re type of P. mirabilis O3 LPSs. Antibodies recognizing lysine-galacturonic acid epitopes of O3 LPS were detected by ELISA in some plasmas of healthy individuals and sera of rheumatoid arthritis patients. RA patients antibodies reacting with P. mirabilis S1959 S and R LPSs may indicate a potential role of anti-LPS antibodies in molecular mimicry in RA diseases.
Lück, P. Christian; Schmitt, Jürgen W.; Hengerer, Arne; Helbig, Jürgen H.
1998-01-01
We determined the MICs of ampicillin, ciprofloxacin, erythromycin, imipenem, and rifampin for two clinical isolates of Legionella pneumophila serogroup 1 by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay and by quantitative culture. To test the influence of subinhibitory concentrations (sub-MICs) of antimicrobial agents on Legionella uptake into Acanthamoeba castellanii and U937 macrophage-like cells, both strains were pretreated with 0.25 MICs of the antibiotics for 24 h. In comparison to that for the untreated control, subinhibitory concentrations of antibiotics significantly reduced Legionella uptake into the host cells. Measurement of the binding of monoclonal antibodies against several Legionella antigens by enzyme-linked immunoassays indicated that sub-MIC antibiotic treatment reduced the expression of the macrophage infectivity potentiator protein (Mip), the Hsp 60 protein, the outer membrane protein (OmpM), an as-yet-uncharacterized protein of 55 kDa, and a few lipopolysaccharide (LPS) epitopes. In contrast, the expression of some LPS epitopes recognized by monoclonal antibodies 8/5 and 30/4 as well as a 45-kDa protein, a 58-kDa protein, and the major outer membrane protein (OmpS) remained unaffected. PMID:9797218
Phosphorylcholine Allows for Evasion of Bactericidal Antibody by Haemophilus influenzae
Clark, Sarah E.; Snow, Julian; Li, Jianjun; Zola, Tracey A.; Weiser, Jeffrey N.
2012-01-01
The human pathogen Haemophilus influenzae has the ability to quickly adapt to different host environments through phase variation of multiple structures on its lipooligosaccharide (LPS), including phosphorylcholine (ChoP). During colonization with H. influenzae, there is a selection for ChoP+ phase variants. In a murine model of nasopharyngeal colonization, this selection is lost in the absence of adaptive immunity. Based on previous data highlighting the importance of natural antibody in limiting H. influenzae colonization, the effect of ChoP expression on antibody binding and its bactericidal activity was investigated. Flow cytometric analysis revealed that ChoP+ phase variants had decreased binding of antibody to LPS epitopes compared to ChoP− phase variants. This difference in antibody binding correlated with increased survival of ChoP+ phase variants in the presence of antibody-dependent, complement-mediated killing. ChoP+ phase variants were also more resistant to trypsin digestion, suggesting a general effect on the physical properties of the outer membrane. Moreover, ChoP-mediated protection against antibody binding correlated with increased resilience of outer membrane integrity. Collectively, these data suggest that ChoP expression provides a selective advantage during colonization through ChoP-mediated effects on the accessibility of bactericidal antibody to the cell surface. PMID:22396641
Mitarai, O.; Xiao, C.; McColl, D.; ...
2015-03-24
A plasma current up to 15 kA has been driven with outer ohmic heating (OH) coils in the STOR-M iron core tokamak. Even when the inner OH coil is disconnected, the outer OH coils alone can induce the plasma current as primary windings and initial breakdown are even easier in this coil layout. Our results suggest a possibility to use an iron core in a spherical tokamak to start up the plasma current without a central solenoid. Finally, the effect of the iron core saturation on the extension of the discharge pulse length has been estimated for further experiments inmore » the STOR-M tokamak.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Mitarai, O.; Xiao, C.; McColl, D.
A plasma current up to 15 kA has been driven with outer ohmic heating (OH) coils in the STOR-M iron core tokamak. Even when the inner OH coil is disconnected, the outer OH coils alone can induce the plasma current as primary windings and initial breakdown are even easier in this coil layout. Our results suggest a possibility to use an iron core in a spherical tokamak to start up the plasma current without a central solenoid. Finally, the effect of the iron core saturation on the extension of the discharge pulse length has been estimated for further experiments inmore » the STOR-M tokamak.« less
Seismic Velocity Anomalies in the Outer Core: The Final Frontier
NASA Astrophysics Data System (ADS)
Stevenson, D. J.
2008-12-01
Variation in density along outer core geoid surfaces must be very small (of order one part in a billion) since the resulting fluid motions and buoyancy fluxes would otherwise be prohibitively large for any reasonable choice of outer core viscosity. In any situation where seismic velocity variations are proportional to density variations (a generalized Birch's "law") this means that the resulting seismic travel time variations in the outer core would be unobservable. The largest lateral variations in the outer core are thus likely to arise from the distortion of geoid surfaces caused by density anomalies in the mantle or inner core. However, these do not change on decadal timescales and would be very difficult to separate from the inner core or mantle variations that cause them. Nonetheless, a recent study (Dai and Song, GRL, vol. 35, L16311, doi:10.1029/2008GL034895) provides evidence for time-variable outer core seismic velocity at the level of ten parts per million. Assuming this is real, I argue that the best candidate explanation is that all or part of the outer core is a two-phase medium consisting of a small mass fraction of small (ten or 100 micron-sized) particles of exsolving silicate material suspended in the convecting liquid. The seismic velocity of this two phase medium can vary at the desired level should the size distribution of particles vary from place to place (and with time) as one would expect in a convecting system, even though the mean density of the medium is invariant at the level of a part per billion, as required by dynamical considerations (thus invalidating Birch's "law"). The seismic velocity variation depends on the ratio of diffusion times to seismic periods, where the diffusion times are thermal or compositional for the particles or the particle spacing. This idea is not new (cf. Stevenson, JGR, 1983) but gains increased impetus from recent work on the nature of core formation and the desirability of an additional energy source for driving the geodynamo, as would arise if of order 10km of mantle underplating occurred over all of geologic time. The amount of suspended material will be tiny at any one time, illustrating the remarkable sensitivity of seismic waves to the microstructure of the medium. Consequences of this picture include some dissipation (finite Q) in the outer core and a significant frequency dependence of this effect, but precise predictions are difficult because of uncertainties in particle kinetics and convective velocities. The two-phase region may also influence radial seismic velocity profiles, particularly in the layers immediately adjacent to the boundaries (e.g., the layer just below the core-mantle boundary), an effect that has been suggested in the literature on many occasions. Even so, this explanation for lateral variability remains marginal at best, suggesting that the claimed observation is either not real or that some other explanation still awaits discovery.
Meyer, Audrey F; Gruba, Sarah M; Kim, Donghyuk; Meyer, Ben M; Koseoglu, Secil; Dalluge, Joseph J; Haynes, Christy L
2017-08-01
Platelets are small (1-2μm in diameter), circulating anuclear cell fragments with important roles in hemostasis and thrombosis that provide an excellent platform for studying the role of membrane components in cellular communication. Platelets use several forms of communication including exocytosis of three distinct granule populations, formation of bioactive lipid mediators, and shape change (allowing for adhesion). This work explores the role of stereochemistry and concentration of exogenous phosphatidylserine (PS) on platelet exocytosis and adhesion. PS, most commonly found in the phosphatidyl-l-serine (l-PS) form, is exposed on the outer leaflet of the cell membrane after the platelet is activated. Knowledge about the impact of exogenous phosphatidylserine on cell-to-cell communication is limited (particularly concentration and stereochemistry effects). This study found that platelets incubated in l-PS or phosphatidyl-d-serine (d-PS) are enriched to the same extent with their respective incubated PS. All levels of l-PS enrichment also showed an increase in platelet cholesterol, but only the 50μM d-PS incubation showed an increase in cholesterol. The uptake of d-PS induced the secretion of granules and manufactured platelet activating factor (PAF) in otherwise unstimulated platelets. The uptake of l-PS had a greater impact on platelet stimulation by decreasing both the amount of δ-granule secretion and the amount of PAF that was manufactured. Copyright © 2017 Elsevier B.V. All rights reserved.
Drulis-Kawa, Zuzanna; Dorotkiewicz-Jach, Agata; Gubernator, Jerzy; Gula, Grzegorz; Bocer, Tomasz; Doroszkiewicz, Wlodzimierz
2009-02-09
The interactions between cationic liposomal formulations (PC:Chol:DOTAP 3:4:3) and 23 Pseudomonas aeruginosa strains were tested. The study was undertaken because different antimicrobial results had been obtained by the authors for Pseudomonas aeruginosa strains and liposomal antibiotics (Drulis-Kawa, Z., Gubernator, J., Dorotkiewicz-Jach, A., Doroszkiewicz, W., Kozubek, A., 2006. The comparison of in vitro antimicrobial activity of liposomes containing meropenem and gentamicin. Cell. Mol. Biol. Lett., 11, 360-375; Drulis-Kawa, Z., Gubernator, J., Dorotkiewicz-Jach, A., Doroszkiewicz W., Kozubek, A., 2006. In vitro antimicrobial activity of liposomal meropenem against Pseudomonas aeruginosa strains. Int. J. Pharm., 315, 59-66). The experiments evaluate the roles of the bacterial outer-membrane structure, especially outer-membrane proteins and LPS, and envelope properties (hydrophobicity and electrostatic potential) in the interactions/fusion process between cells and lipid vesicles. The interactions were examined by fluorescent microscopy using PE-rhodamine-labelled liposomes. Some of the strains exhibited red-light emission (fusion with vesicles or vesicles surrounding the cell) and some showed negative reaction (no red-light emission). The main aim of the study was to determine what kinds of bacterial structure or envelope properties have a major influence on the fusion process. Negatively charged cells and hydrophobic properties promote interaction with cationic lipid vesicles, but no specific correlation was noted for the tested strains. A similar situation concerned LPS structure, where parent strains and their mutants possessing identical ladder-like band patterns in SDS-PAGE analysis exhibited totally different results with fluorescent microscopy. Outer-membrane protein analysis showed that an 18-kDA protein occurred in the isolates showing fusion with rhodamine-labelled vesicles and, conversely, strains lacking the 18-kDA protein exhibited no positive reaction (red emission). This suggests that even one protein may be responsible for favouring stronger interactions between Pseudomonas aeruginosa cells and cationic liposomal formulations (PC:Chol:DOTAP 3:4:3).
NASA Astrophysics Data System (ADS)
Mount, Van S.; Wilkins, Scott; Comiskey, Cody S.
2017-12-01
The Tuscarora fold system (TFS) is located in the Pennsylvania salient in the foreland of the Valley and Ridge province. The TFS is imaged in high quality 3D seismic data and comprises a system of small-scale folds within relatively flat-lying Lower Silurian Tuscarora Formation strata. We characterize the TFS structures and infer layer parallel shortening (LPS) directions and magnitudes associated with deformation during the Alleghany Orogeny. Previously reported LPS data in our study area are from shallow Devonian and Carboniferous strata (based on outcrop and core analyses) above the shallowest of three major detachments recognized in the region. Seismic data allows us to characterize LPS at depth in strata beneath the shallow detachment. Our LPS data (orientations and inferred magnitudes) are consistent with the shallow data leading us to surmise that LPS during Alleghanian deformation fanned around the salient and was distributed throughout the stratigraphic section - and not isolated to strata above the shallow detachment. We propose that a NW-SE oriented Alleghanian maximum principal stress was perturbed by deep structure associated with the non-linear margin of Laurentia resulting in fanning of shortening directions within the salient.
Putting on the brakes: Bacterial impediment of wound healing
Brothers, Kimberly M.; Stella, Nicholas A.; Hunt, Kristin M.; Romanowski, Eric G.; Liu, Xinyu; Klarlund, Jes K.; Shanks, Robert M. Q.
2015-01-01
The epithelium provides a crucial barrier to infection, and its integrity requires efficient wound healing. Bacterial cells and secretomes from a subset of tested species of bacteria inhibited human and porcine corneal epithelial cell migration in vitro and ex vivo. Secretomes from 95% of Serratia marcescens, 71% of Pseudomonas aeruginosa, 29% of Staphylococcus aureus strains, and other bacterial species inhibited epithelial cell migration. Migration of human foreskin fibroblasts was also inhibited by S. marcescens secretomes indicating that the effect is not cornea specific. Transposon mutagenesis implicated lipopolysaccharide (LPS) core biosynthetic genes as being required to inhibit corneal epithelial cell migration. LPS depletion of S. marcescens secretomes with polymyxin B agarose rendered secretomes unable to inhibit epithelial cell migration. Purified LPS from S. marcescens, but not from Escherichia coli or S. marcescens strains with mutations in the waaG and waaC genes, inhibited epithelial cell migration in vitro and wound healing ex vivo. Together these data suggest that S. marcescens LPS is sufficient for inhibition of epithelial wound healing. This study presents a novel host-pathogen interaction with implications for infections where bacteria impact wound healing and provides evidence that secreted LPS is a key factor in the inhibitory mechanism. PMID:26365869
Laminated electromagnetic pump stator core
Fanning, A.W.
1995-08-08
A stator core for an electromagnetic pump includes a plurality of circumferentially abutting tapered laminations extending radially outwardly from a centerline axis to collectively define a radially inner bore and a radially outer circumference. Each of the laminations includes radially inner and outer edges and has a thickness increasing from the inner edge toward the outer edge to provide a substantially continuous path adjacent the circumference. This pump is used in nuclear fission reactors. 19 figs.
Stevenson, D J
1981-11-06
Combined inferences from seismology, high-pressure experiment and theory, geomagnetism, fluid dynamics, and current views of terrestrial planetary evolution lead to models of the earth's core with the following properties. Core formation was contemporaneous with earth accretion; the core is not in chemical equilibrium with the mantle; the outer core is a fluid iron alloy containing significant quantities of lighter elements and is probably almost adiabatic and compositionally uniform; the more iron-rich inner solid core is a consequence of partial freezing of the outer core, and the energy release from this process sustains the earth's magnetic field; and the thermodynamic properties of the core are well constrained by the application of liquid-state theory to seismic and laboratory data.
Concentric core optical fiber with multiple-mode signal transmission
Muhs, J.D.
1997-05-06
A concentric core optical fiber provides for the simultaneous but independent transmission of signals over a single optical fiber. The concentric optical fiber is constructed of a single-mode or multimode inner optical fiber defined by a core and a cladding of a lower index of refraction than the core and an outer optical fiber defined by additional cladding concentrically disposed around the cladding and of an index of refraction lower than the first mentioned cladding whereby the latter functions as the core of the outer optical fiber. By employing such an optical fiber construction with a single-mode inner core or optical fiber, highly sensitive interferometric and stable less sensitive amplitude based sensors can be placed along the same length of a concentric core optical fiber. Also, by employing the concentric core optical fiber secure telecommunications can be achieved via the inner optical fiber since an intrusion of the concentric optical fiber will first cause a variation in the light being transmitted through the outer optical fiber and this variation of light being used to trigger a suitable alarm indicative of the intrusion. 3 figs.
Concentric core optical fiber with multiple-mode signal transmission
Muhs, Jeffrey D.
1997-01-01
A concentric core optical fiber provides for the simultaneous but independent transmission of signals over a single optical fiber. The concentric optical fiber is constructed of a single-mode or multimode inner optical fiber defined by a core and a cladding of a lower index of refraction than the core and an outer optical fiber defined by additional cladding concentrically disposed around the cladding and of an index of refraction lower than the first mentioned cladding whereby the latter functions as the core of the outer optical fiber. By employing such an optical fiber construction with a single-mode inner core or optical fiber, highly sensitive interferometric and stable less sensitive amplitude based sensors can be placed along the same length of a concentric core optical fiber. Also, by employing the concentric core optical fiber secure telecommunications can be achieved via the inner optical fiber since an intrusion of the concentric optical fiber will first cause a variation in the light being transmitted through the outer optical fiber and this variation of light being used to trigger a suitable alarm indicative of the intrusion.
NASA Astrophysics Data System (ADS)
Arkani-Hamed, J.
2014-12-01
Paleointensity measurements of Archean rocks reveal a strong geodynamo at ~3.45 Ga, while excess nitrogen content of lunar soil samples implies no geodynamo at ~3.9 Ga. Here I propose that initiation of a strong geodynamo is delayed due to accretion style of Earth, involving collision and merging of a few dozen Moon to Mars size planetary embryos. Two accretion scenarios consisting of 25 and 50 embryos are investigated. The collision of an embryo heats the proto-Earth's core differentially and the rotating low-viscosity core stably stratifies, creating a spherically symmetric and radially increasing temperature distribution. Convection starts in the outer core after each impact but is destroyed by the next impact. The iron core of an impacting embryo descends in the mantle and merges to the proto-Earth's core. Both adiabatic and non-adiabatic merging cases are studied. A major part of the gravitational energy released due to core merging is used to lift up the upper portion of the core to emplace the impactor core material at the neutrally buoyant level in the proto-Earth's core. The remaining energy is converted to heat. In the adiabatic case the merging embryo's core retains all of the remaining energy, while in the non-adiabatic merging 50% of the remaining energy is shared with the outer part of the proto-Earth's core where the embryo's core descends. The two merging models result in significantly different temperature distributions in the core at the end of accretion. After the accretion, the convecting shell in the outer core grows monotonically and generates geodynamo gradually. It takes about 50-100 Myr for the convecting shell to generate a strong dipole field at the surface, 50,000 to 100,000 nT, in the presence of a large stably stratified liquid inner core when the convecting outer core thickness exceeds about one half the radius of the Earth's core.
Dissecting Escherichia coli Outer Membrane Biogenesis Using Differential Proteomics
Martorana, Alessandra M.; Motta, Sara; Di Silvestre, Dario; Falchi, Federica; Dehò, Gianni; Mauri, Pierluigi; Sperandeo, Paola; Polissi, Alessandra
2014-01-01
The cell envelope of Gram-negative bacteria is a complex multi-layered structure comprising an inner cytoplasmic membrane and an additional asymmetric lipid bilayer, the outer membrane, which functions as a selective permeability barrier and is essential for viability. Lipopolysaccharide, an essential glycolipid located in the outer leaflet of the outer membrane, greatly contributes to the peculiar properties exhibited by the outer membrane. This complex molecule is transported to the cell surface by a molecular machine composed of seven essential proteins LptABCDEFG that form a transenvelope complex and function as a single device. While advances in understanding the mechanisms that govern the biogenesis of the cell envelope have been recently made, only few studies are available on how bacterial cells respond to severe envelope biogenesis defects on a global scale. Here we report the use of differential proteomics based on Multidimensional Protein Identification Technology (MudPIT) to investigate how Escherichia coli cells respond to a block of lipopolysaccharide transport to the outer membrane. We analysed the envelope proteome of a lptC conditional mutant grown under permissive and non permissive conditions and identified 123 proteins whose level is modulated upon LptC depletion. Most such proteins belong to pathways implicated in cell envelope biogenesis, peptidoglycan remodelling, cell division and protein folding. Overall these data contribute to our understanding on how E. coli cells respond to LPS transport defects to restore outer membrane functionality. PMID:24967819
Rowsey, Pamela Johnson; Metzger, Bonnie L; Carlson, John; Gordon, Christopher J
2006-02-01
Chronic exercise conditioning has been shown to alter basal thermoregulatory processes as well as the response to inflammatory agents. Two such agents, lipopolysaccharide (LPS) and turpentine (TPT) are inducers of fever in rats. LPS, given intraperitoneally (i.p.), involves a systemic inflammatory response whereas TPT given intramuscularly (i.m.) elicits a localized inflammation. We assessed if chronic exercise training in the rat would alter the thermoregulatory response to LPS and TPT. Core temperature (T (c)) and motor activity were monitored by radiotelemetry. Female Sprague Dawley rats were divided into two groups (trained and sedentary) and housed at an ambient temperature of 22 degrees C. Animals voluntarily trained on running wheels for 8 weeks. In the first study, trained and sedentary female rats were injected i.p. with LPS (50 microg/kg) or an equal volume of 0.9% normal saline. In another study, trained and sedentary female rats were injected i.m. with TPT (10 microl)/rat or an equal volume of 0.9% normal saline. The time course of the LPS fever was very short compared to TPT. TPT injected animals displayed a smaller but more prolonged fever compared to LPS; however, training accentuated the febrile response to LPS (DeltaT (c)=0.6 degrees C in sedentary and 1.2 degrees C in trained). Training had a slight suppression on TPT-induced fever during the daytime but had no effect on motor activity or nighttime T (c). In contrast, exercise training led to a marked increase in the pyrogenic effects of LPS. We conclude that the effect of exercise training and source of infection (i.e., systemic versus localized in muscle) on fever is directly linked to type of pyrogenic agent.
The truth about laser fiber diameters.
Kronenberg, Peter; Traxer, Olivier
2014-12-01
To measure the various diameters of laser fibers from various manufacturers and compare them with the advertised diameter. Fourteen different unused laser fibers from 6 leading manufacturers with advertised diameters of 200, 270, 272, 273, 365, and 400 μm were measured by light microscopy. The outer diameter (including the fiber coating, cladding, and core), cladding diameter (including the cladding and the fiber core), and core diameter were measured. Industry representatives of the manufacturers were interviewed about the diameter of their fibers. For all fibers, the outer and cladding diameters differed significantly from the advertised diameter (P <.00001). The outer diameter, which is of most practical relevance for urologists, exhibited a median increase of 87.3% (range, 50.7%-116.7%). The outer, cladding, and core diameters of fibers with equivalent advertised diameters differed by up to 180, 100, and 78 μm, respectively. Some 200-μm fibers had larger outer diameters than the 270- to 273-μm fibers. All packaging material and all laser fibers lacked clear and precise fiber diameter information labels. Of 12 representatives interviewed, 8, 3, and 1 considered the advertised diameter to be the outer, the cladding, and the core diameter, respectively. Representatives within the same company frequently gave different answers. This study suggests that, at present, there is a lack of uniformity between laser fiber manufacturers, and most of the information conveyed to urologists regarding laser fiber diameter may be incorrect. Because fibers larger than the advertised laser fibers are known to influence key interventional parameters, this misinformation can have surgical repercussions. Copyright © 2014 Elsevier Inc. All rights reserved.
Loughlin, M F; Jones, M V; Lambert, P A
2002-04-01
Our objective was to determine whether strains of Pseudomonas aeruginosa can adapt to growth in increasing concentrations of the disinfectant benzalkonium chloride (BKC), and whether co-resistance to clinically relevant antimicrobial agents occurs. Attempts were made to determine what phenotypic alterations accompanied resistance and whether these explained the mechanism of resistance. Strains were serially passaged in increasing concentrations of BKC in static nutrient broth cultures. Serotyping and genotyping were used to determine purity of the cultures. Two strains were examined for cross-resistance to other disinfectants and antibiotics by broth dilution MIC determination. Alterations in outer membrane proteins and lipopolysaccharide (LPS) expressed were examined by SDS-PAGE. Cell surface hydrophobicity and charge, uptake of disinfectant and proportion of specific fatty acid content of outer and cytoplasmic membranes were determined. Two P. aeruginosa strains showed a stable increase in resistance to BKC. Co-resistance to other quaternary ammonium compounds was observed in both strains; chloramphenicol and polymyxin B resistance were observed in one and a reduction in resistance to tobramycin observed in the other. However, no increased resistance to other biocides (chlorhexidine, triclosan, thymol) or antibiotics (ceftazidime, imipenem, ciprofloxacin, tobramycin) was detected. Characteristics accompanying resistance included alterations in outer membrane proteins, uptake of BKC, cell surface charge and hydrophobicity, and fatty acid content of the cytoplasmic membrane, although no evidence was found for alterations in LPS. Each of the two strains had different alterations in phenotype, indicating that such adaptation is unique to each strain of P. aeruginosa and does not result from a single mechanism shared by the whole species.
Phage-Coupled Piezoelectric Biodetector for Salmonella Typhimurium
2005-08-01
protein. (POR) porin. (A) lipid A. (LPS) lipopolysaccharide (core polysaccharide and O-antigen). (F) fimbriae or flagella or pili...large protein and polysaccharide molecules in solution gave responses that did not correlate with mass changes imposed at the solid- liquid interface...chains, which are linked to lipid A via a genera-specific core polysaccharide . These 94 differences account for serotype specificity. To date, well over
NASA Technical Reports Server (NTRS)
Stevenson, D. J.
1981-01-01
Combined inferences from seismology, high-pressure experiment and theory, geomagnetism, fluid dynamics, and current views of terrestrial planetary evolution lead to models of the earth's core with five basic properties. These are that core formation was contemporaneous with earth accretion; the core is not in chemical equilibrium with the mantle; the outer core is a fluid iron alloy containing significant quantities of lighter elements and is probably almost adiabatic and compositionally uniform; the more iron-rich inner solid core is a consequence of partial freezing of the outer core, and the energy release from this process sustains the earth's magnetic field; and the thermodynamic properties of the core are well constrained by the application of liquid-state theory to seismic and labroatory data.
NASA Astrophysics Data System (ADS)
Jing, Z.; Wang, Y.; Kono, Y.; Yu, T.; Sakamaki, T.; Park, C.; Rivers, M. L.; Sutton, S. R.; Shen, G.
2013-12-01
Geophysical observations based on lunar seismology and laser ranging strongly suggest that the Moon's iron core is partially molten. Similar to Earth and other terrestrial planets, light elements, such as sulfur, silicon, carbon, and oxygen, are likely present in the lunar core. Determining the light element concentration in the outer core is of vital importance to the understanding of the structure, dynamics, and chemical evolution of the Moon, as well as the enigmatic history of the lunar dynamo. Among the candidate elements, sulfur is the preferred major light element in the lunar outer due to its high abundance in the parent bodies of iron meteorites, its high solubility in liquid Fe at the lunar core pressure (~5 GPa), and its strong effects on reducing the density, velocity, and freezing temperature of the core. In this study, we conducted in-situ sound velocity measurements on liquid samples of four different compositions, including pure Fe, Fe-10wt%S, Fe-20wt%S, and Fe-27wt%S, at pressure and temperature conditions up to 8 GPa and 1973 K (encompassing the entire lunar depth range), using the Kawai-type multi-anvil device at the GSECARS beamline 13-ID-D and the Paris-Edinburgh cell at HPCAT beamline 16-BM-B. Our results show that the velocity of Fe-rich liquids increases upon compression, decreases with increasing sulfur content, and is nearly independent of temperature. Compared to the seismic velocity of the outer core, our velocity data constrain the sulfur content at 4×2 wt%, indicating a significantly denser (6.4×0.4 g/cm3) and hotter (1860×60 K) outer core than previously estimated. A new lunar structure model incorporating available geophysical observations points to a smaller core radius. Our model also suggests a top-down solidification scenario for the evolution of the lunar core. Such an 'iron snow' process may have been an important mechanism for the growth of the inner core.
High-gradient compact linear accelerator
Carder, B.M.
1998-05-26
A high-gradient linear accelerator comprises a solid-state stack in a vacuum of five sets of disc-shaped Blumlein modules each having a center hole through which particles are sequentially accelerated. Each Blumlein module is a sandwich of two outer conductive plates that bracket an inner conductive plate positioned between two dielectric plates with different thicknesses and dielectric constants. A third dielectric core in the shape of a hollow cylinder forms a casing down the series of center holes, and it has a dielectric constant different that the two dielectric plates that sandwich the inner conductive plate. In operation, all the inner conductive plates are charged to the same DC potential relative to the outer conductive plates. Next, all the inner conductive plates are simultaneously shorted to the outer conductive plates at the outer diameters. The signal short will propagate to the inner diameters at two different rates in each Blumlein module. A faster wave propagates quicker to the third dielectric core across the dielectric plates with the closer spacing and lower dielectric constant. When the faster wave reaches the inner extents of the outer and inner conductive plates, it reflects back outward and reverses the field in that segment of the dielectric core. All the field segments in the dielectric core are then in unipolar agreement until the slower wave finally propagates to the third dielectric core across the dielectric plates with the wider spacing and higher dielectric constant. During such unipolar agreement, particles in the core are accelerated with gradients that exceed twenty megavolts per meter. 10 figs.
High-gradient compact linear accelerator
Carder, Bruce M.
1998-01-01
A high-gradient linear accelerator comprises a solid-state stack in a vacuum of five sets of disc-shaped Blumlein modules each having a center hole through which particles are sequentially accelerated. Each Blumlein module is a sandwich of two outer conductive plates that bracket an inner conductive plate positioned between two dielectric plates with different thicknesses and dielectric constants. A third dielectric core in the shape of a hollow cylinder forms a casing down the series of center holes, and it has a dielectric constant different that the two dielectric plates that sandwich the inner conductive plate. In operation, all the inner conductive plates are charged to the same DC potential relative to the outer conductive plates. Next, all the inner conductive plates are simultaneously shorted to the outer conductive plates at the outer diameters. The signal short will propagate to the inner diameters at two different rates in each Blumlein module. A faster wave propagates quicker to the third dielectric core across the dielectric plates with the closer spacing and lower dielectric constant. When the faster wave reaches the inner extents of the outer and inner conductive plates, it reflects back outward and reverses the field in that segment of the dielectric core. All the field segments in the dielectric core are then in unipolar agreement until the slower wave finally propagates to the third dielectric core across the dielectric plates with the wider spacing and higher dielectric constant. During such unipolar agreement, particles in the core are accelerated with gradients that exceed twenty megavolts per meter.
Rasmussen, Jed A.; Fletcher, Joshua R.; Long, Matthew E.; Allen, Lee-Ann H.; Jones, Bradley D.
2015-01-01
The lipopolysaccharide (LPS) and O-antigen polysaccharide capsule structures of Francisella tularensis play significant roles in helping these highly virulent bacteria avoid detection within a host. We previously created pools of F. tularensis mutants that we screened to identify strains that were not reactive to a monoclonal antibody to the O-antigen capsule. To follow up previously published work, we characterize further seven of the F. tularensis Schu S4 mutant strains identified by our screen. These F. tularensis strains carry the following transposon mutations: FTT0846::Tn5, hemH::Tn5, wbtA::Tn5, wzy::Tn5, FTT0673p/prsA::Tn5, manB::Tn5, or dnaJ::Tn5. Each of these strains displayed sensitivity to human serum, to varying degrees, when compared to wild-type F. tularensis Schu S4. By Western blot, only FTT0846::Tn5, wbtA::Tn5, wzy::Tn5, and manB::Tn5 strains did not react to the capsule and LPS O-antigen antibody 11B7, although the wzy::Tn5 strain did have a single O-antigen reactive band that was detected by the FB11 monoclonal antibody. Of these strains, manB::Tn5 and FTT0846 appear to have LPS core truncations, whereas wbtA::Tn5 and wzy::Tn5 had LPS core structures that are similar to the parent F. tularensis Schu S4. These strains were also shown to have poor growth within human monocyte derived macrophages (MDMs) and bone marrow derived macrophages (BMDMs). We examined the virulence of these strains in mice, following intranasal challenge, and found that each was attenuated compared to wild type Schu S4. Our results provide additional strong evidence that LPS and/or capsule are F. tularensis virulence factors that most likely function by providing a stealth shield that prevents the host immune system from detecting this potent pathogen. PMID:25999917
Assembly of Lipopolysaccharide in Escherichia coli Requires the Essential LapB Heat Shock Protein*
Klein, Gracjana; Kobylak, Natalia; Lindner, Buko; Stupak, Anna; Raina, Satish
2014-01-01
Here, we describe two new heat shock proteins involved in the assembly of LPS in Escherichia coli, LapA and LapB (lipopolysaccharide assembly protein A and B). lapB mutants were identified based on an increased envelope stress response. Envelope stress-responsive pathways control key steps in LPS biogenesis and respond to defects in the LPS assembly. Accordingly, the LPS content in ΔlapB or Δ(lapA lapB) mutants was elevated, with an enrichment of LPS derivatives with truncations in the core region, some of which were pentaacylated and exhibited carbon chain polymorphism. Further, the levels of LpxC, the enzyme that catalyzes the first committed step of lipid A synthesis, were highly elevated in the Δ(lapA lapB) mutant. Δ(lapA lapB) mutant accumulated extragenic suppressors that mapped either to lpxC, waaC, and gmhA, or to the waaQ operon (LPS biosynthesis) and lpp (Braun's lipoprotein). Increased synthesis of either FabZ (3-R-hydroxymyristoyl acyl carrier protein dehydratase), slrA (novel RpoE-regulated non-coding sRNA), lipoprotein YceK, toxin HicA, or MurA (UDP-N-acetylglucosamine 1-carboxyvinyltransferase) suppressed some of the Δ(lapA lapB) defects. LapB contains six tetratricopeptide repeats and, at the C-terminal end, a rubredoxin-like domain that was found to be essential for its activity. In pull-down experiments, LapA and LapB co-purified with LPS, Lpt proteins, FtsH (protease), DnaK, and DnaJ (chaperones). A specific interaction was also observed between WaaC and LapB. Our data suggest that LapB coordinates assembly of proteins involved in LPS synthesis at the plasma membrane and regulates turnover of LpxC, thereby ensuring balanced biosynthesis of LPS and phospholipids consistent with its essentiality. PMID:24722986
Inoue, Wataru; Luheshi, Giamal N
2010-12-01
A decrease in leptin levels with the onset of starvation triggers a myriad of physiological responses including immunosuppression and hypometabolism/hypothermia, both of which can counteract the fever response to pathogens. Here we examined the role of leptin in LPS-induced fever in rats that were fasted for 48 h prior to inflammation with or without leptin replacement (12 μg/day). The preinflammation fasting alone caused a progressive hypothermia that was almost completely reversed by leptin replacement. The LPS (100 μg/kg)-induced elevation in core body temperature (T(core)) was attenuated in the fasted animals at 2-6 h after the injection, an effect that was not reversed by leptin replacement. Increasing the LPS dose to 1,000 μg/kg caused a long-lasting fever that remained unabated for up to 36 h after the injection in the fed rats. This sustained response was strongly attenuated in the fasted rats whose T(core) started to decrease by 18 h after the injection. Leptin replacement almost completely restored the prolonged fever. The attenuation of the prolonged fever in the fasted animals was accompanied by the diminution of proinflammatory PGE(2) in the cerebrospinal fluid and mRNA of proopiomelanocortin (POMC) in the hypothalamus. Leptin replacement prevented the fasting-induced reduction of POMC but not PGE(2). Moreover, the leptin-dependent fever maintenance correlated closely with hypothalamic POMC levels (r = 0.77, P < 0.001). These results suggest that reduced leptin levels during starvation attenuate the sustained fever response by lowering hypothalamic POMC tone but not PGE(2) synthesis.
LC and ferromagnetic resonance in soft/hard magnetic microwires
NASA Astrophysics Data System (ADS)
Tian, Bin; Vazquez, Manuel
2015-12-01
The magnetic behavior of soft/hard biphase microwires is introduced here. The microwires consist of a Co59.1Fe14.8Si10.2B15.9 soft magnetic nucleus and a Co90Ni10 hard outer shell separated by an intermediate insulating Pyrex glass microtube. By comparing the resistance spectrums of welding the ends of metallic core (CC) or welding the metallic core and outer shell (CS) to the connector, it is found that one of the two peaks in the resistance spectrum is because the LC resonance depends on the inductor and capacitors in which one is the capacitor between the metallic core and outer shell, and the other is between the outer shell and connector. Correspondingly, another peak is for the ferromagnetic resonance of metallic core. After changing the capacitance of the capacitors, the frequency of LC resonance moves to high frequency band, and furthermore, the peak of LC resonance in the resistance spectrum disappeared. These magnetostatically coupled biphase systems are thought to be of large potential interest as sensing elements in sensor devices.
Transient state kinetic investigation of ferritin iron release
NASA Astrophysics Data System (ADS)
Ciasca, G.; Papi, M.; Chiarpotto, M.; Rodio, M.; Campi, G.; Rossi, C.; De Sole, P.; Bianconi, A.
2012-02-01
Increased iron concentration in tissues appears to be a factor in the genesis and development of inflammatory and degenerative diseases. By means of real-time small angle x-ray scattering measurements, we studied the kinetics of iron release from the ferritin inorganic core as a function of time and distance from the iron core centre. Accordingly, the iron release process follows a three step model: (i) a defect nucleation in the outer part of the mineral core, (ii) the diffusion of the reducing agent towards the inner part of the core, and (iii) the erosion of the core from the inner to the outer part.
Capture of lipopolysaccharide (endotoxin) by the blood clot: a comparative study.
Armstrong, Margaret T; Rickles, Frederick R; Armstrong, Peter B
2013-01-01
In vertebrates and arthropods, blood clotting involves the establishment of a plug of aggregated thrombocytes (the cellular clot) and an extracellular fibrillar clot formed by the polymerization of the structural protein of the clot, which is fibrin in mammals, plasma lipoprotein in crustaceans, and coagulin in the horseshoe crab, Limulus polyphemus. Both elements of the clot function to staunch bleeding. Additionally, the extracellular clot functions as an agent of the innate immune system by providing a passive anti-microbial barrier and microbial entrapment device, which functions directly at the site of wounds to the integument. Here we show that, in addition to these passive functions in immunity, the plasma lipoprotein clot of lobster, the coagulin clot of Limulus, and both the platelet thrombus and the fibrin clot of mammals (human, mouse) operate to capture lipopolysaccharide (LPS, endotoxin). The lipid A core of LPS is the principal agent of gram-negative septicemia, which is responsible for more than 100,000 human deaths annually in the United States and is similarly toxic to arthropods. Quantification using the Limulus Amebocyte Lysate (LAL) test shows that clots capture significant quantities of LPS and fluorescent-labeled LPS can be seen by microscopy to decorate the clot fibrils. Thrombi generated in the living mouse accumulate LPS in vivo. It is suggested that capture of LPS released from gram-negative bacteria entrapped by the blood clot operates to protect against the disease that might be caused by its systemic dispersal.
NASA Technical Reports Server (NTRS)
Myrick, Thomas M. (Inventor)
2003-01-01
A mechanism for breaking off and retaining a core sample of a drill drilled into a ground substrate has an outer drill tube and an inner core break-off tube sleeved inside the drill tube. The break-off tube breaks off and retains the core sample by a varying geometric relationship of inner and outer diameters with the drill tube. The inside diameter (ID) of the drill tube is offset by a given amount with respect to its outer diameter (OD). Similarly, the outside diameter (OD) of the break-off tube is offset by the same amount with respect to its inner diameter (ID). When the break-off tube and drill tube are in one rotational alignment, the two offsets cancel each other such that the drill can operate the two tubes together in alignment with the drill axis. When the tubes are rotated 180 degrees to another positional alignment, the two offsets add together causing the core sample in the break-off tube to be displaced from the drill axis and applying shear forces to break off the core sample.
Richie, Daryl L.; Takeoka, Kenneth T.; Bojkovic, Jade; Metzger, Louis E.; Rath, Christopher M.; Sawyer, William S.; Wei, Jun-Rong; Dean, Charles R.
2016-01-01
The lipid A moiety of lipopolysaccharide (LPS) is the main constituent of the outer leaflet of the Gram-negative bacterial outer membrane (OM) and is essential in many Gram-negative pathogens. An exception is Acinetobacter baumannii ATCC 19606, where mutants lacking enzymes occurring early in lipid A biosynthesis (LpxA, LpxC or LpxD), and correspondingly lacking LPS, can grow. In contrast, we show here that LpxH, an enzyme that occurs downstream of LpxD in the lipid A biosynthetic pathway, is essential for growth in this strain. Multiple attempts to disrupt lpxH on the genome were unsuccessful, and when LpxH expression was controlled by an isopropyl β-d-1-thiogalactopyranoside (IPTG) inducible promoter, cell growth under typical laboratory conditions required IPTG induction. Mass spectrometry analysis of cells shifted from LpxH-induced to uninduced (and whose growth was correspondingly slowing as LpxH was depleted) showed a large cellular accumulation of UDP-2,3-diacyl-GlcN (substrate of LpxH), a C14:0(3-OH) acyl variant of the LpxD substrate (UDP-3-O-[(R)-3-OH-C14]-GlcN), and disaccharide 1-monophosphate (DSMP). Furthermore, the viable cell counts of the LpxH depleted cultures dropped modestly, and electron microscopy revealed clear defects at the cell (inner) membrane, suggesting lipid A intermediate accumulation was toxic. Consistent with this, blocking the synthesis of these intermediates by inhibition of the upstream LpxC enzyme using CHIR-090 abrogated the requirement for IPTG induction of LpxH. Taken together, these data indicate that LpxH is essential for growth in A. baumannii ATCC19606, because, unlike earlier pathway steps like LpxA or LpxC, blockage of LpxH causes accumulation of detergent-like pathway intermediates that prevents cell growth. PMID:27526195
NASA Astrophysics Data System (ADS)
Sobot, Dunja; Mura, Simona; Yesylevskyy, Semen O.; Dalbin, Laura; Cayre, Fanny; Bort, Guillaume; Mougin, Julie; Desmaële, Didier; Lepetre-Mouelhi, Sinda; Pieters, Grégory; Andreiuk, Bohdan; Klymchenko, Andrey S.; Paul, Jean-Louis; Ramseyer, Christophe; Couvreur, Patrick
2017-05-01
Once introduced in the organism, the interaction of nanoparticles with various biomolecules strongly impacts their fate. Here we show that nanoparticles made of the squalene derivative of gemcitabine (SQGem) interact with lipoproteins (LPs), indirectly enabling the targeting of cancer cells with high LP receptors expression. In vitro and in vivo experiments reveal preeminent affinity of the squalene-gemcitabine bioconjugates towards LP particles with the highest cholesterol content and in silico simulations further display their incorporation into the hydrophobic core of LPs. To the best of our knowledge, the use of squalene to induce drug insertion into LPs for indirect cancer cell targeting is a novel concept in drug delivery. Interestingly, not only SQGem but also other squalene derivatives interact similarly with lipoproteins while such interaction is not observed with liposomes. The conjugation to squalene represents a versatile platform that would enable efficient drug delivery by simply exploiting endogenous lipoproteins.
Reverse Flow Engine Core Having a Ducted Fan with Integrated Secondary Flow Blades
NASA Technical Reports Server (NTRS)
Kisska, Michael K. (Inventor); Princen, Norman H. (Inventor); Kuehn, Mark S. (Inventor); Cosentino, Gary B. (Inventor)
2014-01-01
Secondary air flow is provided for a ducted fan having a reverse flow turbine engine core driving a fan blisk. The fan blisk incorporates a set of thrust fan blades extending from an outer hub and a set of integral secondary flow blades extending intermediate an inner hub and the outer hub. A nacelle provides an outer flow duct for the thrust fan blades and a secondary flow duct carries flow from the integral secondary flow blades as cooling air for components of the reverse flow turbine engine.
NASA Astrophysics Data System (ADS)
Yu, W.; Wen, L.; Niu, F.
2002-05-01
We have extensively collected PKP waveforms around the PKP caustic distance range (141o - 147o) recorded in several dense regional arrays and the Global Seismic Network covering from 1990 to 2000. PKP observations at this distance range (141o - 147o) are usually purposely avoided in travel time analyses, because of the interference of various PKP branches. The observations there, however, will be extremely useful for constraining the seismic structures at both the top of the inner core and the bottom of the outer core. Moreover, because PKIKP phases sample a depth range of 100 km - 170 km below the inner-core boundary at this distant range, their observations fill the sampling depth gap between the PKiKP-PKIKP observations at the smaller distances and the PKPbc-PKIKP phases at the larger distances. Before the PKP caustics (141o - 145o), the diffracted PKP phases near the B caustics (PKPBdiff) and PKiKP phases are discernible in the long-period seismograms, and their differential travel times and waveforms could be used to constrain seismic structures at the bottom of the outer core and/or at the base of the mantle. The observed long-period PKiKP-PKPBdiff waveforms exhibit a hemispheric difference between those sampling the "eastern" and "western" hemispheres, with those sampling the "western" hemisphere showing larger time separations between the two phases. These observations can be explained by models with P velocity gradients of 0.0806 (km/s)/ 200 km for the "western" hemisphere and 0.114 (km/s)/200 km for the "eastern" hemisphere at the bottom of the outer core. Alternatively, these observations can also be explained by models with different velocity structures at the bottom 200 km of the mantle with P velocity variations in an order of 3 percent with respect to PREM. Broadband PKP observations after the PKP caustics (145o - 147o), on the other hand, provide high-quality constraints on the seismic structures at both the top of the inner core and the bottom of the outer core, as PKPbc phases can be used as excellent reference phases. We explore seismic models in both the bottom of the outer core and the top of the inner core, which can consistently explain the seismic observations at the caustic distance range (141o - 147o) and the PKiKP-PKIKP observations at the closer distances (Niu and Wen, Nature, 410, 1081-1084, 2001, Wen and Niu, JGR, submitted).
Oka, Takakazu; Oka, Kae; Kobayashi, Takuya; Sugimoto, Yukihiko; Ichikawa, Atsushi; Ushikubi, Fumitaka; Narumiya, Shuh; Saper, Clifford B
2003-01-01
Previous studies have disagreed about whether prostaglandin EP1 or EP3 receptors are critical for producing febrile responses. We therefore injected lipopolysaccharide (LPS) at a variety doses (1 μg kg−1−1 mg kg−1) intraperitoneally (I.P.) into wild-type (WT) mice and mice lacking the EP1 or the EP3 receptors and measured changes in core temperature (Tc) by using telemetry. In WT mice, I.P. injection of LPS at 10 μg kg−1 increased Tc about 1 °C, peaking 2 h after injection. At 100 μg kg−1, LPS increased Tc, peaking 5–8 h after injection. LPS at 1 mg kg−1 decreased Tc, reaching a nadir at 5–8 h after injection. In EP1 receptor knockout (KO) mice injected with 10 μg kg−1 LPS, only the initial (< 40 min) increase in Tc was lacking; with 100 μg kg−1 LPS the mice showed no febrile response. In EP3 receptor KO mice, LPS decreased Tc in a dose- and time-dependent manner. Furthermore, in EP3 receptor KO mice subcutaneous injection of turpentine did not induce fever. Both EP1 and EP3 receptor KO mice showed a normal circadian cycle of Tc and brief hyperthermia following psychological stress (cage-exchange stress and buddy-removal stress). The present study suggests that both the EP1 and the EP3 receptors play a role in fever induced by systemic inflammation but neither EP receptor is involved in the circadian rise in Tc or psychological stress-induced hyperthermia in mice. PMID:12837930
Gu, Shunchao; Kondo, Tomohiro; Mine, Eiichi; Nagao, Daisuke; Kobayashi, Yoshio; Konno, Mikio
2004-11-01
Jingle bell-shaped hollow spheres were fabricated starting from multilayered particles composed of a silica core, a polystyrene inner shell, and a titania outer shell. Composite particles of silica core-polystyrene shell, synthesized by coating a 339-nm-sized silica core with a polystyrene shell of thickness 238 nm in emulsion polymerization, were used as core particles for a succeeding titania-coating. A sol-gel method was employed to form the titania outer shell with a thickness of 37 nm. The inner polystyrene shell in the multilayered particles was removed by immersing them in tetrahydrofuran. These successive procedures could produce jingle bell-shaped hollow spheres that contained a silica core in the titania shell.
Experimental and Theoretical Investigations on Viscosity of Fe-Ni-C Liquids at High Pressures
NASA Astrophysics Data System (ADS)
Chen, B.; Lai, X.; Wang, J.; Zhu, F.; Liu, J.; Kono, Y.
2016-12-01
Understanding and modeling of Earth's core processes such as geodynamo and heat flow via convection in liquid outer cores hinges on the viscosity of candidate liquid iron alloys under core conditions. Viscosity estimates from various methods of the metallic liquid of the outer core, however, span up to 12 orders of magnitude. Due to experimental challenges, viscosity measurements of iron liquids alloyed with lighter elements are scarce and conducted at conditions far below those expected for the outer core. In this study, we adopt a synergistic approach by integrating experiments at experimentally-achievable conditions with computations up to core conditions. We performed viscosity measurements based on the modified Stokes' floating sphere viscometry method for the Fe-Ni-C liquids at high pressures in a Paris-Edinburgh press at Sector 16 of the Advanced Photon Source, Argonne National Laboratory. Our results show that the addition of 3-5 wt.% carbon to iron-nickel liquids has negligible effect on its viscosity at pressures lower than 5 GPa. The viscosity of the Fe-Ni-C liquids, however, becomes notably higher and increases by a factor of 3 at 5-8 GPa. Similarly, our first-principles molecular dynamics calculations up to Earth's core pressures show a viscosity change in Fe-Ni-C liquids at 5 GPa. The significant change in the viscosity is likely due to a liquid structural transition of the Fe-Ni-C liquids as revealed by our X-ray diffraction measurements and first-principles molecular dynamics calculations. The observed correlation between structure and physical properties of liquids permit stringent benchmark test of the computational liquid models and contribute to a more comprehensive understanding of liquid properties under high pressures. The interplay between experiments and first-principles based modeling is shown to be a practical and effective methodology for studying liquid properties under outer core conditions that are difficult to reach with the current static high-pressure capabilities. The new viscosity data from experiments and computations would provide new insights into the internal dynamics of the outer core.
1988-01-01
rate was deposited predominantly on the outer surfaces of in the pathogn~nesis of endotoxernia and septic shock. The the RER of hepatocytes. in additron...es; and (c) tin it- the basal (perisinusoidal) surfaces and in the cisternae G-6-Pase activity. LPS treatment also leads to reduced num- of tough...by Kupffer cells (Cook et al., 1985’ Gut et al., sue fibronectin results in widening intercellular junctions anci in- 198: ~nkaa ndIwsk,18
Electromagnetic pump stator core
Fanning, A.W.; Olich, E.E.; Dahl, L.R.
1995-01-17
A stator core for supporting an electrical coil includes a plurality of groups of circumferentially abutting flat laminations which collectively form a bore and perimeter. A plurality of wedges are interposed between the groups, with each wedge having an inner edge and a thicker outer edge. The wedge outer edges abut adjacent ones of the groups to provide a continuous path around the perimeter. 21 figures.
Electromagnetic pump stator core
Fanning, Alan W.; Olich, Eugene E.; Dahl, Leslie R.
1995-01-01
A stator core for supporting an electrical coil includes a plurality of groups of circumferentially abutting flat laminations which collectively form a bore and perimeter. A plurality of wedges are interposed between the groups, with each wedge having an inner edge and a thicker outer edge. The wedge outer edges abut adjacent ones of the groups to provide a continuous path around the perimeter.
Magnetohydrodynamic Convection in the Outer Core and its Geodynamic Consequences
NASA Technical Reports Server (NTRS)
Kuang, Weijia; Chao, Benjamin F.; Fang, Ming
2004-01-01
The Earth's fluid outer core is in vigorous convection through much of the Earth's history. In addition to generating and maintaining Earth s time-varying magnetic field (geodynamo), the core convection also generates mass redistribution in the core and a dynamical pressure field on the core-mantle boundary (CMB). All these shall result in various core-mantle interactions, and contribute to surface geodynamic observables. For example, electromagnetic core-mantle coupling arises from finite electrically conducting lower mantle; gravitational interaction occurs between the cores and the heterogeneous mantle; mechanical coupling may also occur when the CMB topography is aspherical. Besides changing the mantle rotation via the coupling torques, the mass-redistribution in the core shall produce a spatial-temporal gravity anomaly. Numerical modeling of the core dynamical processes contributes in several geophysical disciplines. It helps explain the physical causes of surface geodynamic observables via space geodetic techniques and other means, e.g. Earth's rotation variation on decadal time scales, and secular time-variable gravity. Conversely, identification of the sources of the observables can provide additional insights on the dynamics of the fluid core, leading to better constraints on the physics in the numerical modeling. In the past few years, our core dynamics modeling efforts, with respect to our MoSST model, have made significant progress in understanding individual geophysical consequences. However, integrated studies are desirable, not only because of more mature numerical core dynamics models, but also because of inter-correlation among the geophysical phenomena, e.g. mass redistribution in the outer core produces not only time-variable gravity, but also gravitational core-mantle coupling and thus the Earth's rotation variation. They are expected to further facilitate multidisciplinary studies of core dynamics and interactions of the core with other components of the Earth.
NASA Technical Reports Server (NTRS)
Gheen, Darrell
2007-01-01
A tool makes a cut perpendicular to the cylindrical axis of a core hole at a predetermined depth to free the core at that depth. The tool does not damage the surrounding material from which the core was cut, and it operates within the core-hole kerf. Coring usually begins with use of a hole saw or a hollow cylindrical abrasive cutting tool to make an annular hole that leaves the core (sometimes called the plug ) in place. In this approach to coring as practiced heretofore, the core is removed forcibly in a manner chosen to shear the core, preferably at or near the greatest depth of the core hole. Unfortunately, such forcible removal often damages both the core and the surrounding material (see Figure 1). In an alternative prior approach, especially applicable to toxic or fragile material, a core is formed and freed by means of milling operations that generate much material waste. In contrast, the present tool eliminates the damage associated with the hole-saw approach and reduces the extent of milling operations (and, hence, reduces the waste) associated with the milling approach. The present tool (see Figure 2) includes an inner sleeve and an outer sleeve and resembles the hollow cylindrical tool used to cut the core hole. The sleeves are thin enough that this tool fits within the kerf of the core hole. The inner sleeve is attached to a shaft that, in turn, can be attached to a drill motor or handle for turning the tool. This tool also includes a cutting wire attached to the distal ends of both sleeves. The cutting wire is long enough that with sufficient relative rotation of the inner and outer sleeves, the wire can cut all the way to the center of the core. The tool is inserted in the kerf until its distal end is seated at the full depth. The inner sleeve is then turned. During turning, frictional drag on the outer core pulls the cutting wire into contact with the core. The cutting force of the wire against the core increases with the tension in the wire and, hence, with the frictional drag acting on the outer sleeve. As the wire cuts toward the center of the core, the inner sleeve rotates farther with respect to the outer sleeve. Once the wire has cut to the center of the core, the tool and the core can be removed from the hole. The proper choice of cutting wire depends on the properties of the core material. For a sufficiently soft core material, a nonmetallic monofilament can be used. For a rubber-like core material, a metal wire can be used. For a harder core material, it is necessary to use an abrasive wire, and the efficiency of the tool can be increased greatly by vacuuming away the particles generated during cutting. For a core material that can readily be melted or otherwise cut by use of heat, it could be preferable to use an electrically heated cutting wire. In such a case, electric current can be supplied to the cutting wire, from an electrically isolated source, via rotating contact rings mounted on the sleeves.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Nakanishi-Matsui, Mayumi, E-mail: nakanim@iwate-med.ac.jp; Yano, Shio; Futai, Masamitsu
2013-11-01
Highlights: •LPS induces multinuclear cells from murine macrophage-derived RAW264.7 cells. •Large beads are internalized by cells actively fusing to become multinuclear. •The multinuclear cell formation is inhibited by anti-inflammatory cytokine, IL10. •Signal transduction for cell fusion is different from that for inflammation. -- Abstract: A murine macrophage-derived line, RAW264.7, becomes multinuclear on stimulation with lipopolysaccharide (LPS), an outer membrane component of Gram-negative bacteria. These multinuclear cells internalized more polystyrene beads than mononuclear cells or osteoclasts (Nakanishi-Matsui, M., Yano, S., Matsumoto, N., and Futai, M., 2012). In this study, we analyzed the time courses of cell fusion in the presence ofmore » large beads. They were internalized into cells actively fusing to become multinuclear. However, the multinuclear cells once formed showed only low phagocytosis activity. These results suggest that formation of the multinuclear cells and bead internalization took place simultaneously. The formation of multinuclear cells was blocked by inhibitors for phosphoinositide 3-kinase, phospholipase C, calcineurin, and c-Jun N-terminal kinase. In addition, interleukin 6 and 10 also exhibited inhibitory effects. These signaling molecules and cytokines may play a crucial role in the LPS-induced multinuclear cell formation.« less
NASA Astrophysics Data System (ADS)
Lakshminarayanan, Rajamani; Tan, Wei Xiang; Aung, Thet Tun; Goh, Eunice Tze Leng; Muruganantham, Nandhakumar; Li, Jianguo; Chang, Jamie Ya Ting; Dikshit, Neha; Saraswathi, Padmanabhan; Lim, Rayne Rui; Kang, Tse Siang; Balamuralidhar, Vanniarajan; Sukumaran, Bindu; Verma, Chandra S.; Sivaraman, Jayaraman; Chaurasia, Shyam Sunder; Liu, Shouping; Beuerman, Roger W.
2016-05-01
Dissecting the complexities of branched peptide-lipopolysaccharides (LPS) interactions provide rationale for the development of non-cytotoxic antibiotic adjuvants. Using various biophysical methods, we show that the branched peptide, B2088, binds to lipid A and disrupts the supramolecular organization of LPS. The disruption of outer membrane in an intact bacterium was demonstrated by fluorescence spectroscopy and checkerboard assays, the latter confirming strong to moderate synergism between B2088 and various classes of antibiotics. The potency of synergistic combinations of B2088 and antibiotics was further established by time-kill kinetics, mammalian cell culture infections model and in vivo model of bacterial keratitis. Importantly, B2088 did not show any cytotoxicity to corneal epithelial cells for at least 96 h continuous exposure or hemolytic activity even at 20 mg/ml. Peptide congeners containing norvaline, phenylalanine and tyrosine (instead of valine in B2088) displayed better synergism compared to other substitutions. We propose that high affinity and subsequent disruption of the supramolecular assembly of LPS by the branched peptides are vital for the development of non-cytotoxic antibiotic adjuvants that can enhance the accessibility of conventional antibiotics to the intracellular targets, decrease the antibiotic consumption and holds promise in averting antibiotic resistance.
Palusiak, Agata
2015-03-01
Proteus sp. and Klebsiella sp. mainly cause infections of the urinary and respiratory tracts or wounds in humans. The representatives of both genera produce virulence factors like lipopolysaccharide (LPS) or outer membrane proteins (OMPs) having much in common in the structures and/or functions. To check how far this similarity is revealed in the serological cross-reactivity, the bacterial masses of 24 tested Klebsiella sp. strains were tested in ELISA with polyclonal rabbit antisera specific to the representatives of 79 Proteus O serogroups. The strongest reacting systems were selected to Western blot, where the majority of Klebsiella masses reacted in a way characteristic for electrophoretic patterns of proteins. The strongest reactions were obtained for proteins of near 67 and 40 kDa and 12.5 kDa. Mass spectrometry analysis of the proteins samples of one Proteus sp. and one Klebsiella sp. strain showed the GroEL like protein of a sequence GI number 2980926 to be similar for both strains. In Western blot some Klebsiella sp. masses reacted similarly to the homologous Proteus LPSs. The LPS contribution in the observed reactions of the high molecular-mass LPS species was confirmed for Klebsiella oxytoca 0.062. Copyright © 2014 Elsevier Ltd. All rights reserved.
Mice exposed to dim light at night exaggerate inflammatory responses to lipopolysaccharide.
Fonken, Laura K; Weil, Zachary M; Nelson, Randy J
2013-11-01
The mammalian circadian system regulates many physiological functions including inflammatory responses. Appropriately timed light information is essential for maintaining circadian organization. Over the past ∼120 years, urbanization and the widespread adoption of electric lights have dramatically altered lighting environments. Exposure to light at night (LAN) is pervasive in modern society and disrupts core circadian clock mechanisms. Because microglia are the resident macrophages in the brain and macrophages contain intrinsic circadian clocks, we hypothesized that chronic exposure to LAN would alter microglia cytokine expression and sickness behavior following LPS administration. Exposure to 4 weeks of dim LAN elevated inflammatory responses in mice. Mice exposed to dimly lit, as compared to dark, nights exaggerated changes in body temperature and elevated microglia pro-inflammatory cytokine expression following LPS administration. Furthermore, dLAN mice had a prolonged sickness response following the LPS challenge. Mice exposed to dark or dimly lit nights had comparable sickness behavior directly following the LPS injection; however, dLAN mice showed greater reductions in locomotor activity, increased anorectic behavior, and increased weight loss than mice maintained in dark nights 24h post-LPS injection. Overall, these data suggest that chronic exposure to even very low levels of light pollution may alter inflammatory responses. These results may have important implications for humans and other urban dwelling species that commonly experience nighttime light exposure. Copyright © 2013 Elsevier Inc. All rights reserved.
NASA Technical Reports Server (NTRS)
Hein, L. A.; Myers, W. N. (Inventor)
1976-01-01
An apparatus is described for converting thermal energy such as solar energy into mechanical motion for driving fluid pumps and similar equipment. The thermal motor comprises an inner concentric cylinder carried by a stationary core member. The core member has a cylindrical disc plate fixed adjacent to a lower portion and extending radially from it. An outer concentric cylinder rotatably carried on the disc plate defining a space between the inner and outer concentric cylinders. A spiral tubular member encircles the inner concentric cylinder and is contained within the space between the inner and outer cylinders. One portion is connected to the inner concentric cylinder and a second portion connected to the outer concentric cylinder. A heated fluid is conveyed through the tubular member and is periodically cooled causing the tubular member to expand and contract. This causes the outer concentric cylinder to reciprocally rotate on the base plate accordingly. The reciprocating motion of the outer concentric cylinder is then utilized to drive a pump member in a pump chamber.
Composition of the low seismic velocity E' layer at the top of Earth's core
NASA Astrophysics Data System (ADS)
Badro, J.; Brodholt, J. P.
2017-12-01
Evidence for a layer (E') at the top of the outer core has been available since the '90s and while different studies suggest slightly different velocity contrasts and thicknesses, the common observation is that the layer has lower velocities than the bulk outer core (PREM). Although there are no direct measurements on the density of this layer, dynamic stability requires it to be less dense than the bulk outer core under those same pressure and temperature conditions. Using ab initio simulations on Fe-Ni-S-C-O-Si liquids we constrain the origin and composition of the low-velocity layer E' at the top of Earth's outer core. We find that increasing the concentration of any light-element always increases velocity and so a low-velocity and low-density layer (for stability) cannot be made by simply increasing light element concentration. This rules out barodiffusion or upwards sedimentation of a light phase for its origin. However, exchanging elements can—depending on the elements exchanged—produce such a layer. We evaluate three possibilities. Firstly, crystallization of a light phase from a core containing more than one light element may make such a layer, but only if the crystalizing phase is very Fe-rich, which is at odds with available phase diagrams at CMB conditions. Secondly, the E' layer may result from incomplete mixing of an early Earth core with a late impactor, depending on the light element compositions of the impactor and Earth's core, but such a primordial stratification is neither supported by dynamical models of the core nor thermodynamic models of core merger after the giant impact. The last and most plausible scenario is core-mantle chemical interaction; using thermodynamic models for metal-silicate partitioning of silicon and oxygen at CMB conditions, we show that a reaction between the core and an FeO-rich basal magma ocean can enrich the core in oxygen while depleting it in silicon, in relative amounts that produce a light and slow layer consistent with seismological observations.
Compact Hybrid Laser Rod and Laser System
NASA Technical Reports Server (NTRS)
Pierrottet, Diego F. (Inventor); Busch, George E. (Inventor); Amzajerdian, Farzin (Inventor)
2017-01-01
A hybrid fiber rod includes a fiber core and inner and outer cladding layers. The core is doped with an active element. The inner cladding layer surrounds the core, and has a refractive index substantially equal to that of the core. The outer cladding layer surrounds the inner cladding layer, and has a refractive index less than that of the core and inner cladding layer. The core length is about 30 to 2000 times the core diameter. A hybrid fiber rod laser system includes an oscillator laser, modulating device, the rod, and pump laser diode(s) energizing the rod from opposite ends. The rod acts as a waveguide for pump radiation but allows for free-space propagation of laser radiation. The rod may be used in a laser resonator. The core length is less than about twice the Rayleigh range. Degradation from single-mode to multi-mode beam propagation is thus avoided.
Study on a New Combination Method and High Efficiency Outer Rotor Type Permanent Magnet Motors
NASA Astrophysics Data System (ADS)
Enomoto, Yuji; Kitamura, Masashi; Motegi, Yasuaki; Andoh, Takashi; Ochiai, Makoto; Abukawa, Toshimi
The segment stator core, high space factor coil, and high efficiency magnet are indispensable technologies in the development of compact and a high efficiency motors. But adoption of the segment stator core and high space factor coil has not progressed in the field of outer rotor type motors, for the reason that the inner components cannot be laser welded together. Therefore, we have examined a segment stator core combination technology for the purposes of getting a large increase in efficiency and realizing miniaturization. We have also developed a characteristic estimation method which provides the most suitable performance for segment stator core motors.
Iron-magnesium alloy in the Earth's Core
NASA Astrophysics Data System (ADS)
Dubrovinskaia, N.; Dubrovinsky, L.; Abrikosov, I.
2005-12-01
Composition of the Earth's outer core is a geochemical parameter crucial for understanding the evolution and current dynamics of our planet. Since it was recognized that the liquid metallic outer core is about 10% less dense than pure iron, different elements lighter than iron, including Si, S, O, C, and H, were proposed as major or at least significantly abundant in Earth's core. However, combination of experimental results with theoretical and geochemical considerations shows that it is unlikely that any one of these elements can account for the density deficit on its own. In series of experiments in a multianvil apparatus and in electrically- and laser-heated diamond anvil cells, we demonstrate that high pressure promotes solubility of magnesium in iron and at megabar pressure range more than 10 at% of Mg can dissolve in Fe. At pressures above 95 to 100 GPa, molten iron reacts with periclase MgO forming an iron-magnesium alloy and iron oxide. Our observations suggest that magnesium can be an important light element in Earth's outer core, but it cannot account for the seismologically determined density deficit on its own.
Teleseismic Array Studies of Earth's Core-Mantle Boundary
NASA Astrophysics Data System (ADS)
Alexandrakis, Catherine
2011-12-01
The core mantle boundary (CMB) is an inaccessible and complex region, knowledge of which is vital to our understanding of many Earth processes. Above it is the heterogeneous lower-mantle. Below the boundary is the outer-core, composed of liquid iron, and/or nickel and some lighter elements. Elucidation of how these two distinct layers interact may enable researchers to better understand the geodynamo, global tectonics, and overall Earth history. One parameter that can be used to study structure and limit potential chemical compositions is seismic-wave velocity. Current global-velocity models have significant uncertainties in the 200 km above and below the CMB. In this thesis, these regions are studied using three methods. The upper outer core is studied using two seismic array methods. First, a modified vespa, or slant-stack method is applied to seismic observations at broadband seismic arrays, and at large, dense groups of broadband seismic stations dubbed 'virtual' arrays. Observations of core-refracted teleseismic waves, such as SmKS, are used to extract relative arrivaltimes. As with previous studies, lower -mantle heterogeneities influence the extracted arrivaltimes, giving significant scatter. To remove raypath effects, a new method was developed, called Empirical Transfer Functions (ETFs). When applied to SmKS waves, this method effectively isolates arrivaltime perturbations caused by outer core velocities. By removing raypath effects, the signals can be stacked further reducing scatter. The results of this work were published as a new 1D outer-core model, called AE09. This model describes a well-mixed outer core. Two array methods are used to detect lower mantle heterogeneities, in particular Ultra-Low Velocity Zones (ULVZs). The ETF method and beam forming are used to isolate a weak P-wave that diffracts along the CMB. While neither the ETF method nor beam forming could adequately image the low-amplitude phase, beam forms of two events indicate precursors to the SKS and SKKS phase, which may be ULVZ indicators. Finally, cross-correlated observed and modelled beams indicate a tendency towards a ULVZ-like lower mantle in the study region.
Topography at the inner core boundary
NASA Astrophysics Data System (ADS)
Lasbleis, M.; Forquenot, Q.; Deguen, R.
2017-12-01
Topography at the inner core boundary has been proposed to explain surprising seismic observations of some regional studies. Such observations are still debatted, and numerical values of possible inner core topography have been proposed ranging from no topography to "inner core mountains" (10km heigth over lengthscales of 20km, as in Dai et al. 2012). The inner core boundary is a peculiar boundary, as it is the place where the iron alloy constituting the core freezes. The existence of a significant topography on such a boundary is possible, but unlikely. At thermodynamic equilibrium, no topography is expected, as any material above the equilibrium radius would have melted and any below would have freezed. However, mechanical forcing may push the system out of equilibrium. Dynamical topography could be forced by convective flows in the inner core or by outer core heterogeneities. A topography induced by outer core convection would be short-lived when compared to geodynamical processes in the bulk of the inner core (τ ≈ 10-100 Myears), but long-lived compared to observations. Here, we would like to give a geodynamical perspective over inner core topography. We constrain plausible amplitude of inner core topography, and discuss the implications for seismic observations. We consider topography created by viscous flows in the bulk of the inner core and by variations of growth rate on regional lengthscale due to outer core convection. This approach allows us to consider both internal and external forcings on the topography. We treat topography forcings as stochastic processes, and calculate the probability of observing a given topography. Based on preliminary results, the high values for observed topography can not be interpreted as a normal behavior of core dynamics. If confirmed, the regions are likely to be anomalous and originated from outliers in the distribution of stochastic processes.
Core Formation Process and Light Elements in the Planetary Core
NASA Astrophysics Data System (ADS)
Ohtani, E.; Sakairi, T.; Watanabe, K.; Kamada, S.; Sakamaki, T.; Hirao, N.
2015-12-01
Si, O, and S are major candidates for light elements in the planetary core. In the early stage of the planetary formation, the core formation started by percolation of the metallic liquid though silicate matrix because Fe-S-O and Fe-S-Si eutectic temperatures are significantly lower than the solidus of the silicates. Therefore, in the early stage of accretion of the planets, the eutectic liquid with S enrichment was formed and separated into the core by percolation. The major light element in the core at this stage will be sulfur. The internal pressure and temperature increased with the growth of the planets, and the metal component depleted in S was molten. The metallic melt contained both Si and O at high pressure in the deep magma ocean in the later stage. Thus, the core contains S, Si, and O in this stage of core formation. Partitioning experiments between solid and liquid metals indicate that S is partitioned into the liquid metal, whereas O is weakly into the liquid. Partitioning of Si changes with the metallic iron phases, i.e., fcc iron-alloy coexisting with the metallic liquid below 30 GPa is depleted in Si. Whereas hcp-Fe alloy above 30 GPa coexisting with the liquid favors Si. This contrast of Si partitioning provides remarkable difference in compositions of the solid inner core and liquid outer core among different terrestrial planets. Our melting experiments of the Fe-S-Si and Fe-O-S systems at high pressure indicate the core-adiabats in small planets, Mercury and Mars, are greater than the slope of the solidus and liquidus curves of these systems. Thus, in these planets, the core crystallized at the top of the liquid core and 'snowing core' formation occurred during crystallization. The solid inner core is depleted in both Si and S whereas the liquid outer core is relatively enriched in Si and S in these planets. On the other hand, the core adiabats in large planets, Earth and Venus, are smaller than the solidus and liquidus curves of the systems. The inner core of these planets crystallized at the center of the core and it has the relatively Si rich inner core and the S enriched outer core. Based on melting and solid-liquid partitioning, the equation of state, and sound velocity of iron-light element alloys, we examined the plausible distribution of light elements in the liquid outer and solid inner cores of the terrestrial planets.
On the consequences of strong stable stratification at the top of earth's outer core
NASA Technical Reports Server (NTRS)
Bloxham, Jeremy
1990-01-01
The consequences of strong stable stratification at the top of the earth's fluid outer core are considered, concentrating on the generation of the geomagnetic secular variation. It is assumed that the core near the core-mantle boundary is both strongly stably stratified and free of Lorentz forces: it is found that this set of assumptions severely limits the class of possible motions, none of which is compatible with the geomagnetic secular variation. Relaxing either assumption is adequate: tangentially geostrophic flows are consistent with the secular variation if the assumption that the core is strongly stably stratified is relaxed (while retaining the assumption that Lorentz forces are negligible); purely toroidal flows may explain the secular variation if Lorentz forces are included.
Aldose reductase mediates retinal microglia activation
DOE Office of Scientific and Technical Information (OSTI.GOV)
Chang, Kun-Che; Shieh, Biehuoy; Petrash, J. Mark, E-mail: mark.petrash@ucdenver.edu
Retinal microglia (RMG) are one of the major immune cells in charge of surveillance of inflammatory responses in the eye. In the absence of an inflammatory stimulus, RMG reside predominately in the ganglion layer and inner or outer plexiform layers. However, under stress RMG become activated and migrate into the inner nuclear layer (INL) or outer nuclear layer (ONL). Activated RMG in cell culture secrete pro-inflammatory cytokines in a manner sensitive to downregulation by aldose reductase inhibitors. In this study, we utilized CX3CR1{sup GFP} mice carrying AR mutant alleles to evaluate the role of AR on RMG activation and migrationmore » in vivo. When tested on an AR{sup WT} background, IP injection of LPS induced RMG activation and migration into the INL and ONL. However, this phenomenon was largely prevented by AR inhibitors or in AR null mice, or was exacerbated in transgenic mice that over-express AR. LPS-induced increases in ocular levels of TNF-α and CX3CL-1 in WT mice were substantially lower in AR null mice or were reduced by AR inhibitor treatment. These studies demonstrate that AR expression in RMG may contribute to the proinflammatory phenotypes common to various eye diseases such as uveitis and diabetic retinopathy. - Highlights: • AR inhibition prevents retinal microglial activation. • Endotoxin-induced ocular cytokine production is reduced in AR null mice. • Overexpression of AR spontaneously induces retinal microglial activation.« less
Bielaszewska, Martina; Marejková, Monika; Bauwens, Andreas; Kunsmann-Prokscha, Lisa; Mellmann, Alexander; Karch, Helge
2018-06-19
Proinflammatory cytokines play important roles in the pathogenesis of diseases caused by enterohemorrhagic Escherichia coli (EHEC) O157, but the spectrum of bacterial components involved in the proinflammatory responses is not fully understood. Here, we investigated the abilities of outer membrane vesicles (OMVs), nanoparticles released by EHEC O157 during growth, to induce production of proinflammatory cytokines in human intestinal epithelial cells. OMVs from both EHEC O157:H7 and sorbitol-fermenting (SF) EHEC O157:H - induced production of interleukin-8 (IL-8) in Caco-2, HCT-8, and HT-29 intestinal epithelial cell lines. H7 flagellin was the key IL-8-inducing component of EHEC O157:H7 OMVs, whereas cytolethal distending toxin V and O157 lipopolysaccharide (LPS) largely contributed to IL-8 production elicited by flagellin-lacking OMVs from SF EHEC O157:H - . The H7 flagellin-mediated signaling via Toll-like receptor (TLR) 5, and O157 LPS-mediated signaling via TLR4/MD-2 complex, which were followed by activation of the nuclear factor NF-κB were major pathways underlying IL-8 production induced by EHEC O157 OMVs. The proinflammatory and immunomodulatory capacities of EHEC O157 OMVs have pathogenetic implications and support the OMVs as suitable vaccine candidates. Copyright © 2018 Elsevier GmbH. All rights reserved.
Equation of state and phase diagram of Fe-16Si alloy as a candidate component of Earth's core
NASA Astrophysics Data System (ADS)
Fischer, Rebecca A.; Campbell, Andrew J.; Caracas, Razvan; Reaman, Daniel M.; Dera, Przymyslaw; Prakapenka, Vitali B.
2012-12-01
The outer core of the Earth contains several weight percent of one or more unknown light elements, which may include silicon. Therefore it is critical to understand the high pressure-temperature properties and behavior of an iron-silicon alloy with a geophysically relevant composition (16 wt% silicon). We experimentally determined the melting curve, subsolidus phase diagram, and equations of state of all phases of Fe-16 wt%Si to 140 GPa, finding a conversion from the D03 crystal structure to a B2+hcp mixture at high pressures. The melting curve implies that 3520 K is a minimum temperature for the Earth's outer core, if it consists solely of Fe-Si alloy, and that the eutectic composition in the Fe-Si system is less than 16 wt% silicon at core-mantle boundary conditions. Comparing our new equation of state to that of iron and the density of the core, we find that for an Fe-Ni-Si outer core, 11.3±1.5 wt% silicon would be required to match the core's observed density at the core-mantle boundary. We have also performed first-principles calculations of the equations of state of Fe3Si with the D03 structure, hcp iron, and FeSi with the B2 structure using density-functional theory.
Complement reduction impairs the febrile response of guinea pigs to endotoxin.
Sehic, E; Li, S; Ungar, A L; Blatteis, C M
1998-06-01
Although it is generally believed that circulating exogenous pyrogens [e.g., lipopolysaccharides (LPS)] induce fever via the mediation of endogenous pyrogens (EP) such as cytokines, the first of these, tumor necrosis factor-alpha, is usually not detectable in blood until at least 30 min after intravenous administration of LPS, whereas the febrile rise begins within 15 min after its administration. Moreover, although abundant evidence indicates that circulating LPS is cleared primarily by liver macrophages [Kupffer cells (KC)], these do not secrete EP in immediate response. This would imply that other factors, presumably evoked earlier than EP, may mediate the onset of the febrile response to intravenous LPS. It is well known that blood-borne LPS very rapidly activates the intravascular complement (C) system, some components of which in turn stimulate the quick release into blood of various substances that have roles in the acute inflammatory reaction. KC contain receptors for C components and are in close contact with afferent vagal terminals in the liver; the involvement of hepatic vagal afferents in LPS-induced fever has recently been shown. In this study, we tested the hypothesis that the initiation of fever by intravenous LPS involves, sequentially, the C system and KC. To test this postulated mechanism, we measured directly the levels of prostaglandin E2 (PGE2) in the interstitial fluid of the preoptic anterior hypothalamus (POA), the presumptive site of the fever-producing controller, of conscious guinea pigs over their entire febrile course, before and after C depletion by cobra venom factor (CVF) and before and after elimination of KC by gadolinium chloride (GdCl3). CVF and GdCl3 pretreatment each individually attenuated the first of the biphasic core temperature (Tc) rises after intravenous LPS, inverted the second into a Tc fall, and greatly reduced the usual fever-associated increase in POA PGE2. We conclude, therefore, that C activation may indeed be pivotal in the induction of fever by intravenous LPS and that substance(s) generated presumably by KC in almost immediate reaction to the presence of LPS and/or C may transmit pyrogenic signals via hepatic vagal afferents to the POA, where they rapidly induce the production of PGE2 and, hence, fever.
CORE SHAPES AND ORIENTATIONS OF CORE-SÉRSIC GALAXIES
DOE Office of Scientific and Technical Information (OSTI.GOV)
Dullo, Bililign T.; Graham, Alister W., E-mail: Bdullo@astro.swin.edu.au
2015-01-01
The inner and outer shapes and orientations of core-Sérsic galaxies may hold important clues to their formation and evolution. We have therefore measured the central and outer ellipticities and position angles for a sample of 24 core-Sérsic galaxies using archival Hubble Space Telescope (HST) images and data. By selecting galaxies with core-Sérsic break radii R{sub b} —a measure of the size of their partially depleted core—that are ≳ 0.''2, we find that the ellipticities and position angles are quite robust against HST seeing. For the bulk of the galaxies, there is a good agreement between the ellipticities and position anglesmore » at the break radii and the average outer ellipticities and position angles determined over R {sub e}/2 < R < R {sub e}, where R {sub e} is the spheroids' effective half light radius. However there are some interesting differences. We find a median ''inner'' ellipticity at R{sub b} of ε{sub med} = 0.13 ± 0.01, rounder than the median ellipticity of the ''outer'' regions ε{sub med} = 0.20 ± 0.01, which is thought to reflect the influence of the central supermassive black hole at small radii. In addition, for the first time we find a trend, albeit weak (2σ significance), such that galaxies with larger (stellar deficit-to-supermassive black hole) mass ratios—thought to be a measure of the number of major dry merger events—tend to have rounder inner and outer isophotes, suggesting a connection between the galaxy shapes and their merger histories. We show that this finding is not simply reflecting the well known result that more luminous galaxies are rounder, but it is no doubt related.« less
Permanent-magnet switched-flux machine
Trzynadlowski, Andrzej M.; Qin, Ling
2010-01-12
A permanent-magnet switched-flux (PMSF) device has a ferromagnetic outer stator mounted to a shaft about a central axis extending axially through the PMSF device. Pluralities of top and bottom stator poles are respectively mounted in first and second circles, radially outwardly in first and second transverse planes extending from first and second sections of the central axis adjacent to an inner surface of the ferromagnetic outer stator. A ferromagnetic inner rotor is coupled to the shaft and has i) a rotor core having a core axis co-axial with the central axis; and ii) first and second discs having respective outer edges with first and second pluralities of permanent magnets (PMs) mounted in first and second circles, radially outwardly from the rotor core axis in the first and second transverse planes. The first and second pluralities of PMs each include PMs of alternating polarity.
Initiation of the TLR4 signal transduction network : deeper understanding for better therapeutics.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Branda, Steven S.; Hayden, Carl C.; Sherman, Michael Y.
2010-09-01
The innate immune system represents our first line of defense against microbial pathogens, and in many cases is activated by recognition of pathogen cellular components (dsRNA, flagella, LPS, etc.) by cell surface membrane proteins known as toll-like receptors (TLRs). As the initial trigger for innate immune response activation, TLRs also represent a means by which we can effectively control or modulate inflammatory responses. This proposal focused on TLR4, which is the cell-surface receptor primarily responsible for initiating the innate immune response to lipopolysaccharide (LPS), a major component of the outer membrane envelope of gram-negative bacteria. The goal was to bettermore » understand TLR4 activation and associated membrane proximal events, in order to enhance the design of small molecule therapeutics to modulate immune activation. Our approach was to reconstitute the receptor in biomimetic systems in-vitro to allow study of the structure and dynamics with biophysical methods. Structural studies were initiated in the first year but were halted after the crystal structure of the dimerized receptor was published early in the second year of the program. Methods were developed to determine the association constant for oligomerization of the soluble receptor. LPS-induced oligomerization was observed to be a strong function of buffer conditions. In 20 mM Tris pH 8.0 with 200 mM NaCl, the onset of receptor oligomerization occurred at 0.2 uM TLR4/MD2 with E coli LPS Ra mutant in excess. However, in the presence of 0.5 uM CD14 and 0.5 uM LBP, the onset of receptor oligomerization was observed to be less than 10 nM TLR4/MD2. Several methods were pursued to study LPS-induced oligomerization of the membrane-bound receptor, including CryoEM, FRET, colocalization and codiffusion followed by TIRF, and fluorescence correlation spectroscopy. However, there approaches met with only limited success.« less
The Effect of Inner Core Translation on Outer Core Flow and the Geomagnetic Field
NASA Astrophysics Data System (ADS)
Mound, J. E.; Davies, C. J.; Silva, L.
2015-12-01
Bulk translation of the inner core has been proposed to explain quasi-hemispheric patterns of seismic heterogeneity. Such a translation would result in differential melting and freezing at the inner core boundary (ICB) and hence a heterogeneous pattern of buoyancy flux that could influence convection in the outer core. This heterogeneous flux at the ICB will tend to promote upwelling on the trailing hemisphere, where enhanced inner core growth results in increased latent heat and light element release, and inhibit upwelling on the leading hemisphere, where melting of the inner core occurs. If this difference in convective driving between the two hemispheres propagated across the thickness of the outer core, then flows near the surface of the core could be linked to the ICB heterogeneity and result in a hemispheric imbalance in the geomagnetic field. We have investigated the influence of such ICB boundary conditions on core flows and magnetic field structure in numerical geodynamo models and analysed the resultant hemispheric imbalance relative to the hemispheric structure in models constructed from observations of Earth's field. Inner core translation at rates consistent with estimates for the Earth produce a strong hemispheric bias in the field, one that should be readily apparent in averages of the field over tens of thousands of years. Current models of the field over the Holocene may be able to rule out the most extreme ICB forcing scenarios, but more information on the dynamic structure of the field over these time scales will be needed to adequately test all cases.
Wu, Xiaojun; Ren, Guoping; Gunning, William T.; Weaver, David A.; Kalinoski, Andrea L.; Khuder, Sadik A.; Huntley, Jason F.
2016-01-01
Francisella tularensis is the causative agent of the lethal disease tularemia. Despite decades of research, little is understood about why F. tularensis is so virulent. Bacterial outer membrane proteins (OMPs) are involved in various virulence processes, including protein secretion, host cell attachment, and intracellular survival. Many pathogenic bacteria require metals for intracellular survival and OMPs often play important roles in metal uptake. Previous studies identified three F. tularensis OMPs that play roles in iron acquisition. In this study, we examined two previously uncharacterized proteins, FTT0267 (named fmvA, for Francisella metal and virulence) and FTT0602c (fmvB), which are homologs of the previously studied F. tularensis iron acquisition genes and are predicted OMPs. To study the potential roles of FmvA and FmvB in metal acquisition and virulence, we first examined fmvA and fmvB expression following pulmonary infection of mice, finding that fmvB was upregulated up to 5-fold during F. tularensis infection of mice. Despite sequence homology to previously-characterized iron-acquisition genes, FmvA and FmvB do not appear to be involved iron uptake, as neither fmvA nor fmvB were upregulated in iron-limiting media and neither ΔfmvA nor ΔfmvB exhibited growth defects in iron limitation. However, when other metals were examined in this study, magnesium-limitation significantly induced fmvB expression, ΔfmvB was found to express significantly higher levels of lipopolysaccharide (LPS) in magnesium-limiting medium, and increased numbers of surface protrusions were observed on ΔfmvB in magnesium-limiting medium, compared to wild-type F. tularensis grown in magnesium-limiting medium. RNA sequencing analysis of ΔfmvB revealed the potential mechanism for increased LPS expression, as LPS synthesis genes kdtA and wbtA were significantly upregulated in ΔfmvB, compared with wild-type F. tularensis. To provide further evidence for the potential role of FmvB in magnesium uptake, we demonstrated that FmvB was outer membrane-localized. Finally, ΔfmvB was found to be attenuated in mice and cytokine analyses revealed that ΔfmvB-infected mice produced lower levels of pro-inflammatory cytokines, including GM-CSF, IL-3, and IL-10, compared with mice infected with wild-type F. tularensis. Taken together, although the function of FmvA remains unknown, FmvB appears to play a role in magnesium uptake and F. tularensis virulence. These results may provide new insights into the importance of magnesium for intracellular pathogens. PMID:27513341
The Initial Physical Conditions of Kepler-36 b and c
NASA Astrophysics Data System (ADS)
Owen, James E.; Morton, Timothy. D.
2016-03-01
The Kepler-36 planetary system consists of two exoplanets at similar separations (0.115 and 0.128 au), which have dramatically different densities. The inner planet has a density consistent with an Earth-like composition, while the outer planet is extremely low density, such that it must contain a voluminous H/He envelope. Such a density difference would pose a problem for any formation mechanism if their current densities were representative of their composition at formation. However, both planets are at close enough separations to have undergone significant evaporation in the past. We constrain the core mass, core composition, initial envelope mass, and initial cooling time of each planet using evaporation models conditioned on their present-day masses and radii, as inferred from Kepler photometry and transit timing analysis. The inner planet is consistent with being an evaporatively stripped core, while the outer planet has retained some of its initial envelope due to its higher core mass. Therefore, both planets could have had a similar formation pathway, with the inner planet having an initial envelope-mass fraction of ≲10% and core mass of ˜4.4 M⊕, while the outer had an initial envelope-mass fraction of the order of 15%-30% and core mass ˜7.3 M⊕. Finally, our results indicate that the outer planet had a long (≳30 Myr) initial cooling time, much longer than would naively be predicted from simple timescale arguments. The long initial cooling time could be evidence for a dramatic early cooling episode such as the recently proposed “boil-off” process.
GRAVITATIONAL ACCRETION OF PARTICLES ONTO MOONLETS EMBEDDED IN SATURN's RINGS
DOE Office of Scientific and Technical Information (OSTI.GOV)
Yasui, Yuki; Ohtsuki, Keiji; Daisaka, Hiroshi, E-mail: y.yasui@whale.kobe-u.ac.jp, E-mail: ohtsuki@tiger.kobe-u.ac.jp
2014-12-20
Using a local N-body simulation, we examine gravitational accretion of ring particles onto moonlet cores in Saturn's rings. We find that gravitational accretion of particles onto moonlet cores is unlikely to occur in the C ring and probably difficult in the inner B ring as well provided that the cores are rigid water ice. Dependence of particle accretion on ring thickness changes when the radial distance from the planet and/or the density of particles is varied: the former determines the size of the core's Hill radius relative to its physical size, while the latter changes the effect of self-gravity ofmore » accreted particles. We find that particle accretion onto high-latitude regions of the core surface can occur even if the rings' vertical thickness is much smaller than the core radius, although redistribution of particles onto the high-latitude regions would not be perfectly efficient in outer regions of the rings such as the outer A ring, where the size of the core's Hill sphere in the vertical direction is significantly larger than the core's physical radius. Our results suggest that large boulders recently inferred from observations of transparent holes in the C ring are not formed locally by gravitational accretion, while propeller moonlets in the A ring would be gravitational aggregates formed by particle accretion onto dense cores. Our results also imply that the main bodies of small satellites near the outer edge of Saturn's rings may have been formed in rather thin rings.« less
Lateral restraint assembly for reactor core
Gorholt, Wilhelm; Luci, Raymond K.
1986-01-01
A restraint assembly for use in restraining lateral movement of a reactor core relative to a reactor vessel wherein a plurality of restraint assemblies are interposed between the reactor core and the reactor vessel in circumferentially spaced relation about the core. Each lateral restraint assembly includes a face plate urged against the outer periphery of the core by a plurality of compression springs which enable radial preloading of outer reflector blocks about the core and resist low-level lateral motion of the core. A fixed radial key member cooperates with each face plate in a manner enabling vertical movement of the face plate relative to the key member but restraining movement of the face plate transverse to the key member in a plane transverse to the center axis of the core. In this manner, the key members which have their axes transverse to or subtending acute angles with the direction of a high energy force tending to move the core laterally relative to the reactor vessel restrain such lateral movement.
NASA Astrophysics Data System (ADS)
Deprun, C.; Karibian, D.; Caroff, M.
1993-07-01
Endotoxic lipopolysaccharides (LPSs) are the major components of Gram-negative bacterial outer membrane. Like many amphipathic molecules, they pose problems of heterogeneity, purity, solubility, and aggregation. Nevertheless, PDMS has recently have been applied to unmodified endotoxins composed of LPS having uip to five sugar units in their saccharide chain. The B. Pertussis LPSs, most of which have a dodecasaccharide domain, ahve been analysed by classical methods and the masses of the separate lipid and saccharide domains determined after rupture of the bond linking them. However, the acid treatment employed for these and most chemical analyses can also modify structures in the vicinity of the bond. In order to investigate this biologically-important region, the endotoxin was treated to nitrous deamination, which shortens the saccharide chain to five sugars, but preserves the acid-labile region of the LPS. The PDM spectrum of this derivative, which required new conditions for its desorption, confirmed the structure analysis and demonstrated the presence of at least four molecular species.
Differential Rotation within the Earth's Outer Core
NASA Technical Reports Server (NTRS)
Hide, R.; Boggs, D. H.; Dickey, J. O.
1998-01-01
Non-steady differential rotation drive by bouyancy forces within the Earth's liquid outer core (OC) plays a key role not only in the generation of the main geomagnetic field by the magnetohydrodynamic (MHD) dynamo process but also in the excitation of irregular fluctuations in the angular speed of rotation of the overlying solid mantle, as evidenced by changes in the length of the day (LOD) on decadal and longer timescales (1-8).
Stratification of earth's outermost core inferred from SmKS array data
NASA Astrophysics Data System (ADS)
Kaneshima, Satoshi; Matsuzawa, Takanori
2015-12-01
S mKS arrivals recorded by large-scale broadband seismometer arrays are analyzed to investigate the depth profile of P wave speed ( V p ) in the outermost core. The V p structure of the upper 700 km of the outer core has been determined using S mKS waves of Fiji-Tonga events recorded at stations in Europe. According to a recent outer core model (KHOMC), the V p value is 0.45 % slower at the core mantle boundary (CMB) than produced by the Preliminary Reference Earth Model (PREM), and the slow anomaly gradually diminishes to insignificant values at ˜300 km below the CMB. In this study, after verifying these KHOMC features, we show that the differential travel times measured for S mKS waves that are recorded by other large-scale arrays sampling laterally different regions are well matched by KHOMC. We also show that KHOMC precisely fits the observed relative slowness values between S2KS, S3KS, and S4KS (S mKS waves with m= 2, 3, and 4). Based on these observations, we conclude that S mKS predominantly reflect the outer core structure. Then we evaluate biases of secondary importance which may be caused by mantle heterogeneity. The KHOMC V p profile can be characterized by a significant difference in the radial V p gradient between the shallower 300 km and the deeper part of the upper 700 km of the core. The shallower part has a V p gradient of -0.0018 s -1, which is steeper by 0.0001 s -1 when compared to the deeper core presented by PREM. The steeper V p gradient anomaly of the uppermost core corresponds to a radial variation in the pressure derivative of the bulk modulus, K '= d K/ d P. The K ' value is 3.7, which is larger by about 0.2 than that of the deeper core. The radial variation in K ' is too large to have a purely thermal origin, according to recent ab initio calculations on liquid iron alloys, and thus requires a thick and compositionally stratified layering at the outermost outer core.
Thermal Equation of State of Iron: Constraint on the Density Deficit of Earth's Core
NASA Astrophysics Data System (ADS)
Fei, Y.; Murphy, C. A.; Shibazaki, Y.; Huang, H.
2013-12-01
The seismically inferred densities of Earth's solid inner core and the liquid outer core are smaller than the measured densities of solid hcp-iron and liquid iron, respectively. The inner core density deficit is significantly smaller than the outer core density deficit, implying different amounts and/or identities of light-elements incorporated in the inner and outer cores. Accurate measurements of the thermal equation-of-state of iron over a wide pressure and temperature range are required to precisely quantify the core density deficits, which are essential for developing a quantitative composition model for the core. The challenge has been evaluating the experimental uncertainties related to the choice of pressure scales and the sample environment, such as hydrostaticity at multi-megabar pressures and extreme temperatures. We have conducted high-pressure experiments on iron in MgO, NaCl, and Ne pressure media and obtained in-situ X-ray diffraction data up to 200 GPa at room temperature. Using inter-calibrated pressure scales including the MgO, NaCl, Ne, and Pt scales, we have produced a consistent compression curve of hcp-Fe at room temperature. We have also performed laser-heated diamond-anvil cell experiments on both Fe and Pt in a Ne pressure medium. The experiment was designed to quantitatively compare the thermal expansion of Fe and Pt in the same sample environment using Ne as the pressure medium. The thermal expansion data of hcp-Fe at high pressure were derived based on the thermal equation of state of Pt. Using the 300-K isothermal compression curve of iron derived from our static experiments as a constraint, we have developed a thermal equation of state of hcp-Fe that is consistent with the static P-V-T data of iron and also reproduces the shock wave Hugoniot data for pure iron. The thermodynamic model, based on both static and dynamic data, is further used to calculate the density and bulk sound velocity of liquid iron. Our results define the solid inner core and liquid outer core density deficits, which can serve as the basis for any core composition models.
Brynsvold, Glen V.; Lopez, John T.; Olich, Eugene E.; West, Calvin W.
1989-01-01
An electromagnetic submerged pump has an outer cylindrical stator with an inner cylindrical conductive core for the submerged pumping of sodium in the cylindrical interstitial volume defined between the stator and core. The cylindrical interstitial volume is typically vertically oriented, and defines an inlet at the bottom and an outlet at the top. The outer stator generates upwardly conveyed toroidal magnetic fields, which fields convey preferably from the bottom of the pump to the top of the pump liquid sodium in the cold leg of a sodium cooled nuclear reactor. The outer cylindrical stator has a vertically disposed duct surrounded by alternately stacked layers of coil units and laminates.
Brynsvold, G.V.; Lopez, J.T.; Olich, E.E.; West, C.W.
1989-11-21
An electromagnetic submerged pump has an outer cylindrical stator with an inner cylindrical conductive core for the submerged pumping of sodium in the cylindrical interstitial volume defined between the stator and core. The cylindrical interstitial volume is typically vertically oriented, and defines an inlet at the bottom and an outlet at the top. The outer stator generates upwardly conveyed toroidal magnetic fields, which fields convey preferably from the bottom of the pump to the top of the pump liquid sodium in the cold leg of a sodium cooled nuclear reactor. The outer cylindrical stator has a vertically disposed duct surrounded by alternately stacked layers of coil units and laminates. 14 figs.
Xiong, GuanNan; Zhang, YunHui; Duan, YongHong; Cai, ChuanYang; Wang, Xin; Li, JingYa; Tao, Shu; Liu, WenXin
2017-08-01
Samples of ambient air (including gaseous and particulate phases), dust fall, surface soil, rhizosphere soil, core (edible part), outer leaf, and root of cabbage from eight vegetable plots near a large coking manufacturer were collected during the harvest period. Concentrations, compositions, and distributions of parent PAHs in different samples were determined. Our results indicated that most of the parent PAHs in air occurred in the gaseous phase, dominated by low molecular weight (LMW) species with two to three rings. Specific isomeric ratios and principal component analysis were employed to preliminarily identify the local sources of parent PAHs emitted. The main emission sources of parent PAHs could be apportioned as a mixture of coal combustion, coking production, and traffic tailing gas. PAH components with two to four rings were prevailing in dust fall, surface soil, and rhizosphere soil. Concentrations of PAHs in surface soil exhibited a significant positive correlation with topsoil TOC fractions. Compositional profiles in outer leaf and core of cabbage, dominated by LMW species, were similar to those in the local air. Overall, the order of parent PAH concentration in cabbage was outer leaf > root > core. Partial correlation analysis and multivariate linear stepwise regression revealed that PAH concentrations in cabbage core were closely associated with PAHs present both in root and in outer leaf, namely, affected by adsorption, then absorption, and translocation of PAHs from rhizosphere soil and ambient air, respectively.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Cheng, Hai-Xia; Wang, Xiao-Xu; Beijing Computing Center, Beijing 100094
Ag@ZnO core-shell nanoparticles of around 72 atoms have been investigated by the density functional theory, revealing proving for the first time that the core-shell structure exhibits a shrinkage phenomenon from outer shell in agreement with the other studies in literatures. Our calculations predict that the Ag@ZnO core-shell structure is a ferromagnetic spin polarized state, and the magnetism mainly stems from the spin splitting of 2p electrons of O atoms. In addition, the total and partial DOS of Ag@ZnO indicate that the nanostructure is a half-metallic nanoparticle and has the characters of the p-type semiconductor. Furthermore, the optical properties calculations showmore » that the absorption edge of Ag@ZnO have a red shift and good photocatalysis compare to that of the bulk ZnO. These results of the Ag@ZnO core-shell structure obtain a well agreement with the experimental measurement. - Graphical abstract: Geometric structure of (a) Ag@ZnO core-shell nanostructure; (b) the core of Ag; (c) the shell of ZnO The core-shell nanoparticle Ag@ZnO contains Ag inner core of radius of 4 Å and ZnO outer shell with thickness of 2 Å. Ag@ZnO core-shell nanoparticles of around 72 atoms have been proved for the first time that the core-shell structure exhibit a shrinkage phenomenon from outer shell. Our calculations predict that the Ag@ZnO core-shell structure is a half-metallic nanoparticle and has the characters of the p-type semiconductor. The absorption edge of Ag@ZnO have a red shift and get good photo-catalysis compare to that of the bulk ZnO.« less
Behrens, Peter; Wienecke, Soenke; Chakradeo, Tanmay; Glasmacher, Birgit
2014-01-01
We report on the performance of composite nerve grafts with an inner 3D multichannel porous chitosan core and an outer electrospun polycaprolactone shell. The inner chitosan core provided multiple guidance channels for regrowing axons. To analyze the in vivo properties of the bare chitosan cores, we separately implanted them into an epineural sheath. The effects of both graft types on structural and functional regeneration across a 10 mm rat sciatic nerve gap were compared to autologous nerve transplantation (ANT). The mechanical biomaterial properties and the immunological impact of the grafts were assessed with histological techniques before and after transplantation in vivo. Furthermore during a 13-week examination period functional tests and electrophysiological recordings were performed and supplemented by nerve morphometry. The sheathing of the chitosan core with a polycaprolactone shell induced massive foreign body reaction and impairment of nerve regeneration. Although the isolated novel chitosan core did allow regeneration of axons in a similar size distribution as the ANT, the ANT was superior in terms of functional regeneration. We conclude that an outer polycaprolactone shell should not be used for the purpose of bioartificial nerve grafting, while 3D multichannel porous chitosan cores could be candidate scaffolds for structured nerve grafts. PMID:24818158
Duda, Sven; Dreyer, Lutz; Behrens, Peter; Wienecke, Soenke; Chakradeo, Tanmay; Glasmacher, Birgit; Haastert-Talini, Kirsten
2014-01-01
We report on the performance of composite nerve grafts with an inner 3D multichannel porous chitosan core and an outer electrospun polycaprolactone shell. The inner chitosan core provided multiple guidance channels for regrowing axons. To analyze the in vivo properties of the bare chitosan cores, we separately implanted them into an epineural sheath. The effects of both graft types on structural and functional regeneration across a 10 mm rat sciatic nerve gap were compared to autologous nerve transplantation (ANT). The mechanical biomaterial properties and the immunological impact of the grafts were assessed with histological techniques before and after transplantation in vivo. Furthermore during a 13-week examination period functional tests and electrophysiological recordings were performed and supplemented by nerve morphometry. The sheathing of the chitosan core with a polycaprolactone shell induced massive foreign body reaction and impairment of nerve regeneration. Although the isolated novel chitosan core did allow regeneration of axons in a similar size distribution as the ANT, the ANT was superior in terms of functional regeneration. We conclude that an outer polycaprolactone shell should not be used for the purpose of bioartificial nerve grafting, while 3D multichannel porous chitosan cores could be candidate scaffolds for structured nerve grafts.
Rezzonico, Fabio; Braun-Kiewnick, Andrea; Mann, Rachel A; Rodoni, Brendan; Goesmann, Alexander; Duffy, Brion; Smits, Theo H M
2012-10-01
Comparative genomic analysis revealed differences in the lipopolysaccharide (LPS) biosynthesis gene cluster between the Rubus-infecting strain ATCC BAA-2158 and the Spiraeoideae-infecting strain CFBP 1430 of Erwinia amylovora. These differences corroborate rpoB-based phylogenetic clustering of E. amylovora into four different groups and enable the discrimination of Spiraeoideae- and Rubus-infecting strains. The structure of the differences between the two groups supports the hypothesis that adaptation to Rubus spp. took place after species separation of E. amylovora and E. pyrifoliae that contrasts with a recently proposed scenario, based on CRISPR data, in which the shift to domesticated apple would have caused an evolutionary bottleneck in the Spiraeoideae-infecting strains of E. amylovora which would be a much earlier event. In the core region of the LPS biosynthetic gene cluster, Spiraeoideae-infecting strains encode three glycosyltransferases and an LPS ligase (Spiraeoideae-type waaL), whereas Rubus-infecting strains encode two glycosyltransferases and a different LPS ligase (Rubus-type waaL). These coding domains share little to no homology at the amino acid level between Rubus- and Spiraeoideae-infecting strains, and this genotypic difference was confirmed by polymerase chain reaction analysis of the associated DNA region in 31 Rubus- and Spiraeoideae-infecting strains. The LPS biosynthesis gene cluster may thus be used as a molecular marker to distinguish between Rubus- and Spiraeoideae-infecting strains of E. amylovora using primers designed in this study. © 2012 THE AUTHORS. MOLECULAR PLANT PATHOLOGY © 2012 BSPP AND BLACKWELL PUBLISHING LTD.
Demirdjian, Sally; Schutz, Kristin; Wargo, Matthew J; Lam, Joseph S; Berwin, Brent
2017-12-01
The bacterial pathogen Pseudomonas aeruginosa undergoes adaptation and selection over the course of chronic respiratory tract infections which results in repeatedly-observed phenotypic changes that are proposed to enable its persistence. Two of the clinically significant P. aeruginosa phenotypic changes are loss of flagellar motility and modifications to LPS structure, including loss of O-antigen expression. The effect of loss of O-antigen, frequently described as conversion from smooth to rough LPS, and the combined effect of loss of motility and O-antigen on phagocytic susceptibility by immune cells remain unknown. To address this, we generated genetic deletion mutants of waaL, which encodes the O-antigen ligase responsible for linking O-antigen to lipid A-core oligosaccharide, in both motile and non-motile P. aeruginosa strains. With the use of these bacterial strains we provide the first demonstration that, despite a progressive selection for P. aeruginosa with rough LPS during chronic pulmonary infections, loss of the LPS O-antigen does not confer phagocytic resistance in vitro. However, use of the waaLmotABmotCD mutant revealed that loss of motility confers resistance to phagocytosis regardless of the smooth or rough LPS phenotype. These findings reveal how the O-antigen of P. aeruginosa can influence bacterial clearance during infection and expand our current knowledge about the impact of bacterial phenotypic changes during chronic infection. Copyright © 2017 Elsevier Ltd. All rights reserved.
Thermal barriers for compartments
Kreutzer, Cory J.; Lustbader, Jason A.
2017-10-17
An aspect of the present disclosure is a thermal barrier that includes a core layer having a first surface, a second surface, and a first edge, and a first outer layer that includes a third surface and a second edge, where the third surface substantially contacts the first surface, the core layer is configured to minimize conductive heat transfer through the barrier, and the first outer layer is configured to maximize reflection of light away from the barrier.
Datta, Aritreyee; Bhattacharyya, Dipita; Singh, Shalini; Ghosh, Anirban; Schmidtchen, Artur; Malmsten, Martin; Bhunia, Anirban
2016-01-01
KYE28 (KYEITTIHNLFRKLTHRLFRRNFGYT-LR), the representative sequence of helix D of heparin co-factor II, was demonstrated to be potent against agronomically important Gram-negative plant pathogens Xanthomonas vesicatoria and Xanthomonas oryzae, capable of inhibiting disease symptoms in detached tomato leaves. NMR studies in the presence of lipopolysaccharide provided structural insights into the mechanisms underlying this, notably in relationship to outer membrane permeabilization. The three-dimensional solution structure of KYE28 in LPS is characterized by an N-terminal helical segment, an intermediate loop followed by another short helical stretch, and an extended C terminus. The two termini are in close proximity to each other via aromatic packing interactions, whereas the positively charged residues form an exterior polar shell. To further demonstrate the importance of the aromatic residues for this, a mutant peptide KYE28A, with Ala substitutions at Phe11, Phe19, Phe23, and Tyr25 was designed, which showed attenuated antimicrobial activity at high salt concentrations, as well as lower membrane disruption and LPS binding abilities compared with KYE28. In contrast to KYE28, KYE28A adopted an extended helical structure in LPS with extended N and C termini. Aromatic packing interactions were completely lost, although hydrophobic interaction between the side chains of hydrophobic residues were still partly retained, imparting an amphipathic character and explaining its residual antimicrobial activity and LPS binding as observed from ellipsometry and isothermal titration calorimetry. We thus present key structural aspects of KYE28, constituting an aromatic zipper, of potential importance for the development of novel plant protection agents and therapeutic agents. PMID:27137928
Lalsiamthara, Jonathan; Lee, John Hwa
2017-06-01
Intracellular pathogen Salmonella exhibits natural infection broadly analogous to Brucella, this phenomenon makes Salmonella a pragmatic choice for an anti-Brucella vaccine delivery platform. In this study we developed and formulated a combination of four attenuated Salmonella Typhimurium live vector strains delivering heterologous Brucella antigens (rBs), namely lumazine synthase, proline racemase subunit A, lipoprotein outer membrane protein-19, and Cu-Zn superoxide dismutase. With an aim to develop a cross-protecting vaccine, Brucella pan-species conserved rBs were selected. The present study compared the efficacy of smooth and rough variants of Salmonella delivery vector and also evaluated the inclusion of purified Brucella lipopolysaccharide (LPS) in the formulation. Immunization of SPF-BALB/c mice with the vaccine combinations significantly (P≤0.05) reduced splenic wild-type Brucella abortus 544 colonization as compared to non-immunized mice as well as Salmonella only immunized mice. Increased induction of Brucella specific-IgG, sIgA production, and antigen-specific splenocyte proliferative responses were observed in the mice immunized with the formulations as compared to naïve or vector only immunized mice. Modulatory effects of rB and LPS on production of interleukin (IL)-4, IL-12, and interferon-γ were detected in splenocytes of mice immunized with the formulation. Rough Salmonella variant in combination with LPS could further enhance the efficacy of the delivery when applied intraperitoneally. Taken together, it is compelling that Brucella LPS-augmented Salmonella vector delivering immunogenic Brucella proteins may be more suitable than the current non-ideal live Brucella abortus vaccine. The vaccine system also provides a basis for the development of cross-protecting vaccine capable of preventing multispecies brucellosis. Copyright © 2017 Elsevier B.V. All rights reserved.
Metts, J; West, J; Doares, S H; Matthysse, A G
1991-02-01
Three Agrobacterium tumefaciens mutants with chromosomal mutations that affect bacterial virulence were isolated by transposon mutagenesis. Two of the mutants were avirulent on all hosts tested. The third mutant, Ivr-211, was a host range mutant which was avirulent on Bryophyllum diagremontiana, Nicotiana tabacum, N. debneyi, N. glauca, and Daucus carota but was virulent on Zinnia elegans and Lycopersicon esculentum (tomato). That the mutant phenotype was due to the transposon insertion was determined by cloning the DNA containing the transposon insertion and using the cloned DNA to replace the wild-type DNA in the parent bacterial strain by marker exchange. The transposon insertions in the three mutants mapped at three widely separated locations on the bacterial chromosome. The effects of the mutations on various steps in tumor formation were examined. All three mutants showed no alteration in binding to carrot cells. However, none of the mutants showed any induction of vir genes by acetosyringone under conditions in which the parent strain showed vir gene induction. When the mutant bacteria were examined for changes in surface components, it was found that all three of the mutants showed a similar alteration in lipopolysaccharide (LPS). LPS from the mutants was larger in size and more heavily saccharide substituted than LPS from the parent strain. Two of the mutants showed no detectable alteration in outer membrane and periplasmic space proteins. The third mutant, Ivr-225, was missing a 79-kDa surface peptide. The reason(s) for the failure of vir gene induction in these mutants and its relationship, if any, to the observed alteration in LPS are unknown.
A seismologically consistent compositional model of Earth's core.
Badro, James; Côté, Alexander S; Brodholt, John P
2014-05-27
Earth's core is less dense than iron, and therefore it must contain "light elements," such as S, Si, O, or C. We use ab initio molecular dynamics to calculate the density and bulk sound velocity in liquid metal alloys at the pressure and temperature conditions of Earth's outer core. We compare the velocity and density for any composition in the (Fe-Ni, C, O, Si, S) system to radial seismological models and find a range of compositional models that fit the seismological data. We find no oxygen-free composition that fits the seismological data, and therefore our results indicate that oxygen is always required in the outer core. An oxygen-rich core is a strong indication of high-pressure and high-temperature conditions of core differentiation in a deep magma ocean with an FeO concentration (oxygen fugacity) higher than that of the present-day mantle.
A seismologically consistent compositional model of Earth’s core
Badro, James; Côté, Alexander S.; Brodholt, John P.
2014-01-01
Earth’s core is less dense than iron, and therefore it must contain “light elements,” such as S, Si, O, or C. We use ab initio molecular dynamics to calculate the density and bulk sound velocity in liquid metal alloys at the pressure and temperature conditions of Earth's outer core. We compare the velocity and density for any composition in the (Fe–Ni, C, O, Si, S) system to radial seismological models and find a range of compositional models that fit the seismological data. We find no oxygen-free composition that fits the seismological data, and therefore our results indicate that oxygen is always required in the outer core. An oxygen-rich core is a strong indication of high-pressure and high-temperature conditions of core differentiation in a deep magma ocean with an FeO concentration (oxygen fugacity) higher than that of the present-day mantle. PMID:24821817
Pole-phase modulated toroidal winding for an induction machine
Miller, John Michael; Ostovic, Vlado
1999-11-02
A stator (10) for an induction machine for a vehicle has a cylindrical core (12) with inner and outer slots (26, 28) extending longitudinally along the inner and outer peripheries between the end faces (22, 24). Each outer slot is associated with several adjacent inner slots. A plurality of toroidal coils (14) are wound about the core and laid in the inner and outer slots. Each coil occupies a single inner slot and is laid in the associated outer slot thereby minimizing the distance the coil extends from the end faces and minimizing the length of the induction machine. The toroidal coils are configured for an arbitrary pole phase modulation wherein the coils are configured with variable numbers of phases and poles for providing maximum torque for cranking and switchable to a another phase and pole configuration for alternator operation. An adaptor ring (36) circumferentially positioned about the stator improves mechanical strength, and provides a coolant channel manifold (34) for removing heat produced in stator windings during operation.
Woo, Kyung Jin; Kwon, Taeg Kyu
2007-12-15
Sulforaphane is a natural, biologically active compound extracted from cruciferous vegetables such as broccoli and cabbage. It possesses potent anti-inflammation and anti-cancer properties. The mechanism by which sulforaphane suppresses COX-2 expression remains poorly understood. In the present report, we investigated the effect of sulforaphane on the expression of COX-2 in lipopolysaccharide (LPS)-activated Raw 264.7 cells. Sulforaphane significantly suppressed the LPS-induced COX-2 protein and mRNA expression in a dose-dependent manner. The ability of sulforaphane to suppress the expression of the COX-2 was investigated using luciferase reporters controlled by various cis-elements in COX-2 promoter region. Electrophoretic mobility shift assay (EMSA) verified that NF-kappaB, C/EBP, CREB and AP-1 were identified as responsible for the sulforaphane-mediated COX-2 down-regulation. In addition, we demonstrated the signal transduction pathway of mitogen-activated protein kinase (MAP kinase) in LPS-induced COX-2 expression. Taken together, these results demonstrate that sulforaphane effectively suppressed the LPS-induced COX-2 protein via modulation of multiple core promoter elements (NF-kappaB, C/EBP, CREB and AP-1) in the COX-2 transcriptional regulation. These results will provide new insights into the anti-inflammatory and anti-carcinogenic properties of sulforaphane.
Identification of an O-antigen chain length regulator, WzzP, in Porphyromonas gingivalis
Shoji, Mikio; Yukitake, Hideharu; Sato, Keiko; Shibata, Yasuko; Naito, Mariko; Aduse-Opoku, Joseph; Abiko, Yoshimitsu; Curtis, Michael A; Nakayama, Koji
2013-01-01
The periodontal pathogen Porphyromonas gingivalis has two different lipopolysaccharides (LPSs) designated O-LPS and A-LPS, which are a conventional O-antigen polysaccharide and an anionic polysaccharide that are both linked to lipid A-cores, respectively. However, the precise mechanisms of LPS biosynthesis remain to be determined. In this study, we isolated a pigment-less mutant by transposon mutagenesis and identified that the transposon was inserted into the coding sequence PGN_2005, which encodes a hypothetical protein of P. gingivalis ATCC 33277. We found that (i) LPSs purified from the PGN_2005 mutant were shorter than those of the wild type; (ii) the PGN_2005 protein was located in the inner membrane fraction; and (iii) the PGN_2005 gene conferred Wzz activity upon an Escherichia coli wzz mutant. These results indicate that the PGN_2005 protein, which was designated WzzP, is a functional homolog of the Wzz protein in P. gingivalis. Comparison of amino acid sequences among WzzP and conventional Wzz proteins indicated that WzzP had an additional fragment at the C-terminal region. In addition, we determined that the PGN_1896 and PGN_1233 proteins and the PGN_1033 protein appear to be WbaP homolog proteins and a Wzx homolog protein involved in LPS biosynthesis, respectively. PMID:23509024
Menke, J.R.
1963-06-11
This patent relates to a reactor having a core which comprises an inner active region and an outer active region, each region separately having a k effective less than one and a k infinity greater than one. The inner and outer regions in combination have a k effective at least equal to one and each region contributes substantially to the k effective of the reactor core. The inner region has a low moderator to fuel ratio such that the majority of fissions occurring therein are induced by neutrons having energies greater than thermal. The outer region has a high moderator to fuel ratio such that the majority of fissions occurring therein are induced by thermal neutrons. (AEC)
Physical and Electronic Isolation of Carbon Nanotube Conductors
NASA Technical Reports Server (NTRS)
OKeeffe, James; Biegel, Bryan (Technical Monitor)
2001-01-01
Multi-walled nanotubes are proposed as a method to electrically and physically isolate nanoscale conductors from their surroundings. We use tight binding (TB) and density functional theory (DFT) to simulate the effects of an external electric field on multi-wall nanotubes. Two categories of multi-wall nanotube are investigated, those with metallic and semiconducting outer shells. In the metallic case, simulations show that the outer wall effectively screens the inner core from an applied electric field. This offers the ability to reduce crosstalk between nanotube conductors. A semiconducting outer shell is found not to perturb an electric field incident on the inner core, thereby providing physical isolation while allowing the tube to remain electrically coupled to its surroundings.
Cell rejuvenation and social behaviors promoted by LPS exchange in myxobacteria.
Vassallo, Christopher; Pathak, Darshankumar T; Cao, Pengbo; Zuckerman, David M; Hoiczyk, Egbert; Wall, Daniel
2015-06-02
Bacterial cells in their native environments must cope with factors that compromise the integrity of the cell. The mechanisms of coping with damage in a social or multicellular context are poorly understood. Here we investigated how a model social bacterium, Myxococcus xanthus, approaches this problem. We focused on the social behavior of outer membrane exchange (OME), in which cells transiently fuse and exchange their outer membrane (OM) contents. This behavior requires TraA, a homophilic cell surface receptor that identifies kin based on similarities in a polymorphic region, and the TraB cohort protein. As observed by electron microscopy, TraAB overexpression catalyzed a prefusion OM junction between cells. We then showed that damage sustained by the OM of one population was repaired by OME with a healthy population. Specifically, LPS mutants that were defective in motility and sporulation were rescued by OME with healthy donors. In addition, a mutant with a conditional lethal mutation in lpxC, an essential gene required for lipid A biosynthesis, was rescued by Tra-dependent interactions with a healthy population. Furthermore, lpxC cells with damaged OMs, which were more susceptible to antibiotics, had resistance conferred to them by OME with healthy donors. We also show that OME has beneficial fitness consequences to all cells. Here, in merged populations of damaged and healthy cells, OME catalyzed a dilution of OM damage, increasing developmental sporulation outcomes of the combined population by allowing it to reach a threshold density. We propose that OME is a mechanism that myxobacteria use to overcome cell damage and to transition to a multicellular organism.
Changes in divertor conditions in response to changing core density with RMPs
Briesemeister, Alexis R.; Ahn, Joon -Wook; Canik, John M.; ...
2017-06-07
The effects of changes in core density on divertor electron temperature, density and heat flux when resonant magnetic perturbations (RMPs) are applied are presented, notably a reduction in RMP induced secondary radial peaks in the electron temperature profile at the target plate is observed when the core density is increased, which is consistent with modeling. RMPs is used here to indicated non-axisymmetric magnetic field perturbations, created using in-vessel control coils, which have components which has at least one but typically many resonances with the rotational transform of the plasma. RMPs are found to alter inter-ELM heat flux to the divertormore » by modifying the core plasma density. It is shown that applying RMPs reduces the core density and increases the inter-ELM heat flux to both the inner and outer targets. Using gas puffing to return the core density to the pre-RMP levels more than eliminates the increase in inter-ELM heat flux, but a broadening of the heat flux to the outer target remains. These measurements were made at a single toroidal location, but the peak in the heat flux profile was found near the outer strike point where simulations indicate little toroidal variation should exist and tangentially viewing diagnostics showed no evidence of strong asymmetries. In experiments where divertor Thomson scattering measurements were available it is shown that, local secondary peaks in the divertor electron temperature profile near the target plate are reduced as the core density is increased, while peaks in the divertor electron density profile near the target are increased. Furthermore, these trends observed in the divertor electron temperature and density are qualitatively reproduced by scanning the upstream density in EMC3-Eirene modeling. Measurements are presented showing that higher densities are needed to induce detachment of the outer strike point in a case where an increase in electron temperature, likely due to a change in MHD activity, is seen after RMPs are applied.« less
Changes in divertor conditions in response to changing core density with RMPs
DOE Office of Scientific and Technical Information (OSTI.GOV)
Briesemeister, Alexis R.; Ahn, Joon -Wook; Canik, John M.
The effects of changes in core density on divertor electron temperature, density and heat flux when resonant magnetic perturbations (RMPs) are applied are presented, notably a reduction in RMP induced secondary radial peaks in the electron temperature profile at the target plate is observed when the core density is increased, which is consistent with modeling. RMPs is used here to indicated non-axisymmetric magnetic field perturbations, created using in-vessel control coils, which have components which has at least one but typically many resonances with the rotational transform of the plasma. RMPs are found to alter inter-ELM heat flux to the divertormore » by modifying the core plasma density. It is shown that applying RMPs reduces the core density and increases the inter-ELM heat flux to both the inner and outer targets. Using gas puffing to return the core density to the pre-RMP levels more than eliminates the increase in inter-ELM heat flux, but a broadening of the heat flux to the outer target remains. These measurements were made at a single toroidal location, but the peak in the heat flux profile was found near the outer strike point where simulations indicate little toroidal variation should exist and tangentially viewing diagnostics showed no evidence of strong asymmetries. In experiments where divertor Thomson scattering measurements were available it is shown that, local secondary peaks in the divertor electron temperature profile near the target plate are reduced as the core density is increased, while peaks in the divertor electron density profile near the target are increased. Furthermore, these trends observed in the divertor electron temperature and density are qualitatively reproduced by scanning the upstream density in EMC3-Eirene modeling. Measurements are presented showing that higher densities are needed to induce detachment of the outer strike point in a case where an increase in electron temperature, likely due to a change in MHD activity, is seen after RMPs are applied.« less
Equation of state and phase diagram of Fe-16Si alloy as a candidate component of Earth's core
DOE Office of Scientific and Technical Information (OSTI.GOV)
Fischer, Rebecca A; Campbell, Andrew J; Caracas, Razvan
2016-07-29
The outer core of the Earth contains several weight percent of one or more unknown light elements, which may include silicon. Therefore it is critical to understand the high pressure–temperature properties and behavior of an iron–silicon alloy with a geophysically relevant composition (16 wt% silicon). We experimentally determined the melting curve, subsolidus phase diagram, and equations of state of all phases of Fe–16 wt%Si to 140 GPa, finding a conversion from the D0 3 crystal structure to a B2+hcp mixture at high pressures. The melting curve implies that 3520 K is a minimum temperature for the Earth's outer core, ifmore » it consists solely of Fe–Si alloy, and that the eutectic composition in the Fe–Si system is less than 16 wt% silicon at core–mantle boundary conditions. Comparing our new equation of state to that of iron and the density of the core, we find that for an Fe–Ni–Si outer core, 11.3±1.5 wt% silicon would be required to match the core's observed density at the core–mantle boundary. We have also performed first-principles calculations of the equations of state of Fe 3Si with the D0 3 structure, hcp iron, and FeSi with the B2 structure using density-functional theory.« less
Earth's Fiercely Cooling Core - 24 TW
NASA Astrophysics Data System (ADS)
Morgan, Jason P.; Vannucchi, Paola
2014-05-01
Earth's mantle and core are convecting planetary heat engines. The mantle convects to lose heat from slow cooling, internal radioactivity, and core heatflow across its base. Its convection generates plate tectonics, volcanism, and the loss of ~35 TW of mantle heat through Earth's surface. The core convects to lose heat from slow cooling, small amounts of internal radioactivity, and the freezing-induced growth of a compositionally denser inner core. Core convection produces the geodynamo generating Earth's geomagnetic field. The geodynamo was thought to be powered by ~4 TW of heatloss across the core-mantle boundary, a rate sustainable (cf. Gubbins et al., 2003; Nimmo, 2007) by freezing a compositionally denser inner core over the ~3 Ga that Earth is known to have had a strong geomagnetic field (cf. Tarduno, 2007). However, recent determinations of the outer core's thermal conductivity(Pozzo et al., 2012; Gomi et al., 2013) indicate that >15 TW of power should conduct down its adiabat. Conducted power is unavailable to drive thermal convection, implying that the geodynamo needs a long-lived >17 TW power source. Core cooling was thought too weak for this, based on estimates for the Clapeyron Slope for high-pressure freezing of an idealized pure-iron core. Here we show that the ~500-1000 kg/m3 seismically-inferred jump in density between the liquid outer core and solid inner core allows us to directly infer the core-freezing Clapeyron Slope for the outer core's actual composition which contains ~8±2% lighter elements (S,Si,O,Al, H,…) mixed into a Fe-Ni alloy. A PREM-like 600 kg/m3 - based Clapeyron Slope implies there has been ~774K of core cooling during the freezing and growth of the inner core, releasing ~24 TW of power during the past ~3 Ga. If so, core cooling can easily power Earth's long-lived geodynamo. Another major implication of ~24 TW heatflow across the core-mantle boundary is that the present-day mantle is strongly 'bottom-heated', and diapiric mantle plumes should dominate deep mantle upwelling.
Respiratory potential in sapwood of old versus young ponderosa pine trees in the Pacific Northwest.
Pruyn, Michele L; Gartner, Barbara L; Harmon, Mark E
2002-02-01
Our primary objective was to present and test a new technique for in vitro estimation of respiration of cores taken from old trees to determine respiratory trends in sapwood. Our secondary objective was to quantify effects of tree age and stem position on respiratory potential (rate of CO2 production of woody tissue under standardized laboratory conditions). We extracted cores from one to four vertical positions in boles of +200-, +50- and +15-year-old Pinus ponderosa Dougl. ex Laws. trees. Cores were divided into five segments corresponding to radial depths of inner bark; outer, middle and inner sapwood; and heartwood. Data suggested that core segment CO2 production was an indicator of its respiratory activity, and that potential artifacts caused by wounding and extraction were minimal. On a dry mass basis, respiratory potential of inner bark was 3-15 times greater than that of sapwood at all heights for all ages (P < 0.0001). Within sapwood at all heights and in all ages of trees, outer sapwood had a 30-60% higher respiratory potential than middle or inner sapwood (P < 0.005). Heartwood had only 2-10% of the respiratory potential of outer sapwood. For all ages of trees, sapwood rings produced in the same calendar year released over 50% more CO2 at treetops than at bases (P < 0.0001). When scaled to the whole-tree level on a sapwood volume basis, sapwood of younger trees had higher respiratory potential than sapwood of older trees. In contrast, the trend was reversed when using the outer-bark surface area of stems as a basis for comparing respiratory potential. The differences observed in respiratory potential calculated on a core dry mass, sapwood volume, or outer-bark surface area basis clearly demonstrate that the resulting trends within and among trees are determined by the way in which the data are expressed. Although these data are based on core segments rather than in vivo measurements, we conclude that the relative differences are probably valid even if the absolute differences are not.
Annular core liquid-salt cooled reactor with multiple fuel and blanket zones
Peterson, Per F.
2013-05-14
A liquid fluoride salt cooled, high temperature reactor having a reactor vessel with a pebble-bed reactor core. The reactor core comprises a pebble injection inlet located at a bottom end of the reactor core and a pebble defueling outlet located at a top end of the reactor core, an inner reflector, outer reflector, and an annular pebble-bed region disposed in between the inner reflector and outer reflector. The annular pebble-bed region comprises an annular channel configured for receiving pebble fuel at the pebble injection inlet, the pebble fuel comprising a combination of seed and blanket pebbles having a density lower than the coolant such that the pebbles have positive buoyancy and migrate upward in said annular pebble-bed region toward the defueling outlet. The annular pebble-bed region comprises alternating radial layers of seed pebbles and blanket pebbles.
NASA Astrophysics Data System (ADS)
Adam, J. M.-C.; Ibourichène, A.; Romanowicz, B.
2018-02-01
We measured more than three thousand differential travel-times and amplitude ratios of PKPBC , PKPBC-diff , PKPAB and PKPDF phases in the epicentral distance range [149°-171°], from high quality records of globally distributed broadband stations. In particular, this is the largest collection of differential measurements of PKPBC-diff compared to PKPDF , extending by ∼ 10 ° the epicentral distance range in which the diffracted PKPBC phase has been observed globally. We used forward modelling of waveforms using the Direct Solution Method combined with a grid-search approach to explore attenuation and P-velocity structure in the vicinity of the inner core boundary (ICB) that can explain our observations. We find that, in order to simultaneously explain differential travel times and amplitude ratios of PKPBC , PKPBC-diff with respect to PKPDF out to distances of 165 ° , while fitting PKPAB /PKPDF within measurement errors, it is necessary to introduce a ∼ 450km zone of reduced bulk quality factor (Qκ ∼ 600) at the base of the outer core, while Qκ is close to 200 in a layer ∼ 150km thick at the top of the inner core. Concurrently, the P-velocity in the last 100 km of the outer-core is on average about 0.5 % slower than in the reference model AK 135 , while it is about 0.5 % faster in the top 150 km of the inner-core, resulting in a P-velocity jump at the inner core boundary slightly higher than in model AK 135 . However, this model underpredicts PKPBC-diff /PKPDF amplitude ratios at distances larger than 165 ° . Reducing Qκ even further in the last 100 km of the outer-core (down to Qκ = 50) provides a good fit to these data but it is not compatible with measurements of PKiKP/PKPDF amplitude ratios in the distance range 120-140°. We also considered a previously assembled global collection of "M phase" data. The M phase is a large energy in the coda of the PKPBC and PKPBC-diff that is not predicted by current 1 D reference seismic models, but most likely originates at the base of the outer-core. Our preferred model predicts the presence of an M phase, but significantly underestimates its amplitude. In order to explain the large amplitude of the M-phase and that of PKPBC-diff at distances larger than 165 ° without significantly affecting PKiKP amplitudes, it seems necessary to invoke a process that would produce strong scattering for diffracted phases in the immediate vicinity of the ICB, on the outer core side. Clusters of solid particles suspended in the fluid core or topography of the ICB are possible candidates that should be explored further.
Simon, Raphael; Tennant, Sharon M.; Wang, Jin Y.; Schmidlein, Patrick J.; Lees, Andrew; Ernst, Robert K.; Pasetti, Marcela F.; Galen, James E.; Levine, Myron M.
2011-01-01
Nontyphoidal Salmonella enterica serovars Enteritidis and Typhimurium are a common cause of gastroenteritis but also cause invasive infections and enteric fever in certain hosts (young children in sub-Saharan Africa, the elderly, and immunocompromised individuals). Salmonella O polysaccharides (OPS) and flagellar proteins are virulence factors and protective antigens. The surface polysaccharides of Salmonella are poorly immunogenic and do not confer immunologic memory, limitations overcome by covalently attaching them to carrier proteins. We conjugated core polysaccharide-OPS (COPS) of Salmonella Enteritidis lipopolysaccharide (LPS) to flagellin protein from the homologous strain. COPS and flagellin were purified from a genetically attenuated (ΔguaBA) “reagent strain” (derived from an isolate from a patient with clinical bacteremia) engineered for increased flagellin production (ΔclpPX). Conjugates were constructed by linking flagellin monomers or polymers at random COPS hydroxyls with various polysaccharide/protein ratios by 1-cyano-4-dimethylaminopyridinium tetrafluoroborate (CDAP) or at the 3-deoxy-d-manno-octulosonic acid (KDO) terminus by thioether chemistry. Mice immunized on days 0, 28, and 56 with COPS-flagellin conjugates mounted higher anti-LPS IgG levels than mice receiving unconjugated COPS and exhibited high antiflagellin IgG; anti-LPS and antiflagellin IgG levels increased following booster doses. Antibodies generated by COPS-flagellin conjugates mediated opsonophagocytosis of S. Enteritidis cells into mouse macrophages. Mice immunized with flagellin alone, COPS-CRM197, or COPS-flagellin conjugates were significantly protected from lethal challenge with wild-type S. Enteritidis (80 to 100% vaccine efficacy). PMID:21807909
West, Andrea J.; Brown, Gregory P.; Fanson, Kerry V.; Addison, BriAnne; Rollins, Lee A.; Shine, Richard
2017-01-01
The cane toad (Rhinella marina) has undergone rapid evolution during its invasion of tropical Australia. Toads from invasion front populations (in Western Australia) have been reported to exhibit a stronger baseline phagocytic immune response than do conspecifics from range core populations (in Queensland). To explore this difference, we injected wild-caught toads from both areas with the experimental antigen lipopolysaccharide (LPS, to mimic bacterial infection) and measured whole-blood phagocytosis. Because the hypothalamic-pituitary-adrenal axis is stimulated by infection (and may influence immune responses), we measured glucocorticoid response through urinary corticosterone levels. Relative to injection of a control (phosphate-buffered saline), LPS injection increased both phagocytosis and the proportion of neutrophils in the blood. However, responses were similar in toads from both populations. This null result may reflect the ubiquity of bacterial risks across the toad’s invaded range; utilization of this immune pathway may not have altered during the process of invasion. LPS injection also induced a reduction in urinary corticosterone levels, perhaps as a result of chronic stress. PMID:29018604
Liu, Qiong; Yi, Jie; Liang, Kang; Zhang, Xiangmin; Liu, Qing
2017-08-28
Foodborne contamination and salmonellosis caused by Salmonella Enteritidis ( S . Enteritidis) are a significant threat to human health and poultry enterprises. Outer membrane vesicles (OMVs), which are naturally secreted by gram-negative bacteria, could be a good vaccine option because they have many biologically active substances, including lipopolysaccharides (LPS), outer membrane proteins (OMPs), and phospholipids, as well as periplasmic components. In the present study, we purified OMVs derived from S . Enteritidis and analyzed their characteristics through silver staining and sodium dodecyl sulfate polyacrylamide gel electrophoresis. In total, 108 proteins were identified in S . Enteritidis OMVs through liquid chromatography tandem mass spectrometry analysis, and OMPs, periplasmic proteins, and extracellular proteins (49.9% of total proteins) were found to be enriched in the OMVs compared with bacterial cells. Furthermore, native OMVs used in immunizations by either the intranasal route or the intraperitoneal route could elicit significant humoral and mucosal immune responses and provide strong protective efficiency against a lethal dose (~100-fold LD 50 ) of the wild-type S . Enteritidis infection. These results indicated that S . Enteritidis OMVs might be an ideal vaccine strategy for preventing S . Enteritidis diseases.
A laboratory model for solidification of Earth's core
NASA Astrophysics Data System (ADS)
Bergman, Michael I.; Macleod-Silberstein, Marget; Haskel, Michael; Chandler, Benjamin; Akpan, Nsikan
2005-11-01
To better understand the influence of rotating convection in the outer core on the solidification of the inner core we have constructed a laboratory model for solidification of Earth's core. The model consists of a 15 cm radius hemispherical acrylic tank concentric with a 5 cm radius hemispherical aluminum heat exchanger that serves as the incipient inner core onto which we freeze ice from salt water. Long exposure photographs of neutrally buoyant particles in illuminated planes suggest reduction of flow parallel to the rotation axis. Thermistors in the tank near the heat exchanger show that in experiments with rotation the temperature near the pole is lower than near the equator, unlike for control experiments without rotation or with a polymer that increases the fluid viscosity. The photographs and thermistors suggest that our observation that ice grows faster near the pole than near the equator for experiments with rotation is a result of colder water not readily convecting away from the pole. Because of the reversal of the thermal gradient, we expect faster equatorial solidification in the Earth's core. Such anisotropy in solidification has been suggested as a cause of inner core elastic (and attenuation) anisotropy, though the plausibility of this suggestion will depend on the core Nusselt number and the slope of the liquidus, and the effects of post-solidification deformation. Previous experiments on hexagonal close-packed alloys such as sea ice and zinc-tin have shown that fluid flow in the melt can result in a solidification texture transverse to the solidification direction, with the texture depending on the nature of the flow. A comparison of the visualized flow and the texture of columnar ice crystals in thin sections from these experiments confirms flow-induced transverse textures. This suggests that the convective pattern at the base of the outer core is recorded in the texture of the inner core, and that outer core convection might contribute to the complexity in the seismically inferred pattern of anisotropy in the Earth's inner core.
Equation of state fits to the lower mantle and outer core
NASA Technical Reports Server (NTRS)
Butler, R.; Anderson, D. L.
1978-01-01
The lower mantle and outer core are subjected to tests for homogeneity and adiabaticity. An earth model is used which is based on the inversion of body waves and Q-corrected normal-mode data. Homogeneous regions are found at radii between 5125 and 4825 km, 4600 and 3850 km, and 3200 and 2200 km. The lower mantle and outer core are inhomogeneous on the whole and are only homogeneous in the above local regions. Finite-strain and atomistic equations of state are fit to the homogeneous regions. The apparent convergence of the finite-strain relations is examined to judge their applicability to a given region. In some cases the observed pressure derivatives of the elastic moduli are used as additional constraints. The effect of minor deviations from adiabaticity on the extrapolations is also considered. An ensemble of zero-pressure values of the density and seismic velocities are found for these regions. The range of extrapolated values from these several approaches provides a measure of uncertainties involved.
NASA Astrophysics Data System (ADS)
Brandon, Alan D.; Walker, Richard J.; Puchtel, Igor S.; Becker, Harry; Humayun, Munir; Revillon, Sidonie
2003-02-01
The presence of coupled enrichments in 186Os/ 188Os and 187Os/ 188Os in some mantle-derived materials reflects long-term elevation of Pt/Os and Re/Os relative to the primitive upper mantle. New Os data for the 89 Ma Gorgona Island, Colombia komatiites indicate that these lavas are also variably enriched in 186Os and 187Os, with 186Os/ 188Os ranging between 0.1198397±22 and 0.1198470±38, and with γOs correspondingly ranging from +0.15 to +4.4. These data define a linear trend that converges with the previously reported linear trend generated from data for modern Hawaiian picritic lavas and a sample from the ca. 251 Ma Siberian plume, to a common component with a 186Os/ 188Os of approximately 0.119870 and γOs of +17.5. The convergence of these data to this Os isotopic composition may imply a single ubiquitous source in the Earth's interior that mixes with a variety of different mantle compositions distinguished by variations in γOs. The 187Os- and 186Os-enriched component may have been generated via early crystallization of the solid inner core and consequent increases in Pt/Os and Re/Os in the liquid outer core, with time leading to suprachondritic 186Os/ 188Os and γOs in the outer core. The presence of Os from the outer core in certain portions of the mantle would require a mechanism that could transfer Os from the outer core to the lower mantle, and thence to the surface. If this is the process that generated the isotopic enrichments in the mantle sources of these plume-derived systems, then the current understanding of solid metal-liquid metal partitioning of Pt, Re and Os requires that crystallization of the inner core began prior to 3.5 Ga. Thus, the Os isotopic data reported here provide a new source of data to better constrain the timing of inner core formation, complementing magnetic field paleo-intensity measurements as data sources that constrain models based on secular cooling of the Earth.
NASA Astrophysics Data System (ADS)
Lassiter, J. C.
2006-10-01
The possibility that some mantle plumes may carry a geochemical signature of core/mantle interaction has rightly generated considerable interest and attention in recent years. Correlated 186Os- 187Os enrichments in some plume-derived lavas (Hawaii, Gorgona, Kostomuksha) have been interpreted as deriving from an outer core with elevated Pt/Os and Re/Os ratios due to the solidification of the Earth's inner core (c.f., [A.D. Brandon, R.J. Walker, The debate over core-mantle interaction, Earth Planet. Sci. Lett. 232 (2005) 211-225.] and references therein). Conclusive identification of a "core signal" in plume-derived lavas would profoundly influence our understanding of mantle convection and evolution. This paper reevaluates the Os-isotope evidence for core/mantle interaction by examining other geochemical constraints on core/mantle interaction, geophysical constraints on the thermal evolution of the outer core, and geochemical and cosmochemical constraints on the abundance of heat-producing elements in the core. Additional study of metal/silicate and sulfide/silicate partitioning of K, Pb, and other trace elements is needed to more tightly constrain the likely starting composition of the Earth's core. However, available data suggest that the observed 186Os enrichments in Hawaiian and other plume-derived lavas are unlikely to derive from core/mantle interaction. 1) Core/mantle interaction sufficient to produce the observed 186Os enrichments would likely have significant effects on other tracers such as Pb- and W-isotopes that are not observed. 2) Significant partitioning of K or other heat-producing elements into the core would produce a "core depletion" pattern in the Silicate Earth very different from that observed. 3) In the absence of heat-producing elements in the core, core/mantle heat flow of ˜ 6-15 TW estimated from several independent geophysical constraints suggests an inner core age (< ˜ 2.5 Ga) too young for the outer core to have developed a significant 186Os enrichment. Core/mantle thermal and chemical interaction remains an important problem that warrants future research. However, Os-isotopes may have only limited utility in this area due to the relatively young age of the Earth's inner core.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Preece, G.E.; Bell, F.R.
1963-06-26
A protective arrangement is designed for shielding the environment and for preventing the leakage of radioactive gases from a ship nuclear power plant. In this arrangement, the core has inner and outer pressure vessels and a biological shielding around the outer pressure vessel. The shielding comprises a series of steel cylindrical shells immersed in water, and its inner wall may comprise part of the outer pressure vessel. (D.L.C.)
Seismological evidence for a localized mushy zone at the Earth's inner core boundary.
Tian, Dongdong; Wen, Lianxing
2017-08-01
Although existence of a mushy zone in the Earth's inner core has been hypothesized several decades ago, no seismic evidence has ever been reported. Based on waveform modeling of seismic compressional waves that are reflected off the Earth's inner core boundary, here we present seismic evidence for a localized 4-8 km thick zone across the inner core boundary beneath southwest Okhotsk Sea with seismic properties intermediate between those of the inner and outer core and of a mushy zone. Such a localized mushy zone is found to be surrounded by a sharp inner core boundary nearby. These seismic results suggest that, in the current thermo-compositional state of the Earth's core, the outer core composition is close to eutectic in most regions resulting in a sharp inner core boundary, but deviation from the eutectic composition exists in some localized regions resulting in a mushy zone with a thickness of 4-8 km.The existence of a mushy zone in the Earth's inner core has been suggested, but has remained unproven. Here, the authors have discovered a 4-8 km thick mushy zone at the inner core boundary beneath the Okhotsk Sea, indicating that there may be more localized mushy zones at the inner core boundary.
The innate immune response in fetal lung mesenchymal cells targets VEGFR2 expression and activity.
Medal, Rachel M; Im, Amanda M; Yamamoto, Yasutoshi; Lakhdari, Omar; Blackwell, Timothy S; Hoffman, Hal M; Sahoo, Debashis; Prince, Lawrence S
2017-06-01
In preterm infants, soluble inflammatory mediators target lung mesenchymal cells, disrupting airway and alveolar morphogenesis. However, how mesenchymal cells respond directly to microbial stimuli remains poorly characterized. Our objective was to measure the genome-wide innate immune response in fetal lung mesenchymal cells exposed to the bacterial endotoxin lipopolysaccharide (LPS). With the use of Affymetrix MoGene 1.0st arrays, we showed that LPS induced expression of unique innate immune transcripts heavily weighted toward CC and CXC family chemokines. The transcriptional response was different between cells from E11, E15, and E18 mouse lungs. In all cells tested, LPS inhibited expression of a small core group of genes including the VEGF receptor Vegfr2 Although best characterized in vascular endothelial populations, we demonstrated here that fetal mouse lung mesenchymal cells express Vegfr2 and respond to VEGF-A stimulation. In mesenchymal cells, VEGF-A increased cell migration, activated the ERK/AKT pathway, and promoted FOXO3A nuclear exclusion. With the use of an experimental coculture model of epithelial-mesenchymal interactions, we also showed that VEGFR2 inhibition prevented formation of three-dimensional structures. Both LPS and tyrosine kinase inhibition reduced three-dimensional structure formation. Our data suggest a novel mechanism for inflammation-mediated defects in lung development involving reduced VEGF signaling in lung mesenchyme. Copyright © 2017 the American Physiological Society.
Zhang, Yali; Wu, Jianzhang; Ying, Shilong; Chen, Gaozhi; Wu, Beibei; Xu, Tingting; Liu, Zhiguo; Liu, Xing; Huang, Lehao; Shan, Xiaoou; Dai, Yuanrong; Liang, Guang
2016-01-01
Acute lung injury (ALI) is a life-threatening acute inflammatory disease with limited options available for therapy. Myeloid differentiation protein 2, a co-receptor of TLR4, is absolutely required for TLR4 sense LPS, and represents an attractive target for treating severe inflammatory diseases. In this study, we designed and synthesized 31 chalcone derivatives that contain the moiety of (E)-4-phenylbut-3-en-2-one, which we consider the core structure of current MD2 inhibitors. We first evaluated the anti-inflammatory activities of these compounds in MPMs. For the most active compound 20, we confirmed that it is a specific MD2 inhibitor through a series of biochemical experiments and elucidated that it binds to the hydrophobic pocket of MD2 via hydrogen bonds with Arg90 and Tyr102 residues. Compound 20 also blocked the LPS-induced activation of TLR4/MD2 -downstream pro-inflammatory MAPKs/NF-κB signaling pathways. In a rat model with ALI induced by intracheal LPS instillation, administration with compound 20 exhibited significant protective effect against ALI, accompanied by the inhibition of TLR4/MD2 complex formation in lung tissues. Taken together, the results of this study suggest the specific MD2 inhibitor from chalcone derivatives we identified is a potential candidate for treating acute inflammatory diseases. PMID:27118147
Chemical Convention in the Lunar Core from Melting Experiments on the Ironsulfur System
DOE Office of Scientific and Technical Information (OSTI.GOV)
Li, J.; Liu, J.; Chen, B.
2012-03-26
By reanalyzing Apollo lunar seismograms using array-processing methods, a recent study suggests that the Moon has a solid inner core and a fluid outer core, much like the Earth. The volume fraction of the lunar inner core is 38%, compared with 4% for the Earth. The pressure at the Moon's core-mantle boundary is 4.8 GPa, and that at the ICB is 5.2 GPa. The partially molten state of the lunar core provides constraints on the thermal and chemical states of the Moon: The temperature at the inner core boundary (ICB) corresponds to the liquidus of the outer core composition, andmore » the mass fraction of the solid core allows us to infer the bulk composition of the core from an estimated thermal profile. Moreover, knowledge on the extent of core solidification can be used to evaluate the role of chemical convection in the origin of early lunar core dynamo. Sulfur is considered an antifreeze component in the lunar core. Here we investigate the melting behavior of the Fe-S system at the pressure conditions of the lunar core, using the multi-anvil apparatus and synchrotron and laboratory-based analytical methods. Our goal is to understand compositionally driven convection in the lunar core and assess its role in generating an internal magnetic field in the early history of the Moon.« less
The ab initio simulation of the Earth's core.
Alfè, D; Gillan, M J; Vocadlo, L; Brodholt, J; Price, G D
2002-06-15
The Earth has a liquid outer and solid inner core. It is predominantly composed of Fe, alloyed with small amounts of light elements, such as S, O and Si. The detailed chemical and thermal structure of the core is poorly constrained, and it is difficult to perform experiments to establish the properties of core-forming phases at the pressures (ca. 300 GPa) and temperatures (ca. 5000-6000 K) to be found in the core. Here we present some major advances that have been made in using quantum mechanical methods to simulate the high-P/T properties of Fe alloys, which have been made possible by recent developments in high-performance computing. Specifically, we outline how we have calculated the Gibbs free energies of the crystalline and liquid forms of Fe alloys, and so conclude that the inner core of the Earth is composed of hexagonal close packed Fe containing ca. 8.5% S (or Si) and 0.2% O in equilibrium at 5600 K at the boundary between the inner and outer cores with a liquid Fe containing ca. 10% S (or Si) and 8% O.
Fluid flow near the surface of earth's outer core
NASA Technical Reports Server (NTRS)
Bloxham, Jeremy; Jackson, Andrew
1991-01-01
This review examines the recent attempts at extracting information on the pattern of fluid flow near the surface of the outer core from the geomagnetic secular variation. Maps of the fluid flow at the core surface are important as they may provide some insight into the process of the geodynamo and may place useful constraints on geodynamo models. In contrast to the case of mantle convection, only very small lateral variations in core density are necessary to drive the flow; these density variations are, by several orders of magnitude, too small to be imaged seismically; therefore, the geomagnetic secular variation is utilized to infer the flow. As substantial differences exist between maps developed by different researchers, the possible underlying reasons for these differences are examined with particular attention given to the inherent problems of nonuniqueness.
Array analyses of SmKS waves and the stratification of Earth's outermost core
NASA Astrophysics Data System (ADS)
Kaneshima, Satoshi
2018-03-01
We perform array analyses of SmKS waves in order to investigate the Vp structure of the Earth's outermost core. For earthquakes recorded by broadband seismometer networks in the world, we measure differential travel times between S3KS and S2KS, between S4KS and S3KS, and between S5KS and S3KS by array techniques. The differential times are well fit by a Vp model of the Earth's outermost core, KHOMC (Kaneshima and Helffrich, 2013). Differential slownesses of S4KS and S2KS relative to S2KS are also measured for the highest quality data. The measured slownesses, with unique sensitivity to the outer core 200-400 km below the CMB, are matched by KHOMC. These observations consolidate the evidence for the presence at the top of the outer core of a layer that has a distinctively steeper Vp gradient than the bulk of the outer core. We invert new SmKS differential time data set by a tau-p method and attempt to refine the Vp profile of KHOMC. The essential features of KHOMC are preserved after the model refinement. However, the newly estimated layer thickness is nearly 450 km, which is thicker than that of KHOMC. The Vp anomalies relative to PREM for the depths 400-800 km below the CMB are less than 0.03 km/s, consistent with the degree of agreement between different Vp models for the depth range.
Has Earth's Plate Tectonics Led to Rapid Core Cooling?
NASA Astrophysics Data System (ADS)
de Montserrat Navarro, A.; Morgan, J. P.; Vannucchi, P.; Connolly, J. A.
2016-12-01
Earth's mantle and core are convecting planetary heat engines. The mantle convects to lose heat from secular cooling, internal radioactivity, and core heatflow across its base. Its convection generates plate tectonics, volcanism, and the loss of 35 TW of mantle heat through Earth's surface. The core convects to lose heat from secular cooling, small amounts of internal radioactivity, and the freezing-induced growth of a compositionally denser inner core. Until recently, the geodynamo was thought to be powered by 4 TW of heatloss across the core-mantle boundary. More recent determinations of the outer core's thermal conductivity (Pozzo et al., 2012; Gomi et al., 2013) would imply that >15 TW of power should conduct down its adiabat. Secular core cooling has been previously thought to be too slow for this, based on estimates for the Clapeyron Slope for high-pressure freezing of an idealized pure-iron core (cf. Nimmo, 2007). The 500-1000 kg m-3 seismically-inferred jump in density between the liquid outer core and solid inner core allows a direct estimate of the Clapeyron Slope for the outer core's actual composition which contains 0.08±0.02 lighter elements (S,Si,O,Al, H,…) mixed into a Fe-Ni alloy. A PREM-like 600 kg m-3 density jump yields a Clapeyron Slope for which there has been 774K of core cooling during the freezing and growth of the inner core, cooling that has been releasing an average of 21 TW of power during the past 3 Ga. If so, core cooling could easily have powered Earth's long-lived geodynamo. Another implication is that the present-day mantle is strongly `bottom-heated', and diapiric mantle plumes should dominate deep mantle upwelling. This mode of core and mantle convection is consistent with slow, 37.5K/Ga secular cooling of Earth's mantle linked to more rapid secular cooling of the core (cf. Morgan, Rüpke, and White, 2016). Efficient plate subduction, hence plate tectonics, is a key ingredient for such rapid secular core cooling.We also show how a more complete thermodynamic version of Birch's accretional energy calculation predicts that accretion with FeNi-sinking-linked differentiation between an Earth-like mantle and core would naturally generate a core that, post-accretion, was both hotter than overlying mantle and 1000K hotter than today.
Method of Fault Detection and Rerouting
NASA Technical Reports Server (NTRS)
Gibson, Tracy L. (Inventor); Medelius, Pedro J. (Inventor); Lewis, Mark E. (Inventor)
2013-01-01
A system and method for detecting damage in an electrical wire, including delivering at least one test electrical signal to an outer electrically conductive material in a continuous or non-continuous layer covering an electrically insulative material layer that covers an electrically conductive wire core. Detecting the test electrical signals in the outer conductive material layer to obtain data that is processed to identify damage in the outer electrically conductive material layer.
Comparison of secondary flows and boundary-layer accumulations in several turbine nozzles
NASA Technical Reports Server (NTRS)
Kofskey, Milton G; Allen, Hubert W; Herzig, Howard Z
1953-01-01
An investigation was made of losses and secondary flows in three different turbine nozzle configurations in annular cascade. Appreciable outer shroud loss cores (passage vortices) were found to exist at the discharge of blades which had thickened suction surface boundary layers near the outer shroud. Blade designs having thinner boundary layers did not show such outer shroud loss cores, but indicated greater inward radial flow of low momentum air, in the wake loss is to this extent an indication of the presence or absence of radial flow. The blade wake was a combination of profile loss and low momentum air from the outer shroud, and the magnitude of the wake loss is to this extent an indication of the presence or absence of radial flow. At a high Mach number, shock-boundary-layer thickening on the blade suction surfaces provided an additional radial flow path for low momentum air, which resulted in large inner shroud loss regions accompanied by large deviations from design values of discharge angle. (author)
DOE Office of Scientific and Technical Information (OSTI.GOV)
Shapiro, B I; Tyshkunova, E S; Kondorskiy, A D
2015-12-31
Optical properties of hybrid rod-like nanoparticles, consisting of a gold core, an intermediate passive organic layer (spacer) and outer layer of ordered molecular cyanine dye aggregates, are experimentally and theoretically investigated. It is shown that these dyes can form not only ordered J-aggregates but also H-aggregates (differing by the packing angle of dye molecules in an aggregate and having other spectral characteristics) in the outer shell of the hybrid nanostructure. Absorption spectra of synthesised three-layer nanorods are recorded, and their sizes are determined. The optical properties of the composite nanostructures under study are found to differ significantly, depending on themore » type of the molecular aggregate formed in the outer shell. The experimental data are quantitatively explained based on computer simulation using the finite-difference time-domain (FDTD) method, and characteristic features of the plasmon – exciton interaction in the systems under study are revealed. (nanophotonics)« less
Systemic LPS and inflammatory response during consecutive days of exercise in heat.
Barberio, M D; Elmer, D J; Laird, R H; Lee, K A; Gladden, B; Pascoe, D D
2015-03-01
This investigation studied circulating LPS activity, potential intestinal damage, and the systemic inflammatory response (SIR) during the exercise heat acclimation process. 8 healthy males (Age=24±3 years) ran in a hot environment on 5 consecutive days until core temperature (Tc) was elevated 2°C above rest. Plasma was obtained pre-, post-, 1 h post-, and 3 h post-exercise on the 1(st), 3(rd), and 5(th) day of exercise and analyzed for TNF-α, IL-6, IL-10, IL-1ra, LPS, and intestinal fatty acid-binding protein (I-FABP). Plasma LPS (1.1 EU·ml(-1)±0.1 vs. 0.7 EU·ml(-1)±0.03; P<0.01) and I-FABP (930.7 pg·ml(-1)±149.0 vs. 640.2 pg·ml(-1)±125.0; P<0.001) were significantly increased post-exercise each. The SIR remained largely unchanged during the study except for TNF-α. Plasma TNF-α was significantly lower on Day 5 at 1 h (3.2 pg·ml(-1)±0.6 vs. 4.5 pg·ml(-1)±0.8; P=0.01) and 3 h (3.6 pg·ml(-1)±0.8 vs. 4.8 pg·ml(-1)±0.9; P=0.05) post-exercise as compared to Day 1. Findings indicate that adaptations to exercise in the heat resulting in reductions of intestinal damage and plasma LPS activity require longer time periods in moderately trained males. © Georg Thieme Verlag KG Stuttgart · New York.
Coring device with a improved core sleeve and anti-gripping collar with a collective core catcher
DOE Office of Scientific and Technical Information (OSTI.GOV)
Story, A.L.; Filshtinsky, M.
1986-01-28
This patent describes an improved coring apparatus used in combination with a coring bit and drill string. This device consists of: an outer driving structure adapted to be connected at one end to the coring bit for cutting a core in a borehole, and at the other end to the lower end of the drill string in telescoping and co-rotatable manner therewith; an inner barrel disposed within the outer driving structure and including a lower end portion adjacent to the bit; first means supporting the inner barrel in spaced relationship to the outer driving structure while permitting rotation of themore » driving structure with respect to the inner barrel; a woven metal mesh sleeve mounted in surrounding relation on at least a portion of the exterior surface of the inner barrel; second means, connected to a free end of the sleeve opposite the leading portion of the sleeve, for maintaining the portion of the sleeve which surrounds the inner barrel in compression and to maintain an inside diameter greater than the outside diameter of the inner barrel of the portion of the sleeve surrounding the inner barrel while the portion of the sleeve positioned inside the inner barrel being in tension to grip and compress a core received within the sleeve and having an outside diameter less than the inside diameter of the inner barrel when in tension, wherein the second means is also for engaging the core when the means is drawn into the inner barrel, and third means positioned within the inner barrel and connected to the leading portion of the sleeve to draw the sleeve within the inner barrel and to apply tension to the portion of the sleeve within the barrel to encase and grip the core as it is cut.« less
The chemical composition of the cores of the terrestrial planets and the moon
NASA Technical Reports Server (NTRS)
Kuskov, O. L.; Khitarov, N. I.
1977-01-01
Using models of the quasi-chemical theory of solutions, the activity coefficients of silicon are calculated in the melts Fe-Si, Ni-Si, and Fe-Ni-Si. The calculated free energies of solution of liquid nickel and silicon in liquid iron in the interval 0 to 1400 kbar and 1500 to 4000 K, shows that Fe-Ni-Si alloy is stable under the conditions of the outer core of the earth and the cores of the terrestrial planets. The oxidation-reduction conditions are studied, and the fugacity of oxygen in the mantles of the planets and at the core-mantle boundary are calculated. The mechanism of reduction of silicon is analyzed over a broad interval of p and T. The interaction between the matter of the core and mantle is studied, resulting in the extraction of silicon from the mantle and its solution in the material of the core. It is concluded that silicon can enter into the composition of the outer core of the earth and Venus, but probably does not enter into the composition of the cores of Mercury, Mars, and the moon, if in fact the latter possesses one.
Electrically operated magnetic switch designed to display reduced leakage inductance
Cook, Edward G.
1994-01-01
An electrically operated magnetic switch is disclosed herein for use in opening and closing a circuit between two terminals depending upon the voltage across these terminals. The switch so disclosed is comprised of a ferrite core in the shape of a toroid having opposing ends and opposite inner and outer sides and an arrangement of electrically conductive components defining at least one current flow path which makes a number of turns around the core. This arrangement of components includes a first plurality of electrically conducive rigid rods parallel with and located outside the outer side of the core and a second plurality of electrically conductive rigid rods parallel with and located inside the inner side of the core. The arrangement also includes means for electrically connecting these rods together so that the define the current flow path. In one embodiment, this latter means uses rigid cross-tab means. In another, preferred embodiment, printed circuits on rigid dielectric substrates located on opposite ends of the core are utilized to interconnect the rods together.
NASA Astrophysics Data System (ADS)
Egbers, C.
The'GeoFlow' is an ESA experiment planned for the Fluid Science Laboratory on ISS under the scientific coordination (PI) of the Department of Aerodynamics and Fluid Mechanics (LAS) at the Brandenburg Technical University (BTU) of Cottbus, Germany. The objective of the experiment is to study thermal convection in the gap between two concentric rotating (full) spheres. A central symmetric force field simi- lar to the gravity field acting on planets can be produced by applying a high voltage between inner and outer sphere using the dielectrophoretic effect (rotating capacitor). To counter the unidirectional gravity under terrestrial conditions, this experiment re- quires a microgravity environment. The parameters of the experiment are chosen in analogy to the thermal convective motions in the outer core of the Earth. In analogy to geophysical motions in the Earth`s liquid core the experiment can rotate as solid body as well as differential (inner to outer). Thermal convection is produced by heat- ing the inner sphere and cooling the outer ones. Furtheron, the variation of radius ratio between inner and outer sphere is foreseen as a parameter variation. The flows to be investigated will strongly depend on the gap width and on the Prandtl number.
NASA Astrophysics Data System (ADS)
Cruz, Anna P. S.; Barbosa, Catia F.; Ayres-Neto, Arthur; Munayco, Pablo; Scorzelli, Rosa B.; Amorim, Nívea Santos; Albuquerque, Ana L. S.; Seoane, José C. S.
2018-02-01
In order to investigate the chemical and magnetic characteristics of sediments of the western boundary upwelling system of Southwest Atlantic we analyzed magnetic susceptibility, grain size distribution, total organic carbon, heavy mineral abundance, Fe associated with Mössbauer spectra, and Fe and Mn of pore water to evaluate the deposition patterns of sediments. Four box-cores were collected along a cross-shelf transect. Brazil Current and coastal plume exert a primary control at the inner and outer shelf cores, which exhibited similar depositional patterns characterized by a high abundance of heavy minerals (mean 0.21% and 0.08%, respectively) and very fine sand, whereas middle shelf cores presented low abundances of heavy minerals (mean 0.03%) and medium silt. The inner shelf was dominated by sub-angular grains, while in middle and outer shelf cores well-rounded grains were found. The increasing Fe3+:Fe2+ ratio from the inner to the outer shelf reflects farther distance to the sediment source. The outer shelf presented well-rounded minerals, indicating abrasive processes as a result of transport by the Brazil Current from the source areas. In the middle shelf, cold-water intrusion of the South Atlantic Central Water contributes to the primary productivity, resulting in higher deposition of fine sediment and organic carbon accumulation. The high input of organic carbon and the decreased grain size are indicative of changes in the hydrodynamics and primary productivity fueled by the western boundary upwelling system, which promotes loss of magnetization due to the induction of diagenesis of iron oxide minerals.
NASA Astrophysics Data System (ADS)
Amrouch, Khalid; Lacombe, Olivier; Bellahsen, Nicolas; Daniel, Jean-Marc; Callot, Jean-Paul
2010-02-01
In order to characterize and compare the stress-strain record prior to, during, and just after folding at the macroscopic and the microscopic scales and to provide insights into stress levels sustained by folded rocks, we investigate the relationship between the stress-strain distribution in folded strata derived from fractures, striated microfaults, and calcite twins and the development of the Laramide, basement-cored Sheep Mountain Anticline, Wyoming. Tectonic data were mainly collected in Lower Carboniferous to Permian carbonates and sandstones. In both rock matrix and veins, calcite twins recorded three different tectonic stages: the first stage is a pre-Laramide (Sevier) layer-parallel shortening (LPS) parallel to fold axis, the second one is a Laramide LPS perpendicular to the fold axis, and the third stage corresponds to Laramide late fold tightening with compression also perpendicular to the fold axis. Stress and strain orientations and regimes at the microscale agree with the polyphase stress evolution revealed by populations of fractures and striated microfaults, testifying for the homogeneity of stress record at different scales through time. Calcite twin analysis additionally reveals significant variations of differential stress magnitudes between fold limbs. Our results especially point to an increase of differential stress magnitudes related to Laramide LPS from the backlimb to the forelimb of the fold possibly in relation with motion of an underlying basement thrust fault that likely induced stress concentrations at its upper tip. This result is confirmed by a simple numerical model. Beyond regional implications, this study highlights the potential of calcite twin analyses to yield a representative quantitative picture of stress and strain patterns related to folding.
Torsional Oscillations of the Earths's Core
NASA Technical Reports Server (NTRS)
Hide, Raymond; Boggs, Dale H.; Dickey, Jean O.
1997-01-01
Torsional oscillations of the Earth's liquid metallic outer core are investigated by diving the core into twenty imaginary e1qui-volume annuli coaxial with the axis of ratation of the Earth and determining temproal fluctuations in the axial component of angular memonetum of each annulus under the assumption of iso-rotation on cylindrical surfaces.
The Effects of Earth's Outer Core's Viscosity on Geodynamo Models
NASA Astrophysics Data System (ADS)
Dong, C.; Jiao, L.; Zhang, H.
2017-12-01
Geodynamo process is controlled by mathematic equations and input parameters. To study effects of parameters on geodynamo system, MoSST model has been used to simulate geodynamo outputs under different outer core's viscosity ν. With spanning ν for nearly three orders when other parameters fixed, we studied the variation of each physical field and its typical length scale. We find that variation of ν affects the velocity field intensely. The magnetic field almost decreases monotonically with increasing of ν, while the variation is no larger than 30%. The temperature perturbation increases monotonically with ν, but by a very small magnitude (6%). The averaged velocity field (u) of the liquid core increases with ν as a simple fitted scaling relation: u∝ν0.49. The phenomenon that u increases with ν is essentially that increasing of ν breaks the Taylor-Proudman constraint and drops the critical Rayleigh number, and thus u increases under the same thermal driving force. Forces balance is analyzed and balance mode shifts with variation of ν. When compared with former studies of scaling laws, this study supports the conclusion that in a certain parameter range, the magnetic field strength doesn't vary much with the viscosity, but opposes to the assumption that the velocity field has nothing to do with the outer core viscosity.
Complementary high performance sensing of gases and liquids using silver nanotube
NASA Astrophysics Data System (ADS)
Isro, Suhandoko D.; Iskandar, Alexander A.; Tjia, May-On
2017-11-01
A study on refractive index sensing using a silver nanotube is carried out to investigate the relative advantages of sensing gaseous and liquid samples outside the tube (outer sensing) and inside the core (inner sensing). The geometrical and material parameters of the nanotube are varied to explore the favorable sensing performances covering the range of refractive indices between 1.1 and 1.5. It is shown that the performances at the three sensing points considered are consistently improved with decreased shell thickness and core radius in both sensing modes. While the performance is also monotonously and drastically enhanced with decreased counter permittivity in inner sensing, the similarly large variations in the outer sensing mode are less than strictly consistent. The study further shows that the most favorable FOM values are attained by both sensing modes with 2.5 nm Ag shell thickness and 27.5 nm core radius of the nanotube, whereas the most favorable counter permittivities are different for the two modes. Remarkably, the trend of increasing FOM for samples of lower refractive indices in outer sensing is entirely reversed in inner sensing with roughly the same level of performances. Thus, the core/shell structure of the silver nanotube offers the complementary high performance sensing of gases and liquids using the two sensing modes with appropriately chosen system parameters.
Sayell, E.H.
1973-10-23
A radioisotopic heat source is described which includes a core of heat productive, radioisotopic material, an impact resistant layer of graphite surrounding said core, and a shell of iridium metal intermediate the core and the impact layer. The source may also include a compliant mat of iridium between the core and the iridium shell, as well as an outer covering of iridium metal about the entire heat source. (Official Gazette)
Probing the Structure near the Top of the Earth's Outer Core Using SmKS Traveltimes
NASA Astrophysics Data System (ADS)
Tang, V. C.; Zhao, L.; Hung, S.
2013-12-01
The Earth's solid inner core is composed of heavy Fe and Ni with a fraction of light elements such as O, S, Si. These light elements were expelled from the inner core during its formation and rise up through the outer core as the result of buoyancy, but their existence is still a mystery. Some authors have presented seismological evidence for lowered wave speed beneath the core-mantle boundary (CMB) relative to PREM, suggesting light elements there, but counter argument also exists. In this study, we use traveltime measurements from recorded and modeled SmKS waves to investigate the effect of the velocity under the CMB on the differential traveltimes between SKKS and S3KS waves (TS3KS-TSKKS). Due to the long propagation distance and interference with neighboring phases, the arrival times of SKKS and S3KS waves are difficult to define accurately in the records. Therefore in our analysis we measure both the observed and model-predicted differential traveltime TS3KS-TSKKS by cross-correlating the waveform of Hilbert-transformed S3KS with that of SKKS. We use synthetic seismograms calculated by the Direct-Solution Method (DSM) in a suite of 1D models with different structural profiles under the CMB to examine the existence of a zone of lowered velocity at the top of the outer core. We are conducting a systematic investigation using waveforms available at IRIS from globally distributed large deep earthquakes. Results from events we have processed so far indicate that the velocity under the CMB is slightly slower than that in PREM.
Rosciszewski, Gerardo; Cadena, Vanesa; Murta, Veronica; Lukin, Jeronimo; Villarreal, Alejandro; Roger, Thierry; Ramos, Alberto Javier
2018-05-01
Astrocytes react to brain injury with a generic response known as reactive gliosis, which involves activation of multiple intracellular pathways including several that may be beneficial for neuronal survival. However, by unknown mechanisms, reactive astrocytes can polarize into a proinflammatory phenotype that induces neurodegeneration. In order to study reactive gliosis and astroglial polarization into a proinflammatory phenotype, we used cortical devascularization-induced brain ischemia in Wistar rats and primary astroglial cell cultures exposed to oxygen-glucose deprivation (OGD). We analyzed the profile of TLR4 expression and the consequences of its activation by gain- and loss-of-function studies, and the effects produced by the activation of triggering receptor expressed on myeloid cells-2 (TREM-2), a negative regulator of TLR4 signaling. Both OGD exposure on primary astroglial cell cultures and cortical devascularization brain ischemia in rats induced TLR4 expression in astrocytes. In vivo, astroglial TLR4 expression was specifically observed in the ischemic penumbra surrounding necrotic core. Functional studies showed that OGD increased the astroglial response to the TLR4 agonist lipopolysaccharide (LPS), and conversely, TLR4 knockout primary astrocytes had impaired nuclear factor kappa-B (NF-κB) activation when exposed to LPS. In gain-of-function studies, plasmid-mediated TLR4 over-expression exacerbated astroglial response to LPS as shown by sustained NF-κB activation and increased expression of proinflammatory cytokines IL-1β and TNFα. TREM-2 expression, although present in naïve primary astrocytes, was induced by OGD, LPS, or high-mobility group box 1 protein (HMGB-1) exposure. TREM-2 activation by antibody cross-linking or the overexpression of TREM-2 intracellular adaptor, DAP12, partially suppressed LPS-induced NF-κB activation in purified astrocytic cultures. In vivo, TREM-2 expression was observed in macrophages and astrocytes located in the ischemic penumbra. While TREM-2+ macrophages were abundant at 3 days post-lesion (DPL) in the ischemic core, TREM-2+ astrocytes persisted in the penumbra until 14DPL. This study demonstrates that TLR4 expression increases astroglial sensitivity to ligands facilitating astrocyte conversion towards a proinflammatory phenotype, and that astroglial TREM-2 modulates this response reducing the downstream NF-κB activation. Therefore, the availability of TLR4 and TREM-2 ligands in the ischemic environment may control proinflammatory astroglial conversion to the neurodegenerative phenotype.
Electrophoretic manipulation of multiple-emulsion droplets
NASA Astrophysics Data System (ADS)
Schoeler, Andreas M.; Josephides, Dimitris N.; Chaurasia, Ankur S.; Sajjadi, Shahriar; Mesquida, Patrick
2014-02-01
Electrophoretic manipulation of multiple-emulsion oil-in-water-in-oil (O/W)/O and water-in-oil-in-water-in-oil (W/O/W)/O core-shell droplets is shown. It was found that the electrophoretic mobility of the droplets is determined solely by the outer water shell, regardless of size or composition of the inner droplets. It was observed that the surface charge of the outer water shell can be changed and the polarity can be reversed through contact with a biased electrode in a similar way as with simple W/O droplets. Furthermore, addition of the anionic surfactant, sodium dodecyl sulfate to the outer water shell reverses the initial polarity and hence, electrophoretic mobility of the core-shell droplets before contact with an electrode. The results have practical implications for the manipulation of oil droplets in a continuous oil phase.
Atmospheric Mining in the Outer Solar System: Resource Capturing, Storage, and Utilization
NASA Technical Reports Server (NTRS)
Palaszewski, Bryan
2014-01-01
Atmospheric mining in the outer solar system has been investigated as a means of fuel production for high energy propulsion and power. Fusion fuels such as helium 3 and hydrogen can be wrested from the atmospheres of Uranus and Neptune and either returned to Earth or used in-situ for energy production. Helium 3 and hydrogen (deuterium, etc.) were the primary gases of interest with hydrogen being the primary propellant for nuclear thermal solid core and gas core rocket-based atmospheric flight. A series of analyses were undertaken to investigate resource capturing aspects of atmospheric mining in the outer solar system. This included the gas capturing rate for hydrogen helium 4 and helium 3, storage options, and different methods of direct use of the captured gases. Additional supporting analyses were conducted to illuminate vehicle sizing and orbital transportation issues.
Hmama, Z; Mey, A; Normier, G; Binz, H; Revillard, J P
1994-01-01
A water-soluble acylpolygalactosyl (APG) of 34 kDa was obtained from the Klebsiella pneumoniae membrane by alkaline hydrolysis and delipidation. APG comprises a poly(1,3)galactose chain, a core, and a lipid moiety made of a glucosamine disaccharide with two N-linked beta OH-myristates. The monocyte binding sites for APG were investigated by flow cytometry. Biotin-labelled APG (Biot-APG) bound to monocytes at 4 degrees C in the absence of serum, calcium, and magnesium. The binding was dose dependent, saturable, and displaced by unlabelled APG. Neither the polysaccharide chain present in APG-related molecules nor the PPi group or additional ester-linked myristates and palmitates were required for APG binding. The role of CD11b and CD14 was demonstrated by competitive inhibition with monoclonal antibodies and by the uptake of APG by these solubilized proteins. APG was rapidly internalized into monocytes at 37 degrees C while CD14 and CD11b/CD18 molecules were partially down-modulated. Lipopolysaccharides (LPS) from the same K. pneumoniae strain and from Escherichia coli and Salmonella minnesota partially competed for Biot-APG binding in the absence but not in the presence of serum. When altered by alkaline hydrolysis, those LPS became strong competitors for APG binding. It was concluded that alkaline hydrolysis of the K. pneumoniae membrane yielded molecules structurally related to LPS which bind to LPS membrane receptors in the absence of serum. Images PMID:7513300
Circular Dichroism studies on the interactions of antimicrobial peptides with bacterial cells
NASA Astrophysics Data System (ADS)
Avitabile, Concetta; D'Andrea, Luca Domenico; Romanelli, Alessandra
2014-03-01
Studying how antimicrobial peptides interact with bacterial cells is pivotal to understand their mechanism of action. In this paper we explored the use of Circular Dichroism to detect the secondary structure of two antimicrobial peptides, magainin 2 and cecropin A, with E. coli bacterial cells. The results of our studies allow us to gain two important information in the context of antimicrobial peptides- bacterial cells interactions: peptides fold mainly due to interaction with LPS, which is the main component of the Gram negative bacteria outer membrane and the time required for the folding on the bacterial cells depends on the peptide analyzed.
Kim, Bo-Mi; Jeong, Chang-Bum; Rhee, Jae-Sung; Lee, Jae-Seong
2014-02-01
The immune system and the role of immunity-related genes have rarely been studied in copepods, even though copepods have a primitive immune response system and also have a potential in pathogen transport higher trophic levels. In this study, we firstly cloned and characterized three core immune genes such as nuclear factor κB (NF-κB), inhibitor of NF-κB (IκB), and lipopolysaccharide-induced TNF-α factor (LITAF) genes in the intertidal copepod Tigriopus japonicus. Several in silico analyses based on conserved domains, motifs, and phylogenetic relationships were supporting their annotations. To investigate the immune-related role of three genes, we exposed lipopolysaccharide (LPS) and two Vibrio sp. to T. japonicus. After exposure of different concentrations of LPS and two Vibrio sp., transcripts of TJ-IκB and TJ-LITAF genes were significantly elevated during the time course in a dose-dependent manner, while TJ-NF-κB transcripts were not significantly changed during exposure. These findings demonstrated that the copepod T. japonicus has a conserved immunity against infection. Copyright © 2013 Elsevier Ltd. All rights reserved.
Multi-modality nanoparticles having optically responsive shape
Chen, Fanqing; Bouchard, Louis-Serge
2015-05-19
In certain embodiments novel nanoparticles (nanowontons) are provided that are suitable for multimodal imaging and/or therapy. In one embodiment, the nanoparticles include a first biocompatible (e.g., gold) layer, an inner core layer (e.g., a non-biocompatible material), and a biocompatible (e.g., gold) layer. The first gold layer includes a concave surface that forms a first outer surface of the layered nanoparticle. The second gold layer includes a convex surface that forms a second outer surface of the layered nanoparticle. The first and second gold layers encapsulate the inner core material layer. Methods of fabricating such nanoparticles are also provided.
Zhavoronok, I P; Molchanova, A Iu; Ulashik, V S
2012-01-01
The effects of ultrahigh-frequency electromagnetic radiation (UHF EMR) and low-intensity laser irradiation (LILI) on the body and skin temperature, oxygen consumption, production of carbon dioxide and heat release were investigated in the experiments on intact rats and during LPS-induced polyphasic fever. It was found that UHF EMR with the wavelength of 4,9 mm, 5,6 mm or 7,1 mm and LILI with the wavelength of 0.47 microm, 0.67 microm and 0.87 microm caused modulation of basal metabolism and thermal response to systemically administered lipopolysaccharide (LPS). These findings suggest that the most pronounced antipyretic and hypometabolic effects were observed after the treatment with UHF EMR at 7,1 mm and LILI at 470 microm.
Permanent-magnet switched-flux machine
Trzynadlowski, Andrzej M.; Qin, Ling
2011-06-14
A permanent-magnet switched-flux (PMSF) device has an outer rotor mounted to a shaft about a central axis extending axially through the PMSF device. First and second pluralities of permanent-magnets (PMs) are respectively mounted in first and second circles, radially outwardly in first and second transverse planes extending from first and second sections of the central axis adjacent to an inner surface of the outer rotor. An inner stator is coupled to the shaft and has i) a stator core having a core axis co-axial with the central axis; and ii) first and second pluralities of stator poles mounted in first and second circles, radially outwardly from the stator core axis in the first and second transverse planes. The first and second pluralities of PMs each include PMs of alternating polarity.
Permanent-magnet switched-flux machine
Trzynadlowski, Andrzej M.; Qin, Ling
2012-02-21
A permanent-magnet switched-flux (PMSF) device has an outer rotor mounted to a shaft about a central axis extending axially through the PMSF device. First and second pluralities of permanent-magnets (PMs) are respectively mounted in first and second circles, radially outwardly in first and second transverse planes extending from first and second sections of the central axis adjacent to an inner surface of the outer rotor. An inner stator is coupled to the shaft and has i) a stator core having a core axis co-axial with the central axis; and ii) first and second pluralities of stator poles mounted in first and second circles, radially outwardly from the stator core axis in the first and second transverse planes. The first and second pluralities of PMs each include PMs of alternating polarity.
Evolution of the Kdo2-lipid A Biosynthesis in Bacteria
DOE Office of Scientific and Technical Information (OSTI.GOV)
S Opiyo; R Pardy; H Moriyama
BACKGROUND: Lipid A is the highly immunoreactive endotoxic center of lipopolysaccharide (LPS). It anchors the LPS into the outer membrane of most Gram-negative bacteria. Lipid A can be recognized by animal cells, triggers defense-related responses, and causes Gram-negative sepsis. The biosynthesis of Kdo2-lipid A, the LPS substructure, involves with nine enzymatic steps. RESULTS: In order to elucidate the evolutionary pathway of Kdo2-lipid A biosynthesis, we examined the distribution of genes encoding the nine enzymes across bacteria. We found that not all Gram-negative bacteria have all nine enzymes. Some Gram-negative bacteria have no genes encoding these enzymes and others have genesmore » only for the first four enzymes (LpxA, LpxC, LpxD, and LpxB). Among the nine enzymes, five appeared to have arisen from three independent gene duplication events. Two of such events happened within the Proteobacteria lineage, followed by functional specialization of the duplicated genes and pathway optimization in these bacteria. CONCLUSIONS: The nine-enzyme pathway, which was established based on the studies mainly in Escherichia coli K12, appears to be the most derived and optimized form. It is found only in E. coli and related Proteobacteria. Simpler and probably less efficient pathways are found in other bacterial groups, with Kdo2-lipid A variants as the likely end products. The Kdo2-lipid A biosynthetic pathway exemplifies extremely plastic evolution of bacterial genomes, especially those of Proteobacteria, and how these mainly pathogenic bacteria have adapted to their environment.« less
Endotoxin, Toll-like Receptor-4, and Atherosclerotic Heart Disease
Horseman, Michael A.; Surani, Salim; Bowman, John D.
2017-01-01
Background: Endotoxin is a lipopolysaccharide (LPS) constituent of the outer membrane of most gram negative bacteria. Ubiquitous in the environment, it has been implicated as a cause or con-tributing factor in several disparate disorders from sepsis to heatstroke and Type II diabetes mellitus. Starting at birth, the innate immune system develops cellular defense mechanisms against environmen-tal microbes that are in part modulated through a series of receptors known as toll-like receptors. Endo-toxin, often referred to as LPS, binds to toll-like receptor 4 (TLR4)/ myeloid differentiation protein 2 (MD2) complexes on various tissues including cells of the innate immune system, smooth muscle and endothelial cells of blood vessels including coronary arteries, and adipose tissue. Entry of LPS into the systemic circulation ultimately leads to intracellular transcription of several inflammatory mediators. The subsequent inflammation has been implicated in the development and progression atherosclerosis and subsequent coronary artery disease and heart failure. Objective: The potential roles of endotoxin and TLR4 are reviewed regarding their role in the pathogen-esis of atherosclerotic heart disease. Conclusion: Atherosclerosis is initiated by inflammation in arterial endothelial and subendothelial cells, and inflammatory processes are implicated in its progression to clinical heart disease. Endotoxin and TLR4 play a central role in the inflammatory process, and represent potential targets for therapeutic intervention. Therapy with HMG-CoA inhibitors may reduce the expression of TLR4 on monocytes. Other therapeutic interventions targeting TLR4 expression or function may prove beneficial in athero-sclerotic disease prevention and treatment.
The rotational shear in pre-collapse cores of massive stars
NASA Astrophysics Data System (ADS)
Zilberman, Noa; Gilkis, Avishai; Soker, Noam
2018-02-01
We evolve stellar models to study the rotational profiles of the pre-explosion cores of single massive stars that are progenitors of core collapse supernovae (CCSNe), and find large rotational shear above the iron core that might play an important role in the jet feedback explosion mechanism by amplifying magnetic fields before and after collapse. Initial masses of 15 and 30 M⊙ and various values of the initial rotation velocity are considered, as well as a reduced mass-loss rate along the evolution and the effect of core-envelope coupling through magnetic fields. We find that the rotation profiles just before core collapse differ between models, but share the following properties. (1) There are narrow zones of very large rotational shear adjacent to convective zones. (2) The rotation rate of the inner core is slower than required to form a Keplerian accretion disc. (3) The outer part of the core and the envelope have non-negligible specific angular momentum compared to the last stable orbit around a black hole (BH). Our results suggest the feasibility of magnetic field amplification which might aid a jet-driven explosion leaving behind a neutron star. Alternatively, if the inner core fails in exploding the star, an accretion disc from the outer parts of the core might form and lead to a jet-driven CCSN which leaves behind a BH.
Melting-induced stratification above the Earth's inner core due to convective translation.
Alboussière, Thierry; Deguen, Renaud; Melzani, Mickaël
2010-08-05
In addition to its global North-South anisotropy, there are two other enigmatic seismological observations related to the Earth's inner core: asymmetry between its eastern and western hemispheres and the presence of a layer of reduced seismic velocity at the base of the outer core. This 250-km-thick layer has been interpreted as a stably stratified region of reduced composition in light elements. Here we show that this layer can be generated by simultaneous crystallization and melting at the surface of the inner core, and that a translational mode of thermal convection in the inner core can produce enough melting and crystallization on each hemisphere respectively for the dense layer to develop. The dynamical model we propose introduces a clear asymmetry between a melting and a crystallizing hemisphere which forms a basis for also explaining the East-West asymmetry. The present translation rate is found to be typically 100 million years for the inner core to be entirely renewed, which is one to two orders of magnitude faster than the growth rate of the inner core's radius. The resulting strong asymmetry of buoyancy flux caused by light elements is anticipated to have an impact on the dynamics of the outer core and on the geodynamo.
Rapid-quench axially staged combustor
Feitelberg, Alan S.; Schmidt, Mark Christopher; Goebel, Steven George
1999-01-01
A combustor cooperating with a compressor in driving a gas turbine includes a cylindrical outer combustor casing. A combustion liner, having an upstream rich section, a quench section and a downstream lean section, is disposed within the outer combustor casing defining a combustion chamber having at least a core quench region and an outer quench region. A first plurality of quench holes are disposed within the liner at the quench section having a first diameter to provide cooling jet penetration to the core region of the quench section of the combustion chamber. A second plurality of quench holes are disposed within the liner at the quench section having a second diameter to provide cooling jet penetration to the outer region of the quench section of the combustion chamber. In an alternative embodiment, the combustion chamber quench section further includes at least one middle region and at least a third plurality of quench holes disposed within the liner at the quench section having a third diameter to provide cooling jet penetration to at least one middle region of the quench section of the combustion chamber.
NASA Technical Reports Server (NTRS)
Ober, Daniel M.; Horwitz, J. L.
1998-01-01
We present initial results on the modeling of the circulation of plasmaspheric-origin plasma into the outer magnetosphere and low-latitude boundary layer (LLBL), using a dynamic global core plasma model (DGCPM). The DGCPM includes the influences of spatially and temporally varying convection and refilling processes to calculate the equatorial core plasma density distribution throughout the magnetosphere. We have developed an initial description of the electric and magnetic field structures in the outer magnetosphere region. The purpose of this paper is to examine both the losses of plasmaspheric-origin plasma into the magnetopause boundary layer and the convection of this plasma that remains trapped on closed magnetic field lines. For the LLBL electric and magnetic structures we have adopted here, the plasmaspheric plasma reaching the outer magnetosphere is diverted anti-sunward primarily along the dusk flank. These plasmas reach X= -15 R(sub E) in the LLBL approximately 3.2 hours after the initial enhancement of convection and continues to populate the LLBL for 12 hours as the convection electric field diminishes.
[Reptile-associated salmonellosis as an important epidemiological problem].
Pawlak, Aleksandra
2014-11-17
of food poisoning. One of the reservoirs of Salmonella are reptiles, which are increasingly kept as pets. Most reptiles are asymptomatic carriers of Salmonella. These strains, isolated from reptiles, can cause serious infections, especially in infants, young children and people with immunodeficiencies. The disease called reptile-associated salmonellosis (RAS) may manifest with bloody diarrhea, meningitis, and arthritis, and consequently can cause bacteremia and sepsis. Among the strains described in the literature, Salmonella strains possessing the O48 antigen are an important group. Lipopolysaccharide (LPS) of Salmonella O48 contains sialic acid (NeuAc) in an O-specific-chain. LPS containing NeuAc exhibits antigenic similarity to antigens found in the human body, including blood serum, and therefore is correlated with the occurrence of the dangerous phenomenon of molecular mimicry. Bacteria containing NeuAc in their outer structures can evade the immunological response of the host, which significantly increases their virulence. Most data about RAS come from the USA, but in recent years cases from European countries are more frequent in the literature. Unfortunately, the occurrence of RAS in Poland has not been monitored so far. There is also no campaign to inform the public about the health risks connected with contact of people with reptiles.
Atmospheric Mining in the Outer Solar System: Resource Capturing, Storage, and Utilization
NASA Technical Reports Server (NTRS)
Palaszewski, Bryan
2012-01-01
Atmospheric mining in the outer solar system has been investigated as a means of fuel production for high energy propulsion and power. Fusion fuels such as Helium 3 (3He) and hydrogen can be wrested from the atmospheres of Uranus and Neptune and either returned to Earth or used in-situ for energy production. Helium 3 and hydrogen (deuterium, etc.) were the primary gases of interest with hydrogen being the primary propellant for nuclear thermal solid core and gas core rocket-based atmospheric flight. A series of analyses were undertaken to investigate resource capturing aspects of atmospheric mining in the outer solar system. This included the gas capturing rate for hydrogen helium 4 and helium 3, storage options, and different methods of direct use of the captured gases. Additional supporting analyses were conducted to illuminate vehicle sizing and orbital transportation issues.
Ultra high performance connectors for power transmission applications
Wang, Jy-An; Ren, Fei; Lee, Dominic F; Jiang, Hao
2014-03-04
Disclosed are several examples of an apparatus for connecting the free ends of two electrical power transmission lines having conductor strands disposed around a central, reinforcing core. The examples include an inner sleeve having a body defining an inner bore passing through an axially-extending, central axis, an outer rim surface disposed radially outward from the central bore, and one or more axially-extending grooves penetrating the body at the outer rim surface. Also included is an outer splice having a tubular shaped body with a bore passing coaxially through the central axis, the bore defining an inner rim surface for accepting the inner sleeve. The inner bore of the inner sleeve accepts the reinforcement cores of the two conductors, and the grooves accept the conductor strands in an overlapping configuration so that a majority of the electrical current flows between the overlapped conductor strands when the conductors are transmitting electrical current.
A Large Solid Inner Core at Mercury
NASA Astrophysics Data System (ADS)
Genova, A.; Goossens, S.; Mazarico, E.; Lemoine, F. G.; Neumann, G. A.; Kuang, W.; Sabaka, T. J.; Smith, D. E.; Zuber, M. T.
2018-05-01
New measurements of the polar moments of inertia of the whole planet and of the outer layers (crust+mantle), and simulations of Mercury’s magnetic field dynamo suggest the presence of a solid inner core with a Ric 0.3-0.5 Roc.
NASA Astrophysics Data System (ADS)
Ozawa, H.; Hirose, K.
2010-12-01
Element partitioning between molten iron and mantle minerals was investigated to 146 GPa by a combination of laser-heated diamond-anvil cell and analytical transmission electron microscope. The chemical compositions of co-existing quenched molten iron and (Mg,Fe)SiO3 perovskite/ferropericlase were determined quantitatively with energy-dispersive X-ray spectrometry and electron energy loss spectroscopy. The results demonstrate that the oxygen solubility in liquid iron co-existing with ferropericlase decreases with pressure to 38 GPa and, whereas the pressure effect is small at higher pressures. It was also revealed that the quenched liquid iron in contact with perovskite contained substantial amounts of oxygen and silicon at the core-mantle boundary (CMB) pressure. The chemical equilibrium between perovskite, ferropericlase, and molten iron at the P-T conditions of the CMB was calculated in Mg-Fe-Si-O system from these experimental results. Note that perovskite is a predominant phase instead of post-perovskite above 3500 K at the CMB pressure. We found that molten iron should include oxygen and silicon more than required to account for the core density deficit of below 10% when co-existing with both perovskite and ferropericlase at the CMB. This suggests that the bulk outer core liquid with <10% density deficit is not in direct contact with the mantle. Dissolutions of light elements from the mantle can produce a gravitationally stratified liquid layer at the topmost outer core, which can be responsible for the low-P wave velocity layer observed there. Such layer physically separates the mantle from the bulk outer core liquid, hindering the chemical reaction between them.
Electrically operated magnetic switch designed to display reduced leakage inductance
Cook, E.G.
1994-05-10
An electrically operated magnetic switch is disclosed herein for use in opening and closing a circuit between two terminals depending upon the voltage across these terminals. The switch so disclosed is comprised of a ferrite core in the shape of a toroid having opposing ends and opposite inner and outer sides and an arrangement of electrically conductive components defining at least one current flow path which makes a number of turns around the core. This arrangement of components includes a first plurality of electrically conducive rigid rods parallel with and located outside the outer side of the core and a second plurality of electrically conductive rigid rods parallel with and located inside the inner side of the core. The arrangement also includes means for electrically connecting these rods together so that the define the current flow path. In one embodiment, this latter means uses rigid cross-tab means. In another, preferred embodiment, printed circuits on rigid dielectric substrates located on opposite ends of the core are utilized to interconnect the rods together. 10 figures.
NASA Technical Reports Server (NTRS)
Williams, Quentin; Jeanloz, Raymond
1990-01-01
The melting temperatures of FeS-troilite and of a 10-wt-pct sulfur iron alloy have been measured to pressures of 120 and 90 GPa, respectively. The results document that FeS melts at a temperature of 4100 (+ or - 300) K at the pressure of the core-mantle boundary. Eutecticlike behavior persists in the iron-sulfur system to the highest pressures of measurements, in marked contrast to the solid-solutionlike behavior observed at high pressures in the iron-iron oxide system. Iron with 10-wt-pct sulfur melts at a similar temperature as FeS at core-mantle boundary conditions. If the sole alloying elements of iron within the core are sulfur and oxygen and the outer core is entirely liquid, the minimum temperature at the top of the outer core is 4900 (+ or - 400) K. Calculations of mantle geotherms dictate that there must be a temperature increase of between 1000 and 2000 K across thermal boundary layers within the mantle. If D-double-prime is compositionally stratified, it could accommodate the bulk of this temperature jump.
The Density Jump at the Inner Core Boundary in the Eastern and Western Hemispheres
NASA Astrophysics Data System (ADS)
Krasnoshchekov, D. N.; Ovtchinnikov, V. M.
2018-02-01
The results of analysis of more than 1300 new PKiKP/PcP amplitude ratios measured in Southeast Asia and South America at the epicentral distances of 3.2°-35.2° are presented. The density jump in the Eastern Hemisphere of the Earth's inner core (IC) is 0.3 g/cm3, and it is 0.9 g/cm3 in the Western one. Taking the large discrepancy in the obtained estimates into consideration, maintenance of such large lateral variations in the mosaic properties of the IC reflecting surface requires considerable variations in the thermodynamic parameters (mostly temperature) of the inner-outer core transition. However, if the observed asymmetry in the density jump distribution is of a global character, the data presented support the translation model of the IC dynamics. This model implies IC crystallization in the Western Hemisphere and melting in the Eastern one, not vice versa, as suggested by another geodynamic model based on thermochemical convection in the outer core and the thermal balance of the core-mantle system.
Origin of the Earth's Electromagnetic Field Based on the Pulsating Mantle Hypothesis (PMH)
NASA Astrophysics Data System (ADS)
Gholibeigian, Hassan
2017-11-01
In PMH, the Earth's Inner Core's Dislocation (ICD) and Outer Core's Bulge (OCB) phenomena are generated by unbalanced gravitational fields of the Sun and Moon on the Earth. Distance between the Earth's center and inner core's center varies permanently in magnitude and direction inside two hemispheres. Geometrical loci of the inner core's center has the shape of back and force spiral cone in each hemisphere. In other words, the inner core is rotating fast in the outer core inverse of the Earth's rotation a round per day. This mechanism speed up the processes inside the core and generates a Large Scale Forced Convection System (LSFCS) inverse of the Earth's rotation in the core. The LSFCS is the origin of the Earth's electromagnetic field. The LSFCS generates huge mass transfer and momentum of inertia inside the Earth too. The inner core's axis which is the Earth's electromagnetic axis doesn't cross the Earth's geophysical axis and rotates around it per day. The mechanism of this LSFCS has diurnal, monthly and yearly cycles. These cycles are sources of the Earth's electromagnetic field variability. Direction of the variable Earth's magnetic field lines from the South Pole (hemisphere) to the sky and 146 seconds/years apparent solar day length variations can be two observable factors for this mechanism. This dynamic system may occurred inside the other planets like the Sun and the Jupiter.
Geochemical Constraints on Core-Mantle Interaction from Fe/Mn Ratios
NASA Astrophysics Data System (ADS)
Humayun, M.; Qin, L.
2003-12-01
The greater density of liquid iron alloy, and its immiscibility with silicate, maintains the physical separation of the core from the mantle. There are no a priori reasons, however, why the Earth's mantle should be chemically isolated from the core. Osmium isotopic variations in mantle plumes have been interpreted in terms of interaction between outer core and the source regions of deep mantle plumes. If chemical transport occurs across the core-mantle boundary its mechanism remains to be established. The Os isotope evidence has also been interpreted as the signatures of subducted Mn-sediments, which are known to have relatively high Pt/Os. In the mantle, Fe occurs mainly as the divalent ferrous ion, and Mn occurs solely as a divalent ion, and both behave in a geochemically coherent manner because of similarity in ionic charge and radius. Thus, the Fe/Mn ratio is a planetary constant insensitive to processes of mantle differentiation by partial melting. Two processes may perturb the ambient mantle Fe/Mn of 60: a) the subduction of Mn-sediments should decrease the Fe/Mn ratio in plume sources, while b) chemical transport from the outer core may increase the Fe/Mn ratio. The differentiation of the liquid outer core to form the solid inner core may increase abundances of the light element constituents (FeS, FeO, etc.) to the point of exsolution from the core at the CMB. The exact rate of this process is determined by the rate of inner core growth. Two end-member models include 1) inner core formation mainly prior to 3.5 Ga with heat release dominated by radioactive sources, or 2) inner core formation occurring mainly in the last 1.5 Ga with heat release dominated by latent heat. This latter model would imply large fluxes of Fe into the sources of modern mantle plumes. Existing Fe/Mn data for Gorgona and Hawaiian samples place limits on both these processes. We describe a new procedure for the precise determination of the Fe/Mn ratio in magmatic rocks by ICP-MS. This high-resolution study of the Fe/Mn of mantle-derived samples offers a new set of chemical constraints on the rates of inner core differentiation and the viability of Os isotope interpretations.
Jacob, Shery; Nair, Anroop B; Patil, Pandurang N
2010-01-01
An inert hydrophobic buoyant coated–core was developed as floating drug delivery system (FDDS) for sustained release of cisapride using direct compression technology. Core contained low density, porous ethyl cellulose, which was coated with an impermeable, insoluble hydrophobic coating polymer such as rosin. It was further seal coated with low viscosity hydroxypropyl methyl cellulose (HPMC E15) to minimize moisture permeation and better adhesion with an outer drug layer. It was found that stable buoyant core was sufficient to float the tablet more than 8 h without the aid of sodium bicarbonate and citric acid. Sustained release of cisapride was achieved with HPMC K4M in the outer drug layer. The floating lag time required for these novel FDDS was found to be zero, however it is likely that the porosity or density of the core is critical for floatability of these tablets. The in vitro release pattern of these tablets in simulated gastric fluid showed the constant and controlled release for prolonged time. It can be concluded that the hydrophobic coated buoyant core could be used as FDDS for gastroretentive delivery system of cisapride or other suitable drugs. PMID:24825997
Method for manufacturing magnetohydrodynamic electrodes
Killpatrick, D.H.; Thresh, H.R.
1980-06-24
A method of manufacturing electrodes for use in a magnetohydrodynamic (MHD) generator is described comprising the steps of preparing a billet having a core of a first metal, a tubular sleeve of a second metal, and an outer sheath of an extrusile metal; evacuating the space between the parts of the assembled billet; extruding the billet; and removing the outer jacket. The extruded bar may be made into electrodes by cutting and bending to the shape required for an MHD channel frame. The method forms a bond between the first metal of the core and the second metal of the sleeve strong enough to withstand a hot and corrosive environment.
Scintillator reflective layer coextrusion
Yun, Jae-Chul; Para, Adam
2001-01-01
A polymeric scintillator has a reflective layer adhered to the exterior surface thereof. The reflective layer comprises a reflective pigment and an adhesive binder. The adhesive binder includes polymeric material from which the scintillator is formed. A method of forming the polymeric scintillator having a reflective layer adhered to the exterior surface thereof is also provided. The method includes the steps of (a) extruding an inner core member from a first amount of polymeric scintillator material, and (b) coextruding an outer reflective layer on the exterior surface of the inner core member. The outer reflective layer comprises a reflective pigment and a second amount of the polymeric scintillator material.
Bedini, Emiliano; Cirillo, Luigi; Parrilli, Michelangelo
2012-02-15
The synthesis of β-Gal-(1→3)-α-GalNAc-(1→3)-β-GalNAc allyl trisaccharide as the outer core fragment of Burkholderia cepacia pv. vietnamiensis lipooligosaccharide was accomplished through a concise, optimized, multi-step synthesis, having as key steps three glycosylations, that were in-depth studied performing them under several conditions. The target trisaccharide was designed with an allyl aglycone in order to open a future access to the conjugation with an immunogenic protein en route to the development of a synthetic neoglycoconjugate vaccine against this Burkholderia pathogen. Copyright © 2011 Elsevier Ltd. All rights reserved.
High-Pressure Geophysical Properties of Fcc Phase FeHX
NASA Astrophysics Data System (ADS)
Thompson, E. C.; Davis, A. H.; Bi, W.; Zhao, J.; Alp, E. E.; Zhang, D.; Greenberg, E.; Prakapenka, V. B.; Campbell, A. J.
2018-01-01
Face centered cubic (fcc) FeHX was synthesized at pressures of 18-68 GPa and temperatures exceeding 1,500 K. Thermally quenched samples were evaluated using synchrotron X-ray diffraction (XRD) and nuclear resonant inelastic X-ray scattering (NRIXS) to determine sample composition and sound velocities to 82 GPa. To aid in the interpretation of nonideal (X ≠ 1) stoichiometries, two equations of state for fcc FeHX were developed, combining an empirical equation of state for iron with two distinct synthetic compression curves for interstitial hydrogen. Matching the density deficit of the Earth's core using these equations of state requires 0.8-1.1 wt % hydrogen at the core-mantle boundary and 0.2-0.3 wt % hydrogen at the interface of the inner and outer cores. Furthermore, a comparison of Preliminary Reference Earth Model (PREM) to a Birch's law extrapolation of our experimental results suggests that an iron alloy containing ˜0.8-1.3 wt % hydrogen could reproduce both the density and compressional velocity (VP) of the Earth's outer core.
NASA Technical Reports Server (NTRS)
Wahr, J. M.; Sasao, T.
1981-01-01
The effects of the oceans, which are subject to a resonance due to a free rotational eigenmode of an elliptical, rotating earth with a fluid outer core having an eigenfrequency of (1 + 1/460) cycle/day, on the body tide and nutational response of the earth to the diurnal luni-tidal force are computed. The response of an elastic, rotating, elliptical, oceanless earth with a fluid outer core to a given load distribution on its surface is first considered, and the tidal sea level height for equilibrium and nonequilibrium oceans is examined. Computations of the effects of equilibrium and nonequilibrium oceans on the nutational and deformational responses of the earth are then presented which show small but significant perturbations to the retrograde 18.6-year and prograde six-month nutations, and more important effects on the earth body tide, which is also resonant at the free core notation eigenfrequency.
Thick-shell nanocrystal quantum dots
Hollingsworth, Jennifer A [Los Alamos, NM; Chen, Yongfen [Eugene, OR; Klimov, Victor I [Los Alamos, NM; Htoon, Han [Los Alamos, NM; Vela, Javier [Los Alamos, NM
2011-05-03
Colloidal nanocrystal quantum dots comprising an inner core having an average diameter of at least 1.5 nm and an outer shell, where said outer shell comprises multiple monolayers, wherein at least 30% of the quantum dots have an on-time fraction of 0.80 or greater under continuous excitation conditions for a period of time of at least 10 minutes.
DOE Office of Scientific and Technical Information (OSTI.GOV)
G. S. Chang
2007-09-01
The Advanced Test Reactor (ATR) is a high power density and high neutron flux research reactor operating in the United States. Powered with highly enriched uranium (HEU), the ATR has a maximum thermal power rating of 250 MWth. Because of the large test volumes located in high flux areas, the ATR is an ideal candidate for assessing the feasibility of converting an HEU driven reactor to a low-enriched core. The present work investigates the necessary modifications and evaluates the subsequent operating effects of this conversion. A detailed plate-by-plate MCNP ATR 1/8th core model was developed and validated for a fuelmore » cycle burnup comparison analysis. Using the current HEU U 235 enrichment of 93.0 % as a baseline, an analysis can be performed to determine the low-enriched uranium (LEU) density and U-235 enrichment required in the fuel meat to yield an equivalent K-eff between the HEU core and the LEU core versus effective full power days (EFPD). The MCNP ATR 1/8th core model will be used to optimize the U-235 loading in the LEU core, such that the differences in K-eff and heat flux profile between the HEU and LEU core can be minimized. The depletion methodology MCWO was used to calculate K-eff versus EFPDs in this paper. The MCWO-calculated results for the LEU cases with foil (U-10Mo) types demonstrated adequate excess reactivity such that the K-eff versus EFPDs plot is similar to the reference ATR HEU case. Each HEU fuel element contains 19 fuel plates with a fuel meat thickness of 0.508 mm. In this work, the proposed LEU (U-10Mo) core conversion case with a nominal fuel meat thickness of 0.508 mm and the same U-235 enrichment (15.5 wt%) can be used to optimize the radial heat flux profile by varying the fuel plate thickness from 0.254 to 0.457 mm at the inner 4 fuel plates (1-4) and outer 4 fuel plates (16-19). In addition, a 0.7g of burnable absorber Boron-10 was added in the inner and outer plates to reduce the initial excess reactivity, and the inner/outer heat flux more effectively. The optimized LEU relative radial fission heat flux profile is bounded by the reference ATR HEU case. However, to demonstrate that the LEU core fuel cycle performance can meet the Updated Final Safety Analysis Report (UFSAR) safety requirements, additional studies will be necessary to evaluate and compare safety parameters such as void reactivity and Doppler coefficients, control components worth (outer shim control cylinders, safety rods and regulating rod), and shutdown margins between the HEU and LEU cores.« less
Hathroubi, S.; Hancock, M. A.; Langford, P. R.; Tremblay, Y. D. N.; Labrie, J.
2015-01-01
Actinobacillus pleuropneumoniae is a Gram-negative bacterium belonging to the Pasteurellaceae family and the causative agent of porcine pleuropneumonia, a highly contagious lung disease causing important economic losses. Surface polysaccharides, including lipopolysaccharides (LPS) and capsular polysaccharides (CPS), are implicated in the adhesion and virulence of A. pleuropneumoniae, but their role in biofilm formation is still unclear. In this study, we investigated the requirement for these surface polysaccharides in biofilm formation by A. pleuropneumoniae serotype 1. Well-characterized mutants were used: an O-antigen LPS mutant, a truncated core LPS mutant with an intact O antigen, a capsule mutant, and a poly-N-acetylglucosamine (PGA) mutant. We compared the amount of biofilm produced by the parental strain and the isogenic mutants using static and dynamic systems. Compared to the findings for the biofilm of the parental or other strains, the biofilm of the O antigen and the PGA mutants was dramatically reduced, and it had less cell-associated PGA. Real-time PCR analyses revealed a significant reduction in the level of pgaA, cpxR, and cpxA mRNA in the biofilm cells of the O-antigen mutant compared to that in the biofilm cells of the parental strain. Specific binding between PGA and LPS was consistently detected by surface plasmon resonance, but the lack of O antigen did not abolish these interactions. In conclusion, the absence of the O antigen reduces the ability of A. pleuropneumoniae to form a biofilm, and this is associated with the reduced expression and production of PGA. PMID:26483403
Engler, Harald; Benson, Sven; Wegner, Alexander; Spreitzer, Ingo; Schedlowski, Manfred; Elsenbruch, Sigrid
2016-02-01
Impaired mood and increased anxiety represent core symptoms of sickness behavior that are thought to be mediated by pro-inflammatory cytokines. Moreover, excessive inflammation seems to be implicated in the development of mood/affective disorders. Although women are known to mount stronger pro-inflammatory responses during infections and are at higher risk to develop depressive and anxiety disorders compared to men, experimental studies on sex differences in sickness symptoms are scarce. Thus, the present study aimed at comparing physiological and psychological responses to endotoxin administration between men and women. Twenty-eight healthy volunteers (14 men, 14 women) were intravenously injected with a low dose (0.4 ng/kg) of lipopolysaccharide (LPS) and plasma concentrations of cytokines and neuroendocrine factors as well as negative state emotions were measured before and until six hours after LPS administration. Women exhibited a more profound pro-inflammatory response with significantly higher increases in tumor necrosis factor (TNF)-α and interleukin (IL)-6. In contrast, the LPS-induced increase in anti-inflammatory IL-10 was significantly higher in men. The cytokine alterations were accompanied by changes in neuroendocrine factors known to be involved in inflammation regulation. Endotoxin injection induced a significant increase in noradrenaline, without evidence for sex differences. The LPS-induced increase in cortisol was significantly higher in woman, whereas changes in dehydroepiandrosterone were largely comparable. LPS administration also increased secretion of prolactin, but only in women. Despite these profound sex differences in inflammatory and neuroendocrine responses, men and women did not differ in endotoxin-induced alterations in mood and state anxiety or non-specific sickness symptoms. This suggests that compensatory mechanisms exist that counteract the more pronounced inflammatory response in women, preventing an exaggerated sickness response. Disturbance of these compensatory mechanisms by environmental factors such as stress may promote the development of affective disorders in women. Copyright © 2015 Elsevier Inc. All rights reserved.
Cyclooxygenase-2 mediates the febrile response of mice to interleukin-1beta.
Li, S; Ballou, L R; Morham, S G; Blatteis, C M
2001-08-10
Various lines of evidence have implicated cyclooxygenase (COX)-2 as a modulator of the fever induced by the exogenous pyrogen lipopolysaccharide (LPS). Thus, treatment with specific inhibitors of COX-2 suppresses the febrile response without affecting basal body (core) temperature (T(c)). Furthermore, COX-2 gene-ablated mice are unable to develop a febrile response to intraperitoneal (i.p.) LPS, whereas their COX-1-deficient counterparts produce fevers not different from their wild-type (WT) controls. To extend the apparently critical role of COX-2 for LPS-induced fevers to fevers produced by endogenous pyrogens, we studied the thermal responses of COX-1- and COX-2 congenitally deficient mice to i.p. and intracerebroventricular (i.c.v.) injections of recombinant murine (rm) interleukin (IL)-1beta. We also assessed the effects of one selective COX-1 inhibitor, SC-560, and two selective COX-2 inhibitors, nimesulide (NIM) and dimethylfuranone (DFU), on the febrile responses of WT and COX-1(-/-) mice to LPS and rmIL-1beta, i.p. Finally, we verified the integrity of the animals' responses to PGE2, i.c.v. I.p. and i.c.v. rmIL-1beta induced similar fevers in WT and COX-1 knockout mice, but provoked no rise in the T(c)s of COX-2 null mutants. The fever produced in WT mice by i.p. LPS was not affected by SC-560, but it was attenuated and abolished by NIM and DFU, respectively, while that caused by i.p. rmIL-1beta was converted into a T(c) fall by DFU. There were no differences in the responses to i.c.v. PGE2 among the WT and COX knockout mice. These results, therefore, further support the notion that the production of PGE2 in response to pyrogens is critically dependent on COX-2 expression.
Lukasiewicz, Jolanta; Dzieciatkowska, Monika; Niedziela, Tomasz; Jachymek, Wojciech; Augustyniuk, Anna; Kenne, Lennart; Lugowski, Czeslaw
2006-09-05
Plesiomonas shigelloides is a Gram-negative bacterium associated with waterborne infections, which is common in tropical and subtropical habitats. Contrary to the unified antigenic classification of P. shigelloides, data concerning the structure and activity of their lipopolysaccharides (LPS and endotoxin) are limited. This study completes the structural investigation of phenol- and water-soluble fractions of P. shigelloides O74 (strain CNCTC 144/92) LPS with the emphasis on lipid A heterogeneity, describing the entire molecule and some of its biological in vitro activities. Structures of the lipid A and the affinity-purified decasaccharide obtained by de-N,O-acylation of P. shigelloides O74 LPS were elucidated by chemical analysis combined with electrospray ionization multiple-stage mass spectrometry (ESI-MS(n)), MALDI-TOF MS, and NMR spectroscopy. Lipid A of P. shigelloides O74 is heterogeneous, and three major forms have been identified. They all were asymmetric, phosphorylated, and hexaacylated, showing different acylation patterns. The beta-GlcpN4P-(1-->6)-alpha-GlcpN1P disaccharide was substituted with the primary fatty acids: (R)-3-hydroxytetradecanoic acid [14:0(3-OH)] at N-2 and N-2' and (R)-3-hydroxydodecanoic acid [12:0(3-OH)] at O-3 and O-3'. The heterogeneity among the three forms (I-III) of P. shigelloides O74 lipid A was attributed to the substitution of the acyl residues at N-2' and O-3' with the secondary acyls: (I) cis-9-hexadecenoic acid (9c-16:1) at N-2' and 12:0 at O-3', (II) 14:0 at N-2' and 12:0 at O-3', and (III) 12:0 at N-2' and 12:0 at O-3'. The pro-inflammatory cytokine-inducing activities of P. shigelloides O74 LPS were similar to those of Escherichia coli O55 LPS.
Suspended core subwavelength fibers: towards practical designs for low-loss terahertz guidance.
Rozé, Mathieu; Ung, Bora; Mazhorova, Anna; Walther, Markus; Skorobogatiy, Maksim
2011-05-09
In this work we report two designs of subwavelength fibers packaged for practical terahertz wave guiding. We describe fabrication, modeling and characterization of microstructured polymer fibers featuring a subwavelength-size core suspended in the middle of a large porous outer cladding. This design allows convenient handling of the subwavelength fibers without distorting their modal profile. Additionally, the air-tight porous cladding serves as a natural enclosure for the fiber core, thus avoiding the need for a bulky external enclosure for humidity-purged atmosphere. Fibers of 5 mm and 3 mm in outer diameters with a 150 µm suspended solid core and a 900 µm suspended porous core respectively, were obtained by utilizing a combination of drilling and stacking techniques. Characterization of the fiber optical properties and the subwavelength imaging of the guided modes were performed using a terahertz near-field microscopy setup. Near-field imaging of the modal profiles at the fiber output confirmed the effectively single-mode behavior of such waveguides. The suspended core fibers exhibit transmission from 0.10 THz to 0.27 THz (larger core), and from 0.25 THz to 0.51 THz (smaller core). Due to the large fraction of power that is guided in the holey cladding, fiber propagation losses as low as 0.02 cm(-1) are demonstrated specifically for the small core fiber. Low-loss guidance combined with the core isolated from environmental perturbations make these all-dielectric fibers suitable for practical terahertz imaging and sensing applications. © 2011 Optical Society of America
Sulfur in Earth's Mantle and Its Behavior During Core Formation
NASA Technical Reports Server (NTRS)
Chabot, Nancy L.; Righter,Kevin
2006-01-01
The density of Earth's outer core requires that about 5-10% of the outer core be composed of elements lighter than Fe-Ni; proposed choices for the "light element" component of Earth's core include H, C, O, Si, S, and combinations of these elements [e.g. 1]. Though samples of Earth's core are not available, mantle samples contain elemental signatures left behind from the formation of Earth's core. The abundances of siderophile (metal-loving) elements in Earth's mantle have been used to gain insight into the early accretion and differentiation history of Earth, the process by which the core and mantle formed, and the composition of the core [e.g. 2-4]. Similarly, the abundance of potential light elements in Earth's mantle could also provide constraints on Earth's evolution and core composition. The S abundance in Earth's mantle is 250 ( 50) ppm [5]. It has been suggested that 250 ppm S is too high to be due to equilibrium core formation in a high pressure, high temperature magma ocean on early Earth and that the addition of S to the mantle from the subsequent accretion of a late veneer is consequently required [6]. However, this earlier work of Li and Agee [6] did not parameterize the metalsilicate partitioning behavior of S as a function of thermodynamic variables, limiting the different pressure and temperature conditions during core formation that could be explored. Here, the question of explaining the mantle abundance of S is revisited, through parameterizing existing metal-silicate partitioning data for S and applying the parameterization to core formation in Earth.
Electrocatalysts having gold monolayers on platinum nanoparticle cores, and uses thereof
Adzic, Radoslav; Zhang, Junliang
2010-04-27
The invention relates to gold-coated particles useful as fuel cell electrocatalysts. The particles are composed of an electrocatalytically active core at least partially encapsulated by an outer shell of gold or gold alloy. The invention more particularly relates to such particles having a noble metal-containing core, and more particularly, a platinum or platinum alloy core. In other embodiments, the invention relates to fuel cells containing these electrocatalysts and methods for generating electrical energy therefrom.
A core handling device for the Mars Sample Return Mission
NASA Technical Reports Server (NTRS)
Gwynne, Owen
1989-01-01
A core handling device for use on Mars is being designed. To provide a context for the design study, it was assumed that a Mars Rover/Sample Return (MRSR) Mission would have the following characteristics: a year or more in length; visits by the rover to 50 or more sites; 100 or more meter-long cores being drilled by the rover; and the capability of returning about 5 kg of Mars regolith to Earth. These characteristics lead to the belief that in order to bring back a variegated set of samples that can address the range of scientific objetives for a MRSR mission to Mars there needs to be considerable analysis done on board the rover. Furthermore, the discrepancy between the amount of sample gathered and the amount to be returned suggests that there needs to be some method of choosing the optimal set of samples. This type of analysis will require pristine material-unaltered by the drilling process. Since the core drill thermally and mechanically alters the outer diameter (about 10 pct) of the core sample, this outer area cannot be used. The primary function of the core handling device is to extract subsamples from the core and to position these subsamples, and the core itself if needed, with respect to the various analytical instruments that can be used to perform these analyses.
A model for osmium isotopic evolution of metallic solids at the core-mantle boundary
NASA Astrophysics Data System (ADS)
Humayun, Munir
2011-03-01
Some plumes are thought to originate at the core-mantle boundary, but geochemical evidence of core-mantle interaction is limited to Os isotopes in samples from Hawaii, Gorgona (89 Ma), and Kostomuksha (2.7 Ga). The Os isotopes have been explained by physical entrainment of Earth's liquid outer core into mantle plumes. This model has come into conflict with geophysical estimates of the timing of core formation, high-pressure experimental determinations of the solid metal-liquid metal partition coefficients (D), and the absence of expected 182W anomalies. A new model is proposed where metallic liquid from the outer core is partially trapped in a compacting cumulate pile of Fe-rich nonmetallic precipitates (FeO, FeS, Fe3Si, etc.) at the top of the core and undergoes fractional crystallization precipitating solid metal grains, followed by expulsion of the residual metallic liquid back to the outer core. The Os isotopic composition of the solids and liquids in the cumulate pile is modeled as a function of the residual liquid remaining and the emplacement age using 1 bar D values, with variable amounts of oxygen (0-10 wt %) as the light element. The precipitated solids evolve Os isotope compositions that match the trends for Hawaii (at an emplacement age of 3.5-4.5 Ga; 5%-10% oxygen) and Gorgona (emplacement age < 1.5 Ga; 0%-5% oxygen). The Fe-rich matrix of the cumulate pile dilutes the precipitated solid metal decoupling the Fe/Mn ratio from Os and W isotopes. The advantages to using precipitated solid metal as the Os host include a lower platinum group element and Ni content to the mantle source region relative to excess iron, miniscule anomalies in 182W (<0.1 ɛ), and no effects for Pb isotopes, etc. A gradual thermomechanical erosion of the cumulate pile results in incorporation of this material into the base of the mantle, where mantle plumes subsequently entrain it. Fractional crystallization of metallic liquids within the CMB provides a consistent explanation of both Os isotope correlations, Os-W isotope systematics, and Fe/Mn evidence for core-mantle interaction over the entire Hawaiian source.
Nguyen, Bidong D.; Cunningham, Doreen; Liang, Xiaofei; Chen, Xin; Toone, Eric J.; Raetz, Christian R. H.; Zhou, Pei; Valdivia, Raphael H.
2011-01-01
Lipopolysaccharides (LPS) and lipooligosaccharides (LOS) are the main lipid components of bacterial outer membranes and are essential for cell viability in most Gram-negative bacteria. Here we show that small molecule inhibitors of LpxC [UDP-3-O-(R-3-hydroxymyristoyl)-GlcNAc deacetylase], the enzyme that catalyzes the first committed step in the biosynthesis of lipid A, block the synthesis of LOS in the obligate intracellular bacterial pathogen Chlamydia trachomatis. In the absence of LOS, Chlamydia remains viable and establishes a pathogenic vacuole (“inclusion”) that supports robust bacterial replication. However, bacteria grown under these conditions were no longer infectious. In the presence of LpxC inhibitors, replicative reticulate bodies accumulated in enlarged inclusions but failed to express selected late-stage proteins and transition to elementary bodies, a Chlamydia developmental form that is required for invasion of mammalian cells. These findings suggest the presence of an outer membrane quality control system that regulates Chlamydia developmental transition to infectious elementary bodies and highlights the potential application of LpxC inhibitors as unique class of antichlamydial agents. PMID:21628561
Subsetting and Formatting Landsat-7 LOR ETM+ and Data Products
NASA Technical Reports Server (NTRS)
Reid, Michael R.
2000-01-01
The Landsat-7 Processing System (LPS) processes Landsat-7 Enhanced Thematic Mapper (ETM+) instrument data into large, contiguous segments called "subintervals" and stores them in Level OR (LOR) data files. The LPS processed subinterval products must be subsetted and reformatted before the Level I processing systems can ingest them. The initial full subintervals produced by the LPS are stored mainly in HDF Earth Observing System (HDF-EOS) format which is an extension to the Hierarchical Data Format (HDF). The final LOR products are stored in native HDF format. Primarily the EOS Core System (ECS) and alternately the DAAC Emergency System (DES) subset the subinterval data for the operational Landsat-7 data processing systems. The HDF and HDF-EOS application programming interfaces (APIs) can be used for extensive data subsetting and data reorganization. A stand-alone subsetter tool has been developed which is based on some of the DES code. This tool makes use of the HDF and HDFEOS APIs to perform Landsat-7 LOR product subsetting and demonstrates how HDF and HDFEOS can be used for creating various configurations of full LOR products. How these APIs can be used to efficiently subset, format, and organize Landsat-7 LOR data as demonstrated by the subsetter tool and the DES is discussed.
Langdon, Kristopher D; Maclellan, Crystal L; Corbett, Dale
2010-08-01
The incidence of infection among stroke patients is alarmingly high and both acute and delayed infections increase morbidity and mortality. Experimental studies support the acute clinical data, but little attention has focused on delayed systemic infections. Here, we investigated the effects of prolonged systemic inflammation either before or 24-h after ischemia. Systemic inflammation was induced by injecting rats with three separate doses of lipopolysaccharide (LPS; 50 mug/kg, i.p.) with core temperature monitoring for 48-h after middle cerebral artery occlusion (MCAo). Lipopolysaccharide injected before MCAo increased injury by approximately 30%, whereas delayed injection increased injury by approximately 85% (30-day survival). Proinflammatory cytokines assessed repeatedly for 72 h were significantly and persistently elevated with inflammation. This was accompanied by increases in microglia/macrophage and infiltrating leukocyte numbers in delayed LPS-treated animals. Behavioral assessments at 7 and 30 days revealed approximately 15% deficit in hindlimb function in animals treated with LPS 24-h after ischemia. Clearly, delayed and prolonged postischemic systemic inflammation has devastating effects on stroke outcome, in the absence of a prolonged febrile response. These findings, together with corroborative clinical data, emphasize the importance of early intervention to counteract the deleterious consequences of stroke-associated inflammation and infection.
2012-01-01
The Extradomain A from fibronectin (EDA) has an immunomodulatory role as fusion protein with viral and tumor antigens, but its effect when administered with bacteria has not been assessed. Here, we investigated the adjuvant effect of EDA in mice immunizations against Salmonella enterica subspecies enterica serovar Enteritidis (Salmonella Enteritidis). Since lipopolysaccharide (LPS) is a major virulence factor and the LPS O-polysaccharide (O-PS) is the immunodominant antigen in serological diagnostic tests, Salmonella mutants lacking O-PS (rough mutants) represent an interesting approach for developing new vaccines and diagnostic tests to differentiate infected and vaccinated animals (DIVA tests). Here, antigenic preparations (hot-saline extracts and formalin-inactivated bacterins) from two Salmonella Enteritidis rough mutants, carrying either intact (SEΔwaaL) or deep-defective (SEΔgal) LPS-Core, were used in combination with EDA. Biotinylated bacterins, in particular SEΔwaaL bacterin, decorated with EDAvidin (EDA and streptavidin fusion protein) improved the protection conferred by hot-saline or bacterins alone and prevented significantly the virulent infection at least to the levels of live attenuated rough mutants. These findings demonstrate the adjuvant effect of EDAvidin when administered with biotinylated bacterins from Salmonella Enteritidis lacking O-PS and the usefulness of BEDA-SEΔwaaL as non-live vaccine in the mouse model. PMID:22515195
Axial flow positive displacement worm gas generator
NASA Technical Reports Server (NTRS)
Giffin, Rollin George (Inventor); Fakunle, Oladapo (Inventor); Murrow, Kurt David (Inventor)
2010-01-01
An axial flow positive displacement engine has an inlet axially spaced apart and upstream from an outlet. Inner and outer bodies have offset inner and outer axes extend from the inlet to the outlet through first, second, and third sections of a core assembly in serial downstream flow relationship. At least one of the bodies is rotatable about its axis. The inner and outer bodies have intermeshed inner and outer helical blades wound about the inner and outer axes respectively. The inner and outer helical blades extend radially outwardly and inwardly respectively. The helical blades have first, second, and third twist slopes in the first, second, and third sections respectively. The first twist slopes are less than the second twist slopes and the third twist slopes are less than the second twist slopes. A combustor section extends axially downstream through at least a portion of the second section.
Rotational Splittings of Acoustic Modes in an Experimental Model of a Planetary Core
NASA Astrophysics Data System (ADS)
Adams, M. M.; Stone, D.; Lathrop, D. P.
2014-12-01
Planetary zonal flows can be probed in principle using the tools of helioseismology. We explore this technique using laboratory experiments where the measurement of zonal flows is also of geophysical relevance. The experiments are carried out in a device with a geometry similar to that of Earth's core. It consists of a 60 cm diameter outer spherical shell concentric with a 20 cm diameter inner sphere. Air between the inner sphere and outer shell is used as the working fluid. A turbulent shear flow is driven in the air by independently rotating the inner sphere and outer shell. Acoustic modes are excited in the vessel with a speaker, and microphones are used to measure the rotational splittings of these modes. The radial profile of azimuthal velocities is inferred from these splittings, in an approach analogous to that used in helioseismology to determine solar velocity profiles. By varying the inner and outer rotation rates, different turbulent states can be investigated. Comparison is made to previous experimental investigations of turbulent spherical Couette flow. These experiments also serve as a test of this diagnostic, which may be used in the future in liquid sodium experiments, providing information on zonal flows in hydromagnetic experiments.
Swasthi, Hema M; Mukhopadhyay, Samrat
2017-12-01
Curli is a functional amyloid protein in the extracellular matrix of enteric Gram-negative bacteria. Curli is assembled at the cell surface and consists of CsgA, the major subunit of curli, and a membrane-associated nucleator protein, CsgB. Oligomeric intermediates that accumulate during the lag phase of amyloidogenesis are generally toxic, but the underlying mechanism by which bacterial cells overcome this toxicity during curli assembly at the surface remains elusive. Here, we elucidated the mechanism of curli amyloidogenesis and provide molecular insights into the strategy by which bacteria can potentially bypass the detrimental consequences of toxic amyloid intermediates. Using a diverse range of biochemical and biophysical tools involving circular dichroism, fluorescence, Raman spectroscopy, and atomic force microscopy imaging, we characterized the molecular basis of the interaction of CsgB with a membrane-mimetic anionic surfactant as well as with lipopolysaccharide (LPS) constituting the outer leaflet of Gram-negative bacteria. Aggregation studies revealed that the electrostatic interaction of the positively charged C-terminal region of the protein with a negatively charged head group of surfactant/LPS promotes a protein-protein interaction that results in facile amyloid formation without a detectable lag phase. We also show that CsgB, in the presence of surfactant/LPS, accelerates the fibrillation rate of CsgA by circumventing the lag phase during nucleation. Our findings suggest that the electrostatic interactions between lipid and protein molecules play a pivotal role in efficiently sequestering the amyloid fold of curli on the membrane surface without significant accumulation of toxic oligomeric intermediates. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.
Ertürküner, Salime Pelin; Yaprak Saraç, Elif; Göçmez, Semil Selcen; Ekmekçi, Hakan; Öztürk, Zeynep Banu; Seçkin, İsmail; Sever, Özkan; Keskinbora, Kadircan
2016-01-01
Experimental animal models of acute uveitis, an inflammatory eye disease, can be established via endotoxin-induced inflammation. Propolis, a natural substance collected by honeybees from buds and tree exudates, has antioxidant, antibacterial, antiviral, and anti-inflammatory effects. We investigated the effects of propolis, obtained from the Sakarya province of Turkey, on endotoxin-induced uveitis using immunohistochemical, ultrastructural, and biochemical approaches. Male Wistar albino rats (n = 6/group) received intraperitoneal (ip) lipopolysaccharide (LPS) endotoxin (150 μg/kg) followed by aqueous extract of propolis (50 mg/kg ip) or vehicle; two additional groups received either saline (control) or propolis only. After 24 h, aqueous humor (AH) was collected from both eyes of each animal for analysis of tumor necrosis factor-α (TNF-α) and hypoxia-inducible factor-1α (HIF-1α). Right eyeballs were paraffin-embedded for immunohistochemical staining of nuclear factor κB (NF-κB)/p65 and left eyeballs were araldite-embedded for ultrastructural analysis. Treatment of LPS-induced uveitis with propolis significantly reduced ciliary body NF-κB/p65 immunoreactivity and AH levels of HIF-1α and TNF-α. Ultrastructural analysis showed fewer vacuoles and reduced mitochondrial degeneration in the retinal pigment epithelium, as compared to the uveitis group. The intercellular spaces of the inner nuclear layer and outer limiting membrane were comparable with those of the control group; no polymorphonuclear cells or stasis was observed in intravascular or extravascular spaces. This is the first report demonstrating an anti-inflammatory effect of Turkish propolis in a rat model of LPS-induced acute uveitis, suggesting a therapeutic potential of propolis for the treatment of inflammatory ophthalmic diseases.
Lüneberg, E; Mayer, B; Daryab, N; Kooistra, O; Zähringer, U; Rohde, M; Swanson, J; Frosch, M
2001-03-01
We recently described the phase-variable expression of a virulence-associated lipopolysaccharide (LPS) epitope in Legionella pneumophila. In this study, the molecular mechanism for phase variation was investigated. We identified a 30 kb unstable genetic element as the molecular origin for LPS phase variation. Thirty putative genes were encoded on the 30 kb sequence, organized in two putative opposite transcription units. Some of the open reading frames (ORFs) shared homologies with bacteriophage genes, suggesting that the 30 kb element was of phage origin. In the virulent wild-type strain, the 30 kb element was located on the chromosome, whereas excision from the chromosome and replication as a high-copy plasmid resulted in the mutant phenotype, which is characterized by alteration of an LPS epitope and loss of virulence. Mapping and sequencing of the insertion site in the genome revealed that the chromosomal attachment site was located in an intergenic region flanked by genes of unknown function. As phage release could not be induced by mitomycin C, it is conceivable that the 30 kb element is a non-functional phage remnant. The protein encoded by ORF T on the 30 kb plasmid could be isolated by an outer membrane preparation, indicating that the genes encoded on the 30 kb element are expressed in the mutant phenotype. Therefore, it is conceivable that the phenotypic alterations seen in the mutant depend on high-copy replication of the 30 kb element and expression of the encoded genes. Excision of the 30 kb element from the chromosome was found to occur in a RecA-independent pathway, presumably by the involvement of RecE, RecT and RusA homologues that are encoded on the 30 kb element.
Hosono, Eiji; Wang, Yonggang; Kida, Noriyuki; Enomoto, Masaya; Kojima, Norimichi; Okubo, Masashi; Matsuda, Hirofumi; Saito, Yoshiyasu; Kudo, Tetsuichi; Honma, Itaru; Zhou, Haoshen
2010-01-01
A triaxial LiFePO4 nanowire with a multi wall carbon nanotube (VGCF:Vapor-grown carbon fiber) core column and an outer shell of amorphous carbon was successfully synthesized through the electrospinning method. The carbon nanotube core oriented in the direction of the wire played an important role in the conduction of electrons during the charge-discharge process, whereas the outer amorphous carbon shell suppressed the oxidation of Fe2+. An electrode with uniformly dispersed carbon and active materials was easily fabricated via a single process by heating after the electrospinning method is applied. Mossbauer spectroscopy for the nanowire showed a broadening of the line width, indicating a disordered coordination environment of the Fe ion near the surface. The electrospinning method was proven to be suitable for the fabrication of a triaxial nanostructure.
Convective overshooting in the evolution of very massive stars
NASA Technical Reports Server (NTRS)
Stothers, R.; Chin, C.-W.
1981-01-01
Possible convective overshooting in stars of 30-120 solar masses are considered, including a merger between the convective core and the intermediate zone, and penetration by the outer convection zone into the hydrogen-shell region when the star is a supergiant. Convective mixing between the core and inner envelopes is found to lead to a brief renewal of hydrogen burning in the core, and a moderate widening of the main sequence bond in the H-R diagram. Deep penetration by the outer convection zone is found to force the star out of the red supergiant configuration and into a configuration near the main sequence. This would account for the apparent spread of the uppermost part of the main sequence and the concentration of luminous supergiants towards earlier spectral types. In addition, heavy mass loss need not be assumed to achieve the points of agreement, and are tentatively considered unimportant from an evolutionary point of view.
Modeling of rapid shutdown in the DIII-D tokamak by core deposition of high-Z material
Izzo, Valerie A.; Parks, Paul B.
2017-06-22
MHD modeling of shell-pellet injection for disruption mitigation is carried out under the assumption of idealized delivery of the radiating payload to the core, neglecting the physics of shell ablation. The shell pellet method is designed to produce an inside-out thermal quench in which core thermal heat is radiated while outer flux surfaces remain intact, protecting the divertor from large conducted heat loads. In the simulation, good outer surfaces remain until the thermal quench is nearly complete, and a high radiated energy fraction is achieved. As a result, when the outermost surfaces are destroyed, runaway electron test orbits indicate thatmore » the rate of runaway electron loss is very fast compared with prior massive gas injection simulations, which is attributed to the very different current profile evolution that occurs with central cooling.« less
Motion of the Mantle in the Translational Modes of the Earth and Mercury
NASA Technical Reports Server (NTRS)
Grinfeld, Pavel; Wisdom, Jack
2005-01-01
Slichter modes refer to the translational motion of the inner core with respect to the outer core and the mantle. The polar Slichter mode is the motion of the inner core along the axis of rotation. Busse presented an analysis of the polar mode which yielded an expression for its period. Busse's analysis included the assumption that the mantle was stationary. This approximation is valid for planets with small inner cores, such as the Earth whose inner core is about 1/60 of the total planet mass. On the other hand, many believe that Mercury's core may be enormous. If so, the motion of the mantle should be expected to produce a significant effect. We present a formal framework for including the motion of the mantle in the analysis of the translational motion of the inner core. We analyze the effect of the motion of the mantle on the Slichter modes for a non-rotating planet with an inner core of arbitrary size. We omit the effects of viscosity in the outer core, magnetic effects, and solid tides. Our approach is perturbative and is based on a linearization of Euler's equations for the motion of the fluid and Newton's second law for the motion of the inner core. We find an analytical expression for the period of the Slichter mode. Our result agrees with Busse's in the limiting case of small inner core. We present the unexpected result that even for Mercury the motion of the mantle does not significantly change the period of oscillation.
Preparation of Geophysical Fluid Flow Experiments ( GeoFlow ) in the Fluid Science Laboratory on ISS
NASA Astrophysics Data System (ADS)
Egbers, C.
The ,,GeoFlow" is an ESA experiment planned for the Fluid Science Laboratory on ISS under the scientific coordination (PI) of the Department of Aerodynamics and Fluidmechanics (LAS) at the Brandenburg Technical University (BTU) of Cottbus, Germany. The objective of the experiment is to study thermal convection in the gap between two concentric rotating (full) spheres. A central symmetric force field similar to the gravity field acting on planets can be produced by applying a high voltage between inner and outer sphere using the dielectrophoretic effect (rotating capacitor). To counter the unidirectional gravity under terrestrial conditions, this experiment requires a microgravity environment. The parameters of the experiment are chosen in analogy to the thermal convective motions in the outer core of the Earth. In analogy to geophysical motions in the Earth's liquid core the exp eriment can rotate as solid body as well as differential (inner to outer). Thermal convection is produced by heating the inner sphere and cooling the outer ones. Furtheron, the variation of radius ratio between inner and outer sphere is foreseen as a parameter variation. The flows to be investigated will strongly depend on the gap width and on the Prandtl number. Results of preparatory experiments and numerical simulation of the space experiment will be presented. Funding from DLR under grant 50 WM 0122 is greatfully ackwnoledged.
Method for manufacturing magnetohydrodynamic electrodes
Killpatrick, Don H.; Thresh, Henry R.
1982-01-01
A method of manufacturing electrodes for use in a magnetohydrodynamic (MHD) generator comprising the steps of preparing a billet having a core 10 of a first metal, a tubular sleeve 12 of a second metal, and an outer sheath 14, 16, 18 of an extrusile metal; evacuating the space between the parts of the assembled billet; extruding the billet; and removing the outer jacket 14. The extruded bar may be made into electrodes by cutting and bending to the shape required for an MDH channel frame. The method forms a bond between the first metal of the core 10 and the second metal of the sleeve 12 strong enough to withstand a hot and corrosive environment.
Europa's differentiated internal structure: inferences from four Galileo encounters.
Anderson, J D; Schubert, G; Jacobson, R A; Lau, E L; Moore, W B; Sjogren, W L
1998-09-25
Radio Doppler data from four encounters of the Galileo spacecraft with the jovian moon Europa have been used to refine models of Europa's interior. Europa is most likely differentiated into a metallic core surrounded by a rock mantle and a water ice-liquid outer shell, but the data cannot eliminate the possibility of a uniform mixture of dense silicate and metal beneath the water ice-liquid shell. The size of a metallic core is uncertain because of its unknown composition, but it could be as large as about 50 percent of Europa's radius. The thickness of Europa's outer shell of water ice-liquid must lie in the range of about 80 to 170 kilometers.
FAILURE OF A NEUTRINO-DRIVEN EXPLOSION AFTER CORE-COLLAPSE MAY LEAD TO A THERMONUCLEAR SUPERNOVA
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kushnir, Doron; Katz, Boaz, E-mail: kushnir@ias.edu
We demonstrate that ∼10 s after the core-collapse of a massive star, a thermonuclear explosion of the outer shells is possible for some (tuned) initial density and composition profiles, assuming that the neutrinos failed to explode the star. The explosion may lead to a successful supernova, as first suggested by Burbidge et al. We perform a series of one-dimensional (1D) calculations of collapsing massive stars with simplified initial density profiles (similar to the results of stellar evolution calculations) and various compositions (not similar to 1D stellar evolution calculations). We assume that the neutrinos escaped with a negligible effect on themore » outer layers, which inevitably collapse. As the shells collapse, they compress and heat up adiabatically, enhancing the rate of thermonuclear burning. In some cases, where significant shells of mixed helium and oxygen are present with pre-collapsed burning times of ≲100 s (≈10 times the free-fall time), a thermonuclear detonation wave is ignited, which unbinds the outer layers of the star, leading to a supernova. The energy released is small, ≲10{sup 50} erg, and negligible amounts of synthesized material (including {sup 56}Ni) are ejected, implying that these 1D simulations are unlikely to represent typical core-collapse supernovae. However, they do serve as a proof of concept that the core-collapse-induced thermonuclear explosions are possible, and more realistic two-dimensional and three-dimensional simulations are within current computational capabilities.« less
Secular changes of LOD associated with a growth of the inner core
NASA Astrophysics Data System (ADS)
Denis, C.; Rybicki, K. R.; Varga, P.
2006-05-01
From recent estimates of the age of the inner core based on the theory of thermal evolution of the core, we estimate that nowadays the growth of the inner core may perhaps contribute to the observed overall secular increase of LOD caused mainly by tidal friction (i.e., 1.72 ms per century) by a relative decrease of 2 to 7 μs per century. Another, albeit much less plausible, hypothesis is that crystallization of the inner core does not produce any change of LOD, but makes the inner core rotate differentially with respect to the outer core and mantle.
Fransen, Floris; Heckenberg, Sebastiaan G. B.; Hamstra, Hendrik Jan; Feller, Moniek; Boog, Claire J. P.; van Putten, Jos P. M.; van de Beek, Diederik
2009-01-01
Neisseria meningitidis is a major cause of bacterial meningitis and sepsis worldwide. Lipopolysaccharide (LPS), a major component of the Gram-negative bacterial outer membrane, is sensed by mammalian cells through Toll-like receptor 4 (TLR4), resulting in activation of proinflammatory cytokine pathways. TLR4 recognizes the lipid A moiety of the LPS molecule, and the chemical composition of the lipid A determines how well it is recognized by TLR4. N. meningitidis has been reported to produce lipid A with six acyl chains, the optimal number for TLR4 recognition. Indeed, meningococcal sepsis is generally seen as the prototypical endotoxin-mediated disease. In the present study, we screened meningococcal disease isolates from 464 patients for their ability to induce cytokine production in vitro. We found that around 9% of them were dramatically less potent than wild-type strains. Analysis of the lipid A of several of the low-activity strains by mass spectrometry revealed they were penta-acylated, suggesting a mutation in the lpxL1 or lpxL2 genes required for addition of secondary acyl chains. Sequencing of these genes showed that all the low activity strains had mutations that inactivated the lpxL1 gene. In order to see whether lpxL1 mutants might give a different clinical picture, we investigated the clinical correlate of these mutations in a prospective nationwide observational cohort study of adults with meningococcal meningitis. Patients infected with an lpxL1 mutant presented significantly less frequently with rash and had higher thrombocyte counts, consistent with reduced cytokine induction and less activation of tissue-factor mediated coagulopathy. In conclusion, here we report for the first time that a surprisingly large fraction of meningococcal clinical isolates have LPS with underacylated lipid A due to mutations in the lpxL1 gene. The resulting low-activity LPS may have an important role in virulence by aiding the bacteria to evade the innate immune system. Our results provide the first example of a specific mutation in N. meningitidis that can be correlated with the clinical course of meningococcal disease. PMID:19390612
Oscarsson, Jan; Karched, Maribasappa; Thay, Bernard; Chen, Casey; Asikainen, Sirkka
2008-11-27
Aggregatibacter actinomycetemcomitans is an oral bacterium associated with aggressive forms of periodontitis. Increasing evidence points to a link between periodontitis and cardiovascular diseases, however, the underlying mechanisms are poorly understood. This study investigated the pathogenic potential of free-soluble surface material, released from live planktonic and biofilm A. actinomycetemcomitans cells. By employing an ex vivo insert model (filter pore size 20 nm) we demonstrated that the A. actinomycetemcomitans strain D7S and its derivatives, in both planktonic and in biofilm life-form, released free-soluble surface material independent of outer membrane vesicles. This material clearly enhanced the production of several proinflammatory cytokines (IL-1 beta, TNF-alpha, IL-6, IL-8, MIP-1 beta) in human whole blood, as evidenced by using a cytokine antibody array and dissociation-enhanced-lanthanide-fluorescent-immunoassay. In agreement with this, quantitative real-time PCR indicated a concomitant increase in transcription of each of these cytokine genes. Experiments in which the LPS activity was blocked with polymyxin B showed that the stimulatory effect was only partly LPS-dependent, suggesting the involvement of additional free-soluble factors. Consistent with this, MALDI-TOF-MS and immunoblotting revealed release of GroEL-like protein in free-soluble form. Conversely, the immunomodulatory toxins, cytolethal distending toxin and leukotoxin, and peptidoglycan-associated lipoprotein, appeared to be less important, as evidenced by studying strain D7S cdt/ltx double, and pal single mutants. In addition to A. actinomycetemcomitans a non-oral species, Escherichia coli strain IHE3034, tested in the same ex vivo model also released free-soluble surface material with proinflammatory activity. A. actinomycetemcomitans, grown in biofilm and planktonic form, releases free-soluble surface material independent of outer membrane vesicles, which induces proinflammatory responses in human whole blood. Our findings therefore suggest that release of surface components from live bacterial cells could constitute a mechanism for systemic stimulation and be of particular importance in chronic localized infections, such as periodontitis.
Oscarsson, Jan; Karched, Maribasappa; Thay, Bernard; Chen, Casey; Asikainen, Sirkka
2008-01-01
Background Aggregatibacter actinomycetemcomitans is an oral bacterium associated with aggressive forms of periodontitis. Increasing evidence points to a link between periodontitis and cardiovascular diseases, however, the underlying mechanisms are poorly understood. This study investigated the pathogenic potential of free-soluble surface material, released from live planktonic and biofilm A. actinomycetemcomitans cells. Results By employing an ex vivo insert model (filter pore size 20 nm) we demonstrated that the A. actinomycetemcomitans strain D7S and its derivatives, in both planktonic and in biofilm life-form, released free-soluble surface material independent of outer membrane vesicles. This material clearly enhanced the production of several proinflammatory cytokines (IL-1β, TNF-α, IL-6, IL-8, MIP-1β) in human whole blood, as evidenced by using a cytokine antibody array and dissociation-enhanced-lanthanide-fluorescent-immunoassay. In agreement with this, quantitative real-time PCR indicated a concomitant increase in transcription of each of these cytokine genes. Experiments in which the LPS activity was blocked with polymyxin B showed that the stimulatory effect was only partly LPS-dependent, suggesting the involvement of additional free-soluble factors. Consistent with this, MALDI-TOF-MS and immunoblotting revealed release of GroEL-like protein in free-soluble form. Conversely, the immunomodulatory toxins, cytolethal distending toxin and leukotoxin, and peptidoglycan-associated lipoprotein, appeared to be less important, as evidenced by studying strain D7S cdt/ltx double, and pal single mutants. In addition to A. actinomycetemcomitans a non-oral species, Escherichia coli strain IHE3034, tested in the same ex vivo model also released free-soluble surface material with proinflammatory activity. Conclusion A. actinomycetemcomitans, grown in biofilm and planktonic form, releases free-soluble surface material independent of outer membrane vesicles, which induces proinflammatory responses in human whole blood. Our findings therefore suggest that release of surface components from live bacterial cells could constitute a mechanism for systemic stimulation and be of particular importance in chronic localized infections, such as periodontitis. PMID:19038023
Rossi, Omar; Pesce, Isabella; Giannelli, Carlo; Aprea, Susanna; Caboni, Mariaelena; Citiulo, Francesco; Valentini, Sara; Ferlenghi, Ilaria; MacLennan, Calman Alexander; D'Oro, Ugo; Saul, Allan; Gerke, Christiane
2014-09-05
Outer membrane particles from Gram-negative bacteria are attractive vaccine candidates as they present surface antigens in their natural context. We previously developed a high yield production process for genetically derived particles, called generalized modules for membrane antigens (GMMA), from Shigella. As GMMA are derived from the outer membrane, they contain immunostimulatory components, especially lipopolysaccharide (LPS). We examined ways of reducing their reactogenicity by modifying lipid A, the endotoxic part of LPS, through deletion of late acyltransferase genes, msbB or htrB, in GMMA-producing Shigella sonnei and Shigella flexneri strains. GMMA with resulting penta-acylated lipid A from the msbB mutants showed a 600-fold reduced ability, and GMMA from the S. sonnei ΔhtrB mutant showed a 60,000-fold reduced ability compared with GMMA with wild-type lipid A to stimulate human Toll-like receptor 4 (TLR4) in a reporter cell line. In human peripheral blood mononuclear cells, GMMA with penta-acylated lipid A showed a marked reduction in induction of inflammatory cytokines (S. sonnei ΔhtrB, 800-fold; ΔmsbB mutants, 300-fold). We found that the residual activity of these GMMA is largely due to non-lipid A-related TLR2 activation. In contrast, in the S. flexneri ΔhtrB mutant, a compensatory lipid A palmitoleoylation resulted in GMMA with hexa-acylated lipid A with ∼10-fold higher activity to stimulate peripheral blood mononuclear cells than GMMA with penta-acylated lipid A, mostly due to retained TLR4 activity. Thus, for use as vaccines, GMMA will likely require lipid A penta-acylation. The results identify the relative contributions of TLR4 and TLR2 activation by GMMA, which need to be taken into consideration for GMMA vaccine development. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.
NASA Technical Reports Server (NTRS)
Palaszewski, Bryan A.
2014-01-01
Atmospheric mining in the outer solar system has been investigated as a means of fuel production for high energy propulsion and power. Fusion fuels such as Helium 3 (3He) and hydrogen can be wrested from the atmospheres of Uranus and Neptune and either returned to Earth or used in-situ for energy production. Helium 3 and hydrogen (deuterium, etc.) were the primary gases of interest with hydrogen being the primary propellant for nuclear thermal solid core and gas core rocket-based atmospheric flight. A series of analyses were undertaken to investigate resource capturing aspects of atmospheric mining in the outer solar system. This included the gas capturing rate, storage options, and different methods of direct use of the captured gases. Additional supporting analyses were conducted to illuminate vehicle sizing and orbital transportation issues. While capturing 3He, large amounts of hydrogen and 4He are produced. With these two additional gases, the potential for fueling small and large fleets of additional exploration and exploitation vehicles exists. Additional aerospacecraft or other aerial vehicles (UAVs, balloons, rockets, etc.) could fly through the outer planet atmospheres, for global weather observations, localized storm or other disturbance investigations, wind speed measurements, polar observations, etc. Deep-diving aircraft (built with the strength to withstand many atmospheres of pressure) powered by the excess hydrogen or helium 4 may be designed to probe the higher density regions of the gas giants. Outer planet atmospheric properties, atmospheric storm data, and mission planning for future outer planet UAVs are presented.
NASA Astrophysics Data System (ADS)
Penny, Samantha J.; Conselice, Christopher J.; de Rijcke, Sven; Held, Enrico V.; Gallagher, John S.; O'Connell, Robert W.
2011-01-01
We present the results of a Hubble Space Telescope (HST) study of dwarf galaxies in the outer regions of the nearby rich Perseus cluster, down to MV=-12, and compare these with the dwarf population in the cluster core from our previous HST imaging. In this paper, we examine how properties such as the colour-magnitude relation, structure and morphology are affected by environment for the lowest mass galaxies. Dwarf galaxies are excellent tracers of the effects of environment due to their low masses, allowing us to derive their environmentally based evolution, which is more subtle in more massive galaxies. We identify 11 dwarf elliptical (dE) and dwarf spheroidal (dSph) galaxies in the outer regions of Perseus, all of which are previously unstudied. We measure the (V-I)0 colours of our newly discovered dEs, and find that these dwarfs lie on the same red sequence as those in the cluster core. The morphologies of these dwarfs are examined by quantifying their light distributions using concentration, asymmetry and clumpiness (CAS) parameters, and we find that dEs in the cluster outskirts are on average more disturbed than those in the core, with = 0.13 ± 0.09 and = 0.18 ± 0.08, compared to = 0.02 ± 0.04, = 0.01 ± 0.07 for those in the core. Based on these results, we infer that these objects are `transition dwarfs', likely in the process of transforming from late-type to early-type galaxies as they infall into the cluster, with their colours transforming before their structures. When we compare the number counts for both the core and outer regions of the cluster, we find that below MV=-12, the counts in the outer regions of the cluster exceed those in the core. This is evidence that in the very dense region of the cluster, dwarfs are unable to survive unless they are sufficiently massive to prevent their disruption by the cluster potential and interactions with other galaxies. Based on observations made with the NASA/ESA HST, obtained (from the Data Archive) at the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc., under NASA contract NAS 5-26555. These observations are associated with programs GO-10201 and GO-10789
Rollo, Benjamin N.; Zhang, Dongcheng; Simkin, Johanna E.; Menheniott, Trevelyan R.; Newgreen, Donald F.
2015-01-01
The avian enteric nervous system (ENS) consists of a vast number of unusually small ganglia compared to other peripheral ganglia. Each ENS ganglion at mid-gestation has a core of neurons and a shell of mesenchymal precursor/glia-like enteric neural crest (ENC) cells. To study ENS cell ganglionation we isolated midgut ENS cells by HNK-1 fluorescence-activated cell sorting (FACS) from E5 and E8 quail embryos, and from E9 chick embryos. We performed cell-cell aggregation assays which revealed a developmentally regulated functional increase in ENS cell adhesive function, requiring both Ca 2+ -dependent and independent adhesion. This was consistent with N-cadherin and NCAM labelling. Neurons sorted to the core of aggregates, surrounded by outer ENC cells, showing that neurons had higher adhesion than ENC cells. The outer surface of aggregates became relatively non-adhesive, correlating with low levels of NCAM and N-cadherin on this surface of the outer non-neuronal ENC cells. Aggregation assays showed that ENS cells FACS selected for NCAM-high and enriched for enteric neurons formed larger and more coherent aggregates than unsorted ENS cells. In contrast, ENS cells of the NCAM-low FACS fraction formed small, disorganised aggregates. This suggests a novel mechanism for control of ENS ganglion morphogenesis where i) differential adhesion of ENS neurons and ENC cells controls the core/shell ganglionic structure and ii) the ratio of neurons to ENC cells dictates the equilibrium ganglion size by generation of an outer non-adhesive surface. PMID:26064478
A study of the required Rayleigh number to sustain dynamo with various inner core radius
NASA Astrophysics Data System (ADS)
Nishida, Y.; Katoh, Y.; Matsui, H.; Kumamoto, A.
2017-12-01
It is widely accepted that the geomagnetic field is sustained by thermal and compositional driven convections of a liquid iron alloy in the outer core. The generation process of the geomagnetic field has been studied by a number of MHD dynamo simulations. Recent studies of the ratio of the Earth's core evolution suggest that the inner solid core radius ri to the outer liquid core radius ro changed from ri/ro = 0 to 0.35 during the last one billion years. There are some studies of dynamo in the early Earth with smaller inner core than the present. Heimpel et al. (2005) revealed the Rayleigh number Ra of the onset of dynamo process as a function of ri/ro from simulation, while paleomagnetic observation shows that the geomagnetic field has been sustained for 3.5 billion years. While Heimpel and Evans (2013) studied dynamo processes taking into account the thermal history of the Earth's interior, there were few cases corresponding to the early Earth. Driscoll (2016) performed a series of dynamo based on a thermal evolution model. Despite a number of dynamo simulations, dynamo process occurring in the interior of the early Earth has not been fully understood because the magnetic Prandtl numbers in these simulations are much larger than that for the actual outer core.In the present study, we performed thermally driven dynamo simulations with different aspect ratio ri/ro = 0.15, 0.25 and 0.35 to evaluate the critical Ra for the thermal convection and required Ra to maintain the dynamo. For this purpose, we performed simulations with various Ra and fixed the other control parameters such as the Ekman, Prandtl, and magnetic Prandtl numbers. For the initial condition and boundary conditions, we followed the dynamo benchmark case 1 by Christensen et al. (2001). The results show that the critical Ra increases with the smaller aspect ratio ri/ro. It is confirmed that larger amplitude of buoyancy is required in the smaller inner core to maintain dynamo.
Evidence for Radial Anisotropy in Earth's Upper Inner Core from Normal Modes
NASA Astrophysics Data System (ADS)
Lythgoe, K.; Deuss, A. F.
2017-12-01
The structure of the uppermost inner core is related to solidification of outer core material at the inner core boundary. Previous seismic studies using body waves indicate an isotropic upper inner core, although radial anisotropy has not been considered since it cannot be uniquely determined by body waves. Normal modes, however, do constrain radial anisotropy in the inner core. Centre frequency measurements indicate 2-5 % radial anisotropy in the upper 100 km of the inner core, with a fast direction radially outwards and a slow direction along the inner core boundary. This seismic structure provides constraints on solidification processes at the inner core boundary and appears consistent with texture predicted due to anisotropic inner core growth.
Nuclear reactor internals alignment configuration
Gilmore, Charles B [Greensburg, PA; Singleton, Norman R [Murrysville, PA
2009-11-10
An alignment system that employs jacking block assemblies and alignment posts around the periphery of the top plate of a nuclear reactor lower internals core shroud to align an upper core plate with the lower internals and the core shroud with the core barrel. The distal ends of the alignment posts are chamfered and are closely received within notches machined in the upper core plate at spaced locations around the outer circumference of the upper core plate. The jacking block assemblies are used to center the core shroud in the core barrel and the alignment posts assure the proper orientation of the upper core plate. The alignment posts may alternately be formed in the upper core plate and the notches may be formed in top plate.
Applying Mathematical Tools to Accelerate Vaccine Development: Modeling Shigella Immune Dynamics
Davis, Courtney L.; Wahid, Rezwanul; Toapanta, Franklin R.; Simon, Jakub K.
2013-01-01
We establish a mathematical framework for studying immune interactions with Shigella, a bacteria that kills over one million people worldwide every year. The long-term goal of this novel approach is to inform Shigella vaccine design by elucidating which immune components and bacterial targets are crucial for establishing Shigella immunity. Our delay differential equation model focuses on antibody and B cell responses directed against antigens like lipopolysaccharide in Shigella’s outer membrane. We find that antibody-based vaccines targeting only surface antigens cannot elicit sufficient immunity for protection. Additional boosting prior to infection would require a four-orders-of-magnitude increase in antibodies to sufficiently prevent epithelial invasion. However, boosting anti-LPS B memory can confer protection, which suggests these cells may correlate with immunity. We see that IgA antibodies are slightly more effective per molecule than IgG, but more total IgA is required due to spatial functionality. An extension of the model reveals that targeting both LPS and epithelial entry proteins is a promising avenue to advance vaccine development. This paper underscores the importance of multifaceted immune targeting in creating an effective Shigella vaccine. It introduces mathematical models to the Shigella vaccine development effort and lays a foundation for joint theoretical/experimental/clinical approaches to Shigella vaccine design. PMID:23589755
Applying mathematical tools to accelerate vaccine development: modeling Shigella immune dynamics.
Davis, Courtney L; Wahid, Rezwanul; Toapanta, Franklin R; Simon, Jakub K; Sztein, Marcelo B; Levy, Doron
2013-01-01
We establish a mathematical framework for studying immune interactions with Shigella, a bacteria that kills over one million people worldwide every year. The long-term goal of this novel approach is to inform Shigella vaccine design by elucidating which immune components and bacterial targets are crucial for establishing Shigella immunity. Our delay differential equation model focuses on antibody and B cell responses directed against antigens like lipopolysaccharide in Shigella's outer membrane. We find that antibody-based vaccines targeting only surface antigens cannot elicit sufficient immunity for protection. Additional boosting prior to infection would require a four-orders-of-magnitude increase in antibodies to sufficiently prevent epithelial invasion. However, boosting anti-LPS B memory can confer protection, which suggests these cells may correlate with immunity. We see that IgA antibodies are slightly more effective per molecule than IgG, but more total IgA is required due to spatial functionality. An extension of the model reveals that targeting both LPS and epithelial entry proteins is a promising avenue to advance vaccine development. This paper underscores the importance of multifaceted immune targeting in creating an effective Shigella vaccine. It introduces mathematical models to the Shigella vaccine development effort and lays a foundation for joint theoretical/experimental/clinical approaches to Shigella vaccine design.
van der Meijden, Benjamin; Robinson, John A
2015-03-01
The antimicrobial activity of polymyxins against Gram-negative bacteria has been known for several decades, but the mechanism of action leading to cell death has not been fully explored. A key step after binding of the antibiotic to lipopolysaccharide (LPS) exposed at the cell surface is 'self-promoted uptake' across the outer membrane (OM), in which the antibiotic traverses the asymmetric LPS-phospholipid bilayer before reaching the periplasm and finally targeting and disrupting the bacterial phospholipid inner membrane. The work described here was prompted by the hypothesis that polymyxins might interact with proteins in the OM, as part of their self-promoted uptake and permeabilizing effects. One way to test this is through photolabeling experiments. We describe the design and synthesis of a photoprobe based upon polymyxin B, containing photoleucine and an N-acyl group with a terminal alkyne suitable for coupling to a biotin tag using click chemistry. The resulting photoprobe retains potent antimicrobial activity, and in initial photolabeling experiments with Escherichia coli ATCC25922 is shown to photolabel several OM proteins. This photoprobe might be a valuable tool in more detailed studies on the mechanism of action of this family of antibiotics. Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Chang, G.S.
2008-07-15
The Advanced Test Reactor (ATR) is a high power density and high neutron flux research reactor operating in the United States. Powered with highly enriched uranium (HEU), the ATR has a maximum thermal power rating of 250 MWth. Because of the large test volumes located in high flux areas, the ATR is an ideal candidate for assessing the feasibility of converting an HEU driven reactor to a low-enriched core. The present work investigates the necessary modifications and evaluates the subsequent operating effects of this conversion. A detailed plate-by-plate MCNP ATR 1/8th core model was developed and validated for a fuelmore » cycle burnup comparison analysis. Using the current HEU U-235 enrichment of 93.0 % as a baseline, an analysis can be performed to determine the low-enriched uranium (LEU) density and U-235 enrichment required in the fuel meat to yield an equivalent K-eff between the HEU core th and the LEU core versus effective full power days (EFPD). The MCNP ATR 1/8th core model will be used to optimize the U-235 loading in the LEU core, such that the differences in K-eff and heat flux profile between the HEU and LEU core can be minimized. The depletion methodology MCWO was used to calculate K-eff versus EFPDs in this paper. The MCWO-calculated results for the LEU cases with foil (U-10Mo) types demonstrated adequate excess reactivity such that the K-eff versus EFPDs plot is similar to the reference ATR HEU case. Each HEU fuel element contains 19 fuel plates with a fuel meat thickness of 0.508 mm. In this work, the proposed LEU (U-10Mo) core conversion case with a nominal fuel meat thickness of 0.381 mm and the same U-235 enrichment (19.7 wt%) can be used to optimize the radial heat flux profile by varying the fuel meat thickness from 0.191 mm (7.5 mil) to 0.343 mm (13.5 mil) at the inner 4 fuel plates (1-4) and outer 4 fuel plates (16-19). In addition, 0.8g of a burnable absorber, Boron-10, was added in the inner and outer plates to reduce the initial excess reactivity, and the inner/outer heat flux more effectively. The optimized LEU relative radial fission heat flux profile is bounded by the reference ATR HEU case. However, to demonstrate that the LEU core fuel cycle performance can meet the Updated Final Safety Analysis Report (UFSAR) safety requirements, additional studies will be necessary to evaluate and compare safety parameters such as void reactivity and Doppler coefficients, control components worth (outer shim control cylinders, safety rods and regulating rod), and shutdown margins between the HEU and LEU cores. (author)« less
NASA Astrophysics Data System (ADS)
de Jong, B. H.
2007-12-01
Variations in surface tension affect the buoyancy of objects floating in a liquid. Thus an object floating in water will sink deeper in the presence of dishwater fluid. This is a very minor but measurable effect. It causes for instance ducks to drown in aqueous solutions with added surfactant. The surface tension of liquid iron is very strongly affected by the presence of sulfur which acts as a surfactant in this system varying between 1.9 and 0.4 N/m at 10 mass percent Sulfur (Lee & Morita (2002), This last value is inferred to be the maximum value for Sulfur inferred to be present in the liquid outer core. Venting of Sulfur from the liquid core manifests itself on the Earth surface by the 105 to 106 ton of sulfur vented into the atmosphere annually (Wedepohl, 1984). Inspection of surface Sulfur emission indicates that venting is non-homogeneously distributed over the Earth's surface. The implication of such large variation in surface tension in the liquid outer core are that at locally low Sulfur concentration, the liquid outer core does not wet the predominantly MgSiO3 matrix with which it is in contact. However at a local high in Sulfur, the liquid outer core wets this matrix which in the fluid state has a surface tension of 0.4 N/m (Bansal & Doremus, 1986), couples with it, and causes it to sink. This differential and diapiric movement is transmitted through the essentially brittle mantle (1024 Pa.s, Lambeck & Johnson, 1998; the maximum value for ice being about 1030 Pa.s at 0 K, in all likely hood representing an upper bound of viscosity for all materials) and manifests itself on the surface by the roughly 20 km differentiation, about 0.1 % of the total mantle thickness, between topographical heights and lows with concomitant lateral movement in the crust and upper mantle resulting in thin skin tectonics. The brittle nature of the medium though which this movement is transmitted suggests that the extremes in topography of the D" layer are similar in range to those observed on the Earth's surface and are mimicked by lows under the oceans and highs under the altiplanos. Careful and area selective S wave core mantle ellipsometry might be able to discern these core-mantle topographic variations. As such this process demonstrates the validity of the Gaia hypothesis enunciated by Baas Becking(1931) that no ecological niche on our planet is closed off from other niches "nothing in the world is single".
NASA Astrophysics Data System (ADS)
Zhang, Youjun; Sekine, Toshimori; He, Hongliang; Yu, Yin; Liu, Fusheng; Zhang, Mingjian
2014-07-01
The shock Hugoniot of an Fe-9 wt %Ni-10 wt %Si system as a model of the Earth's core has been measured up to ~280 GPa using a two-stage light-gas gun. The samples had an average density of 6.853 (±0.036) g/cm3. The relationship between shock velocity (Us) and particle velocity (up) can be described by Us (km/s) = 3.95 (±0.15) + 1.53 (±0.05) up (km/s). The calculated Hugoniot temperatures and the melting curve indicate that the model composition melts above a shock pressure of ~168 GPa, which is significantly lower than the shock-melting pressure of iron (~225 GPa). A comparison of the pressure-density (P-ρ) profiles between the model composition and the preliminary reference Earth model gives a silicon content close to 10 wt %, necessary to compensate the density deficit in the Earth's outer core from seismological observations, if silicon is present as a major light element in the Fe-Ni core system.
Some anticipated contributions to core fluid dynamics from the GRM
NASA Technical Reports Server (NTRS)
Vanvorhies, C.
1985-01-01
It is broadly maintained that the secular variation (SV) of the large scale geomagnetic field contains information on the fluid dynamics of Earth's electrically conducting outer core. The electromagnetic theory appropriate to a simple Earth model has recently been combined with reduced geomagnetic data in order to extract some of this information and ascertain its significance. The simple Earth model consists of a rigid, electrically insulating mantle surrounding a spherical, inviscid, and perfectly conducting liquid outer core. This model was tested against seismology by using truncated spherical harmonic models of the observed geomagnetic field to locate Earth's core-mantle boundary, CMB. Further electromagnetic theory has been developed and applied to the problem of estimating the horizontal fluid motion just beneath CMB. Of particular geophysical interest are the hypotheses that these motions: (1) include appreciable surface divergence indicative of vertical motion at depth, and (2) are steady for time intervals of a decade or more. In addition to the extended testing of the basic Earth model, the proposed GRM provides a unique opportunity to test these dynamical hypotheses.
Interstellar and Cometary Dust
NASA Technical Reports Server (NTRS)
Mathis, John S.
1997-01-01
'Interstellar dust' forms a continuum of materials with differing properties which I divide into three classes on the basis of observations: (a) diffuse dust, in the low-density interstellar medium; (b) outer-cloud dust, observed in stars close enough to the outer edges of molecular clouds to be observed in the optical and ultraviolet regions of the spectrum, and (c) inner-cloud dust, deep within the cores of molecular clouds, and observed only in the infrared by means of absorption bands of C-H, C=O, 0-H, C(triple bond)N, etc. There is a surprising regularity of the extinction laws between diffuse- and outer-cloud dust. The entire mean extinction law from infrared through the observable ultraviolet spectrum can be characterized by a single parameter. There are real deviations from this mean law, larger than observational uncertainties, but they are much smaller than differences of the mean laws in diffuse- and outer-cloud dust. This fact shows that there are processes which operate over the entire distribution of grain sizes, and which change size distributions extremely efficiently. There is no evidence for mantles on grains in local diffuse and outer-cloud dust. The only published spectra of the star VI Cyg 12, the best candidate for showing mantles, does not show the 3.4 micro-m band which appreciable mantles would produce. Grains are larger in outer-cloud dust than diffuse dust because of coagulation, not accretion of extensive mantles. Core-mantle grains favored by J. M. Greenberg and collaborators, and composite grains of Mathis and Whiffen (1989), are discussed more extensively (naturally, I prefer the latter). The composite grains are fluffy and consist of silicates, amorphous carbon, and some graphite in the same grain. Grains deep within molecular clouds but before any processing within the solar system are presumably formed from the accretion of icy mantles on and within the coagulated outer-cloud grains. They should contain a mineral/carbonaceous matrix, without organic refractory mantles, in between the ices. Unfortunately, they may be significantly processed by chemical processes accompanying the warming (over the 10 K of the dark cloud cores) which occurs in the outer solar system. Evidence of this processing is the chemical anomalies present in interplanetary dust particles collected in the stratosphere, which may be the most primitive materials we have obtained to date. The comet return mission would greatly clarify the situation, and probably provide samples of genuine interstellar grains.
1992-06-24
system, such as pneumococcal polysaccharide (Hiernaux et aI., 1989) or those that are presented by malignant tumors (O’Malley et ai., 1963). LPS...isolated the active ingredient, which they called ’’bacterial polysaccharide " (Shear and Andervont, 1936). The practice of inducing "therapeutic febrile...acylated, diphosphorylated, ~-1,6-linked D-glucosamine disaccharide (referred to as lipid A) which is attached covalently to a core polysaccharide that
Viscosity of the earth's core.
NASA Technical Reports Server (NTRS)
Gans, R. F.
1972-01-01
Calculation of the viscosity of the core at the boundary of the inner and outer core. It is assumed that this boundary is a melting transition and the viscosity limits of the Andrade (1934,1952) hypothesis (3.7 to 18.5 cp) are adopted. The corresponding kinematic viscosities are such that the precessional system explored by Malkus (1968) would be unstable. Whether it would be sufficiently unstable to overcome a severely subadiabatic temperature gradient cannot be determined.
Leon-Velarde, Carlos G; Happonen, Lotta; Pajunen, Maria; Leskinen, Katarzyna; Kropinski, Andrew M; Mattinen, Laura; Rajtor, Monika; Zur, Joanna; Smith, Darren; Chen, Shu; Nawaz, Ayesha; Johnson, Roger P; Odumeru, Joseph A; Griffiths, Mansel W; Skurnik, Mikael
2016-09-01
Bacteriophages present huge potential both as a resource for developing novel tools for bacterial diagnostics and for use in phage therapy. This potential is also valid for bacteriophages specific for Yersinia enterocolitica To increase our knowledge of Y. enterocolitica-specific phages, we characterized two novel yersiniophages. The genomes of the bacteriophages vB_YenM_TG1 (TG1) and vB_YenM_ϕR1-RT (ϕR1-RT), isolated from pig manure in Canada and from sewage in Finland, consist of linear double-stranded DNA of 162,101 and 168,809 bp, respectively. Their genomes comprise 262 putative coding sequences and 4 tRNA genes and share 91% overall nucleotide identity. Based on phylogenetic analyses of their whole-genome sequences and large terminase subunit protein sequences, a genus named Tg1virus within the family Myoviridae is proposed, with TG1 and ϕR1-RT (R1RT in the ICTV database) as member species. These bacteriophages exhibit a host range restricted to Y. enterocolitica and display lytic activity against the epidemiologically significant serotypes O:3, O:5,27, and O:9 at and below 25°C. Adsorption analyses of lipopolysaccharide (LPS) and OmpF mutants demonstrate that these phages use both the LPS inner core heptosyl residues and the outer membrane protein OmpF as phage receptors. Based on RNA sequencing and quantitative proteomics, we also demonstrate that temperature-dependent infection is due to strong repression of OmpF at 37°C. In addition, ϕR1-RT was shown to be able to enter into a pseudolysogenic state. Together, this work provides further insight into phage-host cell interactions by highlighting the importance of understanding underlying factors which may affect the abundance of phage host receptors on the cell surface. Only a small number of bacteriophages infecting Y. enterocolitica, the predominant causative agent of yersiniosis, have been previously described. Here, two newly isolated Y. enterocolitica phages were studied in detail, with the aim of elucidating the host cell receptors required for infection. Our research further expands the repertoire of phages available for consideration as potential antimicrobial agents or as diagnostic tools for this important bacterial pathogen. Copyright © 2016, American Society for Microbiology. All Rights Reserved.
Happonen, Lotta; Pajunen, Maria; Leskinen, Katarzyna; Kropinski, Andrew M.; Mattinen, Laura; Rajtor, Monika; Zur, Joanna; Smith, Darren; Chen, Shu; Nawaz, Ayesha; Johnson, Roger P.; Odumeru, Joseph A.; Griffiths, Mansel W.
2016-01-01
ABSTRACT Bacteriophages present huge potential both as a resource for developing novel tools for bacterial diagnostics and for use in phage therapy. This potential is also valid for bacteriophages specific for Yersinia enterocolitica. To increase our knowledge of Y. enterocolitica-specific phages, we characterized two novel yersiniophages. The genomes of the bacteriophages vB_YenM_TG1 (TG1) and vB_YenM_ϕR1-RT (ϕR1-RT), isolated from pig manure in Canada and from sewage in Finland, consist of linear double-stranded DNA of 162,101 and 168,809 bp, respectively. Their genomes comprise 262 putative coding sequences and 4 tRNA genes and share 91% overall nucleotide identity. Based on phylogenetic analyses of their whole-genome sequences and large terminase subunit protein sequences, a genus named Tg1virus within the family Myoviridae is proposed, with TG1 and ϕR1-RT (R1RT in the ICTV database) as member species. These bacteriophages exhibit a host range restricted to Y. enterocolitica and display lytic activity against the epidemiologically significant serotypes O:3, O:5,27, and O:9 at and below 25°C. Adsorption analyses of lipopolysaccharide (LPS) and OmpF mutants demonstrate that these phages use both the LPS inner core heptosyl residues and the outer membrane protein OmpF as phage receptors. Based on RNA sequencing and quantitative proteomics, we also demonstrate that temperature-dependent infection is due to strong repression of OmpF at 37°C. In addition, ϕR1-RT was shown to be able to enter into a pseudolysogenic state. Together, this work provides further insight into phage-host cell interactions by highlighting the importance of understanding underlying factors which may affect the abundance of phage host receptors on the cell surface. IMPORTANCE Only a small number of bacteriophages infecting Y. enterocolitica, the predominant causative agent of yersiniosis, have been previously described. Here, two newly isolated Y. enterocolitica phages were studied in detail, with the aim of elucidating the host cell receptors required for infection. Our research further expands the repertoire of phages available for consideration as potential antimicrobial agents or as diagnostic tools for this important bacterial pathogen. PMID:27342557
Core Composition and the Magnetic Field of Mercury
NASA Astrophysics Data System (ADS)
Spohn, T.; Breuer, D.
2005-05-01
The density of Mercury suggests a core of approximately 1800 km radius and a mantle of approximately 600 km thickness. Convection in the mantle is often claimed to be capable of freezing the core over the lifetime of the solar system if the core is nearly pure iron. The thermal history calculations of Stevenson et al. (1983) and Schubert et al. (1988) suggest that about 5 weight-% sulphur are required to lower the core liquidus sufficiently to prevent complete freezing of the core and maintain a significant fluid outer core shell. Other candidates for a light alloying element require similarly large concentrations. The requirement of a significant concentration of volatile elements in the core is likely to be at variance with cosmochemical arguments for a mostly refractory, volatile poor composition of the planet. We have re-addressed the question of the freezing of Mercury's core using parameterized convection models based on the stagnant lid theory of planetary mantle convection. We have compared these results to earlier calculations (Conzelmann and Spohn, 1999) of Hermian mantle convection using a finite-amplitude convection code. We find consistently that the stagnant lid tends to thermally insulate the deep interior and we find mantle and core temperatures significantly larger than those calculated by Stevenson et al. (1983) and Schubert et al. (1988). As a consequence we find fluid outer core shells for reasonable mantle rheology parameters even for compositions with as little as 0.1 weight-% sulphur. Stevenson, D.J., T. Spohn, and G. Schubert. Icarus, 54, 466, 1983. Schubert, G. M.N. Ross, D.J. Stevenson, and T. Spohn, in Mercury, F. Vilas, C.R. Chapman and M.S. Matthews, eds., p.429, 1988. Conzelmann, V. and T. Spohn, Bull. Am. Astr. Soc., 31, 1102, 1999.
Constraints on Mercury's Core-Mantle Boundary Region
NASA Astrophysics Data System (ADS)
Hauck, S. A., II; Chabot, N. L.; Sun, P.; Jing, Z.; Johnson, C. L.; Margot, J. L.; Padovan, S.; Peale, S. J.; Phillips, R. J.; Solomon, S. C.
2014-12-01
Understanding the boundary between a planet's metallic core and silicate mantle is important for constraining processes that dominate on either side of this boundary. Geophysical measurements of the planet Mercury by the MESSENGER spacecraft have provided evidence of a core larger than earlier, less-constrained estimates. Further, these results, taken in concert with measurements of the elemental composition of the surface by MESSENGER, have led to the suggestion that the uppermost layer of the outer core may be highly enriched in sulfur, and the top of the core may consist of a solid sulfide layer. The low iron and relatively large sulfur contents of the surface indicate highly reducing conditions during planet formation, placing constraints on the potential composition of Mercury's core. Recent metal-silicate partitioning experiments have developed new limits on the amount of sulfur and silicon that may partition into the core as a function of sulfur abundance at the surface. Models for the planet's internal structure constrained by the current best estimates of the bulk density, normalized polar moment of inertia, and fraction of the polar moment of inertia of the solid layer that extends from the surface to the top of the liquid outer core provide an important view of the layering and bulk composition of Mercury. By combining the results of these internal structure models with the experimental relationship between core and mantle composition we place new limits on core composition and structure. Further, imposing measured compositional constraints on the miscibility of iron-sulfur-silicon alloys yields important limits on the presence or absence of an immiscible sulfur-rich liquid layer or a solid sulfide layer at the top of the core.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Haga, Takafumi; Doi, Akihiro; Murata, Yasuhiro
2015-07-01
We report multifrequency phase-referenced observations of the nearby radio galaxy NGC 4261, which has prominent two-sided jets, using the Very Long Baseline Array at 1.4–43 GHz. We measured radio core positions showing observing frequency dependences (known as “core shift”) in both approaching jets and counterjets. The limit of the core position as the frequency approaches infinity, which suggests a jet base, is separated by 82 ± 16 μas upstream in projection, corresponding to (310 ± 60)R{sub s} (R{sub s}: Schwarzschild radius) as a deprojected distance, from the 43 GHz core in the approaching jet. In addition, the innermost component atmore » the counterjet side appeared to approach the same position at infinity of the frequency, indicating that cores on both sides are approaching the same position, suggesting a spatial coincidence with the central engine. Applying a phase-referencing technique, we also obtained spectral index maps, which indicate that emission from the counterjet is affected by free–free absorption (FFA). The result of the core shift profile on the counterjet also requires FFA because the core positions at 5–15 GHz cannot be explained by a simple core shift model based on synchrotron self-absorption (SSA). Our result is apparently consistent with the SSA core shift with an additional disk-like absorber over the counterjet side. Core shift and opacity profiles at the counterjet side suggest a two-component accretion: a radiatively inefficient accretion flow at the inner region and a truncated thin disk in the outer region. We proposed a possible solution about density and temperature profiles in the outer disk on the basis of the radio observation.« less
Multiple Experimental Efforts to Understand the Structure and Dynamics of Earth's Core
NASA Astrophysics Data System (ADS)
Fei, Y.; Han, L.; Bennett, N.; Hou, M.; Kuwayama, Y.; Huang, H.
2014-12-01
It requires integration of data from different types of high-pressure experiments to understand the structure and dynamics of Earth's core. In particular, measurements of physical properties and element partitioning in systems relevant to the core provide complementary data to narrow down the range of possible core compositions. We have performed both static and dynamic compression experiments and combined results from these with literature data to establish a reliable thermal equation of state of iron. This allows us to precisely determine the density deficit in the solid inner core. The combination of density and sound velocity measurements for both solid and liquid iron and its alloys provide tight constraints on the density deficit in the liquid outer core and the amount of sulphur required to match the geophysical observations. We then conducted element-partitioning experiments between solid and liquid iron in both multi-anvil apparatus and the laser-heated diamond-anvil cell to determine the sulphur, silicon, and oxygen partitioning between the liquid outer core and solid inner core. We present newly developed high-pressure experimental and nano-scale analytical techniques that allow us to simulate the conditions of the inner core boundary (ICB) and analyze the chemical compositions of coexisting phases in the recovered samples. We have established protocols to obtain high-quality partitioning data in the laser-heating diamond-anvil cell combined with FIB/SEM crossbeam technology. The partitioning data obtained up to at least 200 GPa provide additional criteria to explain the observed density and velocity jumps at the ICB.
Misra, Rajeev
2012-01-01
In the last decade, there has been an explosion of publications on the assembly of β-barrel outer membrane proteins (OMPs), which carry out diverse cellular functions, including solute transport, protein secretion, and assembly of protein and lipid components of the outer membrane. Of the three outer membrane model systems—Gram-negative bacteria, mitochondria and chloroplasts—research on bacterial and mitochondrial systems has so far led the way in dissecting the β-barrel OMP assembly pathways. Many exciting discoveries have been made, including the identification of β-barrel OMP assembly machineries in bacteria and mitochondria, and potentially the core assembly component in chloroplasts. The atomic structures of all five components of the bacterial β-barrel assembly machinery (BAM) complex, except the β-barrel domain of the core BamA protein, have been solved. Structures reveal that these proteins contain domains/motifs known to facilitate protein-protein interactions, which are at the heart of the assembly pathways. While structural information has been valuable, most of our current understanding of the β-barrel OMP assembly pathways has come from genetic, molecular biology, and biochemical analyses. This paper provides a comparative account of the β-barrel OMP assembly pathways in Gram-negative bacteria, mitochondria, and chloroplasts. PMID:27335668
Atmospheric Mining in the Outer Solar System: Aerial Vehicle Mission and Design Issues
NASA Technical Reports Server (NTRS)
Palaszewski, Bryan
2015-01-01
Atmospheric mining in the outer solar system has been investigated as a means of fuel production for high energy propulsion and power. Fusion fuels such as Helium 3 (3He) and deuterium can be wrested from the atmospheres of Uranus and Neptune and either returned to Earth or used in-situ for energy production. Helium 3 and deuterium were the primary gases of interest with hydrogen being the primary propellant for nuclear thermal solid core and gas core rocket-based atmospheric flight. A series of analyses were undertaken to investigate resource capturing aspects of atmospheric mining in the outer solar system. This included the gas capturing rate, storage options, and different methods of direct use of the captured gases. While capturing 3He, large amounts of hydrogen and 4He are produced. With these two additional gases, the potential for fueling small and large fleets of additional exploration and exploitation vehicles exists. The mining aerospacecraft (ASC) could fly through the outer planet atmospheres, for global weather observations, localized storm or other disturbance investigations, wind speed measurements, polar observations, etc. Analyses of orbital transfer vehicles (OTVs), landers, and in-situ resource utilization (ISRU) mining factories are included. Preliminary observations are presented on near-optimal selections of moon base orbital locations, OTV power levels, and OTV and lander rendezvous points.
Nares, Salvador; Moutsopoulos, Niki M.; Angelov, Nikola; Rangel, Zoila G.; Munson, Peter J.; Sinha, Neha; Wahl, Sharon M.
2009-01-01
Long-lived monocytes, macrophages, and dendritic cells (DCs) are Toll-like receptor-expressing, antigen-presenting cells derived from a common myeloid lineage that play key roles in innate and adaptive immune responses. Based on immunohistochemical and molecular analyses of inflamed tissues from patients with chronic destructive periodontal disease, these cells, found in the inflammatory infiltrate, may drive the progressive periodontal pathogenesis. To investigate early transcriptional signatures and subsequent proteomic responses to the periodontal pathogen, Porphyromonas gingivalis, donor-matched human blood monocytes, differentiated DCs, and macrophages were exposed to P. gingivalis lipopolysaccharide (LPS) and gene expression levels were measured by oligonucleotide microarrays. In addition to striking differences in constitutive transcriptional profiles between these myeloid populations, we identify a P. gingivalis LPS-inducible convergent, transcriptional core response of more than 400 annotated genes/ESTs among these populations, reflected by a shared, but quantitatively distinct, proteomic response. Nonetheless, clear differences emerged between the monocytes, DCs, and macrophages. The finding that long-lived myeloid inflammatory cells, particularly DCs, rapidly and aggressively respond to P. gingivalis LPS by generating chemokines, proteases, and cytokines capable of driving T-helper cell lineage polarization without evidence of corresponding immunosuppressive pathways highlights their prominent role in host defense and progressive tissue pathogenesis. The shared, unique, and/or complementary transcriptional and proteomic profiles may frame the context of the host response to P. gingivalis, contributing to the destructive nature of periodontal inflammation. PMID:19264901
Optimization of a Boiling Water Reactor Loading Pattern Using an Improved Genetic Algorithm
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kobayashi, Yoko; Aiyoshi, Eitaro
2003-08-15
A search method based on genetic algorithms (GA) using deterministic operators has been developed to generate optimized boiling water reactor (BWR) loading patterns (LPs). The search method uses an Improved GA operator, that is, crossover, mutation, and selection. The handling of the encoding technique and constraint conditions is designed so that the GA reflects the peculiar characteristics of the BWR. In addition, some strategies such as elitism and self-reproduction are effectively used to improve the search speed. LP evaluations were performed with a three-dimensional diffusion code that coupled neutronic and thermal-hydraulic models. Strong axial heterogeneities and three-dimensional-dependent constraints have alwaysmore » necessitated the use of three-dimensional core simulators for BWRs, so that an optimization method is required for computational efficiency. The proposed algorithm is demonstrated by successfully generating LPs for an actual BWR plant applying the Haling technique. In test calculations, candidates that shuffled fresh and burned fuel assemblies within a reasonable computation time were obtained.« less
Counter-Rotatable Fan Gas Turbine Engine with Axial Flow Positive Displacement Worm Gas Generator
NASA Technical Reports Server (NTRS)
Giffin, Rollin George (Inventor); Murrow, Kurt David (Inventor); Fakunle, Oladapo (Inventor)
2014-01-01
A counter-rotatable fan turbine engine includes a counter-rotatable fan section, a worm gas generator, and a low pressure turbine to power the counter-rotatable fan section. The low pressure turbine maybe counter-rotatable or have a single direction of rotation in which case it powers the counter-rotatable fan section through a gearbox. The gas generator has inner and outer bodies having offset inner and outer axes extending through first, second, and third sections of a core assembly. At least one of the bodies is rotatable about its axis. The inner and outer bodies have intermeshed inner and outer helical blades wound about the inner and outer axes and extending radially outwardly and inwardly respectively. The helical blades have first, second, and third twist slopes in the first, second, and third sections respectively. A combustor section extends through at least a portion of the second section.
Protein targeting and integration signal for the chloroplastic outer envelope membrane.
Li, H M; Chen, L J
1996-01-01
Most proteins in chloroplasts are encoded by the nuclear genome and synthesized in the cytosol. With the exception of most quter envelope membrane proteins, nuclear-encoded chloroplastic proteins are synthesized with N-terminal extensions that contain the chloroplast targeting information of these proteins. Most outer membrane proteins, however, are synthesized without extensions in the cytosol. Therefore, it is not clear where the chloroplastic outer membrane targeting information resides within these polypeptides. We have analyzed a chloroplastic outer membrane protein, OEP14 (outer envelope membrane protein of 14 kD, previously named OM14), and localized its outer membrane targeting and integration signal to the first 30 amino acids of the protein. This signal consists of a positively charged N-terminal portion followed by a hydrophobic core, bearing resemblance to the signal peptides of proteins targeted to the endoplasmic reticulum. However, a chimeric protein containing this signal fused to a passenger protein did not integrate into the endoplasmic reticulum membrane. Furthermore, membrane topology analysis indicated that the signal inserts into the chloroplastic outer membrane in an orientation opposite to that predicted by the "positive inside" rule. PMID:8953775
Löest, C A; Gilliam, G G; Waggoner, J W; Turner, J L
2018-04-27
Steers exposed to an endotoxin may require additional branched-chain AA (BCAA) to support an increase in synthesis of immune proteins. This study evaluated effects of bacterial lipopolysaccharide (LPS) and BCAA supplementation on blood metabolites and N balance of 20 ruminally-cannulated steers (177 ± 4.2 kg BW). The experiment was a randomized block design, with 14-d adaptation to metabolism stalls and diet (DM fed = 1.5% BW) and 6-d collection. Treatments were a 2 × 2 factorial of LPS (0 vs 1.0 to 1.5 μg/kg BW; -LPS vs +LPS) and BCAA (0 vs 35 g/d; -BCAA vs +BCAA). The LPS in 100 mL sterile saline was infused (1 mL/min via i.v. catheter) on d 15. The BCAA in an essential AA solution were abomasally infused (900 mL/d) 3 times daily in equal portions beginning on d 7. Blood, rumen fluid, and rectal temperature were collected on d 15 at h 0, 2, 4, 8, 12, and 24 after LPS infusion. Feces and urine were collected from d 16 to 20. Rectal temperatures were greater for +LPS vs. -LPS steers at 4 h and lower at 8 h after LPS infusion (LPS h, P < 0.01). Serum cortisol and plasma urea N were greater for +LPS than -LPS steers at 2 (cortisol only), 4, 8, 12, and 24 h after LPS infusion (LPS × h, P < 0.01). Serum cortisol was greater for +BCAA than -BCAA steers at 12 h after LPS infusion (BCAA × h, P < 0.05). Serum glucose was greater for +LPS than -LPS steers at 2 h after LPS infusion (LPS × h, P < 0.01). Plasma Ile, Leu, and Val were lower, and plasma His was greater in +LPS than -LPS steers (LPS, P < 0.05). Plasma Lys, Met, Thr, and Trp of +LPS steers was lower than -LPS steers at 4 (Thr only), 8 (Lys and Trp only), 12, and 24 h after infusion (LPS × h, P < 0.05). Plasma Ile, Leu, and Val were greater (BCAA, P < 0.01), and Met, His, Phe, Thr, and Trp were lower for +BCAA than -BCAA steers at 0 h and 24 h after LPS infusion (BCAA × h, P ≤ 0.05). Steers receiving +LPS had lower rumen pH at 8 h, greater total VFA at 8 h, and lower rumen NH3 at 24 h after LPS infusion compared with -LPS steers (LPS × h, P ≤ 0.04). Total tract passage rates, DM, OM, NDF, ADF, and N intake, fecal N, digested N, and retained N were lower (P < 0.05) for +LPS than -LPS steers. Total N supply (dietary plus infused) and fecal N were greater (P < 0.05) for +BCAA vs -BCAA steers. The absence of LPS × BCAA interactions (P ≥ 0.20) for N balance indicated that post-ruminal supplementation of BCAA did not alleviate the negative effects of endotoxin on N utilization by growing steers.
Komatsu, Toshiya; Aida, Yoshitomi; Fukuda, Takao; Sanui, Terukazu; Hiratsuka, Shunji; Pabst, Michael J; Nishimura, Fusanori
2016-04-01
We studied the interaction of LPS with albumin, hemoglobin or high-density lipoprotein (HDL), and whether the interaction affected the activity of LPS on neutrophils. These proteins disaggregated LPS, depending upon temperature and LPS:protein ratio. Albumin-treated LPS was absorbed by immobilized anti-albumin antibody and was eluted with Triton X-100, indicating that LPS formed a hydrophobic complex with albumin. Rd mutant LPS was not disaggregated by the proteins, and did not form a complex with the proteins. But triethylamine-treated Rd mutant LPS formed complexes. When LPS was incubated with an equal concentration of albumin and with polymyxin B (PMXB), PMXB-LPS-protein three-way complexes were formed. After removal of PMXB, the complexes consisted of 11-15 LPS monomers bound to one albumin or hemoglobin molecule. LPS primed neutrophils for enhanced release of formyl peptide-stimulated superoxide, in a serum- and LPS-binding protein (LBP)-dependent manner. Although LPS plus LBP alone did not prime neutrophils, albumin-, hemoglobin- or HDL-treated LPS primed neutrophils when added with LBP. Triethylamine-treated Rd mutant LPS primed neutrophils only when incubated with one of the proteins and with LBP. Thus, in addition to LBP, disaggregation and complex formation of LPS with one of these proteins is required for LPS to prime neutrophils. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Evolutionary status of the pre-protostellar core L1498
NASA Technical Reports Server (NTRS)
Kuiper, T. B.; Langer, W. D.; Velusamy, T.; Levin, S. M. (Principal Investigator)
1996-01-01
L1498 is a classic example of a dense cold pre-protostellar core. To study the evolutionary status, the structure, dynamics, and chemical properties of this core we have obtained high spatial and high spectral resolution observations of molecules tracing densities of 10(3)-10(5) cm-3. We observed CCS, NH3, C3H2, and HC7N with NASA's DSN 70 m antennas. We also present large-scale maps of C18O and 13CO observed with the AT&T 7 m antenna. For the high spatial resolution maps of selected regions within the core we used the VLA for CCS at 22 GHz, and the Owens Valley Radio Observatory (OVRO) MMA for CCS at 94 GHz and CS (2-1). The 22 GHz CCS emission marks a high-density [n(H2) > 10(4) cm -3] core, which is elongated with a major axis along the SE-NW direction. NH3 and C3H2 emissions are located inside the boundary of the CCS emission. C18O emission traces a lower density gas extending beyond the CCS boundary. Along the major axis of the dense core, CCS, NH3 and C3H2 emission show evidence of limb brightening. The observations are consistent with a chemically differentiated onion-shell structure for the L1498 core, with NH3 in the inner and CCS in the outer parts of the core. The high angular resolution (9"-12") spectral line maps obtained by combining NASA Goldstone 70 m and VLA data resolve the CCS 22 GHz emission in the southeast and northwest boundaries into arclike enhancements, supporting the picture that CCS emission originates in a shell outside the NH3 emitting region. Interferometric maps of CCS at 94 GHz and CS at 98 GHz show that their emitting regions contain several small-scale dense condensations. We suggest that the differences between the CCS, CS, C3H2, and NH3 emission are caused by a time-dependent effect as the core evolves slowly. We interpret the chemical and physical properties of L1498 in terms of a quasi-static (or slowly contracting) dense core in which the outer envelope is still growing. The growth rate of the core is determined by the density increase in the CCS shell resulting from the accretion of the outer low-density gas traced by C18O. We conclude that L1498 could become unstable to rapid collapse to form a protostar in less than 5 x 10(6) yr.
Noe, Gregory B.
2011-01-01
A modification of the resin-core method was developed and tested for measuring in situ soil N and P net mineralization rates in wetland soils where temporal variation in bidirectional vertical water movement and saturation can complicate measurement. The modified design includes three mixed-bed ion-exchange resin bags located above and three resin bags located below soil incubating inside a core tube. The two inner resin bags adjacent to the soil capture NH4+, NO3-, and soluble reactive phosphorus (SRP) transported out of the soil during incubation; the two outer resin bags remove inorganic nutrients transported into the modified resin core; and the two middle resin bags serve as quality-control checks on the function of the inner and outer resin bags. Modified resin cores were incubated monthly for a year along the hydrogeomorphic gradient through a floodplain wetland. Only small amounts of NH4+, NO3-, and SRP were found in the two middle resin bags, indicating that the modified resin-core design was effective. Soil moisture and pH inside the modified resin cores typically tracked changes in the surrounding soil abiotic environment. In contrast, use of the closed polyethylene bag method provided substantially different net P and N mineralization rates than modified resin cores and did not track changes in soil moisture or pH. Net ammonification, nitrifi cation, N mineralization, and P mineralization rates measured using modified resin cores varied through space and time associated with hydrologic, geomorphic, and climatic gradients in the floodplain wetland. The modified resin-core technique successfully characterized spatiotemporal variation of net mineralization fluxes in situ and is a viable technique for assessing soil nutrient availability and developing ecosystem budgets.
Numerical study on the thermo-chemically driven Geodynamo
NASA Astrophysics Data System (ADS)
Trümper, Tobias; Hansen, Ulrich
2014-05-01
In our numerical study we consider magneto-convection in the Earth's outer core driven by buoyancy induced by heterogeneities both in the thermal and the chemical field. The outer core is thus treated as a self-gravitating, rotating, spherical shell with unstable thermal and chemical gradients across its radius. The thermal gradient is maintained by secular cooling of the core and the release of latent heat at the inner core freezing front. Simultaneously, the concentration of the light constituents of the liquid phase increases at the inner core boundary since only a smaller fraction of the light elements can be incorporated during solidification. Thus, the inner core boundary constitutes a source of compositional buoyancy. The molecular diffusivities of the driving agents differ by some orders of magnitude so that a double-diffusive model is employed in order to study the flow dynamics of this system. We investigate the influence of different thermo-chemical driving scenarios on the structure of the flow and the internal magnetic field. A constant ratio of the diffusivities (Le=10) and a constant Ekman number (Ek=10-4) are adopted. Apart from testing different driving scenarios, the double-diffusive approach also allows to implement distinct boundary conditions on temperature and composition. Isochemical and fixed chemical flux boundary conditions are implemented in order to investigate their respective influence on the flow and magnetic field generation.
Iliyasu, U; Ibrahim, Y V; Umar, Sadiq; Agbo, S A; Jibrin, Y
2017-05-01
Investigation of reactivity variation due to flooding of the irradiation channels of Nigeria Research Reactor (NIRR-1) a low power miniature neutron source reactor (MNSR) located at the Centre for Energy Research and Training, Ahmadu Bello University, Zaria Nigeria using the MCNP code for High Enrich Uranium (HEU) and Low Enrich Uranium (LEU) core has been simulated in this present study. In this work, the excess reactivity worth of flooding HEU core for 1 inner, 2 inner, 3 inner, 4 inner and all inner are 0.318mk, 0.577mk, 0.318mk, 1.204mk and 1.503mk respectively, and outer irradiation channels are 0.119mk, 0.169mk, 0.348mk, 0.438mk and 0.418mk respectively, the highest excess reactivity result from flooding both inner and outer irradiation channels is 2.04mk (±1.72×10 -7 ), the excess reactivity for LEU core was 0.299mk, 0.568mk, 0.896mk, 1.195mk and 1.524mk in the inner irradiation channels, and the outer irradiation channels are 0.129mk, 0.189mk, 0.219mk, 0.269mk and 0.548mk where the highest excess reactivity was 1.942mk (±1.64×10 -7 ) resulting from flooding inner and outer irradiation channels. The reactivity induced by flooding of the irradiation channels of NIRR-1 with water is within design safety limit enshrined in Safety Analysis Report of NIRR-1. The results also compare well with literature. Copyright © 2017 Elsevier Ltd. All rights reserved.
Magnetic braking of stellar cores in red giants and supergiants
DOE Office of Scientific and Technical Information (OSTI.GOV)
Maeder, André; Meynet, Georges, E-mail: andre.maeder@unige, E-mail: georges.meynet@unige.ch
2014-10-01
Magnetic configurations, stable on the long term, appear to exist in various evolutionary phases, from main-sequence stars to white dwarfs and neutron stars. The large-scale ordered nature of these fields, often approximately dipolar, and their scaling according to the flux conservation scenario favor a fossil field model. We make some first estimates of the magnetic coupling between the stellar cores and the outer layers in red giants and supergiants. Analytical expressions of the truncation radius of the field coupling are established for a convective envelope and for a rotating radiative zone with horizontal turbulence. The timescales of the internal exchangesmore » of angular momentum are considered. Numerical estimates are made on the basis of recent model grids. The direct magnetic coupling of the core to the extended convective envelope of red giants and supergiants appears unlikely. However, we find that the intermediate radiative zone is fully coupled to the core during the He-burning and later phases. This coupling is able to produce a strong spin down of the core of red giants and supergiants, also leading to relatively slowly rotating stellar remnants such as white dwarfs and pulsars. Some angular momentum is also transferred to the outer convective envelope of red giants and supergiants during the He-burning phase and later.« less
Sound velocity of Fe-S liquids at high pressure: Implications for the Moon's molten outer core
DOE Office of Scientific and Technical Information (OSTI.GOV)
Jing, Zhicheng; Wang, Yanbin; Kono, Yoshio
2014-07-21
Sound velocities of Fe and Fe–S liquids were determined by combining the ultrasonic measurements and synchrotron X-ray techniques under high pressure–temperature conditions from 1 to 8 GPa and 1573 K to 1973 K. Four different liquid compositions were studied including Fe, Fe–10 wt% S, Fe–20 wt% S, and Fe–27 wt% S. Our data show that the velocity of Fe-rich liquids increases upon compression and decreases with increasing sulfur content, whereas temperature has negligible effect on the velocity of Fe–S liquids. The sound velocity data were combined with ambient-pressure densities to fit the Murnaghan equation of state (EOS). Compared to themore » lunar seismic model, our velocity data constrain the sulfur content at 4±3 wt%, indicating a significantly denser (6.5±0.5 g/cm 3) and hotter (1870-70+100 K) outer core than previously estimated. A new lunar structure model incorporating available geophysical observations points to a smaller core radius. Our model suggests a top–down solidification scenario for the evolution of the lunar core. Such “iron snow” process may have been an important mechanism for the growth of the inner core.« less
Uranus and Neptune: Refugees from the Jupiter-Saturn zone?
NASA Astrophysics Data System (ADS)
Thommes, E. W.; Duncan, M. J.; Levison, H. F.
1999-09-01
Plantesimal accretion models of planet formation have been quite successful at reproducing the terrestrial region of the Solar System. However, in the outer Solar System these models run into problems, and it becomes very difficult to grow bodies to the current mass of the ``ice giants," Uranus and Neptune. Here we present an alternative scenario to in-situ formation of the ice giants. In addition to the Jupiter and Saturn solid cores, several more bodies of mass ~ 10 MEarth or more are likely to have formed in the region between 4 and 10 AU. As Jupiter's core, and perhaps Saturn's, accreted nebular gas, the other nearby bodies must have been scattered outward. Dynamical friction with the trans-Saturnian part of the planetesimal disk would have acted to decouple these ``failed cores" from their scatterer, and to circularize their orbits. Numerical simulations presented here show that systems very similar to our outer Solar System (including Uranus, Neptune, the Kuiper belt, and the scattered disk) are a natural product of this process.
A preliminary examination of differential decomposition patterns in mass graves.
Troutman, Lauren; Moffatt, Colin; Simmons, Tal
2014-05-01
Five pairs of mass graves, each containing carcasses of 21 rabbits, were used to examine differential decomposition at four locations within the burial: surface, deep, mid-outer, and core. Every 100 accumulated degree days (ADD), a pair of graves was exhumed, and total body score (TBS) and internal carcass temperature of each rabbit were recorded. Decomposition did not differ for core- and deep-positioned carcasses (p = 0.13); differences were significant (p < 0.001) for all other location comparisons. Decomposition occurred fastest in shallow carcasses, followed by mid-outer carcasses; deep and core carcasses decomposed slowest and at rates not significantly different from one another. Adipocere formation was minimal and confined to deep carcasses. Carcass location within the mass grave significantly influenced internal carcass temperature (p < 0.001); a mean internal temperature difference of ca. 1°C existed between deep and shallow carcasses (30 cm apart). Effects of mass compactness and oxygenation require further investigation. © 2013 American Academy of Forensic Sciences.
Lipopolysaccharide modulation of a CD14-like molecule on porcine alveolar macrophages
NASA Technical Reports Server (NTRS)
Kielian, T. L.; Ross, C. R.; McVey, D. S.; Chapes, S. K.; Blecha, F.; Spooner, B. S. (Principal Investigator)
1995-01-01
Cluster of differentiation antigen 14 (CD14) functions as a receptor for lipopolysaccharide (LPS) LPS-binding protein (LBP) complexes. Because LPS has varying effects on CD14 expression in vitro, we evaluated CD14 expression in response to LPS with a fully differentiated macrophage phenotype, the alveolar macrophage. By using flow microfluorometric analysis and a radioimmunoassay with an anti-human CD14 monoclonal antibody (My4) that cross-reacts with porcine CD14, we found that macrophages stimulated with LPS for 24 h exhibited a two- to fivefold increase in CD14-like antigen compared with unstimulated cells. At low concentrations of LPS, up-regulation of the CD14-like antigen was dependent on serum; at higher concentrations of LPS, serum was not required. In the absence of serum a 10-fold higher dose of LPS (10 ng/ml) was required to increase CD14-like expression. In addition, LPS-induced CD14-like up-regulation correlated with secretion of tumor necrosis factor-alpha, regardless of serum concentration. Blockade with My4 antibody significantly inhibited LPS-induced tumor necrosis factor-alpha secretion at 1 ng/ml of LPS. However, inhibition decreased as we increased the LPS concentration, suggesting the existence of CD14-independent pathways of macrophage activation in response to LPS. Alternatively, My4 may have a lower affinity for the porcine CD14 antigen than LPS, which may have only partially blocked the LPS-LBP binding site at high concentrations of LPS. Therefore, these data suggest that LPS activation of porcine alveolar macrophages for 24 h increased CD14-like receptor expression. The degree of CD14-like up-regulation was related to LPS concentration, however, activation did not require the presence of serum at high concentrations of LPS.
Gisslen, Tate; Hillman, Noah H; Musk, Gabrielle C; Kemp, Matthew W; Kramer, Boris W; Senthamaraikannan, Paranthaman; Newnham, John P; Jobe, Alan H; Kallapur, Suhas G
2014-02-01
Histologic chorioamnionitis, frequently associated with preterm births and adverse outcomes, results in prolonged exposure of preterm fetuses to infectious agents and pro-inflammatory mediators, such as LPS. Endotoxin tolerance-type effects were demonstrated in fetal sheep following repetitive systemic or intra-amniotic (i.a.) exposures to LPS, suggesting that i.a. LPS exposure would cause endotoxin tolerance to a postnatal systemic dose of LPS in preterm sheep. In this study, randomized pregnant ewes received either two i.a. injections of LPS or saline prior to preterm delivery. Following operative delivery, the lambs were treated with surfactant, ventilated, and randomized to receive either i.v. LPS or saline at 30 min of age. Physiologic variables and indicators of systemic and lung inflammation were measured. Intravenous LPS decreased blood neutrophils and platelets values following i.a. saline compared to that after i.a. LPS. Intra-amniotic LPS prevented blood pressure from decreasing following the i.v. LPS, but also caused an increased oxygen index. Intra-amniotic LPS did not cause endotoxin tolerance as assessed by cytokine expression in the liver, lung or plasma, but increased myeloperoxidase-positive cells in the lung. The different compartments of exposure to LPS (i.a. vs i.v.) are unique to the fetal to newborn transition. Intra-amniotic LPS incompletely tolerized fetal lambs to postnatal i.v. LPS.
Ueda, S; Hata, T; Asakura, S; Yamaguchi, H; Kotani, M; Ueda, Y
1994-01-01
A novel controlled drug release system. Time-Controlled Explosion System (TES) has been developed. TES has a four-layered spherical structure, which consists of core, drug, swelling agent and water insoluble polymer membrane. TES is characterized by a rapid drug release with a precisely programmed lag time; i.e. expansion of the swelling agent by water penetrating through the outer membrane, destruction of the membrane by stress due to swelling force and subsequent rapid drug release. For establishing the concept and development strategy, TES was designed using metoprolol and polystyrene balls (size: 3.2 mm in diameter) as a model drug and core particles. Among the polymers screened, low-substituted hydroxypropylcellulose (L-HPC) and ethylcellulose (EC) were selected for a swelling agent and an outer water insoluble membrane, respectively. The release profiles of metoprolol from the system were not affected by the pH of the dissolution media. Lag time was controlled by the thickness of the outer EC membrane; thus, a combination of TES particles possessing different lag times could offer any desired release profile of the model compound, metoprolol.
NASA Astrophysics Data System (ADS)
Fornelli, A.; Langone, A.; Micheletti, F.; Pascazio, A.; Piccarreta, G.
2014-03-01
The recognition of the coeval growth of zircon, orthopyroxene and garnet domains formed during the same metamorphic cycle has been attempted with detailed microanalyses coupled with textural analyses. A coronitic garnet-bearing granulite from the lower crust of Calabria has been considered. U-Pb zircon data and zircon, garnet and orthopyroxene chemistries, at different textural sites, on a thin section of the considered granulite have been used to test possible equilibrium and better constrain the geological significance of the U-Pb ages related to zircon separates from other rocks of the same structural level. The garnet is very rich in REE and is characterised by a decrease in HREE from core to outer core and an increase in the margin. Zircons show core-overgrowth structures showing different chemistries, likely reflecting episodic metamorphic new growth. Zircon grains in matrix, corona around garnet and within the inner rim of garnet, are decidedly poorer in HREE up to Ho than garnet interior. Orthopyroxene in matrix and corona is homogeneously poor in REE. Thus, the outer core of garnet and the analysed zircon grains grew or equilibrated in a REE depleted system due to the former growth of garnet core. Zircon ages ranging from 357 to 333 Ma have been determined in the matrix, whereas ages 327-320 Ma and around 300 Ma have been determined, respectively, on cores and overgrowths of zircons from matrix, corona and inner rim of garnet. The calculated DREEzrn/grt and DREEopx/grt are largely different from the equilibrium values of literature due to strong depletion up to Ho in zircon and orthopyroxene with respect to garnet. On the other hand, the literature data show large variability. In the case study, (1) the D zrn/grt values define positive and linear trends from Gd to Lu as many examples from literature do and the values from Er to Lu approach the experimental results at about 900 °C in the combination zircon dated from 339 to 305 Ma with garnet outer core, and (2) D opx/grt values define positive trends reaching values considered as suggestive of equilibrium from Er to Lu only with respect to the outer core of garnet. The presence of a zircon core dated 320 Ma in the inner rim of garnet suggests that it, as well as those dated at 325-320 Ma in the other textural sites and, probably, those dated at 339-336 Ma showing depletion of HREE, grew after the garnet core, which sequestered a lot of HREE and earlier than the HREE rich margin of garnet. The quite uniform REE contents in orthopyroxene from matrix and corona and the low and uniform contents of HREE in the zircon overgrowths dated at about 300 Ma allow to think that homogenisation occurred during or after the corona formation around this age. The domains dated around 325-320 Ma would approximate the stages of decompression, whereas the metamorphic peak probably occurred earlier than 339 Ma.
HIGH TEMPERATURE, HIGH POWER HETEROGENEOUS NUCLEAR REACTOR
Hammond, R.P.; Wykoff, W.R.; Busey, H.M.
1960-06-14
A heterogeneous nuclear reactor is designed comprising a stationary housing and a rotatable annular core being supported for rotation about a vertical axis in the housing, the core containing a plurality of radial fuel- element supporting channels, the cylindrical empty space along the axis of the core providing a central plenum for the disposal of spent fuel elements, the core cross section outer periphery being vertically gradated in radius one end from the other to provide a coolant duct between the core and the housing, and means for inserting fresh fuel elements in the supporting channels under pressure and while the reactor is in operation.
Properties of iron alloys under the Earth's core conditions
NASA Astrophysics Data System (ADS)
Morard, Guillaume; Andrault, Denis; Antonangeli, Daniele; Bouchet, Johann
2014-05-01
The Earth's core is constituted of iron and nickel alloyed with lighter elements. In view of their affinity with the metallic phase, their relative high abundance in the solar system and their moderate volatility, a list of potential light elements have been established, including sulfur, silicon and oxygen. We will review the effects of these elements on different aspects of Fe-X high pressure phase diagrams under Earth's core conditions, such as melting temperature depression, solid-liquid partitioning during crystallization, and crystalline structure of the solid phases. Once extrapolated to the inner-outer core boundary, these petrological properties can be used to constrain the Earth's core properties.
NASA Astrophysics Data System (ADS)
Asimow, P. D.; Nguyen, J.; Akin, M. C.; Fatýanov, O. V.
2015-12-01
Detailed elasticity data on liquid Fe and candidate molten core alloys should offer new constraints on the under-constrained problem of Earth's core composition. Density, sound speed, and the gradient in sound speed with pressure are each potentially distinct experimental constraints and are each well-known for Earth. The gradient in sound speed, though, has not been used because sound speed depends on both T and P, such that data must be collected or reconstructed along the correct, nearly adiabatic, thermal profile. Reconstruction requires the Grüneisen γ, which is composition-dependent, and data over a large P-T space to allow extrapolation. Both static and dynamic compression methods could be used, but the conditions (140 - 330 GPa and 4000 - 6000 K) are very challenging for static methods and standard shock compression only samples the outer core P-T profile at a single P. Instead we are applying quasi-isentropic dynamic ramp compression, using pre-heating of the target and impedance of the leading edge of a graded-density impactor (GDI) to select a probable outer core isentrope. The target material is melted and raised to a point on the outer core isentrope by the initial shock, then quasi-isentropically ramped to a maximum P by increasing shock impedance of trailing GDI layers. Particle velocity is monitored by photonic doppler velocimetry (PDV) at two step thicknesses at the interface of Fe or Fe-alloy target and MgO windows. The difference in arrival time of each particle velocity at the two steps directly gives the Lagrangian sound speed vs. particle velocity, which is integrated to obtain Pand density. At the writing of this abstract, we have completed one shot of this type. We successfully heated a two-step Fe target in a Mo capsule with MgO windows to 1350 °C, maintaining sufficient alignment and reflectivity to collect PDV signal returns. We characterized the velocity correction factor for PDV observation through MgO windows, and have confirmed that MgO remains sufficiently transparent on this loading path to act as a window. Our shot used a Mg-Ta graded density impactor launched at 5.6 km/s by the Caltech two-stage light gas gun, providing continuous sampling of the sound speed of liquid Fe from 70 GPa and ~2800 K up the isentrope to 243 GPa. Analysis continues. Prepared by LLNL under Contract DE-AC52-07NA27344
Ziaco, Marcello; De Castro, Cristina; Silipo, Alba; Corsaro, Maria Michela; Molinaro, Antonio; Iadonisi, Alfonso; Lanzetta, Rosa; Parrilli, Michelangelo; Bedini, Emiliano
2015-02-11
The first synthesis of the outer core fragment of Burkholderia multivorans lipooligosaccharide [β-D-Glc-(1→3)-α-D-GalNAc-(1→3)-β-D-GalNAc-(1→3)-L-Rha] as α-allyl tetrasaccharide was accomplished. The glycosylations involving GalNAc units were studied in depth testing them under several conditions. This allowed the building of both the α- and the β-configured glycosidic bonds by employing the same GalNAc glycosyl donor, thus considerably shortening the total number of synthetic steps. The target tetrasaccharide was synthesized with an allyl aglycone to allow its future conjugation with an immunogenic protein en route to the development of a synthetic neoglycoconjugate vaccine against the Burkholderia cepacia pathogens. Copyright © 2014 Elsevier Ltd. All rights reserved.
Brittle Materials Design, High Temperature Gas Turbine
1981-03-01
slides and core pins which formed the outer diameter and the hollow struts. Inner inserts were used to form the inside surface of the nose cone...ceramic component development. Figure 1 illustrates this by showing, in turn, ready removal in the test cell of a ceramic regenerator core , combusior...objective. This Executive Summary briefly reviews the highlights of the program. VII ■■■ *»W*w»«»^il»^.3«£*a;-^ -,Al^».t, „ . Regenerator Core Removal
The effects of nickel and sulphur on the core-mantle partitioning of oxygen in Earth and Mars
NASA Astrophysics Data System (ADS)
Tsuno, Kyusei; Frost, Daniel J.; Rubie, David C.
2011-03-01
Constraints on the partitioning of oxygen between silicates, oxides, and metallic liquids are important for determining the amount of oxygen that may have entered the cores of terrestrial planets and to identify likely reactions at the core-mantle boundary. Several previous studies have examined oxygen partitioning between liquid Fe metal and ferropericlase, however, the cores of terrestrial planets also contain nickel and most likely sulphur. We have performed experiments to examine the effects of both nickel and sulphur on the partitioning of oxygen between ferropericlase and liquid Fe alloy up to pressures of 24.5 GPa in the temperature range 2430-2750 K using a multianvil press. The results show that at a fixed oxygen fugacity the proportion of oxygen that partitions into liquid metal will decrease by approximately 1-2 mol% on the addition of 10-20 mol% nickel to the liquid. The addition of around 30 mol% sulphur will, on the other hand, increase the metal oxygen content by approximately 10 mol%. Experiments to examine the combined effects of both nickel and sulphur, show a decrease in the effect of nickel on oxygen partitioning as the sulphur content of the metal increases. We expand an existing thermodynamic model for the partitioning of oxygen at high pressures and temperatures to include the effects of nickel and sulphur by fitting these experimental data, with further constraints provided by existing phase equilibria studies at similar conditions in the Fe-S and Fe-O-S systems. Plausible terrestrial core sulphur contents have little effect on oxygen partitioning. When our model is extrapolated to conditions of the present day terrestrial core-mantle boundary, the presence of nickel is found to lower the oxygen content of the outer core that is in equilibrium with the expected mantle ferropericlase FeO content, by approximately 1 weight %, in comparison to nickel free calculations. In agreement with nickel-free experiments, this implies that the Earth's outer core is undersaturated in oxygen with respect to plausible mantle FeO contents, which will result in either the depletion of FeO from the base of the mantle or cause the development of an outer core layer that is enriched in oxygen. The oxygen content of the more sulphur-rich Martian core would be in the range 2-4 wt.% if it is in equilibrium with the FeO-rich Martian mantle.
Wortman, Jeremy R; Tirumani, Sree Harsha; Tirumani, Harika; Shinagare, Atul B; Jagannathan, Jyothi P; Hornick, Jason L; Ramaiya, Nikhil H
2016-05-01
To evaluate MRI features of response of primary extremity liposarcoma (LPS) to neoadjuvant radiation therapy (RT) with histopathologic correlation. In this IRB-approved study including 125 patients with extremity LPS treated with neoadjuvant RT from 2000 to 2013, MRI of the primary tumour in 18 patients (5 pleomorphic LPS, 13 myxoid LPS) before and after RT were reviewed by two radiologists by consensus. Histopathology of the surgical specimens was reviewed by a pathologist with expertise in sarcomas. In the pleomorphic LPS cohort, 3/5 tumours increased in size; 3/5 decreased in enhancing component; and 3/5 increased in peritumoral oedema, intratumoral haemorrhage, and necrosis. In the myxoid LPS cohort, 12/13 tumours decreased in size, 8/13 decreased in enhancing component, and 5/13 increased in internal fat following RT. Histopathology showed ≥50% residual tumour in 1/5 pleomorphic LPS and 2/13 myxoid LPS. Hyalinization/necrosis of ≥75% was noted in 4/5 pleomorphic LPS and 11/13 myxoid LPS. Cytodifferentiation was noted in 1/5 pleomorphic and 9/13 myxoid LPS. While pleomorphic LPS showed an increase in size, peritumoral oedema, intratumoral haemorrhage, and necrosis on MRI following neoadjuvant RT, myxoid LPS showed a decrease in size and enhancement with an increase in internal fat. • Pleomorphic LPS commonly increase in size and necrosis on MRI following RT. • Myxoid LPS commonly decrease in size and enhancement on MRI following RT. • Myxoid LPS often increase in fatty component on MRI following RT.
NASA Astrophysics Data System (ADS)
Matsumoto, K.; Yamada, R.; Kikuchi, F.; Kamata, S.; Ishihara, Y.; Iwata, T.; Hanada, H.; Sasaki, S.
2014-12-01
We tried to constrain lunar internal structure by combining the Apollo seismic travel time data and selenodetic data including those from GRAIL and LLR. We used a seven-layer model consisting of crust, upper mantle, middle mantle, lower mantle, low-velocity layer (LVL), fluid outer core and solid inner core. The model is constrained by the following observations; three selenodetic data of mass, mean moment of inertia, tidal Love number k2 from [1], and Apollo seismic travel time data from [2]. Markov Chain Monte Carlo method is used to infer the model parameters. We collected 140 million samples from 10 chains. Viscosity is not taken into account in this calculation. Mean crustal thickness of 46 ± 4 km is estimated by fitting a normal distribution curve to the posterior distribution, which is to be compared with the previous estimate of 34 - 43 km [3]. Major part of crustal densities is sampled between 2500 and 2600 kg/m3, which is consistent with the value of 2550 kg/m3 reported by [3]. In general, seismic wave velocities in the mantle are consistent with the previous estimates [4][5]. The ranges of size and density of the outer core which satisfy the observation are relatively wide and it is difficult to tightly constrain them. Strong correlation between outer core size and LVL thickness is observed. The smaller outer core should be accompanied by thick LVL and vice versa. When we take into account the upper bound of the fluid core size of 400 km which is predicted by magnetic observation [6], the thickness of the LVL is at least about 100 km. The S-wave velocity within this low-velocity layer is estimated to be less than about 3 km/s. The effect of low viscosity [7] may change the estimate of the S-wave velocity in the LVL. The inner core radius is expected to be smaller than 280 km. The lunar displacement Love number is predicted to be h2= 0.0423 ± 0.0004. References [1] Williams et al. (2014), JGR, doi:10.1002/2013JE004559 [2] Lognonne et al. (2003), EPSL, 211, 27-44 [3] Wieczorek et al. (2012), Science, doi:10.1126/science.1231530 [4] Weber et al. (2011), Science, 331, 309-312, doi:10.1126/science.1199375 [5] Garcia et al. (2011), PEPI, doi:10.1016/j.pepi.2011.06.015 [6] Shimizu et al. (2013), Icarus, doi:10.1016/j.icarus.2012.10.029 [7] Harada et al. (2014), Nature geoscience, doi:10.1038/NGEO2211
Kukoamine B promotes TLR4-independent lipopolysaccharide uptake in murine hepatocytes.
Yang, Dong; Zheng, Xinchuan; Wang, Ning; Fan, Shijun; Yang, Yongjun; Lu, Yongling; Chen, Qian; Liu, Xin; Zheng, Jiang
2016-09-06
Free bacterial lipopolysaccharide (LPS) is generally removed from the bloodstream through hepatic uptake via TLR4, the LPS pattern recognition receptor, but mechanisms for internalization and clearance of conjugated LPS are less clear. Kukoamine B (KB) is a novel cationic alkaloid that interferes with LPS binding to TLR4. In this study, KB accelerated blood clearance of LPS. KB also enhanced LPS distribution in the hepatic tissues of C57 BL/6 mice, along with LPS uptake in primary hepatocytes and HepG2 cells. By contrast, KB inhibited LPS internalization in Kupffer and RAW 264.7 cells. Loss of TLR4 did not affect LPS uptake into KB-treated hepatocytes. We also detected selective upregulation of the asialoglycoprotein receptor (ASGPR) upon KB treatment, and ASGPR colocalized with KB in cultured hepatocytes. Molecular docking showed that KB bound to ASGPR in a manner similar to GalNAc, a known ASGPR agonist. GalNAc dose-dependently reduced KB internalization, suggesting it competes with KB for ASGPR binding, and ASGPR knockdown also impaired LPS uptake into hepatocytes. Finally, while KB enhanced LPS uptake, it was protective against LPS-induced inflammation and hepatocyte injury. Our study provides a new mechanism for conjugated LPS hepatic uptake induced by the LPS neutralizer KB and mediated by membrane ASGPR binding.
Highly birefringent suspended-core photonic microcells for refractive-index sensing
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wang, Chao; The Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen 518057; Jin, Wa
2014-08-11
An in-line photonic microcell with a highly birefringent suspended microfiber core is fabricated by locally heating and pressurizing selected air-holes of an endless single mode photonic crystal fiber. The microfiber core has rhombus-like cross-sectional geometry and could achieve a high birefringence of up to 10{sup −2}. The microfiber core is fixed at the center of the microcell by thin struts attached to an outer jacket tube, which protects and isolates the microfiber from environmental contaminations. Highly sensitive and robust refractive index sensors based on such microcells are experimentally demonstrated.
Collodel, Giulia; Moretti, Elena; Del Vecchio, Maria Teresa; Biagi, Marco; Cardinali, Raffaella; Mazzi, Lucia; Brecchia, Gabriele; Maranesi, Margherita; Manca, Daniela; Castellini, Cesare
2014-08-01
The aims of the study were to evaluate the effects of chocolate and propolis-enriched diets on rabbit spermatogenesis, sperm motility, and ultrastructure following bacterial lipopolysaccharide (LPS) treatment. Thirty-two New Zealand White rabbits were divided into four groups. The LPS-Propolfenol(®) group received propolis (500 mg/kg/day) in their diet for 15 days, while the LPS-chocolate group was fed 70% cacao chocolate (1 g/1 kg/day) for the same period. Following the diet treatments, rabbits in the LPS-Propolfenol(®) and LPS-chocolate groups, and an LPS group received a single intraperitoneal dose of 50 μg/kg LPS, and the control group received only saline. Kinematic sperm traits were evaluated with a computer assisted sperm analyzer (CASA) system, and ultrastructural characteristics were examined by transmission electron microscopy (TEM). Testicular and epididymal tissues were observed by light microscopy and TEM and multiplex real time reverse transcriptase-polymerase chain reaction (RT-PCR) assay was used to detect and quantify toll-like receptor-4 (TLR-4) gene expression. The values of the analyzed semen parameters of rabbits treated with LPS-Propolfenol(®) and LPS-chocolate did not show any variations compared with the control group, but they were lower in rabbits treated only with LPS. Alterations observed in the testicular tissue of LPS treated-rabbits were not detected in specimens from the LPS-chocolate and LPS-Propolfenol(®) groups, which showed normal spermatogenesis. The TLR-4 mRNA expression was similar in controls, in LPS treated, and in LPS-chocolate groups, but it was significantly (p < 0.01) decreased in LPS-Propolfenol(®) rabbits. In conclusion, a chocolate and propolis-enriched diet showed a protective effect on the spermatogenetic process of buck rabbits following LPS treatment.
Flow cytometric analysis of crayfish haemocytes activated by lipopolysaccharides
Cardenas, W.; Dankert, J.R.; Jenkins, J.A.
2004-01-01
Lipopolysaccharides (LPS) from Gram-negative bacteria are strong stimulators of white river crayfish, Procambarus zonangulus, haemocytes in vitro. Following haemocyte treatment with LPS and with LPS from rough mutant R5 (LPS Rc) from Salmonella minnesota, flow cytometric analysis revealed a conspicuous and reproducible decrease in cell size as compared to control haemocytes. These LPS molecules also caused a reduction in haemocyte viability as assessed by flow cytometry with the fluorescent dyes calcein-AM and ethidium homodimer. The onset of cell size reduction was gradual and occurred prior to cell death. Haemocytes treated with LPS from S. minnesota without the Lipid A moiety (detoxified LPS) decreased in size without a reduction of viability. The action of LPS on crayfish haemocytes appeared to be related to the activation of the prophenoloxidase system because phenoloxidase (PO)-specific activity in the supernatants from control and detoxified LPS-treated cells was significantly lower than that from LPS and LPS-Rc treated cells (P < 0.05). Furthermore, addition of trypsin inhibitor to the LPS treatments caused noticeable delays in cell size and viability changes. These patterns of cellular activation by LPS formulations indicated that crayfish haemocytes react differently to the polysaccharide and lipid A moieties of LPS, where lipid A is cytotoxic and the polysaccharide portion is stimulatory. These effects concur with the general pattern of mammalian cell activation by LPS, thereby indicting commone innate immune recognition mechanisms to bacterial antigens between cells from mammals and invertebrates. These definitive molecular approaches used to verify and identify mechanisms of invertbrate haemocyte responses to LPS could be applied with other glycoconjugates, soluble mediators, or xenobiotic compounds.
DOE Office of Scientific and Technical Information (OSTI.GOV)
G. S. Chang; M. A. Lillo; R. G. Ambrosek
2008-06-01
The Advanced Test Reactor (ATR) is a high power density and high neutron flux research reactor operating in the United States. Powered with highly enriched uranium (HEU), the ATR has a maximum thermal power rating of 250 MWth. Because of the large test volumes located in high flux areas, the ATR is an ideal candidate for assessing the feasibility of converting an HEU driven reactor to a low-enriched core. The present work investigates the necessary modifications and evaluates the subsequent operating effects of this conversion. A detailed plate-by-plate MCNP ATR 1/8th core model was developed and validated for a fuelmore » cycle burnup comparison analysis. Using the current HEU U 235 enrichment of 93.0 % as a baseline, an analysis was performed to determine the low-enriched uranium (LEU) density and U-235 enrichment required in the fuel meat to yield an equivalent K-eff versus effective full power days (EFPDs) between the HEU and the LEU cores. The MCNP ATR 1/8th core model was used to optimize the U 235 loading in the LEU core, such that the differences in K-eff and heat flux profiles between the HEU and LEU cores were minimized. The depletion methodology MCWO was used to calculate K-eff versus EFPDs in this paper. The MCWO-calculated results for the LEU demonstrated adequate excess reactivity such that the K-eff versus EFPDs plot is similar to the ATR reference HEU case study. Each HEU fuel element contains 19 fuel plates with a fuel meat thickness of 0.508 mm (20 mil). In this work, the proposed LEU (U-10Mo) core conversion case with nominal fuel meat thickness of 0.330 mm (13 mil) and U-235 enrichment of 19.7 wt% is used to optimize the radial heat flux profile by varying the fuel meat thickness from 0.191 mm (7.0 mil) to 0.330 mm (13.0 mil) at the inner 4 fuel plates (1-4) and outer 4 fuel plates (16-19). A 0.8g of Boron-10, a burnable absorber, was added in the inner and outer plates to reduce the initial excess reactivity, and the peak to average ratio of the inner/outer heat flux more effectively. Because the B-10 (n,a) reaction will produce Helium-4 (He-4), which might degrade the LEU foil type fuel performance, an alternative absorber option is proposed. The proposed LEU case study will have 6.918 g of Cadmium (Cd) mixed with the LEU at the inner 4 fuel plates (1-4) and outer 4 fuel plates (16-19) as a burnable absorber to achieve peak to average ratios similar to those for the ATR reference HEU case study.« less
The Effect of Surface Topography on the Nonlinear Dynamics of Rossby Waves
NASA Technical Reports Server (NTRS)
Abarzhi, S. I.; Desjardins, O.; Pitsch, H.
2003-01-01
Boussinesq convection in rotating systems attracts a sustained attention of the fluid dynamics community, because it has intricate non-linear dynamics (Cross & Hohenberg 1993) and plays an important role in geophysical and astrophysical applications, such as the motion of the liquid outer core of Earth, the Red Spot in Jupiter, the giant cells in the Sun etc. (Alridge et al. 1990). A fundamental distinction between the real geo- and astrophysical problems and the idealized laboratory studies is that natural systems are inhomogeneous (Alridge et al. 1990). Heterogeneities modulate the flow and influence significantly the dynamics of convective patterns (Alridge et al. 1990; Hide 1971). The effect of modulations on pattern formation and transition to turbulence in Boussinesq convection is far from being completely understood (Cross & Hohenberg 1993; Aranson & Kramer 2002). It is generally accepted that in the liquid outer core of the Earth the transport of the angular momentum and internal heat occurs via thermal Rossby waves (Zhang et al. 2001; Kuang & Bloxham 1999). These waves been visualized in laboratory experiments in rotating liquid-filled spheres and concentric spherical shells (Zhang et al. 2001; Kuang & Bloxham 1999). The basic dynamical features of Rossby waves have been reproduced in a cylindrical annulus, a system much simpler than the spherical ones (Busse & Or 1986; Or & Busse 1987). For convection in a cylindrical annulus, the fluid motion is two-dimensional, and gravity is replaced by a centrifugal force, (Busse & Or 1986; Or & Busse 1987). Hide (1971) has suggested that the momentum and heat transport in the core might be influenced significantly by so-called bumps, which are heterogeneities on the mantle-core boundary. To model the effect of surface topography on the transport of momentum and energy in the liquid outer core of the Earth, Bell & Soward (1996), Herrmann & Busse (1998) and Westerburg & Busse (2001) have studied the nonlinear dynamics of thermal Rossby waves in a cylindrical annulus with azimuthally modulated height.
NASA Technical Reports Server (NTRS)
Palaszewski, Bryan
2017-01-01
Atmospheric mining in the outer solar system has been investigated as a means of fuel production for high energy propulsion and power. Fusion fuels such as Helium 3 (3He) and deuterium can be wrested from the atmospheres of Uranus and Neptune and either returned to Earth or used in-situ for energy production. Helium 3 and deuterium were the primary gases of interest with hydrogen being the primary propellant for nuclear thermal solid core and gas core rocket-based atmospheric flight. A series of analyses were undertaken to investigate resource capturing aspects of atmospheric mining in the outer solar system. This included the gas capturing rate, storage options, and different methods of direct use of the captured gases. While capturing 3He, large amounts of hydrogen and 4He are produced. The propulsion and transportation requirements for all of the major moons of Uranus and Neptune are presented. Analyses of orbital transfer vehicles (OTVs), landers, factories, and the issues with in-situ resource utilization (ISRU) low gravity processing factories are included. Preliminary observations are presented on near-optimal selections of moon base orbital locations, OTV power levels, and OTV and lander rendezvous points. Several artificial gravity in-space base designs and orbital sites at Uranus and Neptune and the OTV requirements to support them are also addressed.
Improved immunogenicity of tetanus toxoid by Brucella abortus S19 LPS adjuvant.
Mohammadi, Mohsen; Kianmehr, Zahra; Kaboudanian Ardestani, Sussan; Gharegozlou, Behnaz
2014-09-01
Adjuvants are used to increase the immunogenicity of new generation vaccines, especially those based on recombinant proteins. Despite immunostimulatory properties, the use of bacterial lipopolysaccharide (LPS) as an adjuvant has been hampered due to its toxicity and pyrogenicity. Brucella abortus LPS is less toxic and has no pyrogenic properties compared to LPS from other gram negative bacteria. To evaluate the adjuvant effect of B. abortus (vaccine strain, S19) LPS for tetanus toxoid antigen (TT) and to investigate the protective effect of different tetanus vaccine preparations. LPS was extracted and purified from B. abortus S19 and KDO, glycan, phosphate content, and protein contamination were measured. Adipic acid dihydrazide (ADH) was used as a linker for conjugation of TT to LPS. Different amounts of B. abortus LPS, TT, TT conjugated with LPS, and TT mixed with LPS or complete Freund's adjuvant (CFA) were injected into mice and antibody production against TT was measured. The protective effect of induced antibodies was determined by LD50. Immunization of mice with TT+LPS produced the highest anti-TT antibody titer in comparison to the group immunized with TT without any adjuvant or the groups immunized with TT-LPS or TT+CFA. Tetanus toxid-S19 LPS also produced a 100% protective effect against TT in immunized mice. These data indicate that B. abortus LPS enhances the immune responses to TT and suggest the possible use of B. abortus LPS as an adjuvant in vaccine preparations.
Burns, Mark R; Jenkins, Scott A; Vermeulen, Nicolas M; Balakrishna, Rajalakshmi; Nguyen, Thuan B; Kimbrell, Matthew R; David, Sunil A
2006-12-15
Lipopolysaccharides (LPS), otherwise termed 'endotoxins', are outer-membrane constituents of Gram-negative bacteria, and play a key role in the pathogenesis of 'Septic Shock', a major cause of mortality in the critically ill patient. We had previously defined the pharmacophore necessary for small molecules to specifically bind and neutralize this complex carbohydrate. A series of aryl and aliphatic spermine-sulfonamide analogs were synthesized and tested in a series of binding and cell-based assays in order to probe the effect of lipophilicity on sequestration ability. A strong correlation was indeed found, supporting the hypothesis that endotoxin-neutralizing ability involves a lipophilic or membrane attachment event. The research discussed herein may be useful for the design of additional carbohydrate recognizing molecules and endotoxin-neutralizing drugs.
Mielke, Howard W; Gonzales, Christopher R; Powell, Eric T; Mielke, Paul W
2017-05-01
Anthropogenic re-distribution of lead (Pb) principally through its use in gasoline additives and lead-based paints have transformed the urban exposome. This unique study tracks urban-scale soil Pb (SPb) and blood Pb (BPb) responses of children living in public and private communities in New Orleans before and ten years after Hurricane Katrina (29 August 2005). To compare and evaluate associations of pre- and ten years post-Katrina SPb and children's BPb on public and private residential census tracts in the core and outer areas of New Orleans, and to examine correlations between SPb and nine other soil metals. The Louisiana Healthy Housing and Childhood Lead Poisoning Prevention Program BPb (µg/dL) data from pre- (2000-2005) and post-Katrina (2010-2015) for ≤6-year-old children. Data from public and adjacent private residential census tracts within core and outer areas are stratified from a database that includes 916 and 922 SPb and 13,379 and 4830 BPb results, respectively, from pre- and post-Katrina New Orleans. Statistical analyses utilize Multi-Response Permutation Procedure and Spearman's Rho Correlation. Pre- to Post-Katrina median SPb decreases in public and private core census tracts were from 285 to 55mg/kg and 710-291mg/kg, respectively. In public and private outer census tracts the median SPb decreased from 109 to 56mg/kg and 88-55mg/kg. Children's BPb percent ≥5µg/dL on public and private core areas pre-Katrina was 63.2% and 67.5%, and declined post-Katrina to 7.6% and 20.2%, respectively. BPb decreases also occurred in outer areas. Soil Pb is strongly correlated with other metals. Post-Katrina re-building of public housing plus landscaping amends the exposome and reduces children's BPb. Most importantly, Hurricane Katrina revealed that decreasing the toxicants in the soil exposome is an effective intervention for decreasing children's BPb. Copyright © 2017 Elsevier Inc. All rights reserved.
Bourassa, Dianna V; Kannenberg, Elmar L; Sherrier, D Janine; Buhr, R Jeffrey; Carlson, Russell W
2017-02-01
Rhizobium bacteria live in soil and plant environments, are capable of inducing symbiotic nodules on legumes, invade these nodules, and develop into bacteroids that fix atmospheric nitrogen into ammonia. Rhizobial lipopolysaccharide (LPS) is anchored in the bacterial outer membrane through a specialized lipid A containing a very long-chain fatty acid (VLCFA). VLCFA function for rhizobial growth in soil and plant environments is not well understood. Two genes, acpXL and lpxXL, encoding acyl carrier protein and acyltransferase, are among the six genes required for biosynthesis and transfer of VLCFA to lipid A. Rhizobium leguminosarum mutant strains acpXL, acpXL - /lpxXL - , and lpxXL - were examined for LPS structure, viability, and symbiosis. Mutations in acpXL and lpxXL abolished VLCFA attachment to lipid A. The acpXL mutant transferred a shorter acyl chain instead of VLCFA. Strains without lpxXL neither added VLCFA nor a shorter acyl chain. In all strains isolated from nodule bacteria, lipid A had longer acyl chains compared with laboratory-cultured bacteria, whereas mutant strains displayed altered membrane properties, modified cationic peptide sensitivity, and diminished levels of cyclic β-glucans. In pea nodules, mutant bacteroids were atypically formed and nitrogen fixation and senescence were affected. The role of VLCFA for rhizobial environmental fitness is discussed.
Mariño-Enríquez, Adrián; Fletcher, Christopher D M; Dal Cin, Paola; Hornick, Jason L
2010-08-01
Dedifferentiated liposarcoma (LPS) is a malignant adipocytic neoplasm defined as the transition from well-differentiated LPS to a nonlipogenic sarcoma. Heterologous differentiation is seen in 5% to 10% of dedifferentiated LPS, usually with myogenic or osteo/chondrosarcomatous elements. Adipocytic differentiation in the dedifferentiated component is incompatible with the current definition of dedifferentiated LPS. Pleomorphic LPS is a high-grade sarcoma containing lipoblasts. At least in areas, pleomorphic LPS can be indistinguishable from dedifferentiated LPS, except for the presence of lipoblasts in pleomorphic LPS and well-differentiated LPS areas in dedifferentiated LPS. We evaluated 12 unusual liposarcomas: 11 cases with pleomorphic LPS-like morphology affecting patients with concomitant or previous well-differentiated/dedifferentiated LPS, and 1 case resembling inflammatory "MFH" with scattered lipoblasts. Clinical and histologic features were reviewed. Immunohistochemistry for MDM2 and CDK4 was carried out. Amplification of 12q13 to q15 was studied by FISH analysis of the HMGA2 locus. The tumors arose in the retroperitoneum (7), proximal lower extremity (3), chest wall (1), and neck (1) of 9 males and 3 females (median age 66 y; range 49 to 76). Size ranged from 9 to 32 cm (median 23 cm). In 3 cases, there was an abrupt transition between well-differentiated LPS and sheets of pleomorphic lipoblasts, indistinguishable from pleomorphic LPS. Four cases consisted of otherwise typical dedifferentiated LPS (with adjacent well-differentiated LPS), except for the presence of lipoblasts in the high-grade component. One case contained both nonlipogenic spindle cell areas and an inflammatory "MFH"-like component with numerous admixed lipoblasts. Four cases were composed exclusively of pleomorphic LPS-like areas developing in 1 of the recurrences or metastases of a prior typical dedifferentiated LPS. Two cases also showed heterologous smooth muscle differentiation. MDM2 and CDK4 were positive in both the dedifferentiated LPS and pleomorphic LPS-like components in 12/12 and 11/12 cases, respectively. FISH analysis showed high-level amplification of 12q14.3 in all 8 cases successfully tested. Karyotypes were available for 3 cases and showed ring and giant marker chromosomes. Follow-up, available for 11 patients, ranged from 19 to 196 months (median 36 mo). Seven patients developed local recurrences (multiple in 3), and 3 developed lung metastases. Thus far, 5 patients have died of disease, 3 are alive with recurrent or metastatic disease, and 3 are alive with no evidence of disease. We conclude that dedifferentiated LPS can show lipoblastic differentiation in the high-grade component, resulting in areas indistinguishable from pleomorphic LPS. The available clinical and molecular data support the notion of "homologous" lipoblastic differentiation in dedifferentiated LPS, rather than mixed-type LPS.
Lichtman, S N; Wang, J; Lemasters, J J
1998-07-01
Lipopolysaccharide (LPS) is a bacterial polymer that stimulates macrophages to release tumor necrosis factor-alpha (TNF-alpha). In macrophages (RAW 264.7 and peritoneal cells), LPS binds to the CD14 surface receptor as the first step toward signaling. Liver macrophages, Kupffer cells, are the most numerous fixed-tissue macrophage in the body. The presence of CD14 on Kupffer cells and its role in LPS stimulation of TNF-alpha were examined. TNF-alpha release by Kupffer cells after LPS stimulation was the same in the presence and absence of serum. RAW 264.7 and peritoneal cells, which utilize the CD14 receptor, released significantly less TNF-alpha after LPS stimulation in the absence of serum because of the absence of LPS-binding protein. Phosphatidylinositol-phospholipase C treatment, which cleaves the CD14 receptor, decreased LPS-stimulated TNF-alpha release by RAW 264.7 cells but not by Kupffer cells. Deacylated LPS (dLPS) competes with LPS at the CD14 receptor when incubated in a ratio of 100:1 (dLPS/LPS). Such competition blocked LPS-stimulated TNF-alpha release from RAW 264.7 cells but not from Kupffer cells. Western and fluorescence-activated cell sorter analysis directly demonstrated the presence of CD14 on RAW 264.7 cells and murine peritoneal cells but showed only minimal amounts of CD14 in murine Kupffer cells. LPS stimulation did not increase the amount of CD14 detectable on mouse Kupffer cells. CD14 expression is very low in Kupffer cells, and LPS-stimulated TNF-alpha release is independent of CD14 in these cells.
Method of manufacturing lightweight thermo-barrier material
NASA Technical Reports Server (NTRS)
Blair, Winford (Inventor)
1987-01-01
A method of manufacturing thermal barrier structures comprising at least three dimpled cores separated by flat plate material with the outer surface of the flat plate material joined together by diffusion bonding.
High temperature, flexible, fiber-preform seal
NASA Technical Reports Server (NTRS)
Steinetz, Bruce M. (Inventor); Strocky, Paul J. (Inventor)
1992-01-01
A seal is mounted in a rectangular groove in a movable structural panel. The seal comprises a fiber preform constructed of multiple layers of fiber having a uniaxial core. Helical fibers are wound over the core. The fibers are of materials capable of withstanding high temperatures and are both left-hand and right-hand wound. An outer layer wrapped over said helical fibers prevents abrasion damage.
Effect of Ni Core Structure on the Electrocatalytic Activity of Pt-Ni/C in Methanol Oxidation
Kang, Jian; Wang, Rongfang; Wang, Hui; Liao, Shijun; Key, Julian; Linkov, Vladimir; Ji, Shan
2013-01-01
Methanol oxidation catalysts comprising an outer Pt-shell with an inner Ni-core supported on carbon, (Pt-Ni/C), were prepared with either crystalline or amorphous Ni core structures. Structural comparisons of the two forms of catalyst were made using transmission electron microscopy (TEM), X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS), and methanol oxidation activity compared using CV and chronoamperometry (CA). While both the amorphous Ni core and crystalline Ni core structures were covered by similar Pt shell thickness and structure, the Pt-Ni(amorphous)/C catalyst had higher methanol oxidation activity. The amorphous Ni core thus offers improved Pt usage efficiency in direct methanol fuel cells. PMID:28811402
Brynsvold, Glen V.; Snyder, Jr., Harold J.
1976-06-22
An internal core tightener which is a linear actuated (vertical actuation motion) expanding device utilizing a minimum of moving parts to perform the lateral tightening function. The key features are: (1) large contact areas to transmit loads during reactor operation; (2) actuation cam surfaces loaded only during clamping and unclamping operation; (3) separation of the parts and internal operation involved in the holding function from those involved in the actuation function; and (4) preloaded pads with compliant travel at each face of the hexagonal assembly at the two clamping planes to accommodate thermal expansion and irradiation induced swelling. The latter feature enables use of a "fixed" outer core boundary, and thus eliminates the uncertainty in gross core dimensions, and potential for rapid core reactivity changes as a result of core dimensional change.
Vaghefi, Ehsan; Walker, Kerry; Pontre, Beau P; Jacobs, Marc D; Donaldson, Paul J
2012-06-01
It has been proposed that in the absence of blood supply, the ocular lens operates an internal microcirculation system that delivers nutrients to internalized fiber cells faster and more efficiently than would occur by passive diffusion alone. To visualize the extracellular space solute fluxes potentially generated by this system, bovine lenses were organ cultured in artificial aqueous humor (AAH) for 4 h in the presence or absence of two gadolinium-based contrast agents, ionic Gd(3+), or a chelated form of Gd(3+), Gd-diethylenetriamine penta-acetic acid (Gd-DTPA; mol mass = 590 Da). Contrast reagent penetration into the lens core was monitored in real time using inversion recovery-spin echo (IR-SE) magnetic resonance imaging (MRI), while steady-state accumulation of [Gd-DTPA](-2) was also determined by calculating T1 values. After incubation, lenses were fixed and cryosectioned, and sections were labeled with the membrane marker wheat germ agglutinin (WGA). Sections were imaged by confocal microscopy using standard and reflectance imaging modalities to visualize the fluorescent WGA label and gadolinium reagents, respectively. Real-time IR-SE MRI showed rapid penetration of Gd(3+) into the outer cortex of the lens and a subsequent bloom of signal in the core. These two areas of signal were separated by an area in the inner cortex that limited entry of Gd(3+). Similar results were obtained for Gd-DTPA, but the penetration of the larger negatively charged molecule into the core could only be detected by calculating T1 values. The presence of Gd-DTPA in the extracellular space of the outer cortex and core, but its apparent absence from the inner cortex was confirmed using reflectance imaging of equatorial sections. In axial sections, Gd-DTPA was associated with the sutures, suggesting these structures provide a pathway from the surface, across the inner cortex barrier to the lens core. Our studies have revealed inner and outer boundaries of a zone within which a narrowing of the extracellular space restricts solute diffusion and acts to direct fluxes into the lens core via the sutures.
Mercury's Interior from MESSENGER Radio Science Data
NASA Astrophysics Data System (ADS)
Genova, A.; Mazarico, E.; Goossens, S. J.; Lemoine, F. G.; Neumann, G. A.; Smith, D. E.; Zuber, M. T.
2017-12-01
The MErcury Surface, Space ENvironment, GEochemistry, and Ranging (MESSENGER) spacecraft provided precise radio tracking data in orbit about Mercury for more than 4 years, from March 2011 to April 2015. These geodetic measurements enable us to investigate the interior structure of the planet from the inner core to the crust. The first three years of radio data allowed us to determine the gravity field of Mercury with a resolution of 150 km in the northern hemisphere (degree and order 50 in spherical harmonics) since the periapsis was located at higher latitudes (>65˚N) and 200-500 km altitudes. The comparison of this gravity solution with Mercury's topography, which was retrieved by using over 25 million individual measurements of the Mercury Laser Altimeter (MLA), resulted in a preliminary map of the crustal thickness of the planet. However, those results were limited by the resolution of the gravity field since the topography was defined in spherical harmonics up to degree and order 125. The last year of the MESSENGER extended mission was dedicated to a low-altitude campaign, where the spacecraft periapsis was maintained at altitudes between 25 and 100 km. The radio data collected during this mission phase allowed us to significantly improve the resolution of the gravity field locally in the northern hemisphere up to degree and order 100 in spherical harmonics. We present the gravity anomalies and crustal thickness maps that lead to a better understanding on the formation and evolution of specific regions. We present our estimated orientation model, which slightly differs from the solutions that were obtained by using Earth-based radar measurements and the co-registration of MESSENGER imaging and altimetry data. These previous estimates provide a direct measurement of the surface response, whereas the orientation model from gravity is more sensitive to the inner and outer core. A discrepancy between core and surface obliquities may provide fundamental information on the status of the outer core and the presence of a solid inner core. We also present the latest solution of the tidal Love number k2 that enables us to constrain the basal temperature and rigidity of the outer molten core.
Li, Qiu; Zhao, Wenwen; Zeng, Xi; Hao, Zhihui
2018-05-07
Atherosclerosis, a chronic inflammatory disease, is a major contributor to cardiovascular diseases. Ursolic acid (UA) is a phytonutrient with widely biological effects including anti-oxidative, anti-inflammatory, and so on. At present, the effect of UA on atherosclerosis and the mechanism of action are still obscure. This study focused on investigating the effects of UA on atherosclerosis both in vivo and in vitro. We first selected LOX-1 as our target, which was reckoned as a new promising receptor for treating atherosclerosis. The evaluation in vitro suggested that UA significantly decreased endothelial LOX-1 expression induced by LPS both in mRNA and protein levels. Pre-treatment of UA also inhibited TLR4/MyD88 signaling activated by LPS. Moreover, UA reduced ROS production and suppressed the activation of NF-κB stimulated by LPS. Particularly, the evaluation in vivo further verified the conclusion obtained in vitro. In ApoE −/− mice fed with an atherogenic diet, both UA (100 mg/kg/day) and simvastatin significantly attenuated atherosclerotic plaque formation and shrunk necrotic core areas. The enhanced expression of LOX-1 in atherosclerotic aorta was also dramatically decreased by administration of UA. Taken together, these results suggested that UA, with anti-atherosclerotic activity through inhibition of LOX-1 mediated by ROS/NF-κB signaling pathways, may become a valuable vascular protective candidate for the treatment of atherosclerosis.
Properties of iron under core conditions
NASA Astrophysics Data System (ADS)
Brown, J. M.
2003-04-01
Underlying an understanding of the geodynamo and evolution of the core is knowledge of the physical and chemical properties of iron and iron mixtures under high pressure and temperature conditions. Key properties include the viscosity of the fluid outer core, thermal diffusivity, equations-of-state, elastic properties of solid phases, and phase equilibria for iron and iron-dominated mixtures. As is expected for work that continues to tax technological and intellectual limits, controversy has followed both experimental and theoretical progress in this field. However, estimates for the melting temperature of the inner core show convergence and the equation-of-state for iron as determined in independent experiments and theories are in remarkable accord. Furthermore, although the structure and elastic properties of the solid inner-core phase remains uncertain, theoretical and experimental underpinnings are better understood and substantial progress is likely in the near future. This talk will focus on an identification of properties that are reasonably well known and those that merit further detailed study. In particular, both theoretical and experimental (static and shock wave) determinations of the density of iron under extreme conditions are in agreement at the 1% or better level. The behavior of the Gruneisen parameter (which determines the geothermal gradient and controls much of the outer core heat flux) is constrained by experiment and theory under core conditions for both solid and liquid phases. Recent experiments and theory are suggestive of structure or structures other than the high-pressure hexagonal close-packed (HCP) phase. Various theories and experiments for the elasticity of HCP iron remain in poor accord. Uncontroversial constraints on core chemistry will likely never be possible. However, reasonable bounds are possible on the basis of seismic profiles, geochemical arguments, and determinations of sound velocities and densities at high pressure and temperature.
Presumption of large-scale heterogeneity at the top of the outer core basal layer
NASA Astrophysics Data System (ADS)
Souriau, Annie
2015-04-01
A layer of reduced P-velocity gradient with thickness of about 100-200 km has been identified at the base of the liquid core from seismological methods. It has been interpreted as a dense layer resulting from partial re-melting of the inner core, which is depleted in light elements with respect to the liquid core during freezing. In an attempt to specify where freezing and re-melting occur, the structure of this basal layer is investigated with the seismological core phase PKPbc which has its turning point in the lower third of the outer core. The large PKPbc data set of the EHB catalog distributed by the International Seismological Centre is analyzed. In order to compensate for the uneven distribution of the data and to minimize the influence of mantle heterogeneities, the travel time anomalies are binned inside equal area and equal azimuth sectors sampling the base of the liquid core at different depths. Most of the observed variations in the binned travel time residuals are not significant according to their confidence level. The only features which could be significant are a large patch with a velocity increase of about 0.5% located at the top of the basal layer beneath the eastern hemisphere, and the complementary velocity decrease beneath the western hemisphere and the South pole. This observation suggests that some freezing or re-melting processes occur at the top of the basal layer with a hemispherical dissymmetry. If confirmed, it may give strong constraints on the fate of the light elements during the freezing and re-melting process and on their interaction with the basal layer and the overlying liquid core.
Mac Sharry, John; Shalaby, Karim H.; Marchica, Cinzia; Farahnak, Soroor; Chieh-Li, Tien; Lapthorne, Susan; Qureshi, Salman T.; Shanahan, Fergus; Martin, James G.
2014-01-01
Varying concentrations of lipopolysaccharide (LPS) in ovalbumin (OVA) may influence the airway response to allergic sensitization and challenge. We assessed the contribution of LPS to allergic airway inflammatory responses following challenge with LPS-rich and LPS-free commercial OVA. BALB/c mice were sensitized with LPS-rich OVA and alum and then underwent challenge with the same OVA (10 µg intranasally) or an LPS-free OVA. Following challenge, bronchoalveolar lavage (BAL), airway responsiveness to methacholine and the lung regulatory T cell population (Treg) were assessed. Both OVA preparations induced BAL eosinophilia but LPS-rich OVA also evoked BAL neutrophilia. LPS-free OVA increased interleukin (IL)-2, IL-4 and IL-5 whereas LPS-rich OVA additionally increased IL-1β, IL-12, IFN-γ, TNF-α and KC. Both OVA-challenged groups developed airway hyperresponsiveness. TLR4-deficient mice challenged with either OVA preparation showed eosinophilia but not neutrophilia and had increased IL-5. Only LPS-rich OVA challenged mice had increased lung Tregs and LPS-rich OVA also induced in vitro Treg differentiation. LPS-rich OVA also induced a Th1 cytokine response in human peripheral blood mononuclear cells.We conclude that LPS-rich OVA evokes mixed Th1, Th2 and innate immune responses through the TLR-4 pathway, whereas LPS-free OVA evokes only a Th2 response. Contaminating LPS is not required for induction of airway hyperresponsiveness but amplifies the Th2 inflammatory response and is a critical mediator of the neutrophil, Th1 and T regulatory cell responses to OVA. PMID:24968337
PG1058 Is a Novel Multidomain Protein Component of the Bacterial Type IX Secretion System
Veith, Paul D.; Butler, Catherine A.; Nor Muhammad, Nor A.; Chen, Yu-Yen; Slakeski, Nada; Peng, Benjamin; Zhang, Lianyi; Dashper, Stuart G.; Cross, Keith J.; Cleal, Steven M.; Moore, Caroline; Reynolds, Eric C.
2016-01-01
Porphyromonas gingivalis utilises the Bacteroidetes-specific type IX secretion system (T9SS) to export proteins across the outer membrane (OM), including virulence factors such as the gingipains. The secreted proteins have a conserved carboxy-terminal domain essential for type IX secretion that is cleaved upon export. In P. gingivalis the T9SS substrates undergo glycosylation with anionic lipopolysaccharide (A-LPS) and are attached to the OM. In this study, comparative analyses of 24 Bacteroidetes genomes identified ten putative novel components of the T9SS in P. gingivalis, one of which was PG1058. Computer modelling of the PG1058 structure predicted a novel N- to C-terminal architecture comprising a tetratricopeptide repeat (TPR) domain, a β-propeller domain, a carboxypeptidase regulatory domain-like fold (CRD) and an OmpA_C-like putative peptidoglycan binding domain. Inactivation of pg1058 in P. gingivalis resulted in loss of both colonial pigmentation and surface-associated proteolytic activity; a phenotype common to T9SS mutants. Immunoblot and LC-MS/MS analyses of subcellular fractions revealed T9SS substrates accumulated within the pg1058 mutant periplasm whilst whole-cell ELISA showed the Kgp gingipain was absent from the cell surface, confirming perturbed T9SS function. Immunoblot, TEM and whole-cell ELISA analyses indicated A-LPS was produced and present on the pg1058 mutant cell surface although it was not linked to T9SS substrate proteins. This indicated that PG1058 is crucial for export of T9SS substrates but not for the translocation of A-LPS. PG1058 is a predicted lipoprotein and was localised to the periplasmic side of the OM using whole-cell ELISA, immunoblot and LC-MS/MS analyses of subcellular fractions. The structural prediction and localisation of PG1058 suggests that it may have a role as an essential scaffold linking the periplasmic and OM components of the T9SS. PMID:27711252
Hubert, Kerstin; Pawlik, Marie-Christin; Claus, Heike; Jarva, Hanna; Meri, Seppo; Vogel, Ulrich
2012-01-01
Neisseria meningitidis employs polysaccharides and outer membrane proteins to cope with human serum complement attack. To screen for factors influencing serum resistance, an assay was developed based on a colorimetric serum bactericidal assay. The screening used a genetically modified sequence type (ST)-41/44 clonal complex (cc) strain lacking LPS sialylation, polysaccharide capsule, the factor H binding protein (fHbp) and MutS, a protein of the DNA repair mechanism. After killing of >99.9% of the bacterial cells by serum treatment, the colorimetric assay was used to screen 1000 colonies, of which 35 showed enhanced serum resistance. Three mutant classes were identified. In the first class of mutants, enhanced expression of Opc was identified. Opc expression was associated with vitronectin binding and reduced membrane attack complex deposition confirming recent observations. Lipopolysaccharide (LPS) immunotype switch from immunotype L3 to L8/L1 by lgtA and lgtC phase variation represented the second class. Isogenic mutant analysis demonstrated that in ST-41/44 cc strains the L8/L1 immunotype was more serum resistant than the L3 immunotype. Consecutive analysis revealed that the immunotypes L8 and L1 were frequently observed in ST-41/44 cc isolates from both carriage and disease. Immunotype switch to L8/L1 is therefore suggested to contribute to the adaptive capacity of this meningococcal lineage. The third mutant class displayed a pilE allelic exchange associated with enhanced autoaggregation. The mutation of the C terminal hypervariable region D of PilE included a residue previously associated with increased pilus bundle formation. We suggest that autoaggregation reduced the surface area accessible to serum complement and protected from killing. The study highlights the ability of meningococci to adapt to environmental stress by phase variation and intrachromosomal recombination affecting subcapsular antigens.
Hubert, Kerstin; Pawlik, Marie-Christin; Claus, Heike; Jarva, Hanna; Meri, Seppo; Vogel, Ulrich
2012-01-01
Neisseria meningitidis employs polysaccharides and outer membrane proteins to cope with human serum complement attack. To screen for factors influencing serum resistance, an assay was developed based on a colorimetric serum bactericidal assay. The screening used a genetically modified sequence type (ST)-41/44 clonal complex (cc) strain lacking LPS sialylation, polysaccharide capsule, the factor H binding protein (fHbp) and MutS, a protein of the DNA repair mechanism. After killing of >99.9% of the bacterial cells by serum treatment, the colorimetric assay was used to screen 1000 colonies, of which 35 showed enhanced serum resistance. Three mutant classes were identified. In the first class of mutants, enhanced expression of Opc was identified. Opc expression was associated with vitronectin binding and reduced membrane attack complex deposition confirming recent observations. Lipopolysaccharide (LPS) immunotype switch from immunotype L3 to L8/L1 by lgtA and lgtC phase variation represented the second class. Isogenic mutant analysis demonstrated that in ST-41/44 cc strains the L8/L1 immunotype was more serum resistant than the L3 immunotype. Consecutive analysis revealed that the immunotypes L8 and L1 were frequently observed in ST-41/44 cc isolates from both carriage and disease. Immunotype switch to L8/L1 is therefore suggested to contribute to the adaptive capacity of this meningococcal lineage. The third mutant class displayed a pilE allelic exchange associated with enhanced autoaggregation. The mutation of the C terminal hypervariable region D of PilE included a residue previously associated with increased pilus bundle formation. We suggest that autoaggregation reduced the surface area accessible to serum complement and protected from killing. The study highlights the ability of meningococci to adapt to environmental stress by phase variation and intrachromosomal recombination affecting subcapsular antigens. PMID:23028802
Numerical simulation of axisymmetric valve operation for different outer cone angle
NASA Astrophysics Data System (ADS)
Smyk, Emil
One of the method of flow separation control is application of axisymmetric valve. It is composed of nozzle with core. Normally the main flow is attached to inner cone and flow by preferential collector to primary flow pipe. If through control nozzle starts flow jet (control jet) the main flow is switched to annular secondary collector. In both situation the main flow is deflected to inner or outer cone (placed at the outlet of the valve's nozzle) by Coanda effect. The paper deals with the numerical simulation of this axisymetric annular nozzle with integrated synthetic jet actuator. The aim of the work is influence examination of outer cone angle on deflection on main stream.
Chemical evolution of the Earth: Equilibrium or disequilibrium process?
NASA Technical Reports Server (NTRS)
Sato, M.
1985-01-01
To explain the apparent chemical incompatibility of the Earth's core and mantle or the disequilibrium process, various core forming mechanisms have been proposed, i.e., rapid disequilibrium sinking of molten iron, an oxidized core or protocore materials, and meteorite contamination of the upper mantle after separation from the core. Adopting concepts used in steady state thermodynamics, a method is devised for evaluating how elements should distribute stable in the Earth's interior for the present gradients of temperature, pressure, and gravitational acceleration. Thermochemical modeling gives useful insights into the nature of chemical evolution of the Earth without overly speculative assumptions. Further work must be done to reconcile siderophile elements, rare gases, and possible light elements in the outer core.
Erne, Jay B; Goring, Robert L; Kennedy, Fidelma A; Schoenborn, William C
2009-08-15
To determine the prevalence of lymphoplasmacytic synovitis (LPS) in dogs with naturally occurring cranial cruciate ligament (CCL) rupture and compare clinical, radiographic, cytologic, and histologic findings in dogs with and without LPS. Cross-sectional study. 110 dogs with naturally occurring CCL rupture. Histologic examination of synovial biopsy specimens obtained at the time of surgical treatment was used to identify dogs with LPS. Clinical, radiographic, cytologic, and histologic findings were compared between dogs with and without LPS. 56 (51%) dogs had histologic evidence of LPS. There were no significant differences in age, body weight, duration of lameness, severity of lameness, severity of radiographic signs of degenerative joint disease, extent of CCL rupture (partial vs complete), or gross appearance of the medial meniscus between dogs with and without LPS. Mean tibial plateau angle was significantly lower in dogs with LPS than in dogs without LPS, and dogs with LPS were significantly more likely to have neutrophils in their synovial fluid. Lymphocytes were seen in synovial fluid from a single dog with LPS. Results suggested that LPS was common in dogs with naturally occurring CCL rupture. However, only minor clinical, radiographic, cytologic, and histologic differences were identified between dogs with and without LPS.
Martin, T R; Mathison, J C; Tobias, P S; Letúrcq, D J; Moriarty, A M; Maunder, R J; Ulevitch, R J
1992-01-01
A plasma lipopolysaccharide (LPS)-binding protein (LBP) has been shown to regulate the response of rabbit peritoneal macrophages and human blood monocytes to endotoxin (LPS). We investigated whether LBP is present in lung fluids and the effects of LBP on the response of lung macrophages to LPS. Immunoreactive LBP was detectable in the lavage fluids of patients with the adult respiratory distress syndrome by immunoprecipitation followed by Western blotting, and also by specific immunoassay. In rabbits, the LBP appeared to originate outside of the lungs, inasmuch as mRNA transcripts for LBP were identified in total cellular RNA from liver, but not from lung homogenates or alveolar macrophages. Purified LBP enhanced the response of human and rabbit alveolar macrophages to both smooth form LPS (Escherichia coli O111B:4) and rough form LPS (Salmonella minnesota Re595). In the presence of LBP and LPS, the onset of tumor necrosis factor-alpha (TNF alpha) production occurred earlier and at an LPS threshold dose that was as much as 1,000-fold lower for both types of LPS. In rabbit alveolar macrophages treated with LBP and LPS, TNF alpha mRNA appeared earlier, reached higher levels, and had a prolonged half-life as compared with LPS treatment alone. Neither LPS nor LPS and LBP affected pHi or [Cai++] in alveolar macrophages. Specific monoclonal antibodies to CD14, a receptor that binds LPS/LBP complexes, inhibited TNF alpha production by human alveolar macrophages stimulated with LPS alone or with LPS/LBP complexes, indicating the importance of CD14 in mediating the effects of LPS on alveolar macrophages. Thus, immunoreactive LBP accumulates in lung lavage fluids in patients with lung injury and enhances LPS-stimulated TNF alpha gene expression in alveolar macrophages by a pathway that depends on the CD14 receptor. LBP may play an important role in augmenting TNF alpha expression by alveolar macrophages within the lungs. Images PMID:1281827
Glacigenic landforms and sediments of the Western Irish Shelf
NASA Astrophysics Data System (ADS)
McCarron, Stephen; Monteys, Xavier; Toms, Lee
2013-04-01
Vibrocoring of possible glacigenic landforms identified from high resolution bathymetric coverage of the Irish Shelf by the Irish National Seabed Survey (INSS) has provided several clusters of short (<3m) cores that, due to a regional post-glacial erosional event, comprise last glacial age stratigraphies. In addition, new shallow seismic data and sedimentological information from across the Western Irish Shelf provide new insights into aspects of the nature, timing and pattern of shelf occupation by grounded lobate extensions of the last Irish Ice Sheet. Restricted chronological control of deglacial sequences in several cores indicates that northern parts of the western mid-shelf (south of a prominent outer Donegal Bay ridge) were ice free by ~24 ka B.P., and that ice had also probably retreated from outer shelf positions (as far west as the Porcupine Bank) at or before this time.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kikuchi, Akihiro; Higuchi, Arika; Ida, Shigeru, E-mail: kikuchi.a@geo.titech.ac.jp, E-mail: higuchia@geo.titech.ac.jp, E-mail: ida@elsi.jp
Recently, gas giant planets in nearly circular orbits with large semimajor axes (a ∼ 30-1000 AU) have been detected by direct imaging. We have investigated orbital evolution in a formation scenario for such planets, based on a core accretion model. (1) Icy cores accrete from planetesimals at ≲ 30 AU, (2) they are scattered outward by an emerging nearby gas giant to acquire highly eccentric orbits, and (3) their orbits are circularized through the accretion of disk gas in outer regions, where they spend most of their time. We analytically derived equations to describe the orbital circularization through gas accretion.more » Numerical integrations of these equations show that the eccentricity decreases by a factor of more than 5 while the planetary mass increases by a factor of 10. Because runaway gas accretion increases planetary mass by ∼10-300, the orbits are sufficiently circularized. On the other hand, a is reduced at most only by a factor of two, leaving the planets in the outer regions. If the relative velocity damping by shock is considered, the circularization slows down, but is still efficient enough. Therefore, this scenario potentially accounts for the formation of observed distant jupiters in nearly circular orbits. If the apocenter distances of the scattered cores are larger than the disk sizes, their a shrink to a quarter of the disk sizes; the a-distribution of distant giants could reflect the outer edges of the disks in a similar way that those of hot jupiters may reflect inner edges.« less
Kim, Dong-Hyun; Yeo, Sang Won
2013-01-01
This prospective, randomized, and controlled study examined the effects of normal saline and selenium-enriched hot spring water on experimentally induced rhinosinusitis in rats. The study comprised two control groups (untreated and saline-treated) and three experimental groups of Sprague Dawley rats. The experimental groups received an instillation of lipopolysaccharide (LPS) only, LPS+normal saline (LPS/saline), or LPS+selenium-enriched hot spring water (LPS/selenium). Histopathological changes were identified using hematoxylin-eosin staining. Leakage of exudate was identified using fluorescence microscopy. Microvascular permeability was measured using the Evans blue dye technique. Expression of the Muc5ac gene was measured using reverse transcription-polymerase chain reaction. Mucosal edema and expression of the Muc5ac gene were significantly lower in the LPS/saline group than in the LPS group. Microvascular permeability, mucosal edema, and expression of the Muc5ac gene were significantly lower in the LPS/selenium group than in the LPS group. Mucosal edema was similar in the LPS/selenium group and LPS/saline group, but capillary permeability and Muc5ac expression were lower in the LPS/selenium group. This study shows that normal saline and selenium-enriched hot spring water reduce inflammatory activity and mucus hypersecretion in LPS-induced rhinosinusitis in rats. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
Szijártó, Valéria; Pal, Tibor; Nagy, Gabor; Nagy, Eszter; Ghazawi, Akela; al-Haj, Mohammed; El Kurdi, Sylvia; Sonnevend, Agnes
2012-07-01
The clone Escherichia coli O25 ST131, typically producing extended-spectrum beta-lactamases (ESBLs), has spread globally and became the dominant type among extraintestinal isolates at many parts of the world. However, the reasons behind the emergence and success of this clone are only partially understood. We compared the core type genes by PCR of ESBL-producing and ESBL-nonproducing strains isolated from urinary tract infections in the United Arab Emirates and found a surprisingly high frequency of the K-12 core type (44.6%) among members of the former group, while in the latter one, it was as low (3.7%), as reported earlier. The high figure was almost entirely attributable to the presence of members of the clone O25 ST131 among ESBL producers. Strains from the same clone isolated in Europe also carried the K-12 core type genes. Sequencing the entire core operon of an O25 ST131 isolate revealed a high level of similarity to known K-12 core gene sequences and an almost complete identity with a recently sequenced non-O25 ST131 fecal isolate. The exact chemical structure and whether and how this unusual core type contributed to the sudden emergence of ST131 require further investigations. © 2012 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.
Aditya, S; Humer, E; Pourazad, P; Khiaosa-Ard, R; Huber, J; Zebeli, Q
2017-02-01
Feeding high-grain diets increases the risk of subacute rumen acidosis (SARA) and adversely affects rumen health. This condition might impair the responsiveness of cows when they are exposed to external infectious stimuli such as lipopolysaccharide (LPS). The main objective of this study was to evaluate various responses to intramammary LPS infusion in healthy dairy cows and those experimentally subjected to SARA. Eighteen early-lactating Simmental cows were subjected to SARA (n = 12) or control (CON; n = 6) feeding conditions. Cows of the control group received a diet containing 40% concentrates (DM basis) throughout the experiment. The intermittent SARA feeding regimen consisted in feeding the cows a ration with 60% concentrate (DM basis) for 32 d, consisting of a first SARA induction for 8 d, switched to the CON diet for 7 d, and re-induction during the last 17 d. On d 30 of the experiment, 6 SARA (SARA-LPS) and 6 CON (CON-LPS) cows were intramammary challenged once with a single dose of 50 μg of LPS from Escherichia coli (O26:B6), whereas the other 6 SARA cows (SARA-PLA) received 10 mL of sterile saline solution as placebo. To confirm the induction of SARA, the reticular pH was continuously monitored via wireless pH probes. The DMI remained unchanged between SARA and CON cows during the feeding experiment, but was reduced in both treatment groups receiving the LPS infusion compared with SARA-PLA, whereby a significant decline was observed for cows of the SARA-LPS treatment (-38%) compared with CON-LPS (-19%). The LPS infusion did not affect the reticuloruminal pH dynamics, but significantly enhanced ruminal temperature and negatively affected chewing behavior. The ruminal temperature increased after the LPS infusion and peaked about 1 h earlier in SARA-LPS cows compared with the cows of the CON-LPS treatment. Moreover, a significant decline in milk yield was found in SARA-LPS compared with CON-LPS following the LPS infusion. Cows receiving LPS had elevated somatic cell counts, protein, and fat contents in milk as well as decreased lactose contents and pH following the LPS infusion, whereby the changes in milk constituents were more pronounced in SARA-LPS than CON-LPS cows. Rectal temperature and pulse rate were highest 6 h after LPS infusion, but rumen contractions were not affected by the LPS infusion. The data suggest that a single intramammary LPS infusion induced fever and negatively affected feed intake, chewing activity, rectal temperature, and milk yield and composition, whereby these effects were more pronounced in SARA cows. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.
Antimicrobial peptides and nitric oxide production by neutrophils from periodontitis subjects
Mariano, F.S.; Campanelli, A.P.; Nociti, F.H.; Mattos-Graner, R.O.; Gonçalves, R.B.
2012-01-01
Neutrophils play an important role in periodontitis by producing nitric oxide (NO) and antimicrobial peptides, molecules with microbicidal activity via oxygen-dependent and -independent mechanisms, respectively. It is unknown whether variation in the production of antimicrobial peptides such as LL-37, human neutrophil peptides (HNP) 1-3, and NO by neutrophils influences the pathogenesis of periodontal diseases. We compared the production of these peptides and NO by lipopolysaccharide (LPS)-stimulated neutrophils isolated from healthy subjects and from patients with periodontitis. Peripheral blood neutrophils were cultured with or without Aggregatibacter actinomycetemcomitans-LPS (Aa-LPS), Porphyromonas gingivalis-LPS (Pg-LPS) and Escherichia coli-LPS (Ec-LPS). qRT-PCR was used to determine quantities of HNP 1-3 and LL-37 mRNA in neutrophils. Amounts of HNP 1-3 and LL-37 proteins in the cell culture supernatants were also determined by ELISA. In addition, NO levels in neutrophil culture supernatants were quantitated by the Griess reaction. Neutrophils from periodontitis patients cultured with Aa-LPS, Pg-LPS and Ec-LPS expressed higher HNP 1-3 mRNA than neutrophils from healthy subjects. LL-37 mRNA expression was higher in neutrophils from patients stimulated with Aa-LPS. Neutrophils from periodontitis patients produced significantly higher LL-37 protein levels than neutrophils from healthy subjects when stimulated with Pg-LPS and Ec-LPS, but no difference was observed in HNP 1-3 production. Neutrophils from periodontitis patients cultured or not with Pg-LPS and Ec-LPS produced significantly lower NO levels than neutrophils from healthy subjects. The significant differences in the production of LL-37 and NO between neutrophils from healthy and periodontitis subjects indicate that production of these molecules might influence individual susceptibility to important periodontal pathogens. PMID:22850872
Nanbo, A; Nishimura, H; Muta, T; Nagasawa, S
1999-02-01
Lipopolysaccharide (LPS)-binding protein (LBP), an opsonin for activation of macrophages by bacterial LPS, is synthesized in hepatocytes and is known to be an acute phase protein. Recently, cytokine-induced production of LBP was reported to increase 10-fold in hepatocytes isolated from LPS-treated rats, compared with those from normal rats. However, the mechanism by which the LPS treatment enhances the effect of cytokines remains to be clarified. In the present study, we examined whether LPS alone or an LPS/LBP complex directly stimulates the hepatocytes, leading to acceleration of the cytokine-induced LBP production. HepG2 cells (a human hepatoma cell line) were shown to express CD14, a glycosylphosphatidylinositol-anchored LPS receptor, by both RT/PCR and flow cytometric analyses. An LPS/LBP complex was an effective stimulator for LBP and CD14 production in HepG2 cells, but stimulation of the cells with either LPS or LBP alone did not significantly accelerate the production of these proteins. The findings were confirmed by semiquantitative RT/PCR analysis of mRNA levels of LBP and CD14 in HepG2 cells after stimulation with LPS alone and an LPS/LBP complex. In addition, two monoclonal antibodies (mAbs) to CD14 (3C10 and MEM-18) inhibited LPS/LBP-induced cellular responses of HepG2 cells. Furthermore, prestimulation of HepG2 cells with LPS/LBP augmented cytokine-induced production and gene expression of LBP and CD14. All these findings suggest that an LPS/LBP complex, but not free LPS, stimulates HepG2 cells via CD14 leading to increased basal and cytokine-induced LBP and CD14 production.
Radiative shocks produced from spherical cryogenic implosions at the National Ignition Facility
Pak, A.; Divol, L.; Gregori, G.; ...
2013-05-20
Spherically expanding radiative shock waves have been observed from inertially confined implosion experiments at the National Ignition Facility. In these experiments, a spherical fusion target, initially 2 mm in diameter, is compressed via the pressure induced from the ablation of the outer target surface. At the peak compression of the capsule, x-ray and nuclear diagnostics indicate the formation of a central core, with a radius and ion temperature of ~20 μm and ~ 2 keV, respectively. This central core is surrounded by a cooler compressed shell of deuterium-tritium fuel that has an outer radius of ~40 μm and a densitymore » of >500 g/cm 3. Using inputs from multiple diagnostics, the peak pressure of the compressed core has been inferred to be of order 100 Gbar for the implosions discussed here. Furthermore, the shock front, initially located at the interface between the high pressure compressed fuel shell and surrounding in-falling low pressure ablator plasma, begins to propagate outwards after peak compression has been reached.« less
Staufenberg, Gerrit; Graupner, Nina; Müssig, Jörg
2015-08-20
The babassu nut is the fruit of the babassu palm Orbignya speciosa. The combination of hardness and impact strength is difficult to acquire for artificial materials, making the babassu nut a promising source for biomimetic inspiration. Unnotched Charpy impact tests, Shore D hardness tests and scanning electron microscopy were used for mechanical and microscopical analysis of the pericarp. Four major principles were found for a biomimetic approach: a hard core ((1); endocarp) is embedded in a soft outer layer of high impact strength ((2); epicarp) and is reinforced with fibres of variable fineness (3), some of which are oriented radial to the core (4). Biomimetic fibre-reinforced composites were produced using abstracted mechanisms of the babassu nut based on regenerated cellulose fibres (lyocell, L) with two different fineness values as reinforcement embedded in a polylactide (PLA) core matrix and polypropylene (PP) based outer layers. The biomimetic fibre composite reaches a significantly higher impact strength that is 1.6 times higher than the reference sample produced from a PLA/PP/L-blend. At the same time the hardness is slightly increased compared to PP/L.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Chowdhury, J.; Wan, Weigang; Chen, Yang
2014-11-15
The δ f particle-in-cell code GEM is used to study the transport “shortfall” problem of gyrokinetic simulations. In local simulations, the GEM results confirm the previously reported simulation results of DIII-D [Holland et al., Phys. Plasmas 16, 052301 (2009)] and Alcator C-Mod [Howard et al., Nucl. Fusion 53, 123011 (2013)] tokamaks with the continuum code GYRO. Namely, for DIII-D the simulations closely predict the ion heat flux at the core, while substantially underpredict transport towards the edge; while for Alcator C-Mod, the simulations show agreement with the experimental values of ion heat flux, at least within the range of experimental error.more » Global simulations are carried out for DIII-D L-mode plasmas to study the effect of edge turbulence on the outer core ion heat transport. The edge turbulence enhances the outer core ion heat transport through turbulence spreading. However, this edge turbulence spreading effect is not enough to explain the transport underprediction.« less
Uncertainty quantification and sensitivity analysis with CASL Core Simulator VERA-CS
Brown, C. S.; Zhang, Hongbin
2016-05-24
Uncertainty quantification and sensitivity analysis are important for nuclear reactor safety design and analysis. A 2x2 fuel assembly core design was developed and simulated by the Virtual Environment for Reactor Applications, Core Simulator (VERA-CS) coupled neutronics and thermal-hydraulics code under development by the Consortium for Advanced Simulation of Light Water Reactors (CASL). An approach to uncertainty quantification and sensitivity analysis with VERA-CS was developed and a new toolkit was created to perform uncertainty quantification and sensitivity analysis with fourteen uncertain input parameters. Furthermore, the minimum departure from nucleate boiling ratio (MDNBR), maximum fuel center-line temperature, and maximum outer clad surfacemore » temperature were chosen as the selected figures of merit. Pearson, Spearman, and partial correlation coefficients were considered for all of the figures of merit in sensitivity analysis and coolant inlet temperature was consistently the most influential parameter. We used parameters as inputs to the critical heat flux calculation with the W-3 correlation were shown to be the most influential on the MDNBR, maximum fuel center-line temperature, and maximum outer clad surface temperature.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wells, M.T.; Gaffin, S.L.; Wessels, B.C.
1990-09-01
A previously established primate model was used to evaluate the role of lipopolysaccharide (LPS, endotoxin) in radiation sickness. Vervet monkeys were Co-60 irradiated with an LD100 exposure and had periodic blood samples taken for the determination of LPS and anti-LPS lgG antibodies and for bacteriological studies. On day 2 postirradiation, primates were treated with either sterile 0.9 percent saline, or equine anti-LPS hyperimmune plasma, or tripotassium-dicitrato-bismuthate (Denol). Results indicate that anti-LPS-treated animals survived significantly longer than both the other groups and, since LPS may cause nausea, vomiting, diarrhea, anorexia, and headaches, it is suggested that Anti-LPS administration may be ofmore » value in reducing plasma LPS concentration in humans and improving their performance and survivability. 24 refs.« less
Ossola, Cesar A; Surkin, Pablo N; Mohn, Claudia E; Elverdin, Juan C; Fernández-Solari, Javier
2016-06-01
Anti-inflammatory and immunologic properties of cannabinoids have been reported in several tissues. Expression of cannabinoid receptor Type 2 was reported in osteoblasts and osteoclasts, suggesting a key role in bone metabolism. The aim of this study is to assess the effect of treatment with cannabinoid-2 receptor agonist HU-308 in the oral health of rats subjected to lipopolysaccharide (LPS)-induced periodontitis. Twenty-four rats were distributed in four groups (six rats per group): 1) control rats; 2) sham rats; 3) rats submitted to experimental periodontitis (LPS); and 4) rats submitted to experimental periodontitis and treated with HU-308 (LPS+HU). In groups LPS and LPS+HU, periodontitis was induced by LPS (1 mg/mL) injected into the gingival tissue (GT) of maxillary and mandibular first molars and into the interdental space between the first and second molars, 3 days per week for 6 weeks. In group LPS+HU, HU-308 (500 ng/mL) was applied topically to the GT daily. Alveolar bone loss resulting from LPS-induced periodontitis was significantly attenuated with HU-308 treatment (LPS+HU), measured by macroscopic and histologic examination. Treatment also reduced gingival production of inflammatory mediators augmented in LPS-injected rats, such as: 1) inducible nitric oxide (iNOS) activity (LPS: 90.18 ± 36.51 pmol/minute/mg protein versus LPS+HU: 16.37 ± 4.73 pmol/minute/mg protein; P <0.05); 2) tumor necrosis factor alpha (LPS: 185.70 ± 25.63 pg/mg protein versus LPS+HU: 95.89 ± 17.47 pg/mg protein; P <0.05); and 3) prostaglandin E2 (PGE2) (LPS: 159.20 ± 38.70 pg/mg wet weight versus LPS+HU: 71.25 ± 17.75 pg/mg wet weight; P <0.05). Additionally, HU-308 treatment prevented the inhibitory effect of LPS-induced periodontitis on the salivary secretory response to pilocarpine. Moreover, iNOS activity and PGE2 content, which were increased by LPS-induced periodontitis in the submandibular gland, returned to control values after HU-308 treatment. This study demonstrates anti-inflammatory, osteoprotective, and prohomeostatic effects of HU-308 in oral tissues of rats with LPS-induced periodontitis.
Fast torsional waves and strong magnetic field within the Earth's core.
Gillet, Nicolas; Jault, Dominique; Canet, Elisabeth; Fournier, Alexandre
2010-05-06
The magnetic field inside the Earth's fluid and electrically conducting outer core cannot be directly probed. The root-mean-squared (r.m.s.) intensity for the resolved part of the radial magnetic field at the core-mantle boundary is 0.3 mT, but further assumptions are needed to infer the strength of the field inside the core. Recent diagnostics obtained from numerical geodynamo models indicate that the magnitude of the dipole field at the surface of a fluid dynamo is about ten times weaker than the r.m.s. field strength in its interior, which would yield an intensity of the order of several millitesla within the Earth's core. However, a 60-year signal found in the variation in the length of day has long been associated with magneto-hydrodynamic torsional waves carried by a much weaker internal field. According to these studies, the r.m.s. strength of the field in the cylindrical radial direction (calculated for all length scales) is only 0.2 mT, a figure even smaller than the r.m.s. strength of the large-scale (spherical harmonic degree n
Tsukamoto, Hiroki; Takeuchi, Shino; Kubota, Kanae; Kobayashi, Yohei; Kozakai, Sao; Ukai, Ippo; Shichiku, Ayumi; Okubo, Misaki; Numasaki, Muneo; Kanemitsu, Yoshitomi; Matsumoto, Yotaro; Nochi, Tomonori; Watanabe, Kouichi; Aso, Hisashi; Tomioka, Yoshihisa
2018-05-14
Toll-like receptor 4 (TLR4) is an indispensable immune receptor for lipopolysaccharide (LPS), a major component of the Gram-negative bacterial cell wall. Following LPS stimulation, TLR4 transmits the signal from the cell surface and becomes internalized in an endosome. However, the spatial regulation of TLR4 signaling is not fully understood. Here, we investigated the mechanisms of LPS-induced TLR4 internalization and clarified the roles of the extracellular LPS-binding molecules, LPS-binding protein (LBP), and glycerophosphatidylinositol-anchored protein (CD14). LPS stimulation of CD14-expressing cells induced TLR4 internalization in the presence of serum, and an inhibitory anti-LBP mAb blocked its internalization. Addition of LBP to serum-free cultures restored LPS-induced TLR4 internalization to comparable levels of serum. The secretory form of the CD14 (sCD14) induced internalization but required a much higher concentration than LBP. An inhibitory anti-sCD14 mAb was ineffective for serum-mediated internalization. LBP lacking the domain for LPS transfer to CD14 and a CD14 mutant with reduced LPS binding both attenuated TLR4 internalization. Accordingly, LBP is an essential serum molecule for TLR4 internalization, and its LPS transfer to membrane-anchored CD14 (mCD14) is a prerequisite. LBP induced the LPS-stimulated phosphorylation of TBK1, IKKϵ, and IRF3, leading to IFN-β expression. However, LPS-stimulated late activation of NFκB or necroptosis were not affected. Collectively, our results indicate that LBP controls LPS-induced TLR4 internalization, which induces TLR adaptor molecule 1 (TRIF)-dependent activation of the TBK1-IKKϵ-IRF3-IFN-β pathway. In summary, we showed that LBP-mediated LPS transfer to mCD14 is required for serum-dependent TLR4 internalization and activation of the TRIF pathway. Copyright © 2018, The American Society for Biochemistry and Molecular Biology.
Effect of molecular hydrogen on uterine inflammation during preterm labour
Nakano, Tomoko; Kotani, Tomomi; Imai, Kenji; Iitani, Yukako; Ushida, Takafumi; Tsuda, Hiroyuki; Li, Hua; Iwase, Akira; Toyokuni, Shinya; Kikkawa, Fumitaka
2018-01-01
Intrauterine inflammation causes preterm birth and is associated with complications in preterm neonates. Thus, strategies aimed at suppressing inflammation are expected to be effective for reducing the risk of preterm birth and associated complications. Our previous studies demonstrated that molecular hydrogen (H2), an anti-inflammatory agent, prevented inflammation-induced impairment in foetal brain and lung tissues in lipopolysaccharide (LPS)-induced rodent models. However, it remains unclear whether H2 is capable of inhibiting preterm labour. The aim of the current study was therefore to investigate the effect of H2 on inflammation-induced preterm labour. Pregnant ICR (CD-1) mice were divided into three groups: Control, LPS and H2 water (HW) + LPS. In the control and LPS groups, vehicle and LPS, respectively, were intraperitoneally injected on embryonic day 15.5. In the HW + LPS group, HW was administered 24 h prior to LPS injection. The time from LPS administration to parturition was compared between the LPS and HW + LPS groups. Maternal uterus was collected 6 h after LPS injection and the transcript levels of pro-inflammatory cytokines, contractile-associated proteins (CAPs), matrix metalloproteinase-3 (Mmp3) and endothelin-1 (Et1) were assessed by reverse transcription-quantitative polymerase chain reaction. The protein levels of cyclooxygenase-2 (Cox2) were also evaluated by immunohistochemistry. The time from LPS administration to parturition in the HW + LPS group was significantly increased compared with that in the LPS group (33.5±3.4 vs. 18.3±8.8 h, respectively, P=0.020). H2 administration also resulted in significantly higher progesterone levels compared with LPS treatment alone (P=0.002). The transcript levels of pro-inflammatory cytokines, CAPs, Mmp3 and Et1 in the uteri of the LPS group were significantly higher than those in the control group (all P<0.05). In turn, all these levels with the exception of interleukin-8 and Mmp3 were significantly lower in the HW + LPS group compared with those in the LPS group (all P<0.05). The protein levels of Cox2 in the LPS group were also significantly increased compared with those in the control (P<0.001) and HW + LPS (P=0.003) groups. These results suggest that inflammation-induced changes in the uterus may be ameliorated through maternal H2 administration. Preventive H2 administration may therefore represent an effective strategy for the suppression of inflammation during preterm labour. PMID:29732148
Horst, E A; Kvidera, S K; Mayorga, E J; Shouse, C S; Al-Qaisi, M; Dickson, M J; Ydstie, J; Ramirez Ramirez, H A; Keating, A F; Dickson, D J; Griswold, K E; Baumgard, L H
2018-06-01
Activated immune cells are insulin sensitive and utilize copious amounts of glucose. Because chromium (Cr) increases insulin sensitivity and may be immunomodulatory, our objective was to evaluate the effect of supplemental Cr (KemTrace Cr propionate, 20 g/d; Kemin Industries Inc., Des Moines, IA) on immune system glucose utilization and immune system dynamics following an intravenous endotoxin challenge in lactating Holstein cows. Twenty cows (320 ± 18 d in milk) were randomly assigned to 1 of 4 treatments: (1) pair-fed (PF) control (PF-CON; 5 mL of saline; n = 5), (2) PF and Cr supplemented (PF-Cr; 5 mL of saline; n = 5), (3) lipopolysaccharide (LPS)-euglycemic clamp and control supplemented (LPS-CON; 0.375 µg/kg of body weight LPS; n = 5), and (4) LPS-euglycemic clamp and Cr supplemented (LPS-Cr; 0.375 µg/kg of body weight LPS; n = 5). The experiment was conducted serially in 3 periods (P). During P1 (3 d), cows received their respective dietary treatments and baseline values were obtained. At the initiation of P2 (2 d), either a 12-h LPS-euglycemic clamp was conducted or cows were PF to their respective dietary counterparts. During P3 (3 d), cows consumed feed ad libitum and continued to receive their respective dietary treatment. During P2, LPS administration decreased dry matter intake (DMI; 40%) similarly among diets, and by experimental design the pattern and magnitude of reduced DMI were similar in the PF cohorts. During P3, LPS-Cr cows tended to have decreased DMI (6%) relative to LPS-CON cows. Relative to controls, milk yield from LPS-challenged cows decreased (58%) during P2 and LPS-Cr cows produced less (16%) milk than LPS-CON cows. During P3, milk yield progressively increased similarly in LPS-administered cows, but overall milk yield remained decreased (24%) compared with PF controls. There were no dietary treatment differences in milk yield during P3. Circulating insulin increased 9- and 15-fold in LPS-administered cows at 6 and 12 h postbolus, respectively, compared with PF controls. Compared with LPS-CON cows, circulating insulin in LPS-Cr cows was decreased (48%) at 6 h postbolus. Relative to PF cows, circulating LPS binding protein and serum amyloid A from LPS-administered cows increased 2- and 5-fold, respectively. Compared with PF cows, blood neutrophil counts in LPS-infused cows initially decreased, then gradually increased 163%. Between 18 and 48 h postbolus, the number of neutrophils was increased (12%) in LPS-Cr versus LPS-CON cows. The 12-h total glucose deficit was 220 and 1,777 g for the PF and LPS treatments, respectively, but glucose utilization following immune activation was not influenced by Cr. In summary, supplemental Cr reduced the insulin response and increased circulating neutrophils following an LPS challenge but did not appear to alter the immune system's glucose requirement following acute and intense activation. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.
FUEL ELEMENTS FOR THERMAL-FISSION NUCLEAR REACTORS
Flint, O.
1961-01-10
Fuel elements for thermal-fission nuclear reactors are described. The fuel element is comprised of a core of alumina, a film of a metal of the class consisting of copper, silver, and nickel on the outer face of the core, and a coating of an oxide of a metal isotope of the class consisting of Un/sup 235/, U/ sup 233/, and Pu/sup 239/ on the metal f ilm.
X-33 Tank Failure During Autoclave Fabrication
NASA Technical Reports Server (NTRS)
Nettles, Alan T.; Munafo, Paul (Technical Monitor)
2001-01-01
The composite liquid hydrogen tank (tank #1 of 2) for the X-33 flight vehicle is made up of four lobes that have a sandwich construction, bonded to a frame of longerons. Lobes 1 and 4 showed local disbonds to the longerons they were bonded to. The 'bad' areas were cut away and patched with new material. The new material was cured by placing the entire tank in a heated autoclave with no pressure. Upon removal from the autoclave, it was noted that lobe 1 had severe skin/core disbonds on the inner and outer skins. The skins on this lobe were cracked as well. The core was disbonded from the inner skin across the entire acreage, except for spots around the lobe perimeter. The outer skin was separated from the core in a region near the center of the lobe. Lobe 1 was removed from the tank on January 13, 1999. Bolts were placed through the lobe to hold it together and the cuts on the inner skin were not continuous, but 'tabs' were left for final cutting and removal. Upon closer inspection of the disbonded basesheet, it was noted that there was a lack of filleting into the honeycomb core. Good fillets are critical to bond strength.
Liu, Airong; Zhang, Wei-xian
2014-09-21
An angstrom-resolution physical model of nanoscale zero-valent iron (nZVI) is generated with a combination of spherical aberration corrected scanning transmission electron microscopy (Cs-STEM), selected area electron diffraction (SAED), energy-dispersive X-ray spectroscopy (EDS) and electron energy-loss spectroscopy (EELS) on the Fe L-edge. Bright-field (BF), high-angle annular dark-field (HAADF) and secondary electron (SE) imaging of nZVI acquired by a Hitachi HD-2700 STEM show near atomic resolution images and detailed morphological and structural information of nZVI. The STEM-EDS technique confirms that the fresh nZVI comprises of a metallic iron core encapsulated with a thin layer of iron oxides or oxyhydroxides. SAED patterns of the Fe core suggest the polycrystalline structure in the metallic core and amorphous nature of the oxide layer. Furthermore, Fe L-edge of EELS shows varied structural features from the innermost Fe core to the outer oxide shell. A qualitative analysis of the Fe L(2,3) edge fine structures reveals that the shell of nZVI consists of a mixed Fe(II)/Fe(III) phase close to the Fe (0) interface and a predominantly Fe(III) at the outer surface of nZVI.
Modulation of lipopolysaccharide-induced chorioamnionitis in fetal sheep by maternal betamethasone.
Wolfe, Katherine B; Snyder, Candice C; Gisslen, Tate; Kemp, Matthew W; Newnham, John P; Kramer, Boris W; Jobe, Alan H; Kallapur, Suhas
2013-12-01
We tested the hypothesis that the order of exposure to maternal betamethasone and intra-amniotic (IA) lipopolysaccharide (LPS) will differentially modulate inflammation in the chorioamnion. Time-mated Merino ewes with singleton fetuses received saline alone, IA LPS alone, maternal betamethasone before LPS, or betamethasone after LPS. We assessed inflammatory markers in the chorioamnion and the amniotic fluid. Inflammatory cell infiltration, expression of myeloperoxidase, serum amyloid A3 (acute phase reactant) in the chorioamnion, and levels of interleukin (IL)-8 in the amniotic fluid increased 7 days after LPS exposure. Betamethasone prior to LPS decreased infiltration of the inflammatory cells, CD3+ T cells, and decreased the levels of IL-1β and IL-8 in the amniotic fluid. Betamethasone 7 days prior to LPS exposure suppressed LPS-induced inflammation. The markers of inflammation largely had returned to the baseline 14 days after LPS exposure.
DiPiro, J T; Hamilton, R G; Howdieshell, T R; Adkinson, N F; Mansberger, A R
1994-01-01
Antilipopolysaccharide (anti-LPS) immunoglobulin G (IgG) and IgM have been associated with protection from LPS effects in vivo. We investigated the presence of IgE and anti-LPS in 32 patients that had experienced severe traumatic injury and in 35 healthy volunteers; we also investigated whether IgE anti-LPS was associated with important clinical events. Plasma samples were collected daily from patients in the intensive care unit and on one occasion from volunteers; the samples were assayed for IgE anti-LPS. IgE anti-LPS was assayed by enzyme-linked immunosorbent assay with monoclonal anti-human IgE as the capture antibody. Detection was accomplished with biotin-labeled LPS (Escherichia coli J5 mutant) followed by streptavidin-peroxidase with 2,2'-azino(3-ethylbenzthiazoline)sulfonic acid as the substrate. The assay was demonstrated to be specific for IgE and LPS-biotin by nonreactivity of control sera with high-titer anti-LPS IgG and IgM and by inhibition with unlabeled LPS. IgE anti-LPS was detected in 1 of 35 healthy controls (2.9%) and 25 of 32 traumatically injured patients (78%) (P < 0.001). The presence of IgE anti-LPS was associated with a lower incidence of death (P = 0.026) and of renal failure (P = 0.0012). There was no apparent temporal relationship between detection of IgE anti-LPS and clinical events. IgG anti-LPS was detected more frequently in patients that were positive for IgE anti-LPS (P = 0.06) but was not associated with clinical events. The inability to detect IgE anti-LPS may be related to adverse clinical events through depletion of specific IgE due to LPS exposure after trauma or through saturation of the assay by IgE with other specificities. We have reported increased total IgE concentrations in these patients. (J.T. DiPiro, R.G. Hamilton, T. R. Howdieshell, N. F. Adkinson, and A. R. Mansberger, Ann. Surg. 215:460-466, 1992). PMID:7496965
Chemical Sensors Based on Optical Ring Resonators
NASA Technical Reports Server (NTRS)
Homer, Margie; Manfreda, Allison; Mansour, Kamjou; Lin, Ying; Ksendzov, Alexander
2005-01-01
Chemical sensors based on optical ring resonators are undergoing development. A ring resonator according to this concept is a closed-circuit dielectric optical waveguide. The outermost layer of this waveguide, analogous to the optical cladding layer on an optical fiber, is a made of a polymer that (1) has an index of refraction lower than that of the waveguide core and (2) absorbs chemicals from the surrounding air. The index of refraction of the polymer changes with the concentration of absorbed chemical( s). The resonator is designed to operate with relatively strong evanescent-wave coupling between the outer polymer layer and the electromagnetic field propagating along the waveguide core. By virtue of this coupling, the chemically induced change in index of refraction of the polymer causes a measurable shift in the resonance peaks of the ring. In a prototype that has been used to demonstrate the feasibility of this sensor concept, the ring resonator is a dielectric optical waveguide laid out along a closed path resembling a racetrack (see Figure 1). The prototype was fabricated on a silicon substrate by use of standard techniques of thermal oxidation, chemical vapor deposition, photolithography, etching, and spin coating. The prototype resonator waveguide features an inner cladding of SiO2, a core of SixNy, and a chemical-sensing outer cladding of ethyl cellulose. In addition to the ring Chemical sensors based on optical ring resonators are undergoing development. A ring resonator according to this concept is a closed-circuit dielectric optical waveguide. The outermost layer of this waveguide, analogous to the optical cladding layer on an optical fiber, is a made of a polymer that (1) has an index of refraction lower than that of the waveguide core and (2) absorbs chemicals from the surrounding air. The index of refraction of the polymer changes with the concentration of absorbed chemical( s). The resonator is designed to operate with relatively strong evanescent-wave coupling between the outer polymer layer and the electromagnetic field propagating along the waveguide core. By virtue of this coupling, the chemically induced change in index of refraction of the polymer causes a measurable shift in the resonance peaks of the ring. In a prototype that has been used to demonstrate the feasibility of this sensor concept, the ring resonator is a dielectric optical waveguide laid out along a closed path resembling a racetrack (see Figure 1). The prototype was fabricated on a silicon substrate by use of standard techniques of thermal oxidation, chemical vapor deposition, photolithography, etching, and spin coating. The prototype resonator waveguide features an inner cladding of SiO2, a core of SixNy, and a chemical-sensing outer cladding of ethyl cellulose. In addition to the ring res
Hong, Wei; Gao, Xiang; Qiu, Peng; Yang, Jie; Qiao, Mingxi; Shi, Hong; Zhang, Dexian; Tian, Chunlian; Niu, Shengli; Liu, Mingchun
2017-01-01
Bacitracin A (BA) is an excellent polypeptide antibiotic that is active against gram-positive bacteria without triggering multidrug resistance. However, BA is inactive against gram-negative bacteria because of its inability to cross the outer membrane of these cells, and it has strong nephrotoxicity, thus limiting its clinical applications. Nanoantibiotics can effectively localize antibiotics to the periplasmic space of bacteria while decreasing the adverse effects of antibiotics. In this study, biodegradable hydrophobic copolymers of poly (d,l-lactide-co-glycolide) (PLGA) were attached to the N-termini of BA to design a novel class of self-assembled nano-bacitracin A (nano-BAs), and their potential as antibacterial agents was evaluated in vitro and in vivo. Nano-BAs had a core-shell structure with a mean diameter <150 nm. Impressively, nano-BAs had strong antibacterial properties against both gram-positive and gram-negative bacteria, and the distribution of antibacterial activity as a function of PLGA block length was skewed toward longer PLGA chains. No cytotoxicity against HK-2 cells or human red blood cells (hRBCs) was observed in vitro, suggesting good biocompatibility. A high local density of BA mass on the surface promoted endocytotic cellular uptake, and hydrophobic interactions between the PLGA block and lipopolysaccharide (LPS) facilitated the uptake of nano-BAs, thereby leading to greater antibacterial activities. In addition, Nano-BA5K was found to be effective in vivo, and it served as an anti-infective agent for wound healing. Collectively, this study provides a cost-effective means of developing self-assembling nano-polypeptide antibiotic candidates with a broader antibacterial spectrum and a lower toxicity than commercially available peptide antibiotics, owing to their modification with biodegradable copolymers. PMID:28721045
Hong, Wei; Gao, Xiang; Qiu, Peng; Yang, Jie; Qiao, Mingxi; Shi, Hong; Zhang, Dexian; Tian, Chunlian; Niu, Shengli; Liu, Mingchun
2017-01-01
Bacitracin A (BA) is an excellent polypeptide antibiotic that is active against gram-positive bacteria without triggering multidrug resistance. However, BA is inactive against gram-negative bacteria because of its inability to cross the outer membrane of these cells, and it has strong nephrotoxicity, thus limiting its clinical applications. Nanoantibiotics can effectively localize antibiotics to the periplasmic space of bacteria while decreasing the adverse effects of antibiotics. In this study, biodegradable hydrophobic copolymers of poly (d,l-lactide-co-glycolide) (PLGA) were attached to the N-termini of BA to design a novel class of self-assembled nano-bacitracin A (nano-BAs), and their potential as antibacterial agents was evaluated in vitro and in vivo. Nano-BAs had a core-shell structure with a mean diameter <150 nm. Impressively, nano-BAs had strong antibacterial properties against both gram-positive and gram-negative bacteria, and the distribution of antibacterial activity as a function of PLGA block length was skewed toward longer PLGA chains. No cytotoxicity against HK-2 cells or human red blood cells (hRBCs) was observed in vitro, suggesting good biocompatibility. A high local density of BA mass on the surface promoted endocytotic cellular uptake, and hydrophobic interactions between the PLGA block and lipopolysaccharide (LPS) facilitated the uptake of nano-BAs, thereby leading to greater antibacterial activities. In addition, Nano-BA 5K was found to be effective in vivo, and it served as an anti-infective agent for wound healing. Collectively, this study provides a cost-effective means of developing self-assembling nano-polypeptide antibiotic candidates with a broader antibacterial spectrum and a lower toxicity than commercially available peptide antibiotics, owing to their modification with biodegradable copolymers.
NASA Astrophysics Data System (ADS)
Ortt, D.; Chen, S. S.
2007-12-01
The interaction of the environmental water vapor distribution around a tropical cyclone (TC), rainbands, and inner- core dynamics can affect hurricane structure and intensity change, which is not well understood. Although previous studies have addressed various aspects of this problem, a full three way interaction and its implications for hurricane intensity change has not been documented. Using data collected during the Hurricane Rainband and Intensity Experiment (RAINEX) in Hurricanes Katrina and Rita, the three way interaction of the environment moisture, rainbands, and inner-core dynamics can be evaluated. The TRMM TMI total precipitable water (PW) data with 1/4 degree horizontal resolution, TRMM TMI rainrate data with a 4 km horizontal resolution and the GPS dropsondes with a ½ second temporal resolution are used to characterize the environmental moisture. The high resolution model output from the real-time MM5 forecasts of Hurricanes Katrina and Rita are used to investigate the complex interactions in both storms. The model forecasts were made using a vortex-following nested grid with horizontal resolutions of 15, 5, and 1.67km, respectively. There were 28 vertical sigma levels. The Goddard microphysics scheme was used. The TRMM PW and the GPS dropsonde data show strong moisture gradients in the outer rainband region in Rita with a dry outer environment, which may contribute to the development of outer rainbands with a high circularity. It created a secondary ring of potential vorticity (PV). In addition, the vortex Rossby waves (VRW) propagating radialy outward from the eyewall were unable to propagate beyond the secondary ring of PV. The combination of these VRW and the environmental water vapor distribution may play a role in enhancing the rainbands that developed into a secondary eyewall, which leads to a temporary weakening of the hurricane. In contrast, Katrina had a relative weak moisture gradient surrounding the storm. There were not persistent outer rainbands with high circularity, which may explain the different evolution in Katrina compared with Rita.
Cyanobacterial lipopolysaccharides and human health – a review
Stewart, Ian; Schluter, Philip J; Shaw, Glen R
2006-01-01
Cyanobacterial lipopolysaccharide/s (LPS) are frequently cited in the cyanobacteria literature as toxins responsible for a variety of heath effects in humans, from skin rashes to gastrointestinal, respiratory and allergic reactions. The attribution of toxic properties to cyanobacterial LPS dates from the 1970s, when it was thought that lipid A, the toxic moiety of LPS, was structurally and functionally conserved across all Gram-negative bacteria. However, more recent research has shown that this is not the case, and lipid A structures are now known to be very different, expressing properties ranging from LPS agonists, through weak endotoxicity to LPS antagonists. Although cyanobacterial LPS is widely cited as a putative toxin, most of the small number of formal research reports describe cyanobacterial LPS as weakly toxic compared to LPS from the Enterobacteriaceae. We systematically reviewed the literature on cyanobacterial LPS, and also examined the much lager body of literature relating to heterotrophic bacterial LPS and the atypical lipid A structures of some photosynthetic bacteria. While the literature on the biological activity of heterotrophic bacterial LPS is overwhelmingly large and therefore difficult to review for the purposes of exclusion, we were unable to find a convincing body of evidence to suggest that heterotrophic bacterial LPS, in the absence of other virulence factors, is responsible for acute gastrointestinal, dermatological or allergic reactions via natural exposure routes in humans. There is a danger that initial speculation about cyanobacterial LPS may evolve into orthodoxy without basis in research findings. No cyanobacterial lipid A structures have been described and published to date, so a recommendation is made that cyanobacteriologists should not continue to attribute such a diverse range of clinical symptoms to cyanobacterial LPS without research confirmation. PMID:16563160
Rivas, Priscila M S; Vechiato, Fernanda M V; Borges, Beatriz C; Rorato, Rodrigo; Antunes-Rodrigues, Jose; Elias, Lucila L K
2017-07-01
Acute administration of lipopolysaccharide (LPS) from Gram-negative bacteria induces hypophagia. However, the repeated administration of LPS leads to desensitization of hypophagia, which is associated with increased hypothalamic p-AMPK expression. Because ghrelin and endocannabinoids modulate AMPK activity in the hypothalamus, we hypothesized that these neuromodulators play a role in the reversal of tolerance to hypophagia in rats under long-term exposure to LPS. Male Wistar rats were treated with single (1 LPS, 100μg/kg body weight, ip) or repeated injections of LPS over 6days (6 LPS). Food intake was reduced in the 1 LPS, but not in the 6 LPS group. 6 LPS rats showed an increased serum concentration of acylated ghrelin and reduced ghrelin receptor mRNA expression in the hypothalamus. Ghrelin injection (40μg/kg body weight, ip) increased food intake, body weight gain, p-AMPK hypothalamic expression, neuropeptide Y (NPY) and Agouti related peptide (AgRP) mRNA expression in control animals (Saline). However, in 6 LPS rats, ghrelin did not alter these parameters. Central administration of a CB1R antagonist (AM251, 200ng/μl in 5μl/rat) induced hypophagia in 6 LPS animals, suggesting that the endocannabinoid system contributes to preserved food intake during LPS tolerance. In the presence of AM251, the ability of ghrelin to phosphorylate AMPK in the hypothalamus of 6 LPS group was restored, but not its orexigenic effect. Our data highlight that the orexigenic effects of ghrelin require CB1R signaling downstream of AMPK activation. Moreover, CB1R-mediated pathways contribute to the absence of hypophagia during repeated exposure to endotoxin. Copyright © 2017 Elsevier Inc. All rights reserved.
Melting of Fe-Si-O alloys: the Fate of Coexisting Si and O in the Core
NASA Astrophysics Data System (ADS)
Arveson, S. M.; Lee, K. K. M.
2017-12-01
The light element budget of Earth's core plays an integral role in sustaining outer core convection, which powers the geodynamo. Many experiments have been performed on binary iron compounds, but the results do not robustly agree with seismological observations and geochemical constraints. Earth's core is almost certainly made up of multiple light elements, so the future of core composition studies lies in ternary (or higher order) systems in order to examine interactions between light elements. We perform melting experiments on Fe-Si-O alloys in a laser-heated diamond-anvil cell to 80 GPa and 4000 K. Using 2D multi- wavelength imaging radiometry together with textural and chemical analysis of quenched samples, we measure the high-pressure melting curves and determine partitioning of light elements between the melt and the coexisting solid. Quenched samples are analyzed both in map view and in cross section using scanning electron microscopy (SEM) and electron microprobe analysis (EPMA) to examine the 3D melt structure and composition. Partitioning of light elements between molten and solid alloys dictates (1) the density contrast at the ICB, which drives compositional convection in the outer core and (2) the temperature of the CMB, an integral parameter for understanding the deep Earth. Our experiments suggest silicon and oxygen do not simply coexist in the melt and instead show complex solubility based on temperature. Additionally, we do not find evidence of crystallization of SiO2 at low oxygen content as was recently reported.11 Hirose, K., et al., Crystallization of silicon dioxide and compositional evolution of the Earth's core. Nature, 2017. 543(7643): p. 99-102.
NASA Astrophysics Data System (ADS)
Vocadlo, L.; Martorell, B.; Brodholt, J. P.; Wood, I. G.
2014-12-01
Seismically determined S-wave velocities in the Earth's inner core are observed to be much lower (10-30%) than those generally inferred from mineral physics. This is a remarkably large discrepancy - mineralogical models for the mantle and the outer core match the observed velocities to around 1%. In no other large volume of the Earth does such a difference exist. There have been a number of arguments put forward over the years to account for the difference, but none have been universally accepted and our inability to explain the seismic velocities of the inner core remains an uncomfortable truth. Here, we present results from ab initio molecular dynamics calculations performed at 360 GPa and core temperatures on hcp and fcc iron, and on fcc-Fe alloyed with nickel and hcp-Fe alloyed with silicon. The calculated shear modulus, and therefore seismic velocities, of pure hcp-Fe reduces dramatically just prior to melting, providing an elegant explanation for the observed velocities. Calculations on fcc-Fe show no such strong reduction in VS, with a transformation to an hcp-type structure prior to melting; addition of 6.5 atm% and 13 atm% Ni to fcc-Fe raises the temperature of this transition. When silicon is added to hcp-Fe, the pre-melting behaviour is found to be very similar to that of pure hcp-Fe with a strong nonlinear shear weakening just before melting and a corresponding reduction in VS. Because temperatures range from T/Tm = 1 at the inner-outer core boundary to T/Tm ≈ 0.99 at the centre, this strong nonlinear effect on VS should occur in the inner core, providing a compelling explanation for the low VS observed.
Osmium Isotope Compositions of Komatiite Sources Through Time
NASA Astrophysics Data System (ADS)
Walker, R. J.
2001-12-01
Extending Os isotopic measurements to ancient plume sources may help to constrain how and when the well-documented isotopic heterogeneities in modern systems were created. Komatiites and picrites associated with plume-related volcanism are valuable tracers of the Os isotopic composition of plumes because of their typically high Os concentrations and relatively low Re/Os. Re-Os data are now available for a variety of Phanerozoic, Proterozoic and Archean komatiites and picrites. As with modern plumes, the sources of Archean and Proterozoic komatiites exhibit a large range of initial 187Os/188Os ratios. Most komatiites are dominated by sources with chondritic Os isotopic compositions (e.g. Song La; Norseman-Wiluna; Pyke Hill; Alexo), though some (e.g. Gorgona) derive from heterogeneous sources. Of note, however, two ca. 2.7 Ga systems, Kostomuksha (Russia) and Belingwe (Zimbabwe), have initial ratios enriched by 2-3% relative to the contemporary convecting upper mantle. These results suggest that if the 187Os enrichment was due to the incorporation of minor amounts of recycled crust into the mantle source of the rocks, the crust formed very early in Earth history. Thus, the Os results could reflect derivation of melt from hybrid mantle whose composition was modified by the addition of mafic crustal material that would most likely have formed between 4.2 and 4.5 Ga. Alternately, the mantle sources of these komatiites may have derived a portion of their Os from the putative 187Os - and 186Os -enriched outer core. For this hypothesis to be applicable to Archean rocks, an inner core of sufficient mass would have to have crystallized sufficiently early in Earth history to generate an outer core with 187Os enriched by at least 3% relative to the chondritic average. Using the Pt-Re-Os partition coefficients espoused by our earlier work, and assuming linear growth of the inner core started at 4.5 Ga and continued to present, would yield an outer core at 2.7 Ga with a gamma Os value of only +1.2 and a 186Os/188Os enrichment relative to the contemporary upper mantle of only +13 ppm. Greater isotopic enrichments could have been achieved by 2.7 Ga if either the inner core comprised >2.8% of the mass of the core by 2.7 Ga, or if Re and Os solid metal-liquid metal D's for core crystallization were greater that those applied in the initial calculation.
Armor systems including coated core materials
Chu, Henry S [Idaho Falls, ID; Lillo, Thomas M [Idaho Falls, ID; McHugh, Kevin M [Idaho Falls, ID
2012-07-31
An armor system and method involves providing a core material and a stream of atomized coating material that comprises a liquid fraction and a solid fraction. An initial layer is deposited on the core material by positioning the core material in the stream of atomized coating material wherein the solid fraction of the stream of atomized coating material is less than the liquid fraction of the stream of atomized coating material on a weight basis. An outer layer is then deposited on the initial layer by positioning the core material in the stream of atomized coating material wherein the solid fraction of the stream of atomized coating material is greater than the liquid fraction of the stream of atomized coating material on a weight basis.
Armor systems including coated core materials
Chu, Henry S; Lillo, Thomas M; McHugh, Kevin M
2013-10-08
An armor system and method involves providing a core material and a stream of atomized coating material that comprises a liquid fraction and a solid fraction. An initial layer is deposited on the core material by positioning the core material in the stream of atomized coating material wherein the solid fraction of the stream of atomized coating material is less than the liquid fraction of the stream of atomized coating material on a weight basis. An outer layer is then deposited on the initial layer by positioning the core material in the stream of atomized coating material wherein the solid fraction of the stream of atomized coating material is greater than the liquid fraction of the stream of atomized coating material on a weight basis.
Characterization of the First Molluscicidal Lipopolysaccharide from Moraxella osloensis
Tan, Li; Grewal, Parwinder S.
2003-01-01
Moraxella osloensis is a bacterium that is mutualistically associated with Phasmarhabditis hermaphrodita, a nematode that has potential for the biocontrol of mollusk pests, especially the slug Deroceras reticulatum. We discovered that purified M. osloensis lipopolysaccharide (LPS) possesses a lethal toxicity to D. reticulatum when administered by injection but no contact or oral toxicity to this slug. The toxicity of the LPS resides in the lipid A moiety. M. osloensis LPS was semiquantitated at 6 × 107 endotoxin units per mg. The LPS is a rough-type LPS with an estimated molecular weight of 5,300. Coinjection of galactosamine with the LPS increased the LPS's toxicity to the slug two- to four-fold. The galactosamine-induced sensitization of the slug to the LPS was reversed completely by uridine. PMID:12788774
Characterization of the first molluscicidal lipopolysaccharide from Moraxella osloensis.
Tan, Li; Grewal, Parwinder S
2003-06-01
Moraxella osloensis is a bacterium that is mutualistically associated with Phasmarhabditis hermaphrodita, a nematode that has potential for the biocontrol of mollusk pests, especially the slug Deroceras reticulatum. We discovered that purified M. osloensis lipopolysaccharide (LPS) possesses a lethal toxicity to D. reticulatum when administered by injection but no contact or oral toxicity to this slug. The toxicity of the LPS resides in the lipid A moiety. M. osloensis LPS was semiquantitated at 6 x 10(7) endotoxin units per mg. The LPS is a rough-type LPS with an estimated molecular weight of 5,300. Coinjection of galactosamine with the LPS increased the LPS's toxicity to the slug two- to four-fold. The galactosamine-induced sensitization of the slug to the LPS was reversed completely by uridine.
Margaret, Isabel; Lucas, M. Mercedes; Acosta-Jurado, Sebastián; Buendía-Clavería, Ana M.; Fedorova, Elena; Hidalgo, Ángeles; Rodríguez-Carvajal, Miguel A.; Rodriguez-Navarro, Dulce N.; Ruiz-Sainz, José E.; Vinardell, José M.
2013-01-01
In this work we have characterised the Sinorhizobium fredii HH103 greA lpsB lpsCDE genetic region and analysed for the first time the symbiotic performance of Sinorhizobium fredii lps mutants on soybean. The organization of the S. fredii HH103 greA, lpsB, and lpsCDE genes was equal to that of Sinorhizobium meliloti 1021. S. fredii HH103 greA, lpsB, and lpsE mutant derivatives produced altered LPS profiles that were characteristic of the gene mutated. In addition, S. fredii HH103 greA mutants showed a reduction in bacterial mobility and an increase of auto-agglutination in liquid cultures. RT-PCR and qPCR experiments demonstrated that the HH103 greA gene has a positive effect on the transcription of lpsB. Soybean plants inoculated with HH103 greA, lpsB or lpsE mutants formed numerous ineffective pseudonodules and showed severe symptoms of nitrogen starvation. However, HH103 greA and lps mutants were also able to induce the formation of a reduced number of soybean nodules of normal external morphology, allowing the possibility of studying the importance of bacterial LPS in later stages of the S. fredii HH103-soybean symbiosis. The infected cells of these nodules showed signs of early termination of symbiosis and lytical clearance of bacteroids. These cells also had very thick walls and accumulation of phenolic-like compounds, pointing to induced defense reactions. Our results show the importance of bacterial LPS in later stages of the S. fredii HH103-soybean symbiosis and their role in preventing host cell defense reactions. S. fredii HH103 lpsB mutants also showed reduced nodulation with Vigna unguiculata, although the symbiotic impairment was less pronounced than in soybean. PMID:24098345
Transcriptional regulation of bone sialoprotein gene by Porphyromonas gingivalis lipopolysaccharide.
Li, Xinyue; Kato, Naoko; Mezawa, Masaru; Li, Zhengyang; Wang, Zhitao; Yang, Li; Sasaki, Yoko; Kaneko, Takashi; Takai, Hideki; Yoshimura, Atsutoshi; Ogata, Yorimasa
2010-07-01
Lipopolysaccharide (LPS) is a major mediator of inflammatory response. Periodontopathic bacterium Porphyromonas gingivalis LPS has quite different character from Escherichia coli LPS. E. coli LPS is agonist for Toll-like receptor 4 (TLR4), whereas P. gingivalis LPS worked as antagonist for TLR4. Bone sialoprotein (BSP) is an early marker of osteoblast differentiation. To investigate the effects of P. gingivalis LPS on BSP transcription, we used rat osteoblast-like ROS17/2.8 cells. BSP mRNA levels were decreased by 0.1 microg/ml and increased by 0.01 microg/ml P. gingivalis LPS at 12 h. Results of luciferase assays showed that 0.1 microg/ml decreased and 0.01 microg/ml P. gingivalis LPS increased BSP transcription in -116 to +60 BSP construct. The effects of P. gingivalis LPS were abrogated by double mutations in cAMP response element (CRE) and FGF2 response element (FRE). Tyrosine kinase inhibitor herbimycin A, ERK1/2 inhibitor and antioxidant N-acetylcystein inhibited effects of P. gingivalis LPS. Protein kinase A inhibitor and PI3-kinase/Akt inhibitor only abolished the effect of 0.01 microg/ml P. gingivalis LPS. Furthermore, 0.1 microg/ml LPS decreased the CRE- and FRE-protein complexes formation, whereas 0.01 microg/ml P. gingivalis LPS increased the nuclear protein binding to CRE and FRE. ChIP assays revealed increased binding of CREB1, JunD, Fra2, Runx2, Dlx5, and Smad1 to a chromatin fragment containing the CRE and FRE by 0.01 microg/ml P. gingivalis LPS. These studies therefore indicated that 0.1 microg/ml suppressed, and 0.01 microg/ml P. gingivalis LPS increased BSP gene transcription mediated through CRE and FRE elements in the rat BSP gene promoter. J. Cell. Biochem. 110: 823-833, 2010. (c) 2010 Wiley-Liss, Inc.
EphA2 Receptor Signaling Mediates Inflammatory Responses in Lipopolysaccharide-Induced Lung Injury.
Hong, Ji Young; Shin, Mi Hwa; Chung, Kyung Soo; Kim, Eun Young; Jung, Ji Ye; Kang, Young Ae; Kim, Young Sam; Kim, Se Kyu; Chang, Joon; Park, Moo Suk
2015-07-01
Eph receptors and ephrin ligands have several functions including angiogenesis, cell migration, axon guidance, fluid homeostasis, oncogenesis, inflammation and injury repair. The EphA2 receptor potentially mediates the regulation of vascular permeability and inflammation in response to lung injury. Mice were divided into 3 experimental groups to study the role of EphA2 signaling in the lipopolysaccharide (LPS)-induced lung injury model i.e., IgG+phosphate-buffered saline (PBS) group (IgG instillation before PBS exposure), IgG+LPS group (IgG instillation before LPS exposure) and EphA2 monoclonal antibody (mAb)+LPS group (EphA2 mAb pretreatment before LPS exposure). EphA2 and ephrinA1 were upregulated in LPS-induced lung injury. The lung injury score of the EphA2 mAb+LPS group was lower than that of the IgG+LPS group (4.30±2.93 vs. 11.45±1.20, respectively; p=0.004). Cell counts (EphA2 mAb+LPS: 11.33×10(4)±8.84×10(4) vs. IgG+LPS: 208.0×10(4)±122.6×10(4); p=0.018) and total protein concentrations (EphA2 mAb+LPS: 0.52±0.41 mg/mL vs. IgG+LPS: 1.38±1.08 mg/mL; p=0.192) were decreased in EphA2 mAb+LPS group, as compared to the IgG+LPS group. In addition, EphA2 antagonism reduced the expression of phospho-p85, phosphoinositide 3-kinase 110γ, phospho-Akt, nuclear factor κB, and proinflammatory cytokines. This results of the study indicated a role for EphA2-ephrinA1 signaling in the pathogenesis of LPS-induced lung injury. Furthermore, EphA2 antagonism inhibits the phosphoinositide 3-kinase-Akt pathway and attenuates inflammation.
Fonceca, Angela M; Zosky, Graeme R; Bozanich, Elizabeth M; Sutanto, Erika N; Kicic, Anthony; McNamara, Paul S; Knight, Darryl A; Sly, Peter D; Turner, Debra J; Stick, Stephen M
2018-01-22
Accumulation mode particles (AMP) are formed from engine combustion and make up the inhalable vapour cloud of ambient particulate matter pollution. Their small size facilitates dispersal and subsequent exposure far from their original source, as well as the ability to penetrate alveolar spaces and capillary walls of the lung when inhaled. A significant immuno-stimulatory component of AMP is lipopolysaccharide (LPS), a product of Gram negative bacteria breakdown. As LPS is implicated in the onset and exacerbation of asthma, the presence or absence of LPS in ambient particulate matter (PM) may explain the onset of asthmatic exacerbations to PM exposure. This study aimed to delineate the effects of LPS and AMP on airway inflammation, and potential contribution to airways disease by measuring airway inflammatory responses induced via activation of the LPS cellular receptor, Toll-like receptor 4 (TLR-4). The effects of nebulized AMP, LPS and AMP administered with LPS on lung function, cellular inflammatory infiltrate and cytokine responses were compared between wildtype mice and mice not expressing TLR-4. The presence of LPS administered with AMP appeared to drive elevated airway resistance and sensitivity via TLR-4. Augmented TLR4 driven eosinophilia and greater TNF-α responses observed in AMP-LPS treated mice independent of TLR-4 expression, suggests activation of allergic responses by TLR4 and non-TLR4 pathways larger than those induced by LPS administered alone. Treatment with AMP induced macrophage recruitment independent of TLR-4 expression. These findings suggest AMP-LPS as a stronger stimulus for allergic inflammation in the airways then LPS alone.
The Evolution of the Earth's Magnetic Field.
ERIC Educational Resources Information Center
Bloxham, Jeremy; Gubbins, David
1989-01-01
Describes the change of earth's magnetic field at the boundary between the outer core and the mantle. Measurement techniques used during the last 300 years are considered. Discusses the theories and research for explaining the field change. (YP)
Process Development and Micro-Machining of MARBLE Foam-Cored Rexolite Hemi-Shell Ablator Capsules
Randolph, Randall Blaine; Oertel, John A.; Schmidt, Derek William; ...
2016-06-30
For this study, machined CH hemi-shell ablator capsules have been successfully produced by the MST-7 Target Fabrication Team at Los Alamos National Laboratory. Process development and micro-machining techniques have been developed to produce capsules for both the Omega and National Ignition Facility (NIF) campaigns. These capsules are gas filled up to 10 atm and consist of a machined plastic hemi-shell outer layer that accommodates various specially engineered low-density polystyrene foam cores. Machining and assembly of the two-part, step-jointed plastic hemi-shell outer layer required development of new techniques, processes, and tooling while still meeting very aggressive shot schedules for both campaigns.more » Finally, problems encountered and process improvements will be discussed that describe this very unique, complex capsule design approach through the first Omega proof-of-concept version to the larger NIF version.« less
Gravity Field and Internal Structure of Mercury from MESSENGER
NASA Technical Reports Server (NTRS)
Smith, David E.; Zuber, Maria T.; Phillips, Roger J.; Solomon, Sean C.; Hauck, Steven A., II; Lemoine, Frank G.; Mazarico, Erwan; Neumann, Gregory A.; Peale, Stanton J.; Margot, Jean-Luc;
2012-01-01
Radio tracking of the MESSENGER spacecraft has provided a model of Mercury's gravity field. In the northern hemisphere, several large gravity anomalies, including candidate mass concentrations (mascons), exceed 100 milli-Galileos (mgal). Mercury's northern hemisphere crust is thicker at low latitudes and thinner in the polar region and shows evidence for thinning beneath some impact basins. The low-degree gravity field, combined with planetary spin parameters, yields the moment of inertia C/M(R(exp 2) = 0.353 +/- 0.017, where M and R are Mercury's mass and radius, and a ratio of the moment of inertia of Mercury's solid outer shell to that of the planet of C(sub m)/C = 0.452 +/- 0.035. A model for Mercury s radial density distribution consistent with these results includes a solid silicate crust and mantle overlying a solid iron-sulfide layer and an iron-rich liquid outer core and perhaps a solid inner core.
NUCLEAR SUPERHEATER FOR BOILING WATER REACTOR
Holl, R.J.; Klecker, R.W.; Graham, C.B.
1962-05-15
A description is given of a boiling water reactor having a superheating region integral with the core. The core consists essentially of an annular boiling region surrounding an inner superheating region. Both regions contain fuel elements and are separated by a cylindrical wall, perforations being provided in the lower portion of the cylindrical wall to permit circulation of a common water moderator between the two regions. The superheater region comprises a plurality of tubular fuel assemblies through which the steam emanating from the boiling region passes to the steam outlet. Each superheater fuel assembly has an outer double-walled cylinder, the double walls being concentrically spaced and connected together at their upper ends but open at the bottom to provide for differential thermal expansion of the inner and outer walls. Gas is entrapped in the annulus between the walls which acts as an insulating space between the fissionable material inside and the moderator outside. (AEC)
Numerical investigation of a tunable band-pass plasmonic filter with a hollow-core ring resonator
NASA Astrophysics Data System (ADS)
Setayesh, Amir; Mirnaziry, S. Reza; Sadegh Abrishamian, Mohammad
2011-03-01
In this study, a compact nanoscale plasmonic filter which consists of two metal-insulator-metal (MIM) waveguides coupled to each other by a rectangular ring resonator is presented and investigated numerically. The propagating modes of surface plasmon polaritons (SPPs) are studied in this structure. By replacing a portion of the ring core with air, while the outer dimensions of the structure are kept constant, we illustrate the possibility of the redshift of resonant wavelengths in order to tune the resonance modes. This feature is useful for integrated circuits in which we have limitations on the outer dimensions of the filter structure and it is not possible to enlarge the dimension of the ring resonator to reach longer resonant wavelengths. The corresponding results are illustrated by the 2D finite-difference time-domain (FDTD) method. The proposed structure has potential applications in plasmonic integrated circuits and can be simply fabricated.
Gravity field and internal structure of Mercury from MESSENGER.
Smith, David E; Zuber, Maria T; Phillips, Roger J; Solomon, Sean C; Hauck, Steven A; Lemoine, Frank G; Mazarico, Erwan; Neumann, Gregory A; Peale, Stanton J; Margot, Jean-Luc; Johnson, Catherine L; Torrence, Mark H; Perry, Mark E; Rowlands, David D; Goossens, Sander; Head, James W; Taylor, Anthony H
2012-04-13
Radio tracking of the MESSENGER spacecraft has provided a model of Mercury's gravity field. In the northern hemisphere, several large gravity anomalies, including candidate mass concentrations (mascons), exceed 100 milli-Galileos (mgal). Mercury's northern hemisphere crust is thicker at low latitudes and thinner in the polar region and shows evidence for thinning beneath some impact basins. The low-degree gravity field, combined with planetary spin parameters, yields the moment of inertia C/MR(2) = 0.353 ± 0.017, where M and R are Mercury's mass and radius, and a ratio of the moment of inertia of Mercury's solid outer shell to that of the planet of C(m)/C = 0.452 ± 0.035. A model for Mercury's radial density distribution consistent with these results includes a solid silicate crust and mantle overlying a solid iron-sulfide layer and an iron-rich liquid outer core and perhaps a solid inner core.
Yu, Yang; Cui, Yingjie; Zhao, Yanan; Liu, Shuai; Song, Guohua; Jiao, Peng; Li, Bin; Luo, Tian; Guo, Shoudong; Zhang, Xiangjian; Wang, Hao; Jiang, Xian-Cheng; Qin, Shucun
2016-02-09
Phospholipid transfer protein (PLTP) participates in high density lipoprotein (HDL) metabolism. Increased plasma PLTP activity was observed in lipopolysaccharide (LPS) triggered acute inflammatory diseases. This study aimed to determine the exact role of PLTP in LPS induced inflammation. HDL pool size was shrunk both in PLTP deficient mice (PLTP-/-) and PLTP transgenic mice (PLTP-Tg). PLTP displayed a strong protective effect on lethal endotoxemia in mice survival study. Furthermore, after LPS stimulation, the expression of pro-inflammatory cytokines were increased in bone marrow derived macrophage (BMDM) from PLTP-/-, while decreased in BMDM from PLTP-Tg compared with BMDM from wild-type mice (WT). Moreover, LPS induced nuclear factor kappa-B (NFκB) activation was enhanced in PLTP-/- BMDM or PLTP knockdown RAW264.7. Conversely, PLTP overexpression countered the NFκB activation in LPS challenged BMDM. Additionally, the activation of toll like receptor 4 (TLR4) induced by LPS showed no alteration in PLTP-/- BMDM. Finally, PLTP could bind to LPS, attenuate the pro-inflammatory effects of LPS, and improve the cell viability in vitro. To sum up, these findings elucidated that PLTP repressed LPS induced inflammation due to extracellular LPS binding capability, and the protective effects were not related to HDL pool size in mice.
Effects of BCG infection on the susceptibility of mouse macrophages to endotoxin.
Peavy, D L; Baughn, R E; Musher, D M; Musher, D M
1979-01-01
Mice infected intravenously with Mycobacterium bovis (BCG) are 100 to 1,000 times more sensitive to the lethal effects of bacterial lipopolysaccharides (LPS). Since BCG infection results in macrophage activation and LPS may cause pathophysiological effects through interaction with this cell type, it was of interest to determine whether macrophages from BCG-infected animals were more susceptible to the toxic effects of LPS in vitro. When LPS-susceptible, C57BL/6 mice were infected with BCG, a significant reduction in the 50% lethal dose of LPS was first observed after 7 days and persisted for several weeks. Macrophages from these animals had greatly increased susceptibility to LPS in vitro, which correlated with the development of acquired cellular resistance as determined by their ability to inhibit the growth of Listeria monocytogenes. In contrast, BCG infection of C3H/HeJ mice, a strain resistant to LPS, did not alter the 50% lethal dose of LPS for these animals or increase the sensitivity of their peritoneal macrophages to LPS in vitro. These results indicate that susceptibility of BCG-infected mice to the lethal effects of LPS parallels the susceptibility of their macrophages in vitro; release of vasoactive substances from LPS-susceptible activated macrophages in vivo may be, in part, responsible for lethality. PMID:378847
Alkaline Phosphatase Protects Lipopolysaccharide-Induced Early Pregnancy Defects in Mice
Lei, Wei; Ni, Hua; Herington, Jennifer; Reese, Jeff; Paria, Bibhash C.
2015-01-01
Excessive cytokine inflammatory response due to chronic or superphysiological level of microbial infection during pregnancy leads to pregnancy complications such as early pregnancy defects/loss and preterm birth. Bacterial toxin lipopolysaccharide (LPS), long recognized as a potent proinflammatory mediator, has been identified as a risk factor for pregnancy complications. Alkaline phosphatase (AP) isozymes have been shown to detoxify LPS by dephosphorylation. In this study, we examined the role of alkaline phosphatase (AP) in mitigating LPS-induced early pregnancy complications in mice. We found that 1) the uterus prior to implantation and implantation sites following embryo implantation produce LPS recognition and dephosphorylation molecules TLR4 and tissue non-specific AP (TNAP) isozyme, respectively; 2) uterine TNAP isozyme dephosphorylates LPS at its sites of production; 3) while LPS administration following embryo implantation elicits proinflammatory cytokine mRNA levels at the embryo implantation sites (EISs) and causes early pregnancy loss, dephosphorylated LPS neither triggers proinflammatory cytokine mRNA levels at the EISs nor induces pregnancy complications; 4) AP isozyme supplementation to accelerate LPS detoxification attenuates LPS-induced pregnancy complications following embryo implantation. These findings suggest that a LPS dephosphorylation strategy using AP isozyme may have a unique therapeutic potential to mitigate LPS- or Gram-negative bacteria-induced pregnancy complications in at-risk women. PMID:25910276
Alkaline phosphatase protects lipopolysaccharide-induced early pregnancy defects in mice.
Lei, Wei; Ni, Hua; Herington, Jennifer; Reese, Jeff; Paria, Bibhash C
2015-01-01
Excessive cytokine inflammatory response due to chronic or superphysiological level of microbial infection during pregnancy leads to pregnancy complications such as early pregnancy defects/loss and preterm birth. Bacterial toxin lipopolysaccharide (LPS), long recognized as a potent proinflammatory mediator, has been identified as a risk factor for pregnancy complications. Alkaline phosphatase (AP) isozymes have been shown to detoxify LPS by dephosphorylation. In this study, we examined the role of alkaline phosphatase (AP) in mitigating LPS-induced early pregnancy complications in mice. We found that 1) the uterus prior to implantation and implantation sites following embryo implantation produce LPS recognition and dephosphorylation molecules TLR4 and tissue non-specific AP (TNAP) isozyme, respectively; 2) uterine TNAP isozyme dephosphorylates LPS at its sites of production; 3) while LPS administration following embryo implantation elicits proinflammatory cytokine mRNA levels at the embryo implantation sites (EISs) and causes early pregnancy loss, dephosphorylated LPS neither triggers proinflammatory cytokine mRNA levels at the EISs nor induces pregnancy complications; 4) AP isozyme supplementation to accelerate LPS detoxification attenuates LPS-induced pregnancy complications following embryo implantation. These findings suggest that a LPS dephosphorylation strategy using AP isozyme may have a unique therapeutic potential to mitigate LPS- or Gram-negative bacteria-induced pregnancy complications in at-risk women.
Song, Yeong Ok; Kim, Mijeong; Woo, Minji; Baek, Jang-Mi; Kang, Keon-Hee; Kim, Sang-Ho; Roh, Seong-Soo; Park, Chan Hum; Jeong, Kap-Seop; Noh, Jeong-Sook
2017-06-15
The protective effects of a chondroitin sulfate-rich extract (CSE) from skate cartilage against lipopolysaccharide (LPS)-induced hepatic damage were investigated, and its mechanism of action was compared with that of chondroitin sulfate (CS) from shark cartilage. ICR mice were orally administrated 200 mg/kg body weight (BW) of CS or 400 mg/kg BW of CSE for 3 consecutive days, followed by a one-time intraperitoneal injection of LPS (20 mg/kg BW). The experimental groups were vehicle treatment without LPS injection (NC group), vehicle treatment with LPS injection (LPS group), CS pretreatment with LPS injection (CS group), and CSE pretreatment with LPS injection (CSE group). Hepatic antioxidant enzyme expression levels in the CS and CSE groups were increased relative to those in the LPS group. In LPS-insulted hepatic tissue, inflammatory factors were augmented relative to those in the NC group, but were significantly suppressed by pretreatment with CS or CSE. Moreover, CS and CSE alleviated the LPS-induced apoptotic factors and mitogen-activated protein kinase (MAPK). In addition, CS and CSE effectively decreased the serum lipid concentrations and downregulated hepatic sterol regulatory element-binding proteins expression. In conclusion, the skate CSE could protect against LPS-induced hepatic dyslipidemia, oxidative stress, inflammation, and apoptosis, probably through the regulation of MAPK signaling.
Song, Yeong Ok; Kim, Mijeong; Woo, Minji; Baek, Jang-Mi; Kang, Keon-Hee; Kim, Sang-Ho; Roh, Seong-Soo; Park, Chan Hum; Jeong, Kap-Seop; Noh, Jeong-Sook
2017-01-01
The protective effects of a chondroitin sulfate-rich extract (CSE) from skate cartilage against lipopolysaccharide (LPS)-induced hepatic damage were investigated, and its mechanism of action was compared with that of chondroitin sulfate (CS) from shark cartilage. ICR mice were orally administrated 200 mg/kg body weight (BW) of CS or 400 mg/kg BW of CSE for 3 consecutive days, followed by a one-time intraperitoneal injection of LPS (20 mg/kg BW). The experimental groups were vehicle treatment without LPS injection (NC group), vehicle treatment with LPS injection (LPS group), CS pretreatment with LPS injection (CS group), and CSE pretreatment with LPS injection (CSE group). Hepatic antioxidant enzyme expression levels in the CS and CSE groups were increased relative to those in the LPS group. In LPS-insulted hepatic tissue, inflammatory factors were augmented relative to those in the NC group, but were significantly suppressed by pretreatment with CS or CSE. Moreover, CS and CSE alleviated the LPS-induced apoptotic factors and mitogen-activated protein kinase (MAPK). In addition, CS and CSE effectively decreased the serum lipid concentrations and downregulated hepatic sterol regulatory element-binding proteins expression. In conclusion, the skate CSE could protect against LPS-induced hepatic dyslipidemia, oxidative stress, inflammation, and apoptosis, probably through the regulation of MAPK signaling. PMID:28617322
Kuwae, T; Andoh, M; Fukasawa, S; Kurata, M
1983-01-01
In order to investigate the relationship between host and symbiosis in the luminous marine fish, Physiculus japonicus, the bacterial lipopolysaccharides (LPS) of symbiotic luminous bacteria were compared serologically and electrophoretically. Five symbiotic luminous bacteria (PJ strains) were separately isolated from five individuals of this fish species caught at three points, off the coasts of Chiba, Nakaminato, and Oharai. LPS preparations were made from these bacteria by Westphal's phenol-water method and highly purified by repeated ultracentrifugation. These LPSs contained little or no 2-keto-3-deoxyoctonate and had powerful mitogenic activity. In sodium dodecylsulfate polyacrylamide gel electrophoresis, these PJ-1 to -5 LPSs were separated by their electrophoretic patterns into three groups; the first group included PJ-1 and PJ-4, the second group PJ-2 and PJ-3, and the third group PJ-5 alone. The results agreed with those of the double immunodiffusion test; precipitin lines completely coalesced within each group but not with other groups. In immunoelectrophoresis, one precipitin line was observed between anti PJ-2 LPS serum and PJ-5 LPS but the electrophoretic mobility of PJ-5 LPS was clearly different from that of the PJ-2 LPS group. Furthermore, in a 50% inhibition test with PJ-2 LPS by the passive hemolysis system, the doses of PJ-2 LPS, PJ-3 LPS, and PJ-5 LPS required for 50% inhibition (ID50) in this system were 0.25, 0.25, and 21.6 micrograms/ml for each alkali-treated LPS, respectively, and the ID50's of both PJ-1 LPS and PJ-4 LPS were above 1,000 micrograms/ml. These results indicate that PJ-5 LPS has an antigenic determinant partially in common with LPS from the PJ-2 group but not with LPS from the PJ-1 group and that the symbiotic luminous bacterium PJ-5 is more closely related to the PJ-2 group than to the PJ-1 group. These results show that the species Physiculus japonicus is symbiotically associated with at least three immunologically different strains of luminous marine bacteria in its specialized light organ.
Gomes, Antoniella S; Lima, Lívia M F; Santos, Camila L; Cunha, Fernando Q; Ribeiro, Ronaldo A; Souza, Marcellus H L P
2006-10-10
The effect of lipopolysaccharide (LPS) in gastric protection has not been elucidated, but ATP-sensitive potassium (K(ATP)) channels are known to be involved in gastric defense. We evaluated the effect of LPS administration on indomethacin-induced gastropathy, and the role of K(ATP) channels in this event. Rats received intravenous (i.v.) LPS administration. After 1/2, 6, 24 or 48 h, indomethacin was injected. 3H later, gastric damage and myeloperoxidase activity were determined. Another group received LPS and 5 h later, glibenclamide, diazoxide or glibenclamide plus diazoxide. After 1 h, the rats received indomethacin and 3 h later, gastric damage and myeloperoxidase activity were evaluated. LPS reduced dose dependently gastric damage and myeloperoxidase activity induced by indomethacin. Glibenclamide reversed this LPS effect on indomethacin-induced gastropathy. Glibenclamide plus diazoxide administration did not change this LPS effect. Thus LPS has a protective effect against indomethacin-induced gastropathy, probably through activation of K(ATP) channels.
Song, Hong-Tao; Zhang, Qian; Jiang, Peng; Guo, Tao; Chen, Da-Wei; He, Zhong-Gui
2006-09-01
To prepare a sustained-release formulation of traditional Chinese medicine compound recipe by adopting time-controlled release techniques. Shuxiong tablets were chosen as model drug. The prescription and technique of core tablets were formulated with selecting disintegrating time and swelling volume of core tablets in water as index. The time-controlled release tablets were prepared by adopting press-coated techniques, using PEG6000, HCO and EVA as coating materials. The influences of compositions, preparation process and dissolution conditions in vitro on the lag time (T(lag)) of drug release were investigated. The composition of core tablets was as follow: 30% of drug, 50% MCC and 20% CMS-Na. The T(lag) of time-controlled release tablets was altered remarkably by PEG6000 content of the outer layer, the amount of outer layer and hardness of tablet. The viscosity of dissolution media and basket rotation had less influence on the T(lag) but more on rate of drug release. The core tablets pressed with the optimized composition had preferable swelling and disintegrating properties. The shuxiong sustained-release formulations which contained core tablet and two kinds of time-controlled release tablets with 3 h and 6 h of T(lag) could release drug successively at 0 h, 3 h and 6 h in vitro. The technique made it possible that various components with extremely different physicochemical properties in these preparations could release synchronously.
NASA Astrophysics Data System (ADS)
Park, Y.-R.; Kim, G.-Y.
2009-04-01
The small body, ca. 1.3 by 1.6km, of a hot-air ballon shape hornblende gabbro - diorite Complex, in Gowoonri, Hwacheon, Korea consists of marginal diorite and central hornblende gabbro. The volumetrically dominant hornblende gabbro in the core of the Complex shows a zoned distribution with three layers distinguished by different dominant mafic mineral phases. From the margin toward the core of the hornblende gabbro body, the domintant mafic minerals change from amphibole phenocryst of nearly rounded shape in cross section with pyroxene pseudomorph through prismatic shape of amphibole to polycrystalline biotite aggregates. Systematic variations in geochemical characteristics among three distinct zones of hornblende gabbro body are also observed. From the outer zone toward the core, major oxides such as MnO, MgO, and CaO show a decreasing tendency, whereas total FeO/(total FeO + MgO) value shows an increasing tendency. Concentrations of trace elements also show systematic variations. Where incompatible elements such as Ba and Th increase, compatible elements like Cr and Sc decrease from the margin toward the core. The zonal distribution divided by change in dominant mafic mineral phase from pyroxene through amphibole to biotite, and systematic compositional changes in both major and trace elements from the outer zone toward the core of the hornblende gabbro body suggest that an inward crystallization mechanism played a major role in the formation of the hornblende gabbro in Guwoonri, Hwacheon, Korea.
The inner core thermodynamics of the tropical cyclone boundary layer
NASA Astrophysics Data System (ADS)
Williams, Gabriel J.
2016-10-01
Although considerable progress has been made in understanding the inner-core dynamics of the tropical cyclone boundary layer (TCBL), our knowledge of the inner-core thermodynamics of the TCBL remains limited. In this study, the inner-core budgets of potential temperature (θ), specific humidity ( q), and reversible equivalent potential temperature (θ _e) are examined using a high-resolution multilevel boundary layer model. The potential temperature budgets show that the heat energy is dominated by latent heat release in the eyewall, evaporative cooling along the outer edge of the eyewall, and upward surface fluxes of sensible and latent heat from the underlying warm ocean. It is shown that the vertical θ advection overcompensates the sum of radial advective warming from the boundary layer outflow jet and latent heating for the development of cooling in the eyewall within the TCBL. The moisture budgets show the dominant upward transport of moisture in the eyewall updrafts, partly by the boundary-layer outflow jet from the bottom eye region, so that the eyewall remains nearly saturated. The θ _e budgets reveal that the TCBL is maintained thermodynamically by the upward surface flux of higher-θ _e air from the underlying warm ocean, the radial transport of low-θ _e air from the outer regions of the TCBL, and the dry adiabatic cooling associated by eyewall updrafts. These results underscore the significance of vertical motion and the location of the boundary layer outflow jet in maintaining the inner core thermal structure of the TCBL.
Feng, Zhenhua; Xu, Liang; Wu, Qiong; Tang, Ming; Fu, Songnian; Tong, Weijun; Shum, Perry Ping; Liu, Deming
2017-03-20
Towards 100G beyond large-capacity optical access networks, wavelength division multiplexing (WDM) techniques incorporating with space division multiplexing (SDM) and affordable spectrally efficient advanced modulation formats are indispensable. In this paper, we proposed and experimentally demonstrated a cost-efficient multicore fiber (MCF) based hybrid WDM-SDM optical access network with self-homodyne coherent detection (SHCD) based downstream (DS) and direct detection optical filter bank multi carrier (DDO-FBMC) based upstream (US). In the DS experiments, the inner core of the 7-core fiber is used as a dedicated channel to deliver the local oscillator (LO) lights while the other 6 outer cores are used to transmit 4 channels of wavelength multiplexed 200-Gb/s PDM-16QAM-OFDM signals. For US transmission, 4 wavelengths with channel spacing of 100 GHz are intensity modulated with 30 Gb/s 32-QAM-FBMC and directly detected by a ~7 GHz bandwidth receiver after transmission along one of the outer core. The results show that a 4 × 6 × 200-Gb/s DS transmission can be realized over 37 km 7-core fiber without carrier frequency offset (CFO) and phase noise (PN) compensation even using 10 MHz linewidth DFB lasers. The SHCD based on MCF provides a compromise and cost efficient scheme between conventional intradyne coherent detection and intensity modulation and direct detection (IM/DD) schemes. Both US and DS have acceptable BER performance and high spectral efficiency.
An informative solution to a seismological inverse problem.
Gilbert, F; Dziewonski, A; Brune, J
1973-05-01
Preliminary results are presented that infer that 2 sec should be added to the tabular values for P phases and 4 sec to the tabular values for S phases of seismic travel times. From seismic evidence, the radius of the inner core of the Earth is 1229-1250 km; the radius of the outer core is 3482-3485 km. Data are presented relating resolving power with error of measurement for the Earth's mantle.
Banded electromagnetic stator core
Fanning, Alan W.; Gonzales, Aaron A.; Patel, Mahadeo R.; Olich, Eugene E.
1994-01-01
A stator core for an electromagnetic pump includes a plurality of circumferentially adjoining groups of flat laminations disposed about a common centerline axis and collectively defining a central bore and a discontinuous outer perimeter, with adjacent groups diverging radially outwardly to form V-shaped gaps. An annular band surrounds the groups and is predeterminedly tensioned to clamp together the laminations, and has a predetermined flexibility in a radial direction to form substantially straight bridge sections between the adjacent groups.
Banded electromagnetic stator core
Fanning, Alan W.; Gonzales, Aaron A.; Patel, Mahadeo R.; Olich, Eugene E.
1996-01-01
A stator core for an electromagnetic pump includes a plurality of circumferentially adjoining groups of flat laminations disposed about a common centerline axis and collectively defining a central bore and a discontinuous outer perimeter, with adjacent groups diverging radially outwardly to form V-shaped gaps. An annular band surrounds the groups and is predeterminedly tensioned to clamp together the laminations, and has a predetermined flexibility in a radial direction to form substantially straight bridge sections between the adjacent groups.
Inoue, Ken-Ichiro; Takano, Hirohisa; Sakurai, Miho; Oda, Toshio; Tamura, Hiroshi; Yanagisawa, Rie; Shimada, Akinori; Yoshikawa, Toshikazu
2006-11-01
Pulmonary exposure to diesel exhaust particles (DEP) enhances lung inflammation related to bacterial endotoxin (lipopolysaccharide [LPS]) in mice. Severe lung inflammation can reportedly induce coagulatory abnormalities and systemic inflammation. This study examined the effects of components of DEP on lung inflammation, pulmonary permeability, coagulatory changes, systemic inflammatory response, and lung-to-systemic translocation of LPS in a murine model of lung inflammation. ICR mice were divided into six experimental groups that intratracheally received vehicle, LPS (2.5 mg/kg), organic chemicals in DEP (DEP-OC; 4 mg/kg) extracted with dicloromethane), residual carbonaceous nuclei of DEP (washed DEP: 4 mg/kg), DEP-OC + LPS, or washed DEP + LPS. Both DEP components exacerbated lung inflammation, vascular permeability, and the increased fibrinogen and E-selectin levels induced by LPS. With overall trends, the exacerbation was more prominent with washed DEP than with DEP-OC. Washed DEP + LPS significantly decreased activated protein C and antithrombin-III and elevated circulatory levels of interleukin (IL)-6, keratinocyte chemoattractant (KC), and LPS as compared with LPS alone, whereas DEP-OC + LPS elevated IL-6, KC, and LPS without significance. These results show that DEP components, especially washed DEP, amplify the effects if LPS on the respiratory system and suggest that they contribute to the adverse health effects of particulate air pollution on the sensitive populations with predisposing vascular and/or pulmonary diseases, including ischemic vascular diseases and respiratory infection.
Diya Zhang; Lili Chen; Shenglai Li; Zhiyuan Gu; Jie Yan
2008-04-01
Lipopolysaccharide (LPS) derived from the periodontal pathogen Porphyromonas gingivalis has been shown to differ from enterobacterial LPS in structure and function; therefore, the Toll-like receptors (TLRs) and the intracellular inflammatory signaling pathways are accordingly different. To elucidate the signal transduction pathway of P. gingivalis, LPS-induced pro-inflammatory cytokine production in the human monocytic cell line THP-1 was measured by ELISA, and the TLRs were determined by the blocking test using anti-TLRs antibodies. In addition, specific inhibitors as well as Phospho-ELISA kits were used to analyze the intracellular signaling pathways. Escherichia coli LPS was used as the control. In this study, P. gingivalis LPS showed the ability to induce cytokine production in THP-1 cells and its induction was significantly (P < 0.05) suppressed by anti-TLR2 antibody or JNK inhibitor, and the phosphorylation level of JNK was significantly increased (P < 0.05). These results indicate that TLR2-JNK is the main signaling pathway of P. gingivalis LPS-induced cytokine production, while the cytokine induction by E. coli LPS was mainly via TLR4-NF-kappaB and TLR4-p38MAPK. This suggests that P. gingivalis LPS differs from E. coli LPS in its signaling pathway in THP-1 cells, and that the TLR2-JNK pathway might play a significant role in P. gingivalis LPS-induced chronic inflammatory periodontal disease.
Endogenous pleiotrophin and midkine regulate LPS-induced glial responses.
Fernández-Calle, Rosalía; Vicente-Rodríguez, Marta; Gramage, Esther; de la Torre-Ortiz, Carlos; Pérez-García, Carmen; Ramos, María P; Herradón, Gonzalo
2018-01-01
Pleiotrophin (PTN) and Midkine (MK) are two growth factors that modulate neuroinflammation. PTN overexpression in the brain prevents LPS-induced astrocytosis in mice but potentiates microglial activation. The modest astrocytic response caused by a low dose of LPS (0.5mg/kg) is blocked in the striatum of MK-/- mice whereas microglial response is unaffected. We have now tested the effects of an intermediate dose of LPS (7.5mg/kg) in glial response in PTN-/- and MK-/- mice. We found that LPS-induced astrocytosis is prevented in prefrontal cortex and striatum of both PTN-/- and MK-/- mice. Some of the morphological changes of microglia induced by LPS tended to increase in both genotypes, particularly in PTN-/- mice. Since we previously showed that PTN potentiates LPS-induced activation of BV2 microglial cells, we tested the activation of FYN kinase, a substrate of the PTN receptor RPTPβ/ζ, and the subsequent ERK1/2 phosphorylation on LPS and PTN-treated BV2 cells. LPS effects on BV2 cells were not affected by the addition of PTN, suggesting that PTN does not recruit the FYN-MAP kinase signaling pathway in order to modulate LPS effects on microglial cells. Taking together, evidences demonstrate that regulation of astroglial responses to LPS administration are highly dependent on the levels of expression of PTN and MK. Further studies are needed to clarify the possible roles of endogenous expression of PTN and MK in LPS-induced microglial responses. Copyright © 2017 Elsevier B.V. All rights reserved.
Chen, Yuan-Hua; Zhao, Mei; Chen, Xue; Zhang, Ying; Wang, Hua; Huang, Ying-Ying; Wang, Zhen; Zhang, Zhi-Hui; Zhang, Cheng; Xu, De-Xiang
2012-07-01
LPS is associated with adverse developmental outcomes, including preterm delivery, fetal death, teratogenicity, and intrauterine growth restriction (IUGR). Previous reports showed that zinc protected against LPS-induced teratogenicity. In the current study, we investigated the effects of zinc supplementation during pregnancy on LPS-induced preterm delivery, fetal death and IUGR. All pregnant mice except controls were i.p. injected with LPS (75 μg/kg) daily from gestational day (GD) 15 to GD17. Some pregnant mice were administered zinc sulfate through drinking water (75 mg elemental Zn per liter) throughout the pregnancy. As expected, an i.p. injection with LPS daily from GD15 to GD17 resulted in 36.4% (4/11) of dams delivered before GD18. In dams that completed the pregnancy, 63.2% of fetuses were dead. Moreover, LPS significantly reduced fetal weight and crown-rump length. Of interest, zinc supplementation during pregnancy protected mice from LPS-induced preterm delivery and fetal death. In addition, zinc supplementation significantly alleviated LPS-induced IUGR and skeletal development retardation. Further experiments showed that zinc supplementation significantly attenuated LPS-induced expression of placental inflammatory cytokines and cyclooxygenase-2. Zinc supplementation also significantly attenuated LPS-induced activation of NF-κB and MAPK signaling in mononuclear sinusoidal trophoblast giant cells of the labyrinth zone. It inhibited LPS-induced placental AKT phosphorylation as well. In conclusion, zinc supplementation during pregnancy protects against LPS-induced fetal growth restriction and demise through its anti-inflammatory effect.
Pakzad, Iraj; Rezaee, Abbas; Rasaee, Mohammad J; Hossieni, Ahmad Zavaran; Tabbaraee, Bahman; Kazemnejad, Anoshirvan
2010-01-01
The immunogenic Brucella abortus ribosomal protein L7/L12 and Lipopolysaccharide (LPS) are promising candidate antigens for the development of subunit vaccines against brucellosis. This study was aimed to evaluate the protection of combination of recombinant HSA-L7/L12 fusion protein with LPS in Balb/c mouse. The recombinant HSA-L7/L12 fusion protein in Saccharomyces cerevisiae was expressed and purified by affinity chromatography column. LPS was extracted by n-butanol, purified by ultracentrifugation. BALB/c mouses were immunized in 9 groups with PBS, HSA, tHSA-L7/L12, L7/L12, LPS, LPS+ HSA, LPS+ tHSA-L7/L12, LPS+ L7/L12, B. abortus S19. ELISA, LTT tests and challenging two weeks after last injection were carried out. Bacterial count of spleen of immunized BALB/c mouse was done four weeks after challenging with virulent strain B. abortus 544. In ELISA test the specific antibodies of tHSA-L7/L12 exhibited a dominance of immunoglobulin IgG1 over IgG2a. LPS-HSA and tHSA-L7/L12 + LPS produced a significantly higher antibody titer than LPS alone and L7/L12+LPS (P < 0.05). The predominant IgG subtype for LPS and L7/L12+LPS were IgG3. However, tHSA-L7/L12+ LPS and LPS+ HAS elicited predominantly IgG1 and IgG3 subtypes. In addition, the tHSA-L7/L12 fusion protein and L7/L12 elicited a strong T-cell proliferative response upon restimulation in vitro with recombinant tHSA-L7/L12 and L7/L12, suggesting the induction of a cellular immunity response in vivo. However, there was no significant difference proliferative response in L7/L12 and tHSA-L7/L12 fusion protein (P > 0.05). The combination of tHSA-L7/L12 fusion protein with LPS and B. abortus S19 induce higher level of protection against challenge with the virulent strain B. abortus 544 in BALB/c mice than other groups (P = 0.005). The combination of tHSA-L7/L12 fusion protein with LPS had higher protective ability than LPS and fusion protein distinctly.
Hernáez, Bruno; Guerra, Milagros; Salas, María L.
2016-01-01
African swine fever virus (ASFV) is a nucleocytoplasmic large DNA virus (NCLDV) that causes a highly lethal disease in domestic pigs. As other NCLDVs, the extracellular form of ASFV possesses a multilayered structure consisting of a genome-containing nucleoid successively wrapped by a thick protein core shell, an inner lipid membrane, an icosahedral protein capsid and an outer lipid envelope. This structural complexity suggests an intricate mechanism of internalization in order to deliver the virus genome into the cytoplasm. By using flow cytometry in combination with pharmacological entry inhibitors, as well as fluorescence and electron microscopy approaches, we have dissected the entry and uncoating pathway used by ASFV to infect the macrophage, its natural host cell. We found that purified extracellular ASFV is internalized by both constitutive macropinocytosis and clathrin-mediated endocytosis. Once inside the cell, ASFV particles move from early endosomes or macropinosomes to late, multivesicular endosomes where they become uncoated. Virus uncoating requires acidic pH and involves the disruption of the outer membrane as well as of the protein capsid. As a consequence, the inner viral membrane becomes exposed and fuses with the limiting endosomal membrane to release the viral core into the cytosol. Interestingly, virus fusion is dependent on virus protein pE248R, a transmembrane polypeptide of the inner envelope that shares sequence similarity with some members of the poxviral entry/fusion complex. Collective evidence supports an entry model for ASFV that might also explain the uncoating of other multienveloped icosahedral NCLDVs. PMID:27110717
Isogai, H; Isogai, E; Fujii, N; Oguma, K; Kagota, W; Takano, K
1988-07-01
The biological activities of lipopolysaccharide from Bacteroides gingivalis 381 (B-LPS) were examined in vivo and in vitro. Intra-oral mucosal injection of B-LPS induced an acute inflammation at the injection site. Intravenous injection of B-LPS induced necrotic lesions with many thrombi in the liver and lymphocytic reduction in the spleen. By immunohistochemical examination, B-LPS was detected in macrophages in the liver, spleen and lymph nodes. In vitro analysis showed that B-LPS was a potent activator of both neutrophils and macrophages in luminol-dependent response and IL-1 secretion from macrophages and was mitogenic to the spleen cells not only from BALB/c mice but also from LPS-non-responder C3H/HeJ mice. Interferon production from human peripheral mononuclear leucocytes was induced, in vitro, by stimulation with B-LPS but not with the other enterobacterial LPS. These findings clarified the various biological activities of B-LPS affecting various cells and tissues, especially neutrophils, macrophages and lymphocytes. The potent inflammability of B-LPS shown in the present study indicates that it is one of the effective agents to induce periodontitis.
Mixing model with multi-particle interactions for Lagrangian simulations of turbulent mixing
NASA Astrophysics Data System (ADS)
Watanabe, T.; Nagata, K.
2016-08-01
We report on the numerical study of the mixing volume model (MVM) for molecular diffusion in Lagrangian simulations of turbulent mixing problems. The MVM is based on the multi-particle interaction in a finite volume (mixing volume). A priori test of the MVM, based on the direct numerical simulations of planar jets, is conducted in the turbulent region and the interfacial layer between the turbulent and non-turbulent fluids. The results show that the MVM predicts well the mean effects of the molecular diffusion under various numerical and flow parameters. The number of the mixing particles should be large for predicting a value of the molecular diffusion term positively correlated to the exact value. The size of the mixing volume relative to the Kolmogorov scale η is important in the performance of the MVM. The scalar transfer across the turbulent/non-turbulent interface is well captured by the MVM especially with the small mixing volume. Furthermore, the MVM with multiple mixing particles is tested in the hybrid implicit large-eddy-simulation/Lagrangian-particle-simulation (LES-LPS) of the planar jet with the characteristic length of the mixing volume of O(100η). Despite the large mixing volume, the MVM works well and decays the scalar variance in a rate close to the reference LES. The statistics in the LPS are very robust to the number of the particles used in the simulations and the computational grid size of the LES. Both in the turbulent core region and the intermittent region, the LPS predicts a scalar field well correlated to the LES.
Mixing model with multi-particle interactions for Lagrangian simulations of turbulent mixing
DOE Office of Scientific and Technical Information (OSTI.GOV)
Watanabe, T., E-mail: watanabe.tomoaki@c.nagoya-u.jp; Nagata, K.
We report on the numerical study of the mixing volume model (MVM) for molecular diffusion in Lagrangian simulations of turbulent mixing problems. The MVM is based on the multi-particle interaction in a finite volume (mixing volume). A priori test of the MVM, based on the direct numerical simulations of planar jets, is conducted in the turbulent region and the interfacial layer between the turbulent and non-turbulent fluids. The results show that the MVM predicts well the mean effects of the molecular diffusion under various numerical and flow parameters. The number of the mixing particles should be large for predicting amore » value of the molecular diffusion term positively correlated to the exact value. The size of the mixing volume relative to the Kolmogorov scale η is important in the performance of the MVM. The scalar transfer across the turbulent/non-turbulent interface is well captured by the MVM especially with the small mixing volume. Furthermore, the MVM with multiple mixing particles is tested in the hybrid implicit large-eddy-simulation/Lagrangian-particle-simulation (LES–LPS) of the planar jet with the characteristic length of the mixing volume of O(100η). Despite the large mixing volume, the MVM works well and decays the scalar variance in a rate close to the reference LES. The statistics in the LPS are very robust to the number of the particles used in the simulations and the computational grid size of the LES. Both in the turbulent core region and the intermittent region, the LPS predicts a scalar field well correlated to the LES.« less
Oyler, Benjamin L; Khan, Mohd M; Smith, Donald F; Harberts, Erin M; Kilgour, David P A; Ernst, Robert K; Cross, Alan S; Goodlett, David R
2018-06-01
Recent advances in lipopolysaccharide (LPS) biology have led to its use in drug discovery pipelines, including vaccine and vaccine adjuvant discovery. Desirable characteristics for LPS vaccine candidates include both the ability to produce a specific antibody titer in patients and a minimal host inflammatory response directed by the innate immune system. However, in-depth chemical characterization of most LPS extracts has not been performed; hence, biological activities of these extracts are unpredictable. Additionally, the most widely adopted workflow for LPS structure elucidation includes nonspecific chemical decomposition steps before analyses, making structures inferred and not necessarily biologically relevant. In this work, several different mass spectrometry workflows that have not been previously explored were employed to show proof-of-principle for top down LPS primary structure elucidation, specifically for a rough-type mutant (J5) E. coli-derived LPS component of a vaccine candidate. First, ion mobility filtered precursor ions were subjected to collision induced dissociation (CID) to define differences in native J5 LPS v. chemically detoxified J5 LPS (dLPS). Next, ultra-high mass resolving power, accurate mass spectrometry was employed for unequivocal precursor and product ion empirical formulae generation. Finally, MS 3 analyses in an ion trap instrument showed that previous knowledge about dissociation of LPS components can be used to reconstruct and sequence LPS in a top down fashion. A structural rationale is also explained for differential inflammatory dose-response curves, in vitro, when HEK-Blue hTLR4 cells were administered increasing concentrations of native J5 LPS v. dLPS, which will be useful in future drug discovery efforts. Graphical Abstract ᅟ.
Reisinger, Nicole; Schaumberger, Simone; Nagl, Veronika; Hessenberger, Sabine; Schatzmayr, Gerd
2014-01-01
The pathogenesis of laminitis is not completely identified and the role of endotoxins (lipopolysaccharides, LPS) in this process remains unclear. Phytogenic substances, like milk thistle (MT) and silymarin, are known for their anti-inflammatory and antioxidant properties and might therefore have the potential to counteract endotoxin induced effects on the hoof lamellar tissue. The aim of our study was to investigate the influence of endotoxins on lamellar tissue integrity and to test if MT and silymarin are capable of inhibiting LPS-induced effects in an in vitro/ex vivo model. In preliminary tests, LPS neutralization efficiency of these phytogenics was determined in an in vitro neutralization assay. Furthermore, tissue explants gained from hooves of slaughter horses were tested for lamellar separation after incubation with different concentrations of LPS. By combined incubation of explants with LPS and either Polymyxin B (PMB; positive control), MT or silymarin, the influence of these substances on LPS-induced effects was assessed. In the in vitro neutralization assay, MT and silymarin reduced LPS concentrations by 64% and 75%, respectively, in comparison PMB reduced 98% of the LPS concentration. In hoof explants, LPS led to a concentration dependent separation. Accordantly, separation force was significantly decreased by 10 µg/mL LPS. PMB, MT and silymarin could significantly improve tissue integrity of explants incubated with 10 µg/mL LPS. This study showed that LPS had a negative influence on the structure of hoof explants in vitro. MT and silymarin reduced endotoxin activity and inhibited LPS-induced effects on the lamellar tissue. Hence, MT and silymarin might be used to support the prevention of laminitis and should be further evaluated for this application. PMID:25290524
Which one is more effective for the treatment of rat sepsis model: thalidomide or etanercept?
Ilhan, N; Susam, S; Gul, H F; Bardas, R; Ilhan, N
2017-01-01
We aimed to investigate the protective effect of selected treatment agents on liver injury in lipopolysaccharide (LPS)-induced rat sepsis model. The sepsis includes complex inflammatory responses between a microbial pathogen and the host immune system, and leads to organ failure and also death. This study was performed with 29 male Wistar Albino rats. Rats were divided randomly into five groups: Sham group, LPS-treated sepsis group, LPS+thalidomide treated group, LPS+etanercept treated group and LPS+thalidomide+etanercept treated group, respectively. Liver tissue tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β) and interleukin 6 (IL-6) levels were determined by enzyme-linked immuno-sorbent assay (ELISA) method. The expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) was performed using western blot analysis. The levels of tissue TNF-α, IL-1β and IL-6 were found statistically significantly higher in sepsis group than in the sham group. TNF-α levels were found statistically significantly decreased in LPS+etanercept and LPS+thalidomide+etanercept treated groups when compared with LPS group (p < 0.05). For IL-1β and IL-6 levels a statistically significant decline was observed in the LPS+thalidomide and LPS+etanercept treated groups compared to the LPS group (p < 0.05). Expression of NF-κB protein in liver tissue was significantly elevated in the LPS group compared to sham group (p < 0.001). In treatment groups, a marked decrease was observed in NF-κB protein expression. The results of this investigation suggested that etanercept and thalidomide administration may have a beneficial effect on LPS-induced sepsis. So, the present study may have significant clinical relevance, but clinical trials are needed to confirm these results (Tab. 1, Fig. 1, Ref. 36).