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Sample records for kas lpp kaosele

  1. LPP source system development for HVM

    NASA Astrophysics Data System (ADS)

    Brandt, David C.; Fomenkov, Igor V.; Ershov, Alex I.; Partlo, William N.; Myers, David W.; Sandstrom, Richard L.; La Fontaine, Bruno M.; Lercel, Michael J.; Bykanov, Alexander N.; Böwering, Norbert R.; Vaschenko, Georgiy O.; Khodykin, Oleh V.; Srivastava, Shailendra N.; Ahmad, Imtiaz; Rajyaguru, Chirag; Das, Palash; Fleurov, Vladimir B.; Zhang, Kevin; Golich, Daniel J.; De Dea, Silvia; Hou, Richard R.; Dunstan, Wayne J.; Wittak, Christian J.; Baumgart, Peter; Ishihara, Toshihiko; Simmons, Rod D.; Jacques, Robert N.; Bergstedt, Robert A.

    2011-04-01

    Laser produced plasma (LPP) systems have been developed as a viable approach for the EUV scanner light sources to support optical imaging of circuit features at sub-22nm nodes on the ITRS roadmap. This paper provides a review of development progress and productization status for LPP extreme-ultra-violet (EUV) sources with performance goals targeted to meet specific requirements from leading scanner manufacturers. The status of first generation High Volume Manufacturing (HVM) sources in production and at a leading semiconductor device manufacturer is discussed. The EUV power at intermediate focus is discussed and the lastest data are presented. An electricity consumption model is described, and our current product roadmap is shown.

  2. LPP inhibits collective cell migration during lung cancer dissemination.

    PubMed

    Kuriyama, S; Yoshida, M; Yano, S; Aiba, N; Kohno, T; Minamiya, Y; Goto, A; Tanaka, M

    2016-02-25

    Lipoma preferred partner (LPP) is a LIM domain protein, which has multiple functions as an actin-binding protein and a transcriptional coactivator, and it has been suggested that LPP has some roles in cell migration or invasion, however, its role in cancer cells remains to be elucidated. Here, we showed that LPP degraded N-cadherin in lung cancer, PC14PE6 cells via regulating the expression of matrix metalloproteinase 15 (MMP-15), and loss-of-LPP increases collective cell migration (CCM) and dissemination consequently. Knockdown of LPP and its functional partner, Etv5, markedly restores the full-length N-cadherin and increases cell-cell adhesion. We investigated the common target of LPP and Etv5, and found that MMP-15 is transcribed as their direct transcriptional target. Furthermore, MMP-15 could directly digest the N-cadherin extracellular domain. LPP knockdown in PC14PE6 cells increases N-cadherin-dependent CCM in the three-dimensional collagen gel invasion assays, and promoted the dissemination of cancer cells when they were orthotopically implanted in nude mice. Immunohistochemistry of lung adenocarcinoma specimens revealed the heterogeneity of LPP intensity and complementary expression of LPP and N-cadherin in the primary tumors. These findings suggest that loss-of-LPP, Etv5 or MMP-15 can be a prognostic marker of increasing malignancy. PMID:26028032

  3. The Reverse LPP Process for Nurturing a Community of Practice

    ERIC Educational Resources Information Center

    Hung, David; Chen, Der-Thanq; Koh, Thiam Seng

    2006-01-01

    In this article we suggest a facilitating process for nurturing a community of practice (CoP). This process can be seen as a reverse LPP (legitimate peripheral participation) process where a community starts with a group of core members and gradually grows to encourage new members into a CoP. In the heart of the reverse LPP process is the identity…

  4. Flashback Arrestor for LPP, Low NOx Combustors

    NASA Technical Reports Server (NTRS)

    Kraemer, Gil; Lee, Chi-Ming

    1998-01-01

    Lean premixed, prevaporized (LPP) high temperature combustor designs as explored for the Advanced Subsonic Transport (AST) and High Speed Civil Transport (HSCT) combustors can achieve low NO(x), emission levels. An enabling device is needed to arrest flashback and inhibit preignition at high power conditions and during transients (surge and rapid spool down). A novel flashback arrestor design has demonstrated the ability to arrest flashback and inhibit preignition in a 4.6 cm diameter tubular reactor at full power inlet temperatures (725 C) using Jet-A fuel at 0.4 less than or equal To phi less than or equal to 3.5. Several low pressure loss (0.2 to 0.4% at 30 m/s) flashback arrestor designs were developed which arrested flashback at all of the test conditions. Flame holding was also inhibited off the flash arrestor face or within the downstream tube even velocities (less than or equal to 3 to 6 m/s), thus protecting the flashback arrestor and combustor components. Upstream flow conditions influence the specific configuration based on using either a 45% or 76% upstream geometric blockage. Stationary, lean premixed dry low NO(x) gas turbine combustors would also benefit from this low pressure drop flashback arrestor design which can be easily integrated into new and existing designs.

  5. Tin LPP plasma control in the argon cusp source

    NASA Astrophysics Data System (ADS)

    McGeoch, Malcolm W.

    2016-03-01

    The argon cusp plasma has been introduced [1,2] for 500W class tin LPP exhaust control in view of its high power handling, predicted low tin back-scatter from a beam dump, and avoidance of hydrogen usage. The physics of tin ion control by a plasma is first discussed. Experimentally, cusp stability and exhaust disc geometry have previously been proved at full scale [2], the equivalent of 300W-500W usable EUV. Here we verify operation of the plasma barrier that maintains a high argon density next to the collector, for its protection, and a low density in the long path toward the intermediate focus, for efficiency. A pressure differential of 2Pa has been demonstrated in initial work. Other aspects of tin LPP plasma control by the cusp have now been demonstrated using tin ions from a low Hz 130mJ CO2 laser pulse onto a solid tin surface at the cusp center. Plasma is rejected at the <0.5% level at the collector mirror location using the cusp magnetic field alone. Plasma also is rejected using a low argon density (<1x1014cm-3). We have measured the tin ion flow pattern toward the large area annular beam dump. Scaling of the cusp design to match a specified exhaust power is discussed. In view of this work, argon cusp exhaust control appears to be very promising for 500W class tin LPP sources.

  6. delta. sigma/sub L//(pp) and jet physics

    SciTech Connect

    Richards, D.G.

    1988-01-01

    We show that there is a positive contribution to ..delta..sigma/sub L/(pp; s) = sigma /sub tot/(p(+)p(+); s) /minus/ sigma/sub tot/(p(+)p(/minus/); s) (where the +- refer to proton helicities) associated with the pointlike scattering of fundamental constituents. Simple arguments imply that this positive contribution would, at very high s, be larger in absolute value than the negative contribution to ..delta..sigma/sub L/ predicted from the exchange of the A/sub 1/ reggeon, and furthermore may provide important insight into the shape of the spin weighted quark and gluon distributions. Measurements of ..delta..sigma/sub L/ in the energy range ..sqrt..s = 18 /minus/ 30 GeV also should help clarify theoretical ideas associated with the observations of ''minijets'' and could aid in the prediction of event structure at future high energy colliders. 24 refs. 6 figs.

  7. High power LPP EUV source system development status

    NASA Astrophysics Data System (ADS)

    Lin, Benjamin Szu-Min; Brandt, David; Farrar, Nigel

    2009-12-01

    Extreme ultraviolet (EUV) technology has been recognized as the major lithography technology for 22 nm HP and beyond to fulfill Moore's Law, which predicts that circuit dimensions shrink 70% every 2~3 years in order to achieve cost down and obtain greater functionality per unit area. EUV source power is one of the key factors in determining the cost-effectiveness of EUVL compared to other lithography technologies, like double patterning. Only when EUV power can achieve a certain level, the cost of EUV lithography under high volume manufacturing (HVM) can become much more competitive than that of double patterning techniques. In this paper, the performance of the first production Cymer high power laser produced plasma (LPP) EUV source integrated with a 5 sr multi-layer mirror (MLM) collector and fully integrated debris mitigation will be shown. The latest results on power generation, stable and efficient collection, and clean transmission of EUV light through the intermediate focus will be presented. The lifetime of the MLM collector is a critical parameter in the development of extreme ultraviolet LPP lithography sources. Debris mitigation techniques are used to inhibit reflectivity degradation from deposition of target material, sputtering of the multilayer coating, and implantation of incident particles, which can reduce the efficiency of the MLM collector during exposure. The far field images of MLM collector are recorded by intermediate focus metrology with a CCD camera to determine the reflectivity status of the MLM collector during exposure. The results of these debris mitigation techniques are compared through multiple-hour EUV exposure. Testing shows cleanliness at the source-scanner interface acceptable to the limit of detection.

  8. LPP light source for actinic HVM inspection applications

    NASA Astrophysics Data System (ADS)

    Rollinger, Bob; Gambino, Nadia; Hudgins, Duane; Sanders, Alexander; Brandstätter, Markus; Abhari, Reza S.; Abreau, F.

    2015-03-01

    EUV sources with high brightness and stability are required for actinic photomask inspection. High availability and cleanliness after IF are additional stringent requirements. EUV lithography is only production ready, if these tools are available with HVM specifications. At the Laboratory for Energy Conversion, ETH Zurich, droplet-based EUV LPP sources have been designed, developed and tested at the system level for the last 8 years and has been commercialized by Adlyte AG. The most advanced facility, namely ALPS II, has been operated as a prototype source for hundreds of hours. In the present work, the EUV plasma is imaged with the help of a pinhole camera. The dimension of the plasma in the direction of the laser axis and the direction of the train equal 60 μm and 70 μm, respectively. The plasma is also imaged using an ICCD with an exposure time of 5 ns. The observed droplet plasma has a characteristic kidney shape. The ICCD is a valuable diagnostic as inspection tools require high pulse-to-pulse reproducibility that cannot be assessed to the full extend using a EUV pinhole camera. Various collector configurations, using either NI or GI, have been integrated into the source. The measurements of the emission characteristics at IF for a GI collector configuration reveal a Gaussian spot shape at IF and a pulse-to-pulse stability of 6.8 % (σ), which matches previous stabilities at the source level. The debris mitigation system employs a three layer strategy between the plasma and IF. Introducing a high momentum flow as a first layer of debris mitigation, the load of tin spots on the collector could be reduced by a factor of 9, hence a significant increase of source life-time is obtained. A quantification by Adlyte of IF cleanliness after 24 hours source operation revealed no relevant contamination with respect to the requirements for Blank Inspection Cleanliness after IF.

  9. Overexpression of HMGA2-LPP fusion transcripts promotes expression of the {alpha} 2 type XI collagen gene

    SciTech Connect

    Kubo, Takahiro; Matsui, Yoshito . E-mail: ymatsui@sb4.so-net.ne.jp; Goto, Tomohiro; Yukata, Kiminori; Yasui, Natsuo

    2006-02-10

    In a subset of human lipomas, a specific t (3; 12) chromosome translocation gives rise to HMGA2-LPP fusion protein, containing the amino (N)-terminal DNA binding domains of HMGA2 fused to the carboxyl (C)-terminal LIM domains of LPP. In addition to its role in adipogenesis, several observations suggest that HMGA2-LPP is linked to chondrogenesis. Here, we analyzed whether HMGA2-LPP promotes chondrogenic differentiation, a marker of which is transactivation of the {alpha} 2 type XI collagen gene (Col11a2). Real-time PCR analysis showed that HMGA2-LPP and COL11A2 were co-expressed. Luciferase assay demonstrated that either of HMGA2-LPP, wild-type HMGA2 or the N-terminal HMGA2 transactivated the Col11a2 promoter in HeLa cells, while the C-terminal LPP did not. RT-PCR analysis revealed that HMGA2-LPP transcripts in lipomas with the fusion were 591-fold of full-length HMGA2 transcripts in lipomas without the fusion. These results indicate that in vivo overexpression of HMGA2-LPP promotes chondrogenesis by upregulating cartilage-specific collagen gene expression through the N-terminal DNA binding domains.

  10. A Parametric Study of a Plug Nozzle, Using the Liquid Propellant Program (LPP) Code

    NASA Technical Reports Server (NTRS)

    Dunn, Stuart S.; Coats, Douglas E.

    1996-01-01

    The Liquid Propellant Program (LPP) computer code is a super-set of the industry standard Two Dimensional Kinetics (TDK) computer code. The TDK code uses a two dimensional method of characteristics solution with fully coupled finite rate kinetics for axially symmetric nozzles. The chemical reactions are modeled with a generalized reaction package that include three dimensional body efficiencies and four reaction rate forms. The code performs optional solutions for frozen or equilibrium flow. TDK evaluates discrete shocks, both attached or induced. The Transonic module models variable mixture ratio profiles from the combustion chamber injector. The Mass Addition Boundary Layer module (MABL) calculates the boundary parameters with the same chemistry options, and includes transpiration or tangential slot injection of gas at the wall. The LPP upgrades include: planar nozzle, scarfed nozzles, plug nozzles, and scramjet nozzle configurations. The code evaluates both upper and lower wall flow simulation, and includes the interaction with the external flow. The MABL module evaluates equilibrium radiation heat transfer for both upper and lower walls. In addition, LPP code models combustion effects due to injector inefficiencies with the Spray Combustion Analysis Program (SCAP) module. The LPP package provides extensive post plotting capabilities for flow visualization. The LPP is sufficiently fast and robust to provide performance predictions for extensive parametric studies and sufficiently accurate to provide flow field and performance solutions for detailed studies.

  11. Integration of QFD, AHP, and LPP methods in supplier development problems under uncertainty

    NASA Astrophysics Data System (ADS)

    Shad, Zahra; Roghanian, Emad; Mojibian, Fatemeh

    2014-04-01

    Quality function deployment (QFD) is a customer-driven approach, widely used to develop or process new product to maximize customer satisfaction. Last researches used linear physical programming (LPP) procedure to optimize QFD; however, QFD issue involved uncertainties, or fuzziness, which requires taking them into account for more realistic study. In this paper, a set of fuzzy data is used to address linguistic values parameterized by triangular fuzzy numbers. Proposed integrated approach including analytic hierarchy process (AHP), QFD, and LPP to maximize overall customer satisfaction under uncertain conditions and apply them in the supplier development problem. The fuzzy AHP approach is adopted as a powerful method to obtain the relationship between the customer requirements and engineering characteristics (ECs) to construct house of quality in QFD method. LPP is used to obtain the optimal achievement level of the ECs and subsequently the customer satisfaction level under different degrees of uncertainty. The effectiveness of proposed method will be illustrated by an example.

  12. The role of KasA and KasB in the biosynthesis of meromycolic acids and isoniazid resistance in Mycobacterium tuberculosis.

    PubMed

    Slayden, R A; Barry, C E

    2002-01-01

    Mycobacterium tuberculosis has two discrete beta-ketoacyl synthases encoded by kasA and kasB that are located in tandem within a five-gene operon that has been implicated in isoniazid-sensitivity and mycolic acid synthesis. We have developed an in vitro meromycolic acid synthase assay to elucidate the anabolic role of these enzymes. Overproduction of KasA and KasB individually and together in M. smegmatis enabled cell-free incorporation of [(14)C]malonyl-CoA into lipids whose chain length was dependent upon the M. tuberculosis elongating enzyme used. KasA specifically elongated palmitoyl-CoA to monounsaturated fatty acids that averaged 40 carbons in length. KasB hyperproduction in the presence of KasA produced longer chain multiunsaturated hydrocarbons averaging 54 carbons in length. These products comigrated with a synthetic standard of meromycolic acid and their production was sensitive to isoniazid, thiolactomycin, and triclosan. KasA mutations associated with isoniazid resistance produced an enzyme that had a diminished overall catalytic activity but conferred enhanced resistance to isoniazid. In vivo analysis confirmed that overexpression of each of the four mutant KasAs enhanced isoniazid resistance when compared to overexpression of wild-type KasA. These results suggest discrete anabolic roles for both KasA and KasB in mycolic acid synthesis and substantiate the involvement of KasA mutations in isoniazid resistance. PMID:12464486

  13. Optimum pre-pulsing and target geometry of LPP for efficient EUV and BEUV sources

    NASA Astrophysics Data System (ADS)

    Sizyuk, Tatyana; Hassanein, Ahmed

    2015-03-01

    Light sources for extreme ultraviolet Lithography (EUVL) are continued to face challenges in the demanding performance for high volume manufacture. Currently EUV and beyond EUV (BEUV) community are focused on the dual-pulse laser produced plasma (LPP) using droplets of mass-limited targets. These systems require extensive optimization to enhance the conversion efficiency (CE) and increase components lifetime that requires significant experimental and development efforts. We continued to enhance our comprehensive HEIGHTS simulation package and upgrade our CMUXE laboratories to study and optimize LPP sources and to make projections and realistic predictions of near future powerful devices. HEIGHTS package includes 3-D detail description of all physical processes involved in LPP devices. The models continued to be well benchmarked in each interaction physics phase of plasma evolution and EUV/BEUV production as well as in the integrated LPP systems. We simulated LPP sources in full 3-D geometry using Sn and Gd droplets and fragmented targets composed of microdroplets as a result of prepulse or from mist of tiny droplets distribution. We studied mass dependence, laser parameters effects, atomic and ionic debris generation, and optimization of EUV/BEUV radiation output, the requirements for mitigating systems to reduce debris effects. Our enhanced modeling and simulation include all phases of laser target evolution: from laser/droplet interaction, energy deposition, target vaporization and fragmentation, ionization, plasma hydrodynamic expansion, thermal and radiation energy redistribution, and EUV/BEUV photons collection as well as detail mapping of photons source location and size. Modeling results were benchmarked against experimental studies for the in-band photons production and for debris and ions generation.

  14. Fine mapping of the celiac disease-associated LPP locus reveals a potential functional variant

    PubMed Central

    Almeida, Rodrigo; Ricaño-Ponce, Isis; Kumar, Vinod; Deelen, Patrick; Szperl, Agata; Trynka, Gosia; Gutierrez-Achury, Javier; Kanterakis, Alexandros; Westra, Harm-Jan; Franke, Lude; Swertz, Morris A.; Platteel, Mathieu; Bilbao, Jose Ramon; Barisani, Donatella; Greco, Luigi; Mearin, Luisa; Wolters, Victorien M.; Mulder, Chris; Mazzilli, Maria Cristina; Sood, Ajit; Cukrowska, Bozena; Núñez, Concepción; Pratesi, Riccardo; Withoff, Sebo; Wijmenga, Cisca

    2014-01-01

    Using the Immunochip for genotyping, we identified 39 non-human leukocyte antigen (non-HLA) loci associated to celiac disease (CeD), an immune-mediated disease with a worldwide frequency of ∼1%. The most significant non-HLA signal mapped to the intronic region of 70 kb in the LPP gene. Our aim was to fine map and identify possible functional variants in the LPP locus. We performed a meta-analysis in a cohort of 25 169 individuals from six different populations previously genotyped using Immunochip. Imputation using data from the Genome of the Netherlands and 1000 Genomes projects, followed by meta-analysis, confirmed the strong association signal on the LPP locus (rs2030519, P = 1.79 × 10−49), without any novel associations. The conditional analysis on this top SNP-indicated association to a single common haplotype. By performing haplotype analyses in each population separately, as well as in a combined group of the four populations that reach the significant threshold after correction (P < 0.008), we narrowed down the CeD-associated region from 70 to 2.8 kb (P = 1.35 × 10−44). By intersecting regulatory data from the ENCODE project, we found a functional SNP, rs4686484 (P = 3.12 × 10−49), that maps to several B-cell enhancer elements and a highly conserved region. This SNP was also predicted to change the binding motif of the transcription factors IRF4, IRF11, Nkx2.7 and Nkx2.9, suggesting its role in transcriptional regulation. We later found significantly low levels of LPP mRNA in CeD biopsies compared with controls, thus our results suggest that rs4686484 is the functional variant in this locus, while LPP expression is decreased in CeD. PMID:24334606

  15. Purification and biochemical characterization of the Mycobacterium tuberculosis beta-ketoacyl-acyl carrier protein synthases KasA and KasB.

    PubMed

    Schaeffer, M L; Agnihotri, G; Volker, C; Kallender, H; Brennan, P J; Lonsdale, J T

    2001-12-14

    Mycolic acids are vital components of the Mycobacterium tuberculosis cell wall, and enzymes involved in their formation represent attractive targets for the discovery of novel anti-tuberculosis agents. Biosynthesis of the fatty acyl chains of mycolic acids involves two fatty acid synthetic systems, the multifunctional polypeptide fatty acid synthase I (FASI), which performs de novo fatty acid synthesis, and the dissociated FASII system, which consists of monofunctional enzymes, and acyl carrier protein (ACP) and elongates FASI products to long chain mycolic acid precursors. In this study, we present the initial characterization of purified KasA and KasB, two beta-ketoacyl-ACP synthase (KAS) enzymes of the M. tuberculosis FASII system. KasA and KasB were expressed in E. coli and purified by affinity chromatography. Both enzymes showed activity typical of bacterial KASs, condensing an acyl-ACP with malonyl-ACP. Consistent with the proposed role of FASII in mycolic acid synthesis, analysis of various acyl-ACP substrates indicated KasA and KasB had higher specificity for long chain acyl-ACPs containing at least 16 carbons. Activity of KasA and KasB increased with use of M. tuberculosis AcpM, suggesting that structural differences between AcpM and E. coli ACP may affect their recognition by the enzymes. Both enzymes were sensitive to KAS inhibitors cerulenin and thiolactomycin. These results represent important steps in characterizing KasA and KasB as targets for antimycobacterial drug discovery. PMID:11600501

  16. Laser Absorption Measurements of Equivalence Ratios Studied Along With Their Coupling to Pressure Fluctuations in Lean Premixed Prevaporized (LPP) Combustion

    NASA Technical Reports Server (NTRS)

    Nguyen, Quang-Viet

    2001-01-01

    Concerns about damaging the Earth's ozone layer as a result of high levels of nitrogen oxides (known collectively as NOx) from high-altitude, high-speed aircraft have prompted the study of lean premixed prevaporized (LPP) combustion in aircraft engines. LPP combustion reduces NOx emissions principally by reducing the peak flame temperatures inside an engine. Recent advances in LPP technologies have realized exceptional reductions in pollutant emissions (single-digit ppm NOx for example). However, LPP combustion also presents major challenges: combustion instability and dynamic coupling effects between fluctuations in heat-release rate, dynamic pressure, and fuel pressure. These challenges are formidable and can literally shake an engine apart if uncontrolled. To better understand this phenomenon so that it can be controlled, we obtained real-time laser absorption measurements of the fuel vapor concentration (and equivalence ratio) simultaneously with the dynamic pressure, flame luminosity, and time-averaged gaseous emissions measurements in a research-type jet-A-fueled LPP combustor. The measurements were obtained in NASA Glenn Research Center's CE-5B optically accessible flame tube facility. The CE-5B facility provides inlet air temperatures and pressures similar to the actual operating conditions of real aircraft engines. The laser absorption measurements were performed using an infrared 3.39 micron HeNe laser in conjunction with a visible HeNe laser for liquid droplet scattering compensation.

  17. Effects of pesticides on cyanobacterium Plectonema boryanum and cyanophage LPP-1.

    PubMed Central

    Mallison, S M; Cannon, R E

    1984-01-01

    Cyanobacterium Plectonema boryanum IU 594 and cyanophage LPP-1 were used as indicator organisms in a bioassay of 16 pesticides. Experiments such as spot tests, disk assays, growth curves, and one-step growth experiments were used to examine the effects of pesticides on the host and virus. Also, experiments were done in which host or virus was incubated in pesticide solutions and then assayed for PFU. P. boryanum was inhibited by four herbicides: 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU), 1,1-dimethyl-3-(alpha, alpha,alpha-trifluoro-m-tolyl)urea ( Fluometeron ), 2-chloro-4-(ethylamino)-6-(isopropylamino)-s-triazine (Atrazine), 2-(ethylamino)-4-(isopropylamino)-6-(methylthio)-s-triazine ( Ametryn ). One insecticide, 2-methyl-2-(methylthio)-propionaldehyde O-( methylcarbamoyl )oxime (Aldicarb), also inhibited the cyanobacterium. Two insecticides inactivated LPP-1, O,O-dimethyl phosphorodithioate of diethyl mercaptosuccinate (malathion) and Isotox . Isotox is a mixture of three pesticides: S-[2-( ethylsulfinyl )ethyl]O,O-dimethyl phosphorothioate ( Metasystox -R), 1-naphthyl methylcarbamate ( Sevin ) and 4,4'-dichloro-alpha- (trichloromethyl) benzhydrom ( Kelthane ). Two pesticide-resistant strains of P. boryanum were isolated against DCMU and Atrazine. These mutants showed resistance to all four herbicides, which indicates a relationship between these phototoxic chemicals. The results indicate that P. boryanum may be a useful indicator species for phototoxic agents in bioassay procedures. PMID:6430230

  18. The costs of distraction: The effect of distraction during repeated picture processing on the LPP.

    PubMed

    Paul, Sandra; Kathmann, Norbert; Riesel, Anja

    2016-05-01

    Confrontation with anxiety-provoking situations is an effective treatment for anxiety disorders. However, underlying processes of the effects of exposure and its prevention by avoidance are barely understood. We investigated consequences of repeatedly withdrawing attention from or maintaining it to unpleasant images using ERPs. Thirty-five healthy participants were presented with neutral and unpleasant images in two experimental phases. During habituation phase, participants should attend to or distract themselves from pictures. The same picture-instruction combinations were presented three times. In the re-exposure phase, all pictures were presented again with the attend instruction. In the habituation phase, repeated presentation reduced sustained attention as reflected in decreased late positive potential (LPP) amplitudes when participants attended to pictures. This habituation effect was absent during distraction. In the re-exposure phase, increased LPP amplitudes were found for pictures with a distraction history. This highlights the role of avoidance in the development and maintenance of exaggerated attention to threatening stimuli. PMID:27064106

  19. Development of a scintillation proximity assay for the Mycobacterium tuberculosis KasA and KasB enzymes involved in mycolic acid biosynthesis.

    PubMed

    Schaeffer, M L Merrill L; Carson, J D Jeffrey D; Kallender, Howard; Lonsdale, J T John T

    2004-01-01

    Tuberculosis remains a global health problem, and programs dedicated to discovery of novel compounds against Mycobacterium tuberculosis require robust assays for high-throughput screening of chemical and natural product libraries. Enzymes involved in the biosynthesis of mycolic acids, vital components of the mycobacterial cell wall, have received much attention as potential drug targets. KasA and KasB, examples of the beta-ketoacyl-acyl carrier protein synthase I/II (KASI/II) class of condensing enzymes of the M. tuberculosis fatty acid synthase II system have been the focus of several studies designed to biochemically characterize these enzymes. Whilst robust methods have been developed for FabH-like proteins, fast and sensitive assays for high-throughput screening of KASI/II enzymes have not been available. Here we report the development of a direct scintillation proximity assay (SPA) for the KASI/II enzymes, KasA and KasB. The SPA was more sensitive than existing assays, as shown by its ability to measure activity using less enzyme than other assay formats, and the SPA was validated using the known KAS inhibitor thiolactomycin. In addition, the KasA and KasB SPA was adapted for use with Staphylococcus aureus FabF to show the versatility of this assay format to KAS enzymes from other pathogenic organisms. PMID:15525558

  20. Inhibition of InhA activity, but not KasA activity, induces formation of a KasA-containing complex in mycobacteria.

    PubMed

    Kremer, Laurent; Dover, Lynn G; Morbidoni, Hector R; Vilchèze, Catherine; Maughan, William N; Baulard, Alain; Tu, Shiao-Chun; Honoré, Nadine; Deretic, Vojo; Sacchettini, James C; Locht, Camille; Jacobs, William R; Besra, Gurdyal S

    2003-06-01

    Isoniazid (INH) remains one of the key drugs used to control tuberculosis, with the enoyl-AcpM reductase InhA being the primary target. However, based on the observation that INH-treated Mycobacterium tuberculosis overproduces KasA, an enzyme involved in the biosynthesis of mycolic acids, and induces the formation of a covalent complex consisting of AcpM, KasA, and INH, it has been proposed that KasA represents the primary target of INH. However, the relevance of this complex to INH action remains obscure. This study was aimed at clarifying the role of InhA and KasA in relation to INH activity. By using anti-KasA antibodies we detected the KasA-containing complex in INH-treated Mycobacterium smegmatis. In addition, INH-treated cells also produced constant levels of KasA that were not sequestered in the complex and presumably were sufficient to ensure mycolic acid biosynthesis. Interestingly, a furA-lacking strain induced the complex at lower concentrations of INH compared with the control strain, whereas higher INH concentrations were necessary to induce the complex in a strain that lacks katG, suggesting that INH needs to be activated by KatG to induce the KasA-containing complex. The InhA inhibitors ethionamide and diazaborine also induced the complex; thus, its formation was not specifically relevant to INH action but was because of InhA inhibition. In addition, in vitro assays using purified InhA and KasA demonstrated that KatG-activated INH, triclosan, and diazaborine inhibited InhA but not KasA activity. Moreover, several thermosensitive InhA mutant strains of M. smegmatis constitutively expressed the KasA-containing complex. This study provides the biochemical and genetic evidence. 1) Only inhibition of InhA, but not KasA, induces the KasA-containing complex. 2) INH is not part of the complex. 3) INH does not target KasA, consistent with InhA being the primary target of INH. PMID:12654922

  1. SRTM Anaglyph: Haro and Kas Hills

    NASA Technical Reports Server (NTRS)

    2001-01-01

    On January 26, 2001 the Kachchh region in western India suffered the most deadly earthquake in India's history. This three-dimensional view of landforms northeast of the city of Bhuj depicts geologic structures that are of interest in the study the tectonic processes that may have led to that earthquake. However, preliminary field studies indicate that these structures are composed of Mesozoic rocks that are overlain by younger rocks showing little deformation. Thus these structures may be old, not actively growing, and not directly related to the recent earthquake.

    The Haro Hills are on the left and the Kas Hills are on the right. The Haro Hills are an 'anticline,' which is an upwardly convex elongated fold of layered rocks. The anticline is distinctly ringed by an erosion resistant layer of sandstone. The east-west orientation of the anticline may relate to the crustal compression that has occurred during India's northward movement toward, and collision with, Asia. In contrast, the largest of the Kas Hills appears to be a tilted (to the south) and faulted (on the north) block of layered rocks. Also seen here, the curvilinear ridge trending toward the southwest from the image center is an erosion resistant 'dike,' which is an igneous intrusion into older 'host' rocks along a fault plane or other crack. The dike also appears to extend northeast from the image center as a dark line having very little topography. Its location between the tilted block and a smaller anticline to the north (directly east of the larger anticline) probably indicates that the dike fills the fault that separates these contrasting geologic structures. These features are simple examples of how digital elevation data can stereoscopically enhance satellite imagery to provide a direct input to geologic studies.

    The stereoscopic effect of this anaglyph was created by first draping a Landsat satellite image (taken just two weeks after the earthquake) over preliminary digital elevation

  2. Contextual blending of ingroup/outgroup face stimuli and word valence: LPP modulation and convergence of measures

    PubMed Central

    Hurtado, Esteban; Haye, Andrés; González, Ramiro; Manes, Facundo; Ibáñez, Agustiń

    2009-01-01

    Background Several event related potential (ERP) studies have investigated the time course of different aspects of evaluative processing in social bias research. Various reports suggest that the late positive potential (LPP) is modulated by basic evaluative processes, and some reports suggest that in-/outgroup relative position affects ERP responses. In order to study possible LPP blending between facial race processing and semantic valence (positive or negative words), we recorded ERPs while indigenous and non-indigenous participants who were matched by age and gender performed an implicit association test (IAT). The task involved categorizing faces (ingroup and outgroup) and words (positive and negative). Since our paradigm implies an evaluative task with positive and negative valence association, a frontal distribution of LPPs similar to that found in previous reports was expected. At the same time, we predicted that LPP valence lateralization would be modulated not only by positive/negative associations but also by particular combinations of valence, face stimuli and participant relative position. Results Results showed that, during an IAT, indigenous participants with greater behavioral ingroup bias displayed a frontal LPP that was modulated in terms of complex contextual associations involving ethnic group and valence. The LPP was lateralized to the right for negative valence stimuli and to the left for positive valence stimuli. This valence lateralization was influenced by the combination of valence and membership type relevant to compatibility with prejudice toward a minority. Behavioral data from the IAT and an explicit attitudes questionnaire were used to clarify this finding and showed that ingroup bias plays an important role. Both ingroup favoritism and indigenous/non-indigenous differences were consistently present in the data. Conclusion Our results suggest that frontal LPP is elicited by contextual blending of evaluative judgments of in

  3. Sub-hundred Watt operation demonstration of HVM LPP-EUV source

    NASA Astrophysics Data System (ADS)

    Mizoguchi, Hakaru; Nakarai, Hiroaki; Abe, Tamotsu; Ohta, Takeshi; Nowak, Krzysztof M.; Kawasuji, Yasufumi; Tanaka, Hiroshi; Watanabe, Yukio; Hori, Tsukasa; Kodama, Takeshi; Shiraishi, Yutaka; Yanagida, Tatsuya; Yamada, Tsuyoshi; Yamazaki, Taku; Okazaki, Shinji; Saitou, Takashi

    2014-04-01

    Since 2002, we have been developing a CO2-Sn-LPP EUV light source, the most promising solution as the 13.5 nm high power (>200 W) light source for HVM EUV lithography. Because of its high efficiency, power scalability and spatial freedom around plasma. Our group has proposed several unique original technologies; 1) CO2 laser driven Sn plasma generation, 2) Double laser pulse shooting for higher Sn ionization rate and higher CE. 3) Sn debris mitigation with a magnetic field, 4) Hybrid CO2 laser system that is scalable with a combination of a short pulse oscillator and commercial cw-CO2 amplifiers. 5) High efficient out of band light reduction with grating structured C1 mirror. In past paper we demonstrated in small size (2Hz) experimental device, this experiment shoed the advantage of combining a laser beam at a wavelength of the CO2 laser system with Sn plasma to achieve high CE>4.7% (in maximum) from driver laser pulse energy to EUV in-band energy 1). In this paper we report the further updated results from last paper. (1) 20um droplets at 100kHz operation was successfully ejected by downsized nozzle and demonstrated dramatical improvement of debris on the collector mirror. We have been developing extension of high CE operation condition at 20kHz range, We have reported component technology progress of EUV light source system. (2)New generation collector mirror with IR reduction technology is equipped in mirror maker. (3)20kW CO2 laser amplifier system is demonstrated cooperate with Mitsubishi electric. (4) We develop new Proto #2 EUV LPP source system and demonstrated 200W EUV plasma power (43W EUV clean power at I/F ) at 100kHz operation was confirmed. (5) High conversion efficiency (CE) of 3.9% at 20kHz operation was confirmed in using pico-second pre-pulse laser. (6)Improvement of CO2 laser power from 8kW to 12kW is now on going by installation of new pre-amplifier. (7)Power-up scenario of HVM source is reported, target shipment of first customer beta LPP

  4. Test of an argon cusp plasma for tin LPP power scaling

    NASA Astrophysics Data System (ADS)

    McGeoch, Malcolm W.

    2015-03-01

    Scaling the power of the tin droplet laser-produced-plasma (LPP) extreme ultraviolet (EUV) source to 500W has eluded the industry after a decade of effort. In 2014 we proposed [2] a solution: placing the laser-plasma interaction region within an argon plasma in a magnetic cusp. This would serve to ionize tin atoms and guide them to a large area annular beam dump. We have since demonstrated the feasibility of this approach. We present first results from a full-scale test plasma at power levels relevant to the generation of at least 200W, showing both that the argon cusp plasma is very stable, and that its geometrical properties are ideal for the transport of exhaust power and tin to the beam dump.

  5. TRIP6 and LPP, but not Zyxin, are present at a subset of telomeres in human cells

    PubMed Central

    Sheppard, Samantha A; Savinova, Tatiana

    2011-01-01

    The protection of chromosome ends requires the inhibition of DNA damage responses at telomeres. This inhibition is exerted in great part by the shelterin complex, known to prevent inappropriate ATM and ATR activation. The molecular mechanisms by which shelterin protects telomeres are incompletely understood. Recently, we have implicated for the first time a class of molecules, LIM domain proteins, in telomere protection. This protection occurred through interaction with shelterin, possibly through POT1, and required the pair of LIM proteins TRIP6 and LPP, themselves part of the Zyxin family. The domain similarity between TRIP6, LPP and Zyxin led us to ask whether the latter also interacted with telomeres. Here, we show that there is specificity in the association of LIM proteins with telomeres: Zyxin, despite a high degree of similarity with TRIP6 and LPP, was not detected at telomeres, nor found in a complex with shelterin. TRIP6 and LPP, however, were detected by immunofluorescence at a small subset of telomeres, perhaps those that are critically short. We speculate that specific LIM proteins are part of complex events occurring in the context of the telomere dysfunction response and are possibly at play during the induction of senescence. PMID:21519191

  6. Thiolactomycin and related analogues as novel anti-mycobacterial agents targeting KasA and KasB condensing enzymes in Mycobacterium tuberculosis.

    PubMed

    Kremer, L; Douglas, J D; Baulard, A R; Morehouse, C; Guy, M R; Alland, D; Dover, L G; Lakey, J H; Jacobs, W R; Brennan, P J; Minnikin, D E; Besra, G S

    2000-06-01

    Prevention efforts and control of tuberculosis are seriously hampered by the appearance of multidrug-resistant strains of Mycobacterium tuberculosis, dictating new approaches to the treatment of the disease. Thiolactomycin (TLM) is a unique thiolactone that has been shown to exhibit anti-mycobacterial activity by specifically inhibiting fatty acid and mycolic acid biosynthesis. In this study, we present evidence that TLM targets two beta-ketoacyl-acyl-carrier protein synthases, KasA and KasB, consistent with the fact that both enzymes belong to the fatty-acid synthase type II system involved in fatty acid and mycolic acid biosynthesis. Overexpression of KasA, KasB, and KasAB in Mycobacterium bovis BCG increased in vivo and in vitro resistance against TLM. In addition, a multidrug-resistant clinical isolate was also found to be highly sensitive to TLM, indicating promise in counteracting multidrug-resistant strains of M. tuberculosis. The design and synthesis of several TLM derivatives have led to compounds more potent both in vitro against fatty acid and mycolic acid biosynthesis and in vivo against M. tuberculosis. Finally, a three-dimensional structural model of KasA has also been generated to improve understanding of the catalytic site of mycobacterial Kas proteins and to provide a more rational approach to the design of new drugs. PMID:10747933

  7. Conditional depletion of KasA, a key enzyme of mycolic acid biosynthesis, leads to mycobacterial cell lysis.

    PubMed

    Bhatt, Apoorva; Kremer, Laurent; Dai, Annie Z; Sacchettini, James C; Jacobs, William R

    2005-11-01

    Inhibition or inactivation of InhA, a fatty acid synthase II (FASII) enzyme, leads to mycobacterial cell lysis. To determine whether inactivation of other enzymes of the mycolic acid-synthesizing FASII complex also leads to lysis, we characterized the essentiality of two beta-ketoacyl-acyl carrier protein synthases, KasA and KasB, in Mycobacterium smegmatis. Using specialized transduction for allelic exchange, null kasB mutants, but not kasA mutants, could be generated in Mycobacterium smegmatis, suggesting that unlike kasB, kasA is essential. To confirm the essentiality of kasA, and to detail the molecular events that occur following depletion of KasA, we developed CESTET (conditional expression specialized transduction essentiality test), a genetic tool that combines conditional gene expression and specialized transduction. Using CESTET, we were able to generate conditional null inhA and kasA mutants. We studied the effects of depletion of KasA in M. smegmatis using the former strain as a reference. Depletion of either InhA or KasA led to cell lysis, but with different biochemical and morphological events prior to lysis. While InhA depletion led to the induction of an 80-kDa complex containing both KasA and AcpM, the mycobacterial acyl carrier protein, KasA depletion did not induce the same complex. Depletion of either InhA or KasA led to inhibition of alpha and epoxy mycolate biosynthesis and to accumulation of alpha'-mycolates. Furthermore, scanning electron micrographs revealed that KasA depletion resulted in the cell surface having a "crumpled" appearance, in contrast to the blebs observed on InhA depletion. Thus, our studies support the further exploration of KasA as a target for mycobacterial-drug development. PMID:16267284

  8. Comparative analysis of four lipoproteins from Mycoplasma mycoides subsp. mycoides Small Colony identifies LppA as a major T-cell antigen.

    PubMed

    Dedieu, Laurence; Totte, Philippe; Rodrigues, Valerie; Vilei, Edy M; Frey, Joachim

    2010-07-01

    Control of contagious bovine pleuropneumonia (CBPP), caused by Mycoplasma mycoides subsp. mycoides Small Colony (MmmSC), remains an important goal in Africa. Subunit vaccines triggering B and T-cell responses could represent a promising approach. To this aim, the T-cell immunogenicity of four MmmSC lipoproteins (LppA, LppB, LppC and LppQ), present in African strains and able to elicit humoral response, was evaluated. In vitro assays revealed that only LppA was recognized by lymph node lymphocytes taken from three cattle, 3 weeks after MmmSC exposure. Maintenance of the LppA-specific response, relying on CD4 T-cells and IFN gamma production, was then demonstrated 1 year after infection. LppA is thus an important target for the CD4 T-cells generated early after MmmSC infection and persisting in the lymph nodes of recovered cattle. Its role as a protective antigen and ability to in vivo trigger both arms of the host immune response remain to be evaluated. PMID:19187963

  9. The late positive potential (LPP) in response to varying types of emotional and cigarette stimuli in smokers: a content comparison.

    PubMed

    Minnix, Jennifer A; Versace, Francesco; Robinson, Jason D; Lam, Cho Y; Engelmann, Jeffrey M; Cui, Yong; Brown, Victoria L; Cinciripini, Paul M

    2013-07-01

    Identifying neural mechanisms associated with addiction has substantially improved the overall understanding of addictive processes. Indeed, research suggests that drug-associated cues may take advantage of neural mechanisms originally intended for emotional processing of stimuli relevant to survival. In this study, we investigated cortical responses to several categories of emotional cues (erotic, romance, pleasant objects, mutilation, sadness, and unpleasant objects) as well as two types of smoking-related cues (people smoking and cigarette-related objects). We recorded ERPs from 180 smokers prior to their participation in a smoking cessation clinical trial and assessed emotional salience by measuring the amplitude of the late positive potential (LPP; 400 to 600 ms after picture onset). As expected, emotional and cigarette-related pictures prompted a significantly larger LPP than neutral pictures. The amplitude of the LPP increased as a function of picture arousal level, with high-arousing erotic and mutilation pictures showing the largest response in contrast to low-arousing pleasant and unpleasant objects, which showed the smallest response (other than neutral). Compared to females, male participants showed larger LPPs for high-arousing erotic and mutilation pictures. However, unlike emotional pictures, no difference was noted for the LPP between cigarette stimuli containing people versus those containing only objects, suggesting that in contrast to emotional objects, cigarette-related objects are highly relevant for smokers. We also compared the smokers to a small (N=40), convenience sample of never-smokers. We found that never-smokers had significantly smaller LPPs in response to erotic and cigarette stimuli containing only objects compared to smokers. PMID:23643564

  10. Contribution of kasA analysis to detection of isoniazid-resistant Mycobacterium tuberculosis in Singapore.

    PubMed

    Lee, A S; Lim, I H; Tang, L L; Telenti, A; Wong, S Y

    1999-08-01

    Genotypic analysis of resistance to isoniazid (INH) in Mycobacterium tuberculosis is complex due to the various genes potentially involved. Mutations in ketoacyl acyl carrier protein synthase (encoded by kasA) were present in 16 of 160 (10%) INH-resistant isolates (R121K [n = 1], G269S [n = 3], G312S [n = 11], G387D [n = 1]). However, G312S was also present in 6 of 32 (19%) susceptible strains. kasA analysis contributed marginally to the performance of INH genotypic testing in Singapore. The significance of kasA polymorphisms in INH resistance should be carefully established. PMID:10428945

  11. EUV sources for EUV lithography in alpha-, beta-, and high volume chip manufacturing: an update on GDPP and LPP technology

    NASA Astrophysics Data System (ADS)

    Stamm, U.; Kleinschmidt, J.; Gabel, K.; Hergenhan, G.; Ziener, C.; Schriever, G.; Ahmad, I.; Bolshukhin, D.; Brudermann, J.; de Bruijn, R.; Chin, T. D.; Geier, A.; Gotze, S.; Keller, A.; Korobotchko, V.; Mader, B.; Ringling, J.; Brauner, T.

    2005-05-01

    In the paper we report about the progress made at XTREME technologies in the development of EUV sources based on gas discharge produced plasma (GDPP) technologies and laser produced plasma (LPP) technologies. First prototype xenon GDPP sources of the type XTS 13-35 based on the Z-pinch principle with 35 W power in 2π sr have been integrated into micro-exposure tools from Exitech, UK. Specifications of the EUV sources and experience of integration as well as data about component and optics lifetime are presented. In the source development program for Beta exposure tools and high volume manufacturing exposure tools both tin and xenon have been investigated as fuel for the EUV sources. Development progress in porous metal cooling technology as well as pulsed power circuit design has led to GDPP sources with xenon fuel continuous operating with an output power of 200 W in 2π sr at 4500 Hz repetition rate. With tin fuel an output power of 400 W in 2π sr was obtained leaving all other conditions unaltered with respect to the xenon based source. The performance of the xenon fueled sources is sufficiently good to fulfill all requirements up to the beta tool level. For both the xenon and the tin GDPP sources detailed data about source performance are reported, including component lifetime and optics lifetime. The status of the integration of the sources with grazing incidence collector optics is discussed. Theoretical estimations of collection efficiencies are compared with experimental data to determine the loss mechanisms in the beam path. Specifically contamination issues related to tin as target material as well as debris mitigation in tin sources is addressed. As driver lasers for the LPP source research diode-pumped Nd:YAG lasers have been used to generate EUV emitting plasma. As target material xenon has been employed. Conversion efficiencies have been measured and currently the maximum conversion efficiency amounts to 1 %. The laser driver power of 1.2 kW is

  12. Vaccination of Cattle with the N Terminus of LppQ of Mycoplasma mycoides subsp. mycoides Results in Type III Immune Complex Disease upon Experimental Infection

    PubMed Central

    Frey, Joachim; Smith, Ken; Schnier, Christian; Wesonga, Hezron; Naessens, Jan; McKeever, Declan

    2015-01-01

    Contagious bovine pleuropneumonia (CBPP) is a serious respiratory disease of cattle caused by Mycoplasma mycoides subsp. mycoides. Current vaccines against CBPP induce short-lived immunity and can cause severe postvaccine reactions. Previous studies have identified the N terminus of the transmembrane lipoprotein Q (LppQ-N′) of M. mycoides subsp. mycoides as the major antigen and a possible virulence factor. We therefore immunized cattle with purified recombinant LppQ-N′ formulated in Freund's adjuvant and challenged them with M. mycoides subsp. mycoides. Vaccinated animals showed a strong seroconversion to LppQ, but they exhibited significantly enhanced postchallenge glomerulonephritis compared to the placebo group (P = 0.021). Glomerulonephritis was characterized by features that suggested the development of antigen-antibody immune complexes. Clinical signs and gross pathological scores did not significantly differ between vaccinated and placebo groups. These findings reveal for the first time the pathogenesis of enhanced disease as a result of antibodies against LppQ during challenge and also argue against inclusion of LppQ-N′ in a future subunit vaccine for CBPP. PMID:25733516

  13. MicL, a new σE-dependent sRNA, combats envelope stress by repressing synthesis of Lpp, the major outer membrane lipoprotein

    PubMed Central

    Guo, Monica S.; Updegrove, Taylor B.; Gogol, Emily B.; Shabalina, Svetlana A.; Gross, Carol A.; Storz, Gisela

    2014-01-01

    In enteric bacteria, the transcription factor σE maintains membrane homeostasis by inducing synthesis of proteins involved in membrane repair and two small regulatory RNAs (sRNAs) that down-regulate synthesis of abundant membrane porins. Here, we describe the discovery of a third σE-dependent sRNA, MicL (mRNA-interfering complementary RNA regulator of Lpp), transcribed from a promoter located within the coding sequence of the cutC gene. MicL is synthesized as a 308-nucleotide (nt) primary transcript that is processed to an 80-nt form. Both forms possess features typical of Hfq-binding sRNAs but surprisingly target only a single mRNA, which encodes the outer membrane lipoprotein Lpp, the most abundant protein of the cell. We show that the copper sensitivity phenotype previously ascribed to inactivation of the cutC gene is actually derived from the loss of MicL and elevated Lpp levels. This observation raises the possibility that other phenotypes currently attributed to protein defects are due to deficiencies in unappreciated regulatory RNAs. We also report that σE activity is sensitive to Lpp abundance and that MicL and Lpp comprise a new σE regulatory loop that opposes membrane stress. Together MicA, RybB, and MicL allow σE to repress the synthesis of all abundant outer membrane proteins in response to stress. PMID:25030700

  14. Vaccination of cattle with the N terminus of LppQ of Mycoplasma mycoides subsp. mycoides results in type III immune complex disease upon experimental infection.

    PubMed

    Mulongo, Musa; Frey, Joachim; Smith, Ken; Schnier, Christian; Wesonga, Hezron; Naessens, Jan; McKeever, Declan

    2015-05-01

    Contagious bovine pleuropneumonia (CBPP) is a serious respiratory disease of cattle caused by Mycoplasma mycoides subsp. mycoides. Current vaccines against CBPP induce short-lived immunity and can cause severe postvaccine reactions. Previous studies have identified the N terminus of the transmembrane lipoprotein Q (LppQ-N') of M. mycoides subsp. mycoides as the major antigen and a possible virulence factor. We therefore immunized cattle with purified recombinant LppQ-N' formulated in Freund's adjuvant and challenged them with M. mycoides subsp. mycoides. Vaccinated animals showed a strong seroconversion to LppQ, but they exhibited significantly enhanced postchallenge glomerulonephritis compared to the placebo group (P = 0.021). Glomerulonephritis was characterized by features that suggested the development of antigen-antibody immune complexes. Clinical signs and gross pathological scores did not significantly differ between vaccinated and placebo groups. These findings reveal for the first time the pathogenesis of enhanced disease as a result of antibodies against LppQ during challenge and also argue against inclusion of LppQ-N' in a future subunit vaccine for CBPP. PMID:25733516

  15. Phosphorylation of KasB Regulates Virulence and Acid-Fastness in Mycobacterium tuberculosis

    PubMed Central

    Vilchèze, Catherine; Molle, Virginie; Carrère-Kremer, Séverine; Leiba, Jade; Mourey, Lionel; Shenai, Shubhada; Baronian, Grégory; Tufariello, Joann; Hartman, Travis; Veyron-Churlet, Romain; Trivelli, Xavier; Tiwari, Sangeeta; Weinrick, Brian; Alland, David; Guérardel, Yann; Jacobs, William R.; Kremer, Laurent

    2014-01-01

    Mycobacterium tuberculosis bacilli display two signature features: acid-fast staining and the capacity to induce long-term latent infections in humans. However, the mechanisms governing these two important processes remain largely unknown. Ser/Thr phosphorylation has recently emerged as an important regulatory mechanism allowing mycobacteria to adapt their cell wall structure/composition in response to their environment. Herein, we evaluated whether phosphorylation of KasB, a crucial mycolic acid biosynthetic enzyme, could modulate acid-fast staining and virulence. Tandem mass spectrometry and site-directed mutagenesis revealed that phosphorylation of KasB occurred at Thr334 and Thr336 both in vitro and in mycobacteria. Isogenic strains of M. tuberculosis with either a deletion of the kasB gene or a kasB_T334D/T336D allele, mimicking constitutive phosphorylation of KasB, were constructed by specialized linkage transduction. Biochemical and structural analyses comparing these mutants to the parental strain revealed that both mutant strains had mycolic acids that were shortened by 4–6 carbon atoms and lacked trans-cyclopropanation. Together, these results suggested that in M. tuberculosis, phosphorylation profoundly decreases the condensing activity of KasB. Structural/modeling analyses reveal that Thr334 and Thr336 are located in the vicinity of the catalytic triad, which indicates that phosphorylation of these amino acids would result in loss of enzyme activity. Importantly, the kasB_T334D/T336D phosphomimetic and deletion alleles, in contrast to the kasB_T334A/T336A phosphoablative allele, completely lost acid-fast staining. Moreover, assessing the virulence of these strains indicated that the KasB phosphomimetic mutant was attenuated in both immunodeficient and immunocompetent mice following aerosol infection. This attenuation was characterized by the absence of lung pathology. Overall, these results highlight for the first time the role of Ser/Thr kinase

  16. Identification of KasA as the cellular target of an anti-tubercular scaffold.

    PubMed

    Abrahams, Katherine A; Chung, Chun-Wa; Ghidelli-Disse, Sonja; Rullas, Joaquín; Rebollo-López, María José; Gurcha, Sudagar S; Cox, Jonathan A G; Mendoza, Alfonso; Jiménez-Navarro, Elena; Martínez-Martínez, María Santos; Neu, Margarete; Shillings, Anthony; Homes, Paul; Argyrou, Argyrides; Casanueva, Ruth; Loman, Nicholas J; Moynihan, Patrick J; Lelièvre, Joël; Selenski, Carolyn; Axtman, Matthew; Kremer, Laurent; Bantscheff, Marcus; Angulo-Barturen, Iñigo; Izquierdo, Mónica Cacho; Cammack, Nicholas C; Drewes, Gerard; Ballell, Lluis; Barros, David; Besra, Gurdyal S; Bates, Robert H

    2016-01-01

    Phenotypic screens for bactericidal compounds are starting to yield promising hits against tuberculosis. In this regard, whole-genome sequencing of spontaneous resistant mutants generated against an indazole sulfonamide (GSK3011724A) identifies several specific single-nucleotide polymorphisms in the essential Mycobacterium tuberculosis β-ketoacyl synthase (kas) A gene. Here, this genomic-based target assignment is confirmed by biochemical assays, chemical proteomics and structural resolution of a KasA-GSK3011724A complex by X-ray crystallography. Finally, M. tuberculosis GSK3011724A-resistant mutants increase the in vitro minimum inhibitory concentration and the in vivo 99% effective dose in mice, establishing in vitro and in vivo target engagement. Surprisingly, the lack of target engagement of the related β-ketoacyl synthases (FabH and KasB) suggests a different mode of inhibition when compared with other Kas inhibitors of fatty acid biosynthesis in bacteria. These results clearly identify KasA as the biological target of GSK3011724A and validate this enzyme for further drug discovery efforts against tuberculosis. PMID:27581223

  17. Theoretical estimation of the aqueous pKas of thiols

    NASA Astrophysics Data System (ADS)

    Hunter, Nora E.; Seybold, Paul G.

    2014-02-01

    The ionisation state of a compound is a key parameter influencing the compound's activity as a drug, metabolite, pollutant, or other active chemical agent. Sulfhydrol compounds (thiols) tend to be considerably more acidic than their hydroxyl (alcohol) analogues. In this report, quantum chemical approaches previously used for the estimation of the aqueous pKas of alcohols are applied to the estimation of the acidities of thiols. Acidity estimates obtained from the general-purpose SPARC calculational programme (S.H. Hilal, S.W. Karickhoff, and L.A. Carreira, Quant. Struct.-Act. Relat. 14, 348 (1995)) and the ACD/Labs PhysChem Suite v12 programme package are employed as benchmarks. Quantum chemical calculations were performed using both the semiempirical RM1 method and the density functional theory B3LYP/6-31+G* method. The effectiveness of the SM5.4 and SM8 solvent models in estimating the aqueous-phase acidities was also evaluated. All of the approaches examined demonstrated strong correlations with the experimental acidity values.

  18. Analysis of the role of Mycobacterium tuberculosis kasA gene mutations in isoniazid resistance.

    PubMed

    Sun, Y-J; Lee, A S G; Wong, S-Y; Paton, N I

    2007-08-01

    Previous studies have suggested that Mycobacterium tuberculosis kasA G312S and G269S gene mutations may represent sequence polymorphisms of the M. tuberculosis East-African-Indian (EAI) and T families, respectively, rather than relating to isoniazid resistance. The present study examined polymorphisms of these two codons in 98 drug-susceptible M. tuberculosis isolates (68 EAI and 30 T isolates). Twenty-eight isolates belonging to a sub-lineage of the EAI family had the kasA G312S mutation, but none of the 30 T isolates had the G269S mutation. The data suggest that the kasA G312S mutation is not related to isoniazid resistance, but represents a sequence polymorphism in a sub-lineage of the EAI family. PMID:17501974

  19. Spectral emission properties of a LPP light source in the sub-200nm range for wafer inspection applications

    NASA Astrophysics Data System (ADS)

    Gambino, Nadia; Rollinger, Bob; Hudgins, Duane; Abhari, Reza; Abreau, F.

    2015-03-01

    In this work, the spectral emission proprieties of a droplet-based laser-produced plasma are investigated in the VUV range. These studies are performed with a spectrograph operating from 30 nm to 180 nm at a spectral resolution of 0.1 nm. The emission spectra are recorded for different droplet-based metal fuels such as tin, indium and gallium in the presence of different background gas pressure levels. The experimental results are relevant for alternative light sources that would be needed for future wafer inspection tools. In addition, the experimental results help to determine the Out- Of-Band (OOB) radiation emission of the EUV source. By tuning the type of fuel, the laser energies and the background gas, the LPP light source shows good capabilities to be operated as a tunable light source that covers a spectral emission range from the EUV to the sub-200 nm range.

  20. SRTM Colored and Shaded Topography: Haro and Kas Hills, India

    NASA Technical Reports Server (NTRS)

    2001-01-01

    On January 26, 2001, the Kachchh region in western India suffered the most deadly earthquake in India's history. This shaded topography view of landforms northeast of the city of Bhuj depicts geologic structures that are of interest in the study the tectonic processes that may have led to that earthquake. However, preliminary field studies indicate that these structures are composed of Mesozoic rocks that are overlain by younger rocks showing little deformation. Thus these structures may be old, not actively growing, and not directly related to the recent earthquake.

    The Haro Hills are on the left and the Kas Hills are on the right. The Haro Hills are an 'anticline,' which is an upwardly convex elongated fold of layered rocks. In this view, the anticline is distinctly ringed by an erosion resistant layer of sandstone. The east-west orientation of the anticline may relate to the crustal compression that has occurred during India's northward movement toward, and collision with, Asia. In contrast, the largest of the Kas Hills appears to be a tilted (to the south) and faulted (on the north) block of layered rocks. Also seen here, the linear feature trending toward the southwest from the image center is an erosion-resistant 'dike,' which is an igneous intrusion into older 'host' rocks along a fault plane or other crack. These features are simple examples of how shaded topography can provide a direct input to geologic studies.

    In this image, colors show the elevation as measured by the Shuttle Radar Topography Mission (SRTM). Colors range from green at the lowest elevations, through yellow and red, to purple at the highest elevations. Elevations here range from near sea level to about 300 meters (about 1000 feet). Shading has been added, with illumination from the north (image top).

    Elevation data used in this image was acquired by the Shuttle Radar Topography Mission aboard the Space Shuttle Endeavour, launched on February 11, 2000. SRTM used the same

  1. The protonation state of catalytic residues in the resting state of KasA revisited: detailed mechanism for the activation of KasA by its own substrate.

    PubMed

    Lee, Wook; Engels, Bernd

    2014-02-11

    Mycobacterium tuberculosis is the causative pathogen of tuberculosis, the second leading cause of death from an infectious disease globally. β-Ketoacyl ACP synthase I (KasA) is essential for the survival of M. tuberculosis, because it is one of the key enzymes in the biosynthetic pathway of mycolic acid, the building block of the cell wall in M. tuberculosis. To distinguish among the various suggested mechanisms of KasA that are based on different protonation states of the active site, we characterize its resting state by various theoretical approaches ranging from first-principle-based quantum mechanical/molecular mechanical molecular dynamics simulations (QM/MM MD) with large QM parts to force field-based MD and free energy perturbation computations. In contrast to a previous study that used less reliable semiempirical approaches in combination with smaller QM parts, our improved computations predict that the most important active site residues, Cys171 and His311, are neutral. Because the neutral catalytic residues are too unreactive to attack the substrate, the question of how their activation is achieved arises. Combining our computed results with structural information about the malonyl binding pocket, we devised a detailed model about the activation mechanism. A conformational change of Phe404 possibly triggered by the substrate is central for the activation because it switches KasA to the sufficiently reactive zwitterionic state. PMID:24479625

  2. Electrostatic Environment of Hemes in Proteins: pKas of Hydroxyl Ligands†

    PubMed Central

    Song, Yifan; Mao, Junjun; Gunner, M. R.

    2009-01-01

    The pKas of ferric aquo–heme and aquo–heme electrochemical midpoints (Ems) at pH 7 in sperm whale myoglobin, Aplysia myoblogin, hemoglobin I, heme oxygenase 1, horseradish peroxidase and cytochrome c oxidase were calculated with Multi-Conformation Continuum Electrostatics (MCCE). The pKas span 3.3 pH units from 7.6 in heme oxygenase 1 to 10.9 in peroxidase, and the Ems range from −250 mv in peroxidase to 125 mV in Aplysia myoglobin. Proteins with higher in situ ferric aquo–heme pKas tend to have lower Ems. Both changes arise from the protein stabilizing a positively charged heme. However, compared with values in solution, the protein shifts the aquo–heme Ems more than the pKas. Thus, the protein has a larger effective dielectric constant for the protonation reaction, showing that electron and proton transfers are coupled to different conformational changes that are captured in the MCCE analysis. The calculations reveal a breakdown in the classical continuum electrostatic analysis of pairwise interactions. Comparisons with DFT calculations show that Coulomb’s law overestimates the large unfavorable interactions between the ferric water–heme and positively charged groups facing the heme plane by as much as 60%. If interactions with CuB in cytochrome c oxidase and Arg 38 in horseradish peroxidase are not corrected, the pKa calculations are in error by as much as 6 pH units. With DFT corrected interactions calculated pKas and Ems differ from measured values by less than 1 pH unit or 35 mV, respectively. The in situ aquo–heme pKa is important for the function of cytochrome c oxidase since it helps to control the stoichiometry of proton uptake coupled to electron transfer PMID:16800621

  3. Actinic detection of multilayer defects on EUV mask blanks using LPP light source and dark-field imaging

    NASA Astrophysics Data System (ADS)

    Tezuka, Yoshihiro; Ito, Masaaki; Terasawa, Tsuneo; Tomie, Toshihisa

    2004-05-01

    The development of defect-free mask blanks including inspection is one of the big challenges for the implementation of extreme ultraviolet lithography (EUVL), especially when the introduction of EUVL is rescheduled to a later technology node. Among others, inspection of multilayer coated mask blanks with no oversight of critical defects and with minimal detection of false defects is a challenging issue for providing mask blanks free of defects or with thorough characterization of any existing defects. MIRAI Project has been developing a novel actinic (at-wavelength) inspection tool for detecting critical multilayer defects using a dark-field imaging and a laser-produced plasma (LPP) light source, expecting better sensitivity and better correlation with printability. The first experimental set up is completed for proof-of-concept (POC) demonstration using 20x Schwarzschild imaging optics and a backsideilluminated CCD. An in-house LPP light source is integrated to optimally illuminate the area of interest by EUV with a wavelength of 13.5nm. For its illuminator, a multilayer-coated elliptical mirror is used to illuminate a mask blank with the EUV that is collected within a wide solid angle from the light source. The first EUV dark-field image is obtained from a mask blank with programmed multilayer defects which are manufactured by locating well-defined patterns before depositing Mo/Si multilayer on EUV mask substrate. All the fabricated multilayer defects down to 70nm in width and 3.5nm in height are detected as clear signals that are distinguishable from the background intensity arising from the scattering by the surface roughness of the multilayer-coated mask blank. We have also detected a phase defect as low as 2nm in height. False defect count was not only zero within the area of view but also statistically confirmed to be less than one within the whole area of a mask blank assuming the extrapolation of observed fluctuation of background intensity is applicable

  4. SRTM Stereo Pair: Haro and Kas Hills, India

    NASA Technical Reports Server (NTRS)

    2001-01-01

    On January 26, 2001 the Kachchh region in western India suffered the most deadly earthquake in India's history. This stereoscopic view of landforms northeast of the city of Bhuj depicts geologic structures that are of interest in the study the tectonic processes that may have led to that earthquake. However, preliminary field studies indicate that these structures are composed of Mesozoic rocks that are overlain by younger rocks showing little deformation. Thus these structures may be old, not actively growing, and not directly related to the recent earthquake.

    The Haro Hills are on the left and the Kas Hills are on the right. The Haro Hills are an 'anticline,' which is an upwardly convex elongated fold of layered rocks. The anticline is distinctly ringed by an erosion resistant layer of sandstone. The east-west orientation of the anticline may relate to the crustal compression that has occurred during India's northward movement toward, and collision with, Asia. In contrast, the largest of the Kas Hills appears to be a tilted (to the south) and faulted (on the north) block of layered rocks. Also seen here, the curvilinear ridge trending toward the southwest from the image center is an erosion resistant 'dike,' which is an igneous intrusion into older 'host' rocks along a fault plane or other crack. The dike also appears to extend northeast from the image center as a dark line having very little topography. Its location between the tilted block and a smaller anticline to the north (directly east of the larger anticline) probably indicates that the dike fills the fault that separates these contrasting geologic structures. These features are simple examples of how digital elevation data can stereoscopically enhance satellite imagery to provide a direct input to geologic studies.

    This stereoscopic image was generated by draping a Landsat satellite image (taken just two weeks after the earthquake) over a preliminary Shuttle Radar Topography Mission (SRTM

  5. SRTM Stereo Pair: Haro and Kas Hills, India

    NASA Technical Reports Server (NTRS)

    2001-01-01

    On January 26, 2001 the Kachchh region in western India suffered the most deadly earthquake in India's history. This stereoscopic view of landforms northeast of the city of Bhuj depicts geologic structures that are of interest in the study the tectonic processes that may have led to that earthquake. However, preliminary field studies indicate that these structures are composed of Mesozoic rocks that are overlain by younger rocks showing little deformation. Thus these structures may be old, not actively growing, and not directly related to the recent earthquake.

    The Haro Hills are on the left and the Kas Hills are on the right. The Haro Hills are an 'anticline,' which is an upwardly convex elongated fold of layered rocks. The anticline is distinctly ringed by an erosion resistant layer of sandstone. The east-west orientation of the anticline may relate to the crustal compression that has occurred during India's northward movement toward, and collision with, Asia. In contrast, the largest of the Kas Hills appears to be a tilted (to the south) and faulted (on the north) block of layered rocks. Also seen here, the curvilinear ridge trending toward the southwest from the image center is an erosion resistant 'dike,' which is an igneous intrusion into older 'host' rocks along a fault plane or other crack. The dike also appears to extend northeast from the image center as a dark line having very little topography. Its location between the tilted block and a smaller anticline to the north (directly east of the larger anticline) probably indicates that the dike fills the fault that separates these contrasting geologic structures. These features are simple examples of how digital elevation data can stereoscopically enhance satellite imagery to provide a direct input to geologic studies.

    This stereoscopic image was generated by draping a Landsat satellite image (taken just two weeks after the earthquake) over a preliminary Shuttle Radar Topography Mission (SRTM

  6. Changes in Deceased Donor Kidney Transplantation One Year After KAS Implementation.

    PubMed

    Stewart, D E; Kucheryavaya, A Y; Klassen, D K; Turgeon, N A; Formica, R N; Aeder, M I

    2016-06-01

    After over a decade of discussion, analysis, and consensus-building, a new kidney allocation system (KAS) was implemented on December 4, 2014. Key goals included improving longevity matching between donor kidneys and recipients and broadening access for historically disadvantaged subpopulations, in particular highly sensitized patients and those with an extended duration on dialysis but delayed referral for transplantation. To evaluate the early impact of KAS, we compared Organ Procurement and Transplantation Network data 1 year before versus after implementation. The distribution of transplants across many recipient characteristics has changed markedly and suggests that in many ways the new policy is achieving its goals. Transplants in which the donor and recipient age differed by more than 30 years declined by 23%. Initial, sharp increases in transplants were observed for Calculated Panel-Reactive Antibody 99-100% recipients and recipients with at least 10 years on dialysis, with a subsequent tapering of transplants to these groups suggesting bolus effects. Although KAS has arguably increased fairness in allocation, the potential costs of broadening access must be considered. Kidneys are more often being shipped over long distances, leading to increased cold ischemic times. Delayed graft function rates have increased, but 6-month graft survival rates have not changed significantly. PMID:26932731

  7. Requirement for kasB in Mycobacterium mycolic acid biosynthesis, cell wall impermeability and intracellular survival: implications for therapy.

    PubMed

    Gao, Lian-Yong; Laval, Francoise; Lawson, Elise H; Groger, Richard K; Woodruff, Andy; Morisaki, J Hiroshi; Cox, Jeffery S; Daffe, Mamadou; Brown, Eric J

    2003-09-01

    Mycobacterium tuberculosis infects one-third of the world's population and causes two million deaths annually. The unusually low permeability of its cell wall contributes to the ability of M. tuberculosis to grow within host macrophages, a property required for pathogenesis of infection. Mycobacterium marinum is an established model for discovering genes involved in mycobacterial infection. Mycobacterium marinum mutants with transposon insertions in the beta-ketoacyl-acyl carrier protein synthase B gene (kasB) grew poorly in macrophages, although growth in vitro was unaffected. Detailed analyses by thin-layer chromatography, nuclear magnetic resonance (NMR), matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, infrared spectroscopy, and chemical degradations showed that the kasB mutants synthesize mycolic acids that are 2-4 carbons shorter than wild type; the defect was localized to the proximal portion of the meromycolate chain. In addition, these mutants showed a significant (approximately 30%) reduction in the abundance of keto-mycolates, with a slight compensatory increase of both alpha- and methoxy-mycolates. Despite these small changes in mycolate length and composition, the kasB mutants exhibited strikingly altered cell wall permeability, leading to a marked increase in susceptibility to lipophilic antibiotics and the host antimicrobial molecules defensin and lysozyme. The abnormalities of the kasB mutants were fully complemented by expressing M. tuberculosis kasB, but not by the closely related gene kasA. These studies identify kasB as a novel target for therapeutic intervention in mycobacterial diseases. PMID:12950920

  8. Overexpression of inhA, but not kasA, confers resistance to isoniazid and ethionamide in Mycobacterium smegmatis, M. bovis BCG and M. tuberculosis.

    PubMed

    Larsen, Michelle H; Vilchèze, Catherine; Kremer, Laurent; Besra, Gurdyal S; Parsons, Linda; Salfinger, Max; Heifets, Leonid; Hazbon, Manzour H; Alland, David; Sacchettini, James C; Jacobs, William R

    2002-10-01

    The inhA and kasA genes of Mycobacterium tuberculosis have each been proposed to encode the primary target of the antibiotic isoniazid (INH). Previous studies investigating whether overexpressed inhA or kasA could confer resistance to INH yielded disparate results. In this work, multicopy plasmids expressing either inhA or kasA genes were transformed into M. smegmatis, M. bovis BCG and three different M. tuberculosis strains. The resulting transformants, as well as previously published M. tuberculosis strains with multicopy inhA or kasAB plasmids, were tested for their resistance to INH, ethionamide (ETH) or thiolactomycin (TLM). Mycobacteria containing inhA plasmids uniformly exhibited 20-fold or greater increased resistance to INH and 10-fold or greater increased resistance to ETH. In contrast, the kasA plasmid conferred no increased resistance to INH or ETH in any of the five strains, but it did confer resistance to thiolactomycin, a known KasA inhibitor. INH is known to increase the expression of kasA in INH-susceptible M. tuberculosis strains. Using molecular beacons, quantified inhA and kasA mRNA levels showed that increased inhA mRNA levels corre--lated with INH resistance, whereas kasA mRNA levels did not. In summary, analysis of strains harbouring inhA or kasA plasmids yielded the same conclusion: overexpressed inhA, but not kasA, confers INH and ETH resistance to M. smegmatis, M. bovis BCG and M. tuberculosis. Therefore, InhA is the primary target of action of INH and ETH in all three species. PMID:12406221

  9. X-Ray Crystal Structure of Mycobacterium Tuberculosis β-Ketoacyl Acyl Carrier Protein Synthase II (mtKasB)

    PubMed Central

    Sridharan, Sudharsan; Wang, Lei; Brown, Alistair K.; Dover, Lynn G.; Kremer, Laurent; Besra, Gurdyal S.; Sacchettini, James C.

    2007-01-01

    Summary Mycolic acids are long chain α-alkyl branched, β-hydroxy fatty acids that represent a characteristic component of the Mycobacterium tuberculosis cell wall. Through their covalent attachment to peptidoglycan via an arabinogalactan polysaccharide, they provide the basis for an essential outer envelope membrane. Mycobacteria possess two fatty acid synthases (FAS); FAS-I carries out de novo synthesis of fatty acids while FAS-II is considered to elongate medium chain length fatty acyl primers to provide long chain (C56) precursors of mycolic acids. Here we report the crystal structure of Mycobacterium tuberculosis β-ketoacyl acyl carrier protein synthase (ACP) II mtKasB, a mycobacterial elongation condensing enzyme involved in FAS-II. This enzyme, along with the M. tuberculosis β-ketoacyl ACP synthase I mtKasA, catalyzes the Claisen-type condensation reaction responsible for fatty acyl elongation in FAS-II and are potential targets for development of novel anti-tubercular drugs. The crystal structure refined to 2.4 Å resolution revealed that, like other KAS-II enzymes, mtKasB adopts a thiolase fold but contains unique structural features in the capping region that may be crucial to its preference for longer fatty acyl chains than its counterparts from other bacteria. Modeling of mtKasA using the mtKasB structure as a template predicts the overall structures to be almost identical, but a larger entrance to the active site tunnel is envisaged that might contribute to the greater sensitivity of mtKasA to the inhibitor thiolactomycin (TLM). Modeling of TLM binding in mtKasB shows that the drug fits the active site poorly and results of enzyme inhibition assays using TLM analogues are wholly consistent with our structural observations. Consequently, the structure described here further highlights the potential of TLM as an anti-tubercular lead compound and will aid further exploration of the TLM scaffold towards the design of novel compounds which inhibit

  10. Elucidation of the protonation states of the catalytic residues in mtKasA: implications for inhibitor design.

    PubMed

    Lee, Wook; Luckner, Sylvia R; Kisker, Caroline; Tonge, Peter J; Engels, Bernd

    2011-06-28

    KasA (β-ketoacyl ACP synthase I) is involved in the biosynthetic pathway of mycolic acids, an essential component of the cell wall in Mycobacterium tuberculosis. It was shown that KasA is essential for the survival of the pathogen and thus could serve as a new drug target for the treatment of tuberculosis. The active site of KasA was previously characterized by X-ray crystallography. However, questions regarding the protonation state of specific amino acids, the orientation of the histidine groups within the active site, and additional conformers being accessible at ambient temperatures remain open and have to be addressed prior to the design of new inhibitors. We investigate the active site of KasA in this work by means of structural motifs and relative energies. Molecular dynamics (MD) simulations, free energy perturbation computations, and calculations employing the hybrid quantum mechanics/molecular mechanics (QM/MM) method made it possible to determine the protonation status and reveal important details about the catalytic mechanism of KasA. Additionally, we can rationalize the molecular basis for the acyl-transfer activity in the H311A mutant. Our data strongly suggest that inhibitors should be able to inhibit different protonation states because the enzyme can switch easily between a zwitterionic and neutral state. PMID:21615093

  11. New data on the structure of the Kas Block in the basement of the West Siberian Plate

    NASA Astrophysics Data System (ADS)

    Kheraskova, T. N.; Kaplan, S. A.; Bubnov, V. P.; Galuev, V. I.

    2013-03-01

    A new concept concerning the structure and stages of evolution of the Kas Block of the West Siberian Plate is stated in this paper. The Kas Block is traditionally considered to be a subsided western margin of the Siberian Platform. The new concept is based on the results of the interpretation of the geophysical data recently obtained along the reference and regional profiles in this territory. The geological interpretation of the deep dynamic sections obtained by reprocessing of the CDP seismic reflection records has been performed for the first time. The structural features of the Kas Block, as well as the character of its junction with the Siberian Platform and the Paleozoic framework, are discussed. The tectonic scheme of the territory and the scheme of the pre-Late Devonian surface of the Kas Block have been compiled. The Baikalian age of the basement of the Kas Block is substantiated. The Salairian allochthonous ophiolite-basalt tectonic nappe is localized for the first time within the sedimentary cover of the Kas Block. The available information allowed us to reconstruct the development of the western margin of the Siberian continent in the Riphean and Early Paleozoic before and after the Baikalian Orogeny, respectively. The informational background of the geological and geophysical interpretation involves the results of the CDP seismic reflection profiling, including the deep dynamic seismic sections and parameters of the P-wave velocities along the reference 1-SB seismic line and the regional Vostok 10, 12, 15, and 16 seismic lines; the results of the deep seismic and magnetotelluric soundings; the gravity measurements; the magnetic exploration; and the new coherent physical geological models.

  12. Xyn11E from Paenibacillus barcinonensis BP-23: a LppX-chaperone-dependent xylanase with potential for upgrading paper pulps.

    PubMed

    Valenzuela, Susana V; Diaz, Pilar; Pastor, F I Javier

    2014-07-01

    A new xylanase from Paenibacillus barcinonensis BP-23, Xyn11E, has been identified and characterized. Xyn11E has been cloned and heterologously expressed in Escherichia coli. It is a single-domain xylanase belonging to the family 11 of glycosyl hydrolases (GH11) with a predicted molecular weight of 20.652 kDa and an isoelectric point (pI) of 8.7. Substrate specificity, kinetic properties, and mode of action of the purified xylanase were characterized. Xyn11E exhibited high activity toward branched xylans, being beechwood xylan the preferred substrate. The optimum pH and temperature of the purified enzyme were 6.5 and 50 °C, respectively. Catalytic constants were determined on beechwood xylan, on which Xyn11E showed a Km of 12.98 mg/ml and a Vmax of 3,023 U/mg. The enzyme hydrolyzed long xylooligosaccharides, while oligomers shorter than xylotetraose were not degraded. Products released from glucuronoxylans were shorter than those liberated from cereal arabinoxylans. The xylanase was dependent on P. barcinonensis BP-23 LppX for its expression in an active form. Coexpression of Xyn11E with E. coli chaperones could not replace the need of LppX, which seems to act as a specific chaperone for Xyn11E correct folding. Activity of the enzyme on bleached pulps was evaluated. Xyn11E liberated reducing sugars from ECF and TCF pulps from eucalyptus, sisal, and flax, which makes it a good candidate for the enzymatic-assisted production of high-cellulose-content pulps from paper-grade pulps. PMID:24549767

  13. Identification of hemostatic genes expressed in human and rat leg muscles and a novel gene (LPP1/PAP2A) suppressed during prolonged physical inactivity (sitting)

    PubMed Central

    2012-01-01

    Background Partly because of functional genomics, there has been a major paradigm shift from solely thinking of skeletal muscle as contractile machinery to an understanding that it can have roles in paracrine and endocrine functions. Physical inactivity is an established risk factor for some blood clotting disorders. The effects of inactivity during sitting are most alarming when a person develops the enigmatic condition in the legs called deep venous thrombosis (DVT) or “coach syndrome,” caused in part by muscular inactivity. The goal of this study was to determine if skeletal muscle expresses genes with roles in hemostasis and if their expression level was responsive to muscular inactivity such as occurs in prolonged sitting. Methods Microarray analyses were performed on skeletal muscle samples from rats and humans to identify genes associated with hemostatic function that were significantly expressed above background based on multiple probe sets with perfect and mismatch sequences. Furthermore, we determined if any of these genes were responsive to models of physical inactivity. Multiple criteria were used to determine differential expression including significant expression above background, fold change, and non-parametric statistical tests. Results These studies demonstrate skeletal muscle tissue expresses at least 17 genes involved in hemostasis. These include the fibrinolytic factors tetranectin, annexin A2, and tPA; the anti-coagulant factors TFPI, protein C receptor, PAF acetylhydrolase; coagulation factors, and genes necessary for the posttranslational modification of these coagulation factors such as vitamin K epoxide reductase. Of special interest, lipid phosphate phosphatase-1 (LPP1/PAP2A), a key gene for degrading prothrombotic and proinflammatory lysophospholipids, was suppressed locally in muscle tissue within hours after sitting in humans; this was also observed after acute and chronic physical inactivity conditions in rats, and exercise was

  14. Crystal structures of Mycobacterium tuberculosis KasA show mode of action within cell wall biosynthesis and its inhibition by thiolactomycin.

    PubMed

    Luckner, Sylvia R; Machutta, Carl A; Tonge, Peter J; Kisker, Caroline

    2009-07-15

    Mycobacteria have a unique cell wall consisting of mycolic acids, very-long-chain lipids that provide protection and allow the bacteria to persist within human macrophages. Inhibition of cell wall biosynthesis is fatal for the organism and a starting point for the discovery and development of novel antibiotics. We determined the crystal structures of KasA, a key enzyme involved in the biosynthesis of long-chain fatty acids, in its apo-form and bound to the natural product inhibitor thiolactomycin. Detailed insights into the interaction of the inhibitor with KasA and the identification of a polyethylene glycol molecule that mimics a fatty acid substrate of approximately 40 carbon atoms length, represent the first atomic view of a mycobacterial enzyme involved in the synthesis of long-chain fatty acids and provide a robust platform for the development of novel thiolactomycin analogs with high affinity for KasA. PMID:19604480

  15. The effect of incomplete fuel-air mixing on the lean limit and emissions characteristics of a Lean Prevaporized Premixed (LPP) combustor

    NASA Technical Reports Server (NTRS)

    Santavicca, D. A.; Steinberger, R. L.; Gibbons, K. A.; Citeno, J. V.; Mills, S.

    1993-01-01

    Results are presented from an experimental study of the effect of incomplete fuel-air mixing on the lean limit and emissions characteristics of a lean, prevaporized, premixed (LPP), coaxial mixing tube combustor. Two-dimensional exciplex fluorescence was used to characterize the degree of fuel vaporization and mixing at the combustor inlet under non-combusting conditions. These tests were conducted at a pressure of 4 atm., a temperature of 400 C, a mixer tube velocity of 100 m/sec and an equivalence ratio of .8, using a mixture of tetradecane, 1 methyl naphthalene and TMPD as a fuel simulant. Fuel-air mixtures with two distinct spatial distributions were studied. The exciplex measurements showed that there was a significant amount of unvaporized fuel at the combustor entrance in both cases. One case, however, exhibited a very non-uniform distribution of fuel liquid and vapor at the combustor entrance, i.e., with most of the fuel in the upper half of the combustor tube, while in the other case, both the fuel liquid and vapor were much more uniformly distributed across the width of the combustor entrance. The lean limit and emissions measurements were all made at a pressure of 4 atm. and a mixer tube velocity of 100 m/sec, using Jet A fuel and both fuel-air mixture distributions. Contrary to what was expected, the better mixed case was found to have a substantially leaner operating limit. The two mixture distributions also unexpectedly resulted in comparable NO(x) emissions, for a given equivalence ratio and inlet temperature, however, lower NO(x) emissions were possible in the better mixed case due to its leaner operating limit.

  16. Single-Crystal Growth of Ba1-xKxFe2As2 by KAs Self-Flux Method

    NASA Astrophysics Data System (ADS)

    Kihou, Kunihiro; Saito, Taku; Fujita, Kay; Ishida, Shigeyuki; Nakajima, Masamichi; Horigane, Kazumasa; Fukazawa, Hideto; Kohori, Yoh; Uchida, Shin-ichi; Akimitsu, Jun; Iyo, Akira; Lee, Chul-Ho; Eisaki, Hiroshi

    2016-03-01

    Single crystals of Ba1-xKxFe2As2 with 0.15 ≤ x ≤ 1 have been successfully synthesized by a KAs self-flux method. The potassium (K) concentration x of the grown crystals was systematically changed by changing the mixing ratio of Ba to Fe in the starting materials. The crystals have flat surfaces corresponding to the crystallographic (001) planes, whose planar dimensions increase with decreasing thickness when x increases. The superconducting transition temperature systematically changes with x, ranging from 38 K at x = 0.4 to 3.4 K at x = 1.0, in good agreement with the results for polycrystalline samples.

  17. Computer-assisted prediction of HLA-DR binding and experimental analysis for human promiscuous Th1-cell peptides in the 24 kDa secreted lipoprotein (LppX) of Mycobacterium tuberculosis.

    PubMed

    Al-Attiyah, R; Mustafa, A S

    2004-01-01

    The secreted 24 kDa lipoprotein (LppX) is an antigen that is specific for Mycobacterium tuberculosis complex and M. leprae. The present study was carried out to identify the promiscuous T helper 1 (Th1)-cell epitopes of the M. tuberculosis LppX (MT24, Rv2945c) antigen by using 15 overlapping synthetic peptides (25 mers overlapping by 10 residues) covering the sequence of the complete protein. The analysis of Rv2945c sequence for binding to 51 alleles of nine serologically defined HLA-DR molecules, by using a virtual matrix-based prediction program (propred), showed that eight of the 15 peptides of Rv2945c were predicted to bind promiscuously to >/=10 alleles from more than or equal to three serologically defined HLA-DR molecules. The Th1-cell reactivity of all the peptides was assessed in antigen-induced proliferation and interferon-gamma (IFN-gamma)-secretion assays with peripheral blood mononuclear cells (PBMCs) from 37 bacille Calmette-Guérin (BCG)-vaccinated healthy subjects. The results showed that 17 of the 37 donors, which represented an HLA-DR-heterogeneous group, responded to one or more peptides of Rv2945c in the Th1-cell assays. Although each peptide stimulated PBMCs from one or more donors in the above assays, the best positive responses (12/17 (71%) responders) were observed with the peptide p14 (aa 196-220). This suggested a highly promiscuous presentation of p14 to Th1 cells. In addition, the sequence of p14 is completely identical among the LppX of M. tuberculosis, M. bovis and M. leprae, which further supports the usefulness of Rv2945c and p14 in the subunit vaccine design against both tuberculosis and leprosy. PMID:14723617

  18. Molecular dynamics of Mycobacterium tuberculosis KasA: implications for inhibitor and substrate binding and consequences for drug design.

    PubMed

    Schaefer, Benjamin; Kisker, Caroline; Sotriffer, Christoph A

    2011-11-01

    Inhibition of the production of fatty acids as essential components of the mycobacterial cell wall has been an established way of fighting tuberculosis for decades. However, increasing resistances and an outdated medical treatment call for the validation of new targets involved in this crucial pathway. In this regard, the β-ketoacyl ACP synthase KasA is a promising enzyme. In this study, three molecular dynamics simulations based on the wildtype crystal structures of inhibitor bound and unbound KasA were performed in order to investigate the flexibility and conformational space of this target. We present an exhaustive analysis of the binding-site flexibility and representative pocket conformations that may serve as new starting points for structure-based drug design. We also revealed a mechanism which may account for the comparatively low binding affinity of thiolactomycin. Furthermore, we examined the behavior of water molecules within the binding pocket and provide recommendations how to handle them in the drug design process. Finally, we analyzed the dynamics of a channel that accommodates the long-chain fatty acid substrates and, thereby, propose a mechanism of substrate access to this channel and how products are most likely released. PMID:22076471

  19. Clarification on the decarboxylation mechanism in KasA based on the protonation state of key residues in the acyl-enzyme state.

    PubMed

    Lee, Wook; Engels, Bernd

    2013-07-11

    The β-ketoacyl ACP synthase I (KasA) is a promising drug target because it is essential for the survival of Mycobacterium tuberculosis , a causative agent of tuberculosis. It catalyzes a condensation reaction that comprises three steps. The resulting elongated acyl chains are subsequently needed for the cell wall construction. While the mechanism of the first step (acylation of Cys171 in the active site) is straightforward already, the second step (decarboxylation of malonyl substrate) has been controversial due to the difficulty in determining the correct protonation states of the involved residues (His311, His345, Lys340, Glu354). Available experimental data suggest three possible mechanisms which differ considerably. They are not consistent with each other because these studies could not be performed for KasA at the beginning of decarboxylation step (acyl-enzyme state of KasA). Instead, different mutants had to be used which are expected to resemble this situation. In this first computational study about this topic, we use the free energy perturbation (FEP) method to compute the relevant pKa values in the acyl-enzyme state of KasA and use molecular dynamics (MD) simulations to rationalize the results. Subsequent density functional theory (DFT)-based quantum mechanical/molecular mechanical (QM/MM) MD simulations and umbrella samplings have been used to disentangle the close relationships between the protonation states of the involved residues. By these simulations, we can address the preferred protonation states and roles of the residues involved in decarboxylation reaction, thereby suggesting the possible mechanism for the decarboxylation step. PMID:23768199

  20. Structural basis for the recognition of mycolic acid precursors by KasA, a condensing enzyme and drug target from Mycobacterium tuberculosis.

    PubMed

    Schiebel, Johannes; Kapilashrami, Kanishk; Fekete, Agnes; Bommineni, Gopal R; Schaefer, Christin M; Mueller, Martin J; Tonge, Peter J; Kisker, Caroline

    2013-11-22

    The survival of Mycobacterium tuberculosis depends on mycolic acids, very long α-alkyl-β-hydroxy fatty acids comprising 60-90 carbon atoms. However, despite considerable efforts, little is known about how enzymes involved in mycolic acid biosynthesis recognize and bind their hydrophobic fatty acyl substrates. The condensing enzyme KasA is pivotal for the synthesis of very long (C38-42) fatty acids, the precursors of mycolic acids. To probe the mechanism of substrate and inhibitor recognition by KasA, we determined the structure of this protein in complex with a mycobacterial phospholipid and with several thiolactomycin derivatives that were designed as substrate analogs. Our structures provide consecutive snapshots along the reaction coordinate for the enzyme-catalyzed reaction and support an induced fit mechanism in which a wide cavity is established through the concerted opening of three gatekeeping residues and several α-helices. The stepwise characterization of the binding process provides mechanistic insights into the induced fit recognition in this system and serves as an excellent foundation for the development of high affinity KasA inhibitors. PMID:24108128

  1. Structural Basis for the Recognition of Mycolic Acid Precursors by KasA, a Condensing Enzyme and Drug Target from Mycobacterium Tuberculosis *

    PubMed Central

    Schiebel, Johannes; Kapilashrami, Kanishk; Fekete, Agnes; Bommineni, Gopal R.; Schaefer, Christin M.; Mueller, Martin J.; Tonge, Peter J.; Kisker, Caroline

    2013-01-01

    The survival of Mycobacterium tuberculosis depends on mycolic acids, very long α-alkyl-β-hydroxy fatty acids comprising 60–90 carbon atoms. However, despite considerable efforts, little is known about how enzymes involved in mycolic acid biosynthesis recognize and bind their hydrophobic fatty acyl substrates. The condensing enzyme KasA is pivotal for the synthesis of very long (C38–42) fatty acids, the precursors of mycolic acids. To probe the mechanism of substrate and inhibitor recognition by KasA, we determined the structure of this protein in complex with a mycobacterial phospholipid and with several thiolactomycin derivatives that were designed as substrate analogs. Our structures provide consecutive snapshots along the reaction coordinate for the enzyme-catalyzed reaction and support an induced fit mechanism in which a wide cavity is established through the concerted opening of three gatekeeping residues and several α-helices. The stepwise characterization of the binding process provides mechanistic insights into the induced fit recognition in this system and serves as an excellent foundation for the development of high affinity KasA inhibitors. PMID:24108128

  2. pH-Dependent Conformational Changes in Proteins and Their Effect on Experimental pKas: The Case of Nitrophorin 4

    PubMed Central

    Di Russo, Natali V.; Estrin, Dario A.; Martí, Marcelo A.; Roitberg, Adrian E.

    2012-01-01

    The acid-base behavior of amino acids is an important subject of study due to their prominent role in enzyme catalysis, substrate binding and protein structure. Due to interactions with the protein environment, their pKas can be shifted from their solution values and, if a protein has two stable conformations, it is possible for a residue to have different “microscopic”, conformation-dependent pKa values. In those cases, interpretation of experimental measurements of the pKa is complicated by the coupling between pH, protonation state and protein conformation. We explored these issues using Nitrophorin 4 (NP4), a protein that releases NO in a pH sensitive manner. At pH 5.5 NP4 is in a closed conformation where NO is tightly bound, while at pH 7.5 Asp30 becomes deprotonated, causing the conformation to change to an open state from which NO can easily escape. Using constant pH molecular dynamics we found two distinct microscopic Asp30 pKas: 8.5 in the closed structure and 4.3 in the open structure. Using a four-state model, we then related the obtained microscopic values to the experimentally observed “apparent” pKa, obtaining a value of 6.5, in excellent agreement with experimental data. This value must be interpreted as the pH at which the closed to open population transition takes place. More generally, our results show that it is possible to relate microscopic structure dependent pKa values to experimentally observed ensemble dependent apparent pKas and that the insight gained in the relatively simple case of NP4 can be useful in several more complex cases involving a pH dependent transition, of great biochemical interest. PMID:23133364

  3. Thiolactomycin-based β-ketoacyl-AcpM synthase A (KasA) inhibitors: fragment-based inhibitor discovery using transient one-dimensional nuclear overhauser effect NMR spectroscopy.

    PubMed

    Kapilashrami, Kanishk; Bommineni, Gopal R; Machutta, Carl A; Kim, Pilho; Lai, Cheng-Tsung; Simmerling, Carlos; Picart, Francis; Tonge, Peter J

    2013-03-01

    Thiolactomycin (TLM) is a natural product inhibitor of KasA, the β-ketoacyl synthase A from Mycobacterium tuberculosis. To improve the affinity of TLM for KasA, a series of TLM analogs have been synthesized based on interligand NOEs between TLM and a pantetheine analog when both are bound simultaneously to the enzyme. Kinetic binding data reveal that position 3 of the thiolactone ring is a suitable position for elaboration of the TLM scaffold, and the structure-activity relationship studies provide information on the molecular features that govern time-dependent inhibition in this enzyme system. These experiments also exemplify the utility of transient one-dimensional NOE spectroscopy for obtaining interligand NOEs compared with traditional steady state two-dimensional NOESY spectroscopy. PMID:23306195

  4. [The characteristics of the sensitivity of Mycobacterium tuberculosis to rifampicin and isoniazid through determination of mutations in the genes rpoB, katG, inhA, oxyR, and kasA by different molecular biological assays].

    PubMed

    Skotnikova, O I; Galkina, K Iu; Nosova, E Iu; Krasnova, M A; Moroz, A M

    2005-01-01

    Two hundred and two patients with different forms of pulmonary tuberculosis were examined to study the characteristics of sensitivity with the signs of multidrug resistance to rifampicin and isoniazid, by using a microbiological assay of the absolute concentrations and determining mutations in the genes rpoB, katG, inhA, oxyR, and kasA, by employing different molecular biological assays. Mycobacterium tuberculosis (MBT) DNA was isolated from both a diagnostic material (such as sputum, bronchial secretion), and clinical MBT isolates. By showing a higher sensitivity and a higher specificity, as cultural techniques, molecular biological assays of MBT drug sensitivity in patients with tuberculosis were ascertained to accelerate its diagnosis until the patient was admitted to a clinic. PMID:16209020

  5. Normal incidence collector for LPP sources with integrated debris mitigation

    NASA Astrophysics Data System (ADS)

    Giovannini, Andrea Z.; Dieterich, Franz; Henderson, Ian; Chokani, Ndaona; Abhari, Reza S.

    2010-04-01

    The leading candidate for the manufacture of next generation semi-conductor devices is extreme ultraviolet lithography, with laser-produced plasmas as a candidate 13.5nm light source. A primary challenge for continuous operation is elimination of the debris load on the collector, without compromising the radiation intensity at the intermediate focus. A novel combination of thermal management and debris mitigation is developed in order to reduce the deformation and degradation of collector optics. This patent-pending novel debris mitigation technique enables the continuous operation of the source. The paper shows atomic force microscope measurements of the collector surface deposition. The debris mitigation system run at 50% design operating condition gives 90% debris mitigation effectiveness. The average temperature of the cooled collector is 36.5°C at the design point, with a peak-to-peak difference of 0.8°C. The collector geometry, after being adapted to compensate the thermal deformation, yields a spot size of 30μm at IF. Computational simulations, using ETH's multi-scale computational tools, complement the presented experimental results.

  6. Lean, Premixed-Prevaporized (LPP) combustor conceptual design study

    NASA Technical Reports Server (NTRS)

    Dickman, R. A.; Dodds, W. J.; Ekstedt, E. E.

    1979-01-01

    Four combustion systems were designed and sized for the energy efficient engine. A fifth combustor was designed for the cycle and envelope of the twin-spool, high bypass ratio, high pressure ratio turbofan engine. Emission levels, combustion performance, life, and reliability assessments were made for these five combustion systems. Results of these design studies indicate that cruise NOx emission can be reduced by the use of lean, premixed-prevaporaized combustion and airflow modulation.

  7. Current Issues in LPP Research and Their Impact on Society

    ERIC Educational Resources Information Center

    Darquennes, Jeroen

    2013-01-01

    After a very broad description of what language policy and planning is about this paper presents an overview of some of the current preoccupations of researchers focusing on language policy and planning as one of the blooming fields of applied linguistics. The current issues in language policy and planning research that are dealt with include…

  8. Development of Solar Powered Feeding Scheme for Wireless Sensor Networks in low Solar Density Conditions / Bezvadu Sensoru Tīklu Elektroapgādes Sistēmas Izstrāde, Kas Izmanto Saules Paneļus Un Darbojas Pazeminātas Saules Radiācijas Apstākļos

    NASA Astrophysics Data System (ADS)

    Kondratjevs, K.; Zabasta, A.; Selmanovs-Pless, V.

    2015-08-01

    In the recent years, there has been significant research focus on the safety and reliability of data harvesting and optimal energy consuming by wireless sensor network nodes. If external electrical power fails, the node needs to be able to send notifications to the utility demanding the use of backup energy strategies. The authors of the research offer an approach that can help to use PV panels as an alternative power source for WSN nodes in particular irradiation conditions. Survey and testing of the main types of PV panels offered on the market in conditions closed to real ones, in which WSN nodes are maintained, have been implemented. Based on the test results, maximum power control module parameters can be calculated in order to achieve the best effectiveness of the power control system for a selected type of PV panel or panel group. The novelty of the research is an approach that includes an original test bed design for PV testing, PV testing method and selection of design and MPP control module parameters, which ensure maximum effectiveness of WSN node power feeding. Pēdējos gados vairāki pētījumi ir veltīti problēmām, kas ir saistītas ar enerģijas patēriņa mazināšanu un efektīvu izmantošanu bezvadu sensoru tīklu mezglos. Kad sensors mezgls ir izsmēlis enerģijas krājumu, tas vairs nefunkcionē un atslēdzas no kopēja tīkla, kas var būtiski ietekmēt visa tīkla veiktspēju. Šī pētījuma mērķis ir izveidot barošanas vadības moduli, lai nodrošinātu stabilu elektroapgādes spriegumu autonomi strādājošiem radio signāla atkārtotājiem, sensoriem vai vārtejām, kas darbojas bezvadu sensoru tīklos. Pētījuma ietvaros izstrādāta metode saules paneļu kvalitatīvai salīdzināšanai starp tehnoloģijām vai savā starpā, izvērtējot to atbilstību mērķa pielietojumam. Izstrādātā metode sniedz iespēju veikt kontrolētus testus pie variējošiem, simulētiem gaismas apstākļiem, ļauj prognozēt enerģijas resursus

  9. Measuring Outcomes of Family-Centered Intervention: Development of the Life Participation for Parents (LPP)

    ERIC Educational Resources Information Center

    Fingerhut, Patricia E.

    2009-01-01

    Raising a child with disabilities impacts the ability of parents to participate in life situations. This paper describes the development of a new instrument, Life Participation for Parents, to measure outcomes of pediatric therapy on parental participation. Items were reviewed by six occupational therapists with experience in pediatrics and…

  10. Atomic processes in the LPP and LA-DPP EUV sources

    NASA Astrophysics Data System (ADS)

    Sasaki, Akira; Nishihara, Katsunobu; Sunahara, Atsushi; Furukawa, Hiroyuki; Nishikawa, Takeshi; Koike, Fumihiro

    2009-03-01

    We investigate characteristic feature of the atomic radiation from tin plasmas, which allow one to obtain high power EUV emission at λ=13.5nm efficiently. We develop a collisional radiative model of tin ions to calculate steady-state and time dependent ion abundance, level population, and coefficients of radiative transfer of the plasma. The model, which is based atomic data calculated using the Hullac code is refined both theoretically and experimentally. Calculation of the spectral emissivity and opacity are carried out over a wide range of plasma density and temperature, and pumping conditions to obtain high conversion efficiency are discussed.

  11. Performance of kilowatt-class laser modules in scaling up laser produced plasma (LPP) EUV source

    NASA Astrophysics Data System (ADS)

    Ellwi, Samir; Comley, Andrew; Hay, Nick; Henderson, Ian; Brownell, Michael

    2005-05-01

    Powerlase has made significant steps forward in developing reliable and cost-effective, kilowatt-class laser modules with short pulse duration and small footprint, for use as EUV drivers. These characteristics in parallel to EUV target requirements are essential for the generation of 115W of in-band EUV power at the intermediate focus. These laser modules can be coupled to the EUV target by using our flexible spatial and temporal multiplexing approach in order to scale up the laser average power on target. The multiplexing method developed by Powerlase is modular and optimised for maximum EUV collection angle. To further this goal we are currently evaluating target materials such as xenon in various phases and forms and also have a programme in place to investigate suitable tin targets.

  12. Distributed Database Kriging for Adaptive Sampling (D2 KAS)

    NASA Astrophysics Data System (ADS)

    Roehm, Dominic; Pavel, Robert S.; Barros, Kipton; Rouet-Leduc, Bertrand; McPherson, Allen L.; Germann, Timothy C.; Junghans, Christoph

    2015-07-01

    We present an adaptive sampling method supplemented by a distributed database and a prediction method for multiscale simulations using the Heterogeneous Multiscale Method. A finite-volume scheme integrates the macro-scale conservation laws for elastodynamics, which are closed by momentum and energy fluxes evaluated at the micro-scale. In the original approach, molecular dynamics (MD) simulations are launched for every macro-scale volume element. Our adaptive sampling scheme replaces a large fraction of costly micro-scale MD simulations with fast table lookup and prediction. The cloud database Redis provides the plain table lookup, and with locality aware hashing we gather input data for our prediction scheme. For the latter we use kriging, which estimates an unknown value and its uncertainty (error) at a specific location in parameter space by using weighted averages of the neighboring points. We find that our adaptive scheme significantly improves simulation performance by a factor of 2.5-25, while retaining high accuracy for various choices of the algorithm parameters.

  13. Distributed database kriging for adaptive sampling (D²KAS)

    DOE PAGESBeta

    Roehm, Dominic; Pavel, Robert S.; Barros, Kipton; Rouet-Leduc, Bertrand; McPherson, Allen L.; Germann, Timothy C.; Junghans, Christoph

    2015-03-18

    We present an adaptive sampling method supplemented by a distributed database and a prediction method for multiscale simulations using the Heterogeneous Multiscale Method. A finite-volume scheme integrates the macro-scale conservation laws for elastodynamics, which are closed by momentum and energy fluxes evaluated at the micro-scale. In the original approach, molecular dynamics (MD) simulations are launched for every macro-scale volume element. Our adaptive sampling scheme replaces a large fraction of costly micro-scale MD simulations with fast table lookup and prediction. The cloud database Redis provides the plain table lookup, and with locality aware hashing we gather input data for our predictionmore » scheme. For the latter we use kriging, which estimates an unknown value and its uncertainty (error) at a specific location in parameter space by using weighted averages of the neighboring points. We find that our adaptive scheme significantly improves simulation performance by a factor of 2.5 to 25, while retaining high accuracy for various choices of the algorithm parameters.« less

  14. Distributed database kriging for adaptive sampling (D²KAS)

    SciTech Connect

    Roehm, Dominic; Pavel, Robert S.; Barros, Kipton; Rouet-Leduc, Bertrand; McPherson, Allen L.; Germann, Timothy C.; Junghans, Christoph

    2015-03-18

    We present an adaptive sampling method supplemented by a distributed database and a prediction method for multiscale simulations using the Heterogeneous Multiscale Method. A finite-volume scheme integrates the macro-scale conservation laws for elastodynamics, which are closed by momentum and energy fluxes evaluated at the micro-scale. In the original approach, molecular dynamics (MD) simulations are launched for every macro-scale volume element. Our adaptive sampling scheme replaces a large fraction of costly micro-scale MD simulations with fast table lookup and prediction. The cloud database Redis provides the plain table lookup, and with locality aware hashing we gather input data for our prediction scheme. For the latter we use kriging, which estimates an unknown value and its uncertainty (error) at a specific location in parameter space by using weighted averages of the neighboring points. We find that our adaptive scheme significantly improves simulation performance by a factor of 2.5 to 25, while retaining high accuracy for various choices of the algorithm parameters.

  15. The Lpp lipoprotein suppresses motility in a biofilm-forming strain of Escherichia coli O157:H7

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In Escherichia coli O157:H7 strain ATCC 43895, a guanine to thymine transversion in a gene involved in fimbrial (curlifiber) synthesis created strain 43895OR. Strain 43895OR produces an abundant extracellular matrix rich in curli fibers and generates dense biofilms on solid surfaces. We investigated...

  16. Legitimate Peripheral Participation (LPP)--The Case for Recognition of Prior Learning Sites and Knowledges in South Africa's Transforming Education System

    ERIC Educational Resources Information Center

    Alexander, G.; Van Wyk, M. M.; Bereng, T.; November, I.

    2010-01-01

    By definition and purpose, education is the development of human capital towards meeting the individual and social needs of learners and their societies. This transdisciplinary collaboration parallels the underpinning principle of Lave and Wenger's Legitimate Peripheral Participation (Lave & Wenger, 1990) to South Africa's post-colonial…

  17. The CsgA and Lpp proteins affect motility and cell invasion in a strain of Escherichia coli O157:H7

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In Escherichia coli O157:H7 strain ATCC 43895, a guanine to thymine transversion in the csgD promoter created strain 43895OR. Strain 43895OR produces an abundant extracellular matrix rich in curli fibers, forms biofilm on solid surfaces, invades cultured epithelial cells, and is more virulent in a m...

  18. Measurements of {Delta}{sigma}{sub L}(pp) and {Delta}{sigma}{sub L}({bar p}p) at 200 GeV/c

    SciTech Connect

    Grosnick, D.P.

    1995-02-01

    A measurement was made at Fermilab of the difference in the total cross sections between states with beam and target polarizations aligned antiparallel and parallel, {Delta}{sigma}{sub L} = {Delta}{sigma}({r_reversible}) - {Delta}{sigma}({R_arrow}), using 200-GeV/c, polarized proton and antiproton beams and a polarized proton target. This measurement explores the spin dependence of particle interactions and the constituent dynamics. A difference in the spin-dependent total cross sections has been observed in previous experiments at lower energies, and this experiment was the first to explore possible spin effects in {Delta}{sigma}{sub L} at much higher energies. The polarized proton beam is produced from parity-nonconserving decays of the {Lambda}{sup 0} hyperon, where protons emitted from these decays have their spins aligned along the direction of their momenta. The {Lambda} hyperons are produced, along with other particles, when unpolarized, 800-GeV/c protons strike a beryllium target. A virtual source of protons is produced at the target from these decays and the proton polarization is correlated to the transverse distance from the target. A beam of polarized antiprotons can be produced in an analogous manner using {bar {Lambda}{sup 0}} decays. The beam transport system goal was to produce no net spin precession and to preserve the correlation between the beam particle polarization and the transverse position at the virtual source. The beam transport used four sets of quadrupole magnets to focus the beam at intermediate and final focal points. An electronic, particle-tagging system was located at the intermediate focus, while the polarized target was near the final focus.

  19. The CsgA and Lpp proteins affect HEp-2 cell invasion, motility, and biofilm formation in a strain of Escherichia coli O157:H7

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In Escherichia coli O157:H7 strain ATCC 43895, a guanine to thymine transversion in the csgD promoter created strain 43895OR. Strain 43895OR produces an abundant extracellular matrix rich in curli fibers, forms biofilm on solid surfaces, invades cultured epithelial cells, and is more virulent in mic...

  20. Materials Data on KAs4IO6 (SG:191) by Materials Project

    DOE Data Explorer

    Kristin Persson

    2014-11-02

    Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

  1. Materials Data on KAsOF4 (SG:14) by Materials Project

    DOE Data Explorer

    Kristin Persson

    2016-02-04

    Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

  2. Materials Data on KAsSe2 (SG:9) by Materials Project

    SciTech Connect

    Kristin Persson

    2014-11-02

    Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

  3. Materials Data on KAsF6 (SG:148) by Materials Project

    SciTech Connect

    Kristin Persson

    2014-11-02

    Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

  4. MCCE analysis of the pKas of introduced buried acids and bases in staphylococcal nuclease.

    PubMed

    Gunner, M R; Zhu, Xuyu; Klein, Max C

    2011-12-01

    The pK(a)s of 96 acids and bases introduced into buried sites in the staphylococcal nuclease protein (SNase) were calculated using the multiconformation continuum electrostatics (MCCE) program and the results compared with experimental values. The pK(a)s are obtained by Monte Carlo sampling of coupled side chain protonation and position as a function of pH. The dependence of the results on the protein dielectric constant (ε(prot)) in the continuum electrostatics analysis and on the Lennard-Jones non-electrostatics parameters was evaluated. The pK(a)s of the introduced residues have a clear dependence on ε(prot,) whereas native ionizable residues do not. The native residues have electrostatic interactions with other residues in the protein favoring ionization, which are larger than the desolvation penalty favoring the neutral state. Increasing ε(prot) scales both terms, which for these residues leads to small changes in pK(a). The introduced residues have a larger desolvation penalty and negligible interactions with residues in the protein. For these residues, changing ε(prot) has a large influence on the calculated pK(a). An ε(prot) of 8-10 and a Lennard-Jones scaling of 0.25 is best here. The X-ray crystal structures of the mutated proteins are found to provide somewhat better results than calculations carried out on mutations made in silico. Initial relaxation of the in silico mutations by Gromacs and extensive side chain rotamer sampling within MCCE can significantly improve the match with experiment. PMID:21910138

  5. AIRID: an application of the KAS/Prospector expert system builder to airplane identification

    SciTech Connect

    Aldridge, J.P.

    1984-01-01

    The Knowledge Acquisition System/Prospector expert system building tool developed by SRI, International, has been used to construct an expert system to identify aircraft on the basis of observables such as wing shape, engine number/location, fuselage shape, and tail assembly shape. Additional detailed features are allowed to influence the identification as other favorable features. Constraints on the observations imposed by bad weather and distant observations have been included as contexts to the models. Models for Soviet and US fighter aircraft have been included. Inclusion of other types of aircraft such as bombers, transports, and reconnaissance craft is straightforward. Two models permit exploration of the interaction of semantic and taxonomic networks with the models. A full set of text data for fluid communication with the user has been included. The use of demons as triggered output responses to enhance utility to the user has been explored. This paper presents discussion of the ease of building the expert system using this powerful tool and problems encountered in the construction process.

  6. Targeted disruption of the mouse Lipoma Preferred Partner gene

    SciTech Connect

    Vervenne, Hilke B.V.K.; Crombez, Koen R.M.O.; Delvaux, Els L.; Janssens, Veerle; Ven, Wim J.M. van de Petit, Marleen M.R.

    2009-02-06

    LPP (Lipoma Preferred Partner) is a zyxin-related cell adhesion protein that is involved in the regulation of cell migration. We generated mice with a targeted disruption of the Lpp gene and analysed the importance of Lpp for embryonic development and adult functions. Aberrant Mendelian inheritance in heterozygous crosses suggested partial embryonic lethality of Lpp{sup -/-} females. Fertility of Lpp{sup -/-} males was proven to be normal, however, females from Lpp{sup -/-} x Lpp{sup -/-} crosses produced a strongly reduced number of offspring, probably due to a combination of female embryonic lethality and aberrant pregnancies. Apart from these developmental and reproductive abnormalities, Lpp{sup -/-} mice that were born reached adulthood without displaying any additional macroscopic defects. On the other hand, Lpp{sup -/-} mouse embryonic fibroblasts exhibited reduced migration capacity, reduced viability, and reduced expression of some Lpp interaction partners. Finally, we discovered a short nuclear form of Lpp, expressed mainly in testis via an alternative promoter.

  7. Simulating electrostatic energies in proteins: perspectives and some recent studies of pKas, redox, and other crucial functional properties.

    PubMed

    Warshel, Arieh; Dryga, Anatoly

    2011-12-01

    Electrostatic energies provide what is arguably the most effective tool for structure-function correlation of biological molecules. Here, we provide an overview of the current state-of-the-art simulations of electrostatic energies in macromolecules, emphasizing the microscopic perspective but also relating it to macroscopic approaches. We comment on the convergence issue and other problems of the microscopic models and the ways of keeping the microscopic physics while moving to semi-macroscopic directions. We discuss the nature of the protein dielectric "constants" reiterating our long-standing point that the dielectric "constants" in semi-macroscopic models depend on the definition and the specific treatment. The advances and the challenges in the field are illustrated considering different functional properties including pK(a)'s, redox potentials, ion and proton channels, enzyme catalysis, ligand binding, and protein stability. We emphasize the microscopic overcharging approach for studying pK(a) 's of internal groups in proteins and give a demonstration of power of this approach. We also emphasize recent advances in coarse grained models with a physically based electrostatic treatment and provide some examples including further directions in treating voltage activated ion channels. PMID:21910139

  8. Escherichia coli lipoprotein binds human plasminogen via an intramolecular domain

    PubMed Central

    Gonzalez, Tammy; Gaultney, Robert A.; Floden, Angela M.; Brissette, Catherine A.

    2015-01-01

    Escherichia coli lipoprotein (Lpp) is a major cellular component that exists in two distinct states, bound-form and free-form. Bound-form Lpp is known to interact with the periplasmic bacterial cell wall, while free-form Lpp is localized to the bacterial cell surface. A function for surface-exposed Lpp has yet to be determined. We hypothesized that the presence of C-terminal lysinses in the surface-exposed region of Lpp would facilitate binding to the host zymogen plasminogen (Plg), a protease commandeered by a number of clinically important bacteria. Recombinant Lpp was synthesized and the binding of Lpp to Plg, the effect of various inhibitors on this binding, and the effects of various mutations of Lpp on Lpp–Plg interactions were examined. Additionally, the ability of Lpp-bound Plg to be converted to active plasmin was analyzed. We determined that Lpp binds Plg via an atypical domain located near the center of mature Lpp that may not be exposed on the surface of intact E. coli according to the current localization model. Finally, we found that Plg bound by Lpp can be converted to active plasmin. While the consequences of Lpp binding Plg are unclear, these results prompt further investigation of the ability of surface exposed Lpp to interact with host molecules such as extracellular matrix components and complement regulators, and the role of these interactions in infections caused by E. coli and other bacteria. PMID:26500634

  9. DNA sequencing and transcriptional analysis of the kasugamycin biosynthetic gene cluster from Streptomyces kasugaensis M338-M1.

    PubMed

    Ikeno, Souichi; Aoki, Daisuke; Hamada, Masa; Hori, Makoto; Tsuchiya, Kayoko S

    2006-01-01

    Streptomyces kasugaensis M338-M1 produces the aminoglycoside antibiotic kasugamycin (KSM). We previously cloned, sequenced and characterized the KSM acetyltransferase, transporter, and some of the biosynthetic genes from this strain. To identify other potential genes in a chromosome walk experiment, a 6.8-kb EcoRI-PstI region immediately downstream from the KSM transporter genes was sequenced. Five open reading frames (designated as kasN, kasO, kasP, kasQ, kasR) and the 5' region of kasA were found in this region. The genes are apparently co-transcribed as bicistrons, all of which are co-directional except for the kasPQ transcript. Homology analysis of the deduced products of kasN, kasP, kasQ and kasR revealed similarities with known enzymes: KasN, D-amino acid oxidase from Pseudomonas aeruginosa (35% identity); KasP, F420-dependent H4MPT reductase from Streptomyces lavendulae (33% identity); KasQ, UDP-N-acetylglucosamine 2-epimerase from Streptomyces verticillus (45% identity); and KasR, NDP-hexose 3,4-dehydratase from Streptomyces cyanogenus (38% identity); respectively. A gel retardation assay showed that KasT, a putative pathway-specific regulator for this gene cluster, bound to the upstream region of kasN and to the intergenic region of kasQ-kasR, suggesting that the expression of these operons is under the control of the regulator protein. PMID:16568715

  10. Ichthyosiform Large Plaque Parapsoriasis: Report of a Rare Entity

    PubMed Central

    Nag, Falguni; Ghosh, Arghyaprasun; Biswas, Projna; Chatterjee, Gobinda; Biswas, Saugato

    2013-01-01

    Large plaque parapsoriasis (LPP) is an idiopathic, chronic scaly dermatosis classified within parapsoriasis group of diseases, occurring commonly in middle aged patients of all races and geographic regions. LPP and its variants are closely related to the patch stage of mycosis fungoides. The two types of LPP mostly described are the poikilodermatous and retiform parapsoriasis. We are reporting an ichthyosiform LPP for its rarity. PMID:24082186

  11. High-Tc Nodeless s±-wave Superconductivity in (Y,La)FeAsO1-y with Tc=50K:As75-NMR Study

    NASA Astrophysics Data System (ADS)

    Mukuda, H.; Furukawa, S.; Kinouchi, H.; Yashima, M.; Kitaoka, Y.; Shirage, P. M.; Eisaki, H.; Iyo, A.

    2012-10-01

    We report on an As75-NMR study on the Fe-pnictide high-Tc superconductor Y0.95La0.05FeAsO1-y (Y0.95La0.051111) with Tc=50K that includes no magnetic rare-earth elements. The measurement of the nuclear-spin lattice-relaxation rate (751/T1) has revealed that the nodeless bulk superconductivity takes place at Tc=50K while antiferromagnetic spin fluctuations develop moderately in the normal state. These features are consistently described by the multiple fully gapped s±-wave model based on the Fermi-surface nesting. Incorporating the theory based on band calculations, we propose that the reason that Tc=50K in Y0.95La0.051111 is larger than Tc=28K in La1111 is that the Fermi-surface multiplicity is maximized, and hence the Fermi-surface nesting condition is better than that in La1111.

  12. RGD Motif of Lipoprotein T, Involved in Adhesion of Mycoplasma conjunctivae to Lamb Synovial Tissue Cells ▿ †

    PubMed Central

    Zimmermann, Liza; Peterhans, Ernst; Frey, Joachim

    2010-01-01

    Lipoprotein T (LppT), a membrane-located 105-kDa lipoprotein of Mycoplasma conjunctivae, the etiological agent of infectious keratoconjunctivitis (IKC) of domestic sheep and wild Caprinae, was characterized. LppT was shown to promote cell attachment to LSM 192 primary lamb joint synovial cells. Adhesion of M. conjunctivae to LSM 192 cells is inhibited by antibodies directed against LppT. The RGD (Arg-Gly-Asp) motif of LppT was found to be a specific site for binding of M. conjunctivae to these eukaryotic host cells. Recombinant LppT fixed to polymethylmethacrylate slides binds LSM 192 cells, whereas LppT lacking the RGD site is deprived of binding capacity to LSM 192, and LppT containing RGE rather than RGD shows reduced binding. Synthetic nonapeptides derived from LppT containing RGD competitively inhibit binding of LSM 192 cells to LppT-coated slides, whereas nonapeptides containing RAD rather than RGD do not inhibit. RGD-containing, LppT-derived nonapeptides are able to directly inhibit binding of M. conjunctivae to LSM 192 cells by competitive inhibition, whereas the analogous nonapeptide containing RAD rather than RGD or the fibronectin-derived RGD hexapeptide has no inhibitory effect. These results reveal LppT as the first candidate of a RGD lectin in Mycoplasma species that is assumed to bind to β integrins. PMID:20494988

  13. Mycolic acid biosynthesis and enzymic characterization of the beta-ketoacyl-ACP synthase A-condensing enzyme from Mycobacterium tuberculosis.

    PubMed

    Kremer, Laurent; Dover, Lynn G; Carrère, Séverine; Nampoothiri, K Madhavan; Lesjean, Sarah; Brown, Alistair K; Brennan, Patrick J; Minnikin, David E; Locht, Camille; Besra, Gurdyal S

    2002-06-01

    Mycolic acids consist of long-chain alpha-alkyl-beta-hydroxy fatty acids that are produced by successive rounds of elongation catalysed by a type II fatty acid synthase (FAS-II). A key feature in the elongation process is the condensation of a two-carbon unit from malonyl-acyl-carrier protein (ACP) to a growing acyl-ACP chain catalysed by a beta-ketoacyl-ACP synthase (Kas). In the present study, we provide evidence that kasA from Mycobacterium tuberculosis encodes an enzyme that elongates in vivo the meromycolate chain, in both Mycobacterium smegmatis and Mycobacterium chelonae. We demonstrate that KasA belongs to the FAS-II system, which utilizes primarily palmitoyl-ACP rather than short-chain acyl-ACP primers. Furthermore, in an in vitro condensing assay using purified recombinant KasA, palmitoyl-AcpM and malonyl-AcpM, KasA was found to express Kas activity. Also, mutated KasA proteins, with mutation of Cys(171), His(311), Lys(340) and His(345) to Ala abrogated the condensation activity of KasA in vitro completely. Finally, purified KasA was highly sensitive to cerulenin, a well-known inhibitor of Kas, which may lead to the development of novel anti-mycobacterial drugs targeting KasA. PMID:12023885

  14. Lipid phosphate phosphatase-1 expression in cancer cells attenuates tumor growth and metastasis in mice[S

    PubMed Central

    Tang, Xiaoyun; Benesch, Matthew G. K.; Dewald, Jay; Zhao, Yuan Y.; Patwardhan, Neeraj; Santos, Webster L.; Curtis, Jonathan M.; McMullen, Todd P. W.; Brindley, David N.

    2014-01-01

    Lipid phosphate phosphatase-1 (LPP1) degrades lysophosphatidate (LPA) and attenuates receptor-mediated signaling. LPP1 expression is low in many cancer cells and tumors compared with normal tissues. It was hypothesized from studies with cultured cells that increasing LPP1 activity would decrease tumor growth and metastasis. This hypothesis has never been tested in vivo. To do this, we inducibly expressed LPP1 or a catalytically inactive mutant in cancer cells. Expressing active LPP1 increased extracellular LPA degradation by 5-fold. It also decreased the stimulation of Ca2+ transients by LPA, a nondephosphorylatable LPA1/2 receptor agonist and a protease-activated receptor-1 peptide. The latter results demonstrate that LPP1 has effects downstream of receptor activation. Decreased Ca2+ mobilization and Rho activation contributed to the effects of LPP1 in attenuating the LPA-induced migration of MDA-MB-231 breast cancer cells and their growth in 3D culture. Increasing LPP1 expression in breast and thyroid cancer cells decreased tumor growth and the metastasis by up to 80% compared with expression of inactive LPP1 or green fluorescent protein in syngeneic and xenograft mouse models. The present work demonstrates for the first time that increasing the LPP1 activity in three lines of aggressive cancer cells decreases their abilities to produce tumors and metastases in mice. PMID:25210149

  15. Lipid phosphate phosphatase-1 expression in cancer cells attenuates tumor growth and metastasis in mice.

    PubMed

    Tang, Xiaoyun; Benesch, Matthew G K; Dewald, Jay; Zhao, Yuan Y; Patwardhan, Neeraj; Santos, Webster L; Curtis, Jonathan M; McMullen, Todd P W; Brindley, David N

    2014-11-01

    Lipid phosphate phosphatase-1 (LPP1) degrades lysophosphatidate (LPA) and attenuates receptor-mediated signaling. LPP1 expression is low in many cancer cells and tumors compared with normal tissues. It was hypothesized from studies with cultured cells that increasing LPP1 activity would decrease tumor growth and metastasis. This hypothesis has never been tested in vivo. To do this, we inducibly expressed LPP1 or a catalytically inactive mutant in cancer cells. Expressing active LPP1 increased extracellular LPA degradation by 5-fold. It also decreased the stimulation of Ca(2+) transients by LPA, a nondephosphorylatable LPA1/2 receptor agonist and a protease-activated receptor-1 peptide. The latter results demonstrate that LPP1 has effects downstream of receptor activation. Decreased Ca(2+) mobilization and Rho activation contributed to the effects of LPP1 in attenuating the LPA-induced migration of MDA-MB-231 breast cancer cells and their growth in 3D culture. Increasing LPP1 expression in breast and thyroid cancer cells decreased tumor growth and the metastasis by up to 80% compared with expression of inactive LPP1 or green fluorescent protein in syngeneic and xenograft mouse models. The present work demonstrates for the first time that increasing the LPP1 activity in three lines of aggressive cancer cells decreases their abilities to produce tumors and metastases in mice. PMID:25210149

  16. Expression of the Serratia marcescens lipoproteins gene in Escherichia coli.

    PubMed Central

    Lee, N; Nakamura, K; Inouye, M

    1981-01-01

    The lipoprotein gene (lpp) of Serratia marcescens was cloned in a lambda phage vector (K. Nakamura and M. Inouye, Proc. Natl. Acad. Sci. U.S.A. 77: 1369-1373, 1980). This lpp gene was recloned in plasmid vectors pBR322 and pSC101. When a lipoprotein-deficient (lpp) mutant of Escherichia coli was transformed with pBR322 carrying the S. marcescens lpp gene, cells became nonleaky for ribonuclease, resistant to ethylenediaminetetraacetic acid, and sensitive to globomycin. The lipoprotein was found exclusively in the outer membrane fraction. These results indicate that the S. marcescens lipoprotein was normally secreted across the cytoplasmic membrane, modified, and assembled in the E. coli outer membrane. The amount of the free-form lipoprotein produced in this system was three times higher than that produced in lpp + C. coli cells, whereas there was no difference in the amount of the bound-form lipoprotein. On the other hand, lpp E. coli cells which harbored pSC101 carrying the S. marcescens lpp gene produced only one-third of the free-form lipoprotein produced in lpp E. coli cells which harbored pSC101 carrying the E. coli lpp gene. One of the major factors causing this difference in efficiency of gene expression between the lpp genes of S. marcescens and E. coli appears to be a deletion mutation at the transcription termination region found in the cloned S. marcescens lpp gene. The functional half-life of the S. marcescens lpp messenger ribonucleic acid in E. coli was found to be found half that of the E. coli lpp messenger ribonucleic acid. Images PMID:7016834

  17. Murine lipid phosphate phosphohydrolase-3 acts as a cell-associated integrin ligand

    SciTech Connect

    Humtsoe, Joseph O.; Bowling, Rodney A.; Feng, Shu; Wary, Kishore K. . E-mail: kwary@ibt.tamhsc.edu

    2005-09-30

    Lipid phosphate phosphohydrolase-3 (LPP3) is a cell surface protein that exhibits ectoenzyme activity. Previously, we identified human LPP3 in a functional assay of angiogenesis and showed that the Arg-Gly-Asp (RGD) motif in the proposed second extracellular domain interacts with a subset of integrins to mediate cell-cell adhesion. In contrast to the RGD domain of human LPP3, murine Lpp3 contains a variant sequence, Arg-Gly-Glu (RGE). Whether the RGE motif of murine Lpp3 mediates cell-cell interaction has not been studied. In this report, we test the hypothesis that the cell adhesion function of the LPP3 protein is conserved across mouse and human. A glutathione S-transferase (GST) fusion protein of the proposed second extracellular loop of the murine Lpp3 sequence (GST-mLpp3-RGE) promoted attachment of cells in a long-term cell adhesion assay. GST-mLpp3-RGE interacted with {alpha}{sub 5}{beta}{sub 1} and {alpha}{sub v}{beta}{sub 3} integrins in a solid-phase ELISA, while a mutant control, GST-hLPP3-RAD, did not. Long-term adhesion of endothelial cells to GST-mLpp3-RGE induced phosphorylation of FAK, SHC, and CAS, whereas adhesion to GST-hLPP3-RAD failed to do so. Upon long-term adhesion both the GST-hLPP3-RGD and GST-mLpp3-RGE substrates bound to the {alpha}{sub 5}{beta}{sub 1} integrin of FRT-{alpha}{sub 5}(+) cells, an interaction that was inhibited by an anti-{alpha}{sub 5} integrin antibody. In addition, a cell aggregation assay showed that the intact mLpp3-RGE protein interacts with {alpha}{sub 5}{beta}{sub 1} and {alpha}{sub v}{beta}{sub 3} integrins expressed by adjacent cells, an interaction that can be blocked by GRGDSP peptides and anti-LPP3-RGD antibodies. These data, together with the known importance of integrins in angiogenesis, provide a mechanism for the function of LPP3 in cell-cell interactions in both human and mouse.

  18. First-principle optimal local pseudopotentials construction via optimized effective potential method

    NASA Astrophysics Data System (ADS)

    Mi, Wenhui; Zhang, Shoutao; Wang, Yanchao; Ma, Yanming; Miao, Maosheng

    2016-04-01

    The local pseudopotential (LPP) is an important component of orbital-free density functional theory, a promising large-scale simulation method that can maintain information on a material's electron state. The LPP is usually extracted from solid-state density functional theory calculations, thereby it is difficult to assess its transferability to cases involving very different chemical environments. Here, we reveal a fundamental relation between the first-principles norm-conserving pseudopotential (NCPP) and the LPP. On the basis of this relationship, we demonstrate that the LPP can be constructed optimally from the NCPP for a large number of elements using the optimized effective potential method. Specially, our method provides a unified scheme for constructing and assessing the LPP within the framework of first-principles pseudopotentials. Our practice reveals that the existence of a valid LPP with high transferability may strongly depend on the element.

  19. Two Cases of Lichen Planus Pigmentosus-inversus Arising from Long-standing Lichen Planus-inversus

    PubMed Central

    Park, Kyung Duck; Chi, Seong Geun; Ko, Hyun Chang; Lee, Seok Jong; Kim, Do Won

    2008-01-01

    Lichen planus pigmentosus-inversus (LPP-inversus) is an extremely rare variant of lichen planus (LP), and only a few cases have been reported. Its course is characterized by exacerbations and remissions, and it is known to be more chronic than classical LP is. We report two cases of LPP-inversus and offer the suggestion that LPP-inversus may originate from LP of flexural areas.

  20. Regulation of cellular diacylglycerol through lipid phosphate phosphatases is required for pathogenesis of the rice blast fungus, Magnaporthe oryzae.

    PubMed

    Sadat, Md Abu; Jeon, Junhyun; Mir, Albely Afifa; Choi, Jaeyoung; Choi, Jaehyuk; Lee, Yong-Hwan

    2014-01-01

    Considering implication of diacylglycerol in both metabolism and signaling pathways, maintaining proper levels of diacylglycerol (DAG) is critical to cellular homeostasis and development. Except the PIP2-PLC mediated pathway, metabolic pathways leading to generation of DAG converge on dephosphorylation of phosphatidic acid catalyzed by lipid phosphate phosphatases. Here we report the role of such enzymes in a model plant pathogenic fungus, Magnaporthe oryzae. We identified five genes encoding putative lipid phosphate phosphatases (MoLPP1 to MoLPP5). Targeted disruption of four genes (except MoLPP4) showed that MoLPP3 and MoLPP5 are required for normal progression of infection-specific development and proliferation within host plants, whereas MoLPP1 and MoLPP2 are indispensable for fungal pathogenicity. Reintroduction of MoLPP3 and MoLPP5 into individual deletion mutants restored all the defects. Furthermore, exogenous addition of saturated DAG not only restored defect in appressorium formation but also complemented reduced virulence in both mutants. Taken together, our data indicate differential roles of lipid phosphate phosphatase genes and requirement of proper regulation of cellular DAGs for fungal development and pathogenesis. PMID:24959955

  1. Oral lichen planus preceding concomitant lichen planopilaris.

    PubMed

    Stoopler, Eric T; Alfaris, Sausan; Alomar, Dalal; Alawi, Faizan

    2016-09-01

    Lichen planus (LP) is an immune-mediated mucocutaneous disorder with a wide array of clinical presentations. Oral lichen planus (OLP) is characterized clinically by striae, desquamation, and/or ulceration. Lichen planopilaris (LPP), a variant of LP, affects the scalp, resulting in perifollicular erythema and scarring of cutaneous surfaces accompanied by hair loss. The association between OLP and LPP has been reported previously with scant information on concomitant or sequential disease presentation. We describe a patient with concomitant OLP and LPP, and to the best of our knowledge, this is the first report on OLP preceding the onset of LPP. PMID:27544399

  2. Platelet-rich plasma as a novel treatment for lichen planopillaris.

    PubMed

    Bolanča, Željana; Goren, Andy; Getaldić-Švarc, Biserka; Vučić, Majda; Šitum, Mirna

    2016-07-01

    Treatment of lichen planopillaris (LPP) remains a significant challenge due to the irreversible damage inflicted on hair follicles combined with the low efficacy of existing treatments. We hypothesized that growth factors released by the use of platelet-rich plasma (PRP) may arrest the development of LPP. To test our hypothesis, we treated an LPP patient that has failed previous treatments with a new PRP regimen. Following PRP treatment and six months follow-up, the patient experienced complete regression of itching and hair shedding. To the best of our knowledge, this is the first report of successful treatment of LPP with a PRP regimen. PMID:26988129

  3. Endothelial lipid phosphate phosphatase-3 deficiency that disrupts the endothelial barrier function is a modifier of cardiovascular development

    PubMed Central

    Chatterjee, Ishita; Baruah, Jugajyoti; Lurie, Erin E.; Wary, Kishore K.

    2016-01-01

    Aims Lipid phosphate phosphatase-3 (LPP3) is expressed at high levels in endothelial cells (ECs). Although LPP3 is known to hydrolyse the phosphate group from lysolipids such as spingosine-1-phosphate and its structural homologues, the function of Lpp3 in ECs is not completely understood. In this study, we investigated how tyrosine-protein kinase receptor (TEK or Tie2) promoter–dependent deletion of Lpp3 alters EC activities. Methods and results Lpp3fl/fl mice were crossed with the tg.Tie2Cre transgenic line. Vasculogenesis occurred normally in embryos with Tie2Cre-mediated deletion of Lpp3 (called Lpp3ECKO), but embryonic lethality occurred in two waves, the first wave between E8.5 and E10.5, while the second between E11.5 and E13.5. Lethality in Lpp3ECKO embryos after E11.5 was accompanied by vascular leakage and haemorrhage, which likely resulted in insufficient cardiovascular development. Analyses of haematoxylin- and eosin-stained heart sections from E11.5 Lpp3ECKO embryos showed insufficient heart growth associated with decreased trabeculation, reduced growth of the compact wall, and absence of cardiac cushions. Staining followed by microscopic analyses of Lpp3ECKO embryos revealed the presence of apoptotic ECs. Furthermore, Lpp3-deficient ECs showed decreased gene expression and protein levels of Cyclin-D1, VE-cadherin, Fibronectin, Klf2, and Klf4. To determine the underlying mechanisms of vascular leakage and barrier disruption, we performed knockdown and rescue experiments in cultured ECs. LPP3 knockdown decreased transendothelial electrical resistance and increased permeability. Re-expression of β-catenin cDNA in LPP3-knockdown ECs partially restored the effect of the LPP3 loss, whereas re-expression of p120ctn cDNA did not. Conclusion These findings demonstrate the essential roles of LPP3 in the maturation of EC barrier integrity and normal cardiovascular development. PMID:27125875

  4. Structure of 3-oxoacyl-(acyl-carrier protein) synthase II from Thermus thermophilus HB8

    PubMed Central

    Bagautdinov, Bagautdin; Ukita, Yoko; Miyano, Masashi; Kunishima, Naoki

    2008-01-01

    The β-ketoacyl-(acyl carrier protein) synthases (β-keto-ACP synthases; KAS) catalyse the addition of two-carbon units to the growing acyl chain during the elongation phase of fatty-acid synthesis. As key regulators of bacterial fatty-acid synthesis, they are promising targets for the development of new antibacterial agents. The crystal structure of 3-oxoacyl-ACP synthase II from Thermus thermophilus HB8 (TtKAS II) has been solved by molecular replacement and refined at 2.0 Å resolution. The crystal is orthorhombic, space group P21212, with unit-cell parameters a = 72.07, b = 185.57, c = 62.52 Å, and contains one homodimer in the asymmetric unit. The subunits adopt the well known α-β-α-β-α thiolase fold that is common to ACP synthases. The structural and sequence similarities of TtKAS II to KAS I and KAS II enzymes of known structure from other sources support the hypothesis of comparable enzymatic activity. The dimeric state of TtKAS II is important to create each fatty-acid-binding pocket. Closer examination of KAS structures reveals that compared with other KAS structures in the apo form, the active site of TtKAS II is more accessible because of the ‘open’ conformation of the Phe396 side chain. PMID:18453702

  5. Structure of 3-oxoacyl-(acyl-carrier protein) synthase II from Thermus thermophilus HB8.

    PubMed

    Bagautdinov, Bagautdin; Ukita, Yoko; Miyano, Masashi; Kunishima, Naoki

    2008-05-01

    The beta-ketoacyl-(acyl carrier protein) synthases (beta-keto-ACP synthases; KAS) catalyse the addition of two-carbon units to the growing acyl chain during the elongation phase of fatty-acid synthesis. As key regulators of bacterial fatty-acid synthesis, they are promising targets for the development of new antibacterial agents. The crystal structure of 3-oxoacyl-ACP synthase II from Thermus thermophilus HB8 (TtKAS II) has been solved by molecular replacement and refined at 2.0 A resolution. The crystal is orthorhombic, space group P2(1)2(1)2, with unit-cell parameters a = 72.07, b = 185.57, c = 62.52 A, and contains one homodimer in the asymmetric unit. The subunits adopt the well known alpha-beta-alpha-beta-alpha thiolase fold that is common to ACP synthases. The structural and sequence similarities of TtKAS II to KAS I and KAS II enzymes of known structure from other sources support the hypothesis of comparable enzymatic activity. The dimeric state of TtKAS II is important to create each fatty-acid-binding pocket. Closer examination of KAS structures reveals that compared with other KAS structures in the apo form, the active site of TtKAS II is more accessible because of the ;open' conformation of the Phe396 side chain. PMID:18453702

  6. Learning Physics through Play in an Augmented Reality Environment

    ERIC Educational Resources Information Center

    Enyedy, Noel; Danish, Joshua A.; Delacruz, Girlie; Kumar, Melissa

    2012-01-01

    The Learning Physics through Play Project (LPP) engaged 6-8-year old students (n = 43) in a series of scientific investigations of Newtonian force and motion including a series of augmented reality activities. We outline the two design principles behind the LPP curriculum: 1) the use of socio-dramatic, embodied play in the form of participatory…

  7. Electrocortical Reactivity to Emotional Faces in Young Children and Associations with Maternal and Paternal Depression

    ERIC Educational Resources Information Center

    Kujawa, Autumn; Hajcak, Greg; Torpey, Dana; Kim, Jiyon; Klein, Daniel N.

    2012-01-01

    Background: The late positive potential (LPP) is an event-related potential component that indexes selective attention toward motivationally salient information and is sensitive to emotional stimuli. Few studies have examined the LPP in children. Depression has been associated with reduced reactivity to negative and positive emotional stimuli,…

  8. Makiguchian Perspectives in Language Policy and Planning

    ERIC Educational Resources Information Center

    Hatano, Kazuma

    2013-01-01

    In this article, the author applies Makiguchi Tsunesaburo's (1871-1944) perspectives to language policy and planning (LPP). One theoretical question in LPP theory is why individuals opt to use particular languages and varieties of languages in certain contexts. The author contends that Makiguchi's theory of value can be used to systematically…

  9. Neural Correlates of Cognitive Reappraisal in Children: An ERP Study

    PubMed Central

    DeCicco, Jennifer M.; Solomon, Beylul; Dennis, Tracy A.

    2011-01-01

    Cognitive emotion regulation strategies, such as reappraising the emotional meaning of events, are linked to positive adjustment and are disrupted in individuals showing emotional distress, like anxiety. The late positive potential (LPP) is sensitive to reappraisal: LPP amplitudes are reduced when unpleasant pictures are reappraised in a positive light, suggesting regulation of negative emotion. However, only one study has examined reappraisal in children using the LPP. The present study examined whether directed reappraisals reduce the LPP in a group of 5- to 7-year-olds, and correlate with individual differences in fear and anxiety. EEG was recorded from 32 typically-developing children via 64 scalp electrodes during a directed reappraisal task. Mothers reported on child anxiety. Fearful behavior was observed. As predicted, LPP amplitudes were larger to unpleasant versus neutral pictures; counter to predictions, the LPP was not sensitive to reappraisal. The degree to which unpleasant versus neutral pictures elicited larger LPPs was correlated with greater anxiety and fear. Results suggest that reappraisal in young children is still developing, but that the LPP is sensitive to individual differences related to fear and anxiety. The utility of the LPP as a measure of cognitive emotion regulation and emotional processing biases in children is discussed. PMID:22163262

  10. Legitimate Peripheral Participation in Communities of Practice: Participation Support Structures for Newcomers in Faculty Student Councils

    ERIC Educational Resources Information Center

    Eberle, Julia; Stegmann, Karsten; Fischer, Frank

    2014-01-01

    Participating in communities of practice (CoPs) is an important way of learning. For newcomers in such communities, the learning process can be described as legitimate peripheral participation (LPP). Although a body of knowledge on LPP has been accumulated from qualitative case studies, mostly focusing on the use of practices, the concrete…

  11. Legitimate Peripheral Participation and Home Education

    ERIC Educational Resources Information Center

    Safran, L.

    2010-01-01

    After a description of home education, Lave and Wenger's (1991) theory of legitimate peripheral participation (LPP) is applied to the situation of home educators who join a neighbourhood home education group, a community of practice. Then, it is argued that the theory of LPP, with suitable modification, can also apply to and illuminate the…

  12. The Language Proficiency Profile-2: Assessment of the Global Communication Skills of Deaf Children across Languages and Modalities of Expression.

    ERIC Educational Resources Information Center

    Bebko, James M.; Calderon, Rosemary; Treder, Robert

    2003-01-01

    Two studies investigated the developmental trends and concurrent validity of the Language Proficiency Profile-2 (LPP-2), a measure of language and communication skills for deaf children. Results indicate that the LPP-2 has good utility not only as a measure of overall language development but also as a predictor of achievement for English language…

  13. Languages and Lives through a Critical Eye: The Case of Estonia

    ERIC Educational Resources Information Center

    Skerrett, Delaney Michael

    2011-01-01

    This article seeks to situate Estonian language use and policy within the emerging field of critical language policy and planning (LPP). Critical LPP draws on poststructuralist theory to deconstruct normalized categories that maintain systems of inequality. It is akin to the queer theory project for gender and sexuality. Since the country regained…

  14. Engineering gas-foamed large porous particles for efficient local delivery of macromolecules to the lung.

    PubMed

    Ungaro, Francesca; Giovino, Concetta; Coletta, Ciro; Sorrentino, Raffaella; Miro, Agnese; Quaglia, Fabiana

    2010-09-11

    Gas-foamed large porous particles (gfLPP) based on poly(lactic-co-glycolic) acid (PLGA) have been recently suggested as potential carriers for pulmonary drug delivery. In this work, we attempt to engineer gfLPP for efficient local delivery of macromolecules in the lungs. Particles were fabricated by the double emulsion-solvent evaporation technique using ammonium bicarbonate as porogen. To improve particle technological properties, two lipid aid excipients, namely dipalmitoylphosphatidylcholine (DPPC) and 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), were tested. Preliminary technological studies performed on unloaded gfLPP showed that the addition of an appropriate amount of NH(4)(HCO(3)), which spontaneously produces CO(2) and NH(3) during solvent evaporation, is essential to achieve a homogeneous population of highly porous particles with optimal aerodynamic properties. Then, the effect of the presence of DPPC or DOTAP upon the properties of gfLPP containing a model hydrophilic macromolecule, rhodamine B isothiocyanate-dextran (Rhod-dex), was assessed. We found that in the case of hydrophilic macromolecules unable to interact with PLGA end-groups, such as Rhod-dex, excipient addition is essential to increase the amount of drug entrapped within gfLPP, being as high as 80% only for DPPC- or DOTAP-engineered gfLPP. Also Rhod-dex release profile from gfLPP was strongly affected by excipient addition in the initial formulation, with lipid-engineered gfLPP allowing for a more prolonged release of Rhod-dex as compared to excipient-free gfLPP. A further modulation of Rhod-dex initial release rate could be achieved when DOTAP was used, likely due to the electrostatic interactions occurring between macromolecule and cationic phospholipid. Conceiving the developed gfLPP for drug inhalation, DPPC- and DOTAP-engineered gfLPP displayed optimal MMAD(exp) values falling within the range 6.1-7.6 microm and very low geometric standard deviations (GSD) varying between 1.2 and

  15. Electrocortical and ocular indices of attention to fearful and neutral faces presented under high and low working memory load.

    PubMed

    MacNamara, Annmarie; Schmidt, Joseph; Zelinsky, Gregory J; Hajcak, Greg

    2012-12-01

    Working memory load reduces the late positive potential (LPP), consistent with the notion that functional activation of the DLPFC attenuates neural indices of sustained attention. Visual attention also modulates the LPP. In the present study, we sought to determine whether working memory load might exert its influence on ERPs by reducing fixations to arousing picture regions. We simultaneously recorded eye-tracking and EEG while participants performed a working memory task interspersed with the presentation of task-irrelevant fearful and neutral faces. As expected, fearful compared to neutral faces elicited larger N170 and LPP amplitudes; in addition, working memory load reduced the N170 and the LPP. Participants made more fixations to arousing regions of neutral faces and faces presented under high working memory load. Therefore, working memory load did not induce avoidance of arousing picture regions and visual attention cannot explain load effects on the N170 and LPP. PMID:22951516

  16. Bioinspired Lotus-like Self-Illuminous Coating.

    PubMed

    Shi, Xiaodi; Dou, Renmei; Ma, Tianze; Liu, Weiyi; Lu, Xihua; Shea, Kenneth J; Song, Yanlin; Jiang, Lei

    2015-08-26

    The sensitivity of long persistent phosphor materials (LPP) to moisture greatly limits their applications especially in humid environments, which cause the hydrolysis of LPP and shorten their lifetime. In this work, a facile, environmentally friendly, and low-cost method was developed to prevent the infiltration of water or moisture to the LPP by doping LPP with SiO2 nanoparticles to form a superhydrophobic coating. The superhydrophobic coating provided a stable environment to the self-illuminous system, which not only can resist the infiltration of water but also can have good self-cleaning property, similar to the lotus leaf effect. This facile method will be very beneficial for expending further application of LPP especially in high humidity. PMID:26238797

  17. Emotional picture processing in children: an ERP study.

    PubMed

    Solomon, Beylul; DeCicco, Jennifer M; Dennis, Tracy A

    2012-01-01

    The late positive potential (LPP) reflects increased attention to emotional versus neutral stimuli in adults. To date, very few studies have examined the LPP in children, and whether it can be used to measure patterns of emotional processing that are related to dispositional mood characteristics, such as temperamental fear and anxiety. To examine this question,39 typically developing 5–7 year olds (M age in months = 75.27, SD = 5.83) passively viewed complex emotional and neutral pictures taken from the International Affective Picture System.Maternal report of temperamental fear and anxiety was obtained and fearful behavior during an emotional challenge was observed. As documented in adults, LPP amplitudes to pleasant and unpleasant stimuli were larger than to neutral stimuli, although some gender differences emerged. Larger LPP amplitude differences between unpleasant and neutral stimuli were associated with greater observed fear. The LPP as a measure of individual differences in emotional processing is discussed. PMID:22163263

  18. Late Positive Potential ERP Responses to Social and Nonsocial Stimuli in Youth with Autism Spectrum Disorder.

    PubMed

    Benning, Stephen D; Kovac, Megan; Campbell, Alana; Miller, Stephanie; Hanna, Eleanor K; Damiano, Cara R; Sabatino-DiCriscio, Antoinette; Turner-Brown, Lauren; Sasson, Noah J; Aaron, Rachel V; Kinard, Jessica; Dichter, Gabriel S

    2016-09-01

    We examined the late positive potential (LPP) event related potential in response to social and nonsocial stimuli from youths 9 to 19 years old with (n = 35) and without (n = 34) ASD. Social stimuli were faces with positive expressions and nonsocial stimuli were related to common restricted interests in ASD (e.g., electronics, vehicles, etc.). The ASD group demonstrated relatively smaller LPP amplitude to social stimuli and relatively larger LPP amplitude to nonsocial stimuli. There were no group differences in subjective ratings of images, and there were no significant correlations between LPP amplitude and ASD symptom severity within the ASD group. LPP results suggest blunted motivational responses to social stimuli and heightened motivational responses to nonsocial stimuli in youth with ASD. PMID:27344337

  19. The Influences of Immigration on Health Information Seeking Behaviors among Korean Americans and Native Koreans

    ERIC Educational Resources Information Center

    Oh, Kyeung Mi; Zhou, Qiuping; Kreps, Gary; Kim, Wonsun

    2014-01-01

    Korean Americans (KAs) have low screening rates for cancer and are often not well informed about their chronic diseases. Reduced access to health-related information is one reason for gaps in knowledge and the widening health disparities among minority populations. However, little research exists about KAs' health information seeking…

  20. A Manifest Anxiety Scale from the MMPI-168

    ERIC Educational Resources Information Center

    King, M. G.; Campbell, I. M.

    1986-01-01

    Describes the KAS scale, a new composite anxiety scale that comprises items on the Minnesota Multiphasic Personality Inventory-168 (MMPI-168), a popular short form of the MMPI. Relevant normative statistics and the KAS scale relationship with other MMPI scales are discussed. (Author/KS)

  1. Cloning and characterization of three Eimeria tenella lipid phosphate phosphatases.

    PubMed

    Guo, Aijiang; Cai, Jianping; Luo, Xuenong; Zhang, Shaohua; Hou, Junling; Li, Hui; Cai, Xuepeng

    2015-01-01

    Although lipid phosphate phosphatases (LPPs) play an important role in cellular signaling in addition to lipid biosynthesis, little is thus far known about parasite LPPs. In this study, we characterized three Eimeria tenella cDNA clones encoding LPP named EtLPP1, EtLPP2 and EtLPP3. Key structural features previously described in LPPs, including the three conserved domains proposed as catalytic sites, a single conserved N-glycosylation site, and putative transmembrane domains were discovered in the three resulting EtLPP amino acid sequences. Expression of His6-tagged EtLPP1, -2, and -3 in HEK293 cells produced immunoreactive proteins with variable molecular sizes, suggesting the presence of multiple forms of each of the three EtLPPs. The two faster-migrating protein bands below each of the three EtLPP proteins were found to be very similar to the porcine 35-kDa LPP enzyme in their molecular size and the extent of their N-glycosylation, suggesting that the three EtLPPs are partially N-glycosylated. Kinetic analyses of the activity of the three enzymes against PA, LPA, C1P and S1P showed that Km values for each of the substrates were (in μM) 284, 46, 28, and 22 for EtLPP1; 369, 179, 237, and 52 for EtLPP2; and 355, 83, and 260 for EtLPP3. However, EtLPP3 showed negligible activity on S1P. These results confirmed that the three EtLPPs have broad substrate specificity. The results also indicated that despite structural similarities, the three EtLPPs may play distinct functions through their different models of substrate preference. Furthermore, particularly high expression levels of the three EtLPP genes were detected in the sporozoite stage of the E. tenella life cycle (p<0.001), suggesting that their encoded proteins might play an important biological function in the sporozoite stage. PMID:25861032

  2. Cloning and Characterization of Three Eimeria tenella Lipid Phosphate Phosphatases

    PubMed Central

    Guo, Aijiang; Cai, Jianping; Luo, Xuenong; Zhang, Shaohua; Hou, Junling; Li, Hui; Cai, Xuepeng

    2015-01-01

    Although lipid phosphate phosphatases (LPPs) play an important role in cellular signaling in addition to lipid biosynthesis, little is thus far known about parasite LPPs. In this study, we characterized three Eimeria tenella cDNA clones encoding LPP named EtLPP1, EtLPP2 and EtLPP3. Key structural features previously described in LPPs, including the three conserved domains proposed as catalytic sites, a single conserved N-glycosylation site, and putative transmembrane domains were discovered in the three resulting EtLPP amino acid sequences. Expression of His6-tagged EtLPP1, -2, and -3 in HEK293 cells produced immunoreactive proteins with variable molecular sizes, suggesting the presence of multiple forms of each of the three EtLPPs. The two faster-migrating protein bands below each of the three EtLPP proteins were found to be very similar to the porcine 35-kDa LPP enzyme in their molecular size and the extent of their N-glycosylation, suggesting that the three EtLPPs are partially N-glycosylated. Kinetic analyses of the activity of the three enzymes against PA, LPA, C1P and S1P showed that Km values for each of the substrates were (in μM) 284, 46, 28, and 22 for EtLPP1; 369, 179, 237, and 52 for EtLPP2; and 355, 83, and 260 for EtLPP3. However, EtLPP3 showed negligible activity on S1P. These results confirmed that the three EtLPPs have broad substrate specificity. The results also indicated that despite structural similarities, the three EtLPPs may play distinct functions through their different models of substrate preference. Furthermore, particularly high expression levels of the three EtLPP genes were detected in the sporozoite stage of the E. tenella life cycle (p<0.001), suggesting that their encoded proteins might play an important biological function in the sporozoite stage. PMID:25861032

  3. Dissociating the Influence of Affective Word Content and Cognitive Processing Demands on the Late Positive Potential.

    PubMed

    Nowparast Rostami, Hadiseh; Ouyang, Guang; Bayer, Mareike; Schacht, Annekathrin; Zhou, Changsong; Sommer, Werner

    2016-01-01

    The late positive potential (LPP) elicited by affective stimuli in the event-related brain potential (ERP) is often assumed to be a member of the P3 family. The present study addresses the relationship of the LPP to the classic P3b in a published data set, using a non-parametric permutation test for topographical comparisons, and residue iteration decomposition to assess the temporal features of the LPP and the P3b by decomposing the ERP into several component clusters according to their latency variability. The experiment orthogonally manipulated arousal and valence of words, which were either read or judged for lexicality. High-arousing and positive valenced words induced a larger LPP than low-arousing and negative valenced words, respectively, and the LDT elicited a larger P3b than reading. The experimental manipulation of arousal, valence, and task yielded main effects without any interactions on ERP amplitude in the LPP/P3b time range. The arousal and valence effects partially differed from the task effect in scalp topography; in addition, whereas the late positive component elicited by affective stimuli, defined as LPP, was stimulus-locked, the late positive component elicited by task demand, defined as P3b, was mainly latency-variable. Therefore LPP and P3b manifest different subcomponents. PMID:26012382

  4. An Event-Related Potential Investigation of Fear Generalization and Intolerance of Uncertainty.

    PubMed

    Nelson, Brady D; Weinberg, Anna; Pawluk, Joe; Gawlowska, Magda; Proudfit, Greg H

    2015-09-01

    Fear generalization is a key process in the development and maintenance of anxiety disorders. Psychobiological investigations of fear generalization have predominantly focused on defensive system activation (e.g., startle reflex), and it is unclear whether aberrant attentional processing contributes to fear generalization. The late positive potential (LPP) is an event-related potential component that indexes sustained attention and elaborative processing of motivationally salient information, and is larger in response to arousing compared to nonarousing stimuli. In the present study 48 participants completed a fear generalization paradigm using electric shocks. The LPP and retrospective risk ratings of shock likelihood were measured in response to the conditioned stimulus (CS+) and multiple generalization stimuli (GS) that varied in perceptual similarity to the CS+. In addition, intolerance of uncertainty (IU) was examined in relation to fear generalization. The LPP was enhanced for the CS+relative to the GS, but the GS did not differ from one another. Thus, overall the LPP did not reflect fear generalization. However, the LPP to the GS differed as a function of IU, such that high Prospective IU was associated with an attenuated LPP to the GS, and this was independent of trait anxiety. Risk ratings tracked fear generalization irrespective of IU. We discuss the potential influence of IU and attentional processing on fear generalization. Overall, the present study supports the LPP as a useful tool for examining individual differences in fear generalization. PMID:26459846

  5. Lichen planopilaris following hair transplantation and face-lift surgery.

    PubMed

    Chiang, Y Z; Tosti, A; Chaudhry, I H; Lyne, L; Farjo, B; Farjo, N; Cadore de Farias, D; Griffiths, C E M; Paus, R; Harries, M J

    2012-03-01

    Cosmetic surgical procedures, including hair transplantation and face-lift surgery, are becoming increasingly popular. However, there is very little information regarding the associated development of dermatological conditions following these procedures. Lichen planopilaris (LPP) is an uncommon inflammatory hair disorder of unknown aetiology that results in permanent alopecia and replacement of hair follicles with scar-like fibrous tissue. Frontal fibrosing alopecia (FFA), a variant of LPP, involves the frontal hairline and shares similar histological findings with those of LPP. We report 10 patients who developed LPP/FFA following cosmetic scalp surgery. Seven patients developed LPP following hair transplantation, and three patients developed FFA following face-lift surgery. In all cases there was no previous history of LPP or FFA. There is currently a lack of evidence to link the procedures of hair transplantation and cosmetic face-lift surgery to LPP and FFA, respectively. This is the first case series to describe this connection and to postulate the possible pathological processes underlying the clinical observation. Explanations include Koebner phenomenon induced by surgical trauma, an autoimmune process targeting an (as yet, unknown) hair follicle antigen liberated during surgery or perhaps a postsurgery proinflammatory milieu inducing hair follicle immune privilege collapse and follicular damage in susceptible individuals. PMID:21985326

  6. Lipid phosphate phosphatase 3 participates in transport carrier formation and protein trafficking in the early secretory pathway.

    PubMed

    Gutiérrez-Martínez, Enric; Fernández-Ulibarri, Inés; Lázaro-Diéguez, Francisco; Johannes, Ludger; Pyne, Susan; Sarri, Elisabet; Egea, Gustavo

    2013-06-15

    The inhibition of phosphatidic acid phosphatase (PAP) activity by propanolol indicates that diacylglycerol (DAG) is required for the formation of transport carriers at the Golgi and for retrograde trafficking to the ER. Here we report that the PAP2 family member lipid phosphate phosphatase 3 (LPP3, also known as PAP2b) localizes in compartments of the secretory pathway from ER export sites to the Golgi complex. The depletion of human LPP3: (i) reduces the number of tubules generated from the ER-Golgi intermediate compartment and the Golgi, with those formed from the Golgi being longer in LPP3-silenced cells than in control cells; (ii) impairs the Rab6-dependent retrograde transport of Shiga toxin subunit B from the Golgi to the ER, but not the anterograde transport of VSV-G or ssDsRed; and (iii) induces a high accumulation of Golgi-associated membrane buds. LPP3 depletion also reduces levels of de novo synthesized DAG and the Golgi-associated DAG contents. Remarkably, overexpression of a catalytically inactive form of LPP3 mimics the effects of LPP3 knockdown on Rab6-dependent retrograde transport. We conclude that LPP3 participates in the formation of retrograde transport carriers at the ER-Golgi interface, where it transitorily cycles, and during its route to the plasma membrane. PMID:23591818

  7. Dynamics of femto- and nanosecond laser ablation plumes investigated using optical emission spectroscopy

    SciTech Connect

    Verhoff, B.; Harilal, S. S.; Freeman, J. R.; Diwakar, P. K.; Hassanein, A.

    2012-11-01

    We investigated the spatial and temporal evolution of temperature and electron density associated with femto- and nanosecond laser-produced plasmas (LPP) from brass under similar laser fluence conditions. For producing plasmas, brass targets were ablated in vacuum employing pulses either from a Ti:Sapphire ultrafast laser (40 fs, 800 nm) or from a Nd:YAG laser (6 ns, 1064 nm). Optical emission spectroscopy is used to infer the density and temperature of the plasmas. The electron density (n{sub e}) was estimated using Stark broadened profiles of isolated lines while the excitation temperature (T{sub exc}) was estimated using the Boltzmann plot method. At similar fluence levels, continuum and ion emission are dominant in ns LPP at early times (<50 ns) followed by atomic emission, while the fs LPP provided an atomic plume throughout its visible emission lifetime. Though both ns and fs laser-plasmas showed similar temperatures ({approx}1 eV), the fs LPP is found to be significantly denser at shorter distances from the target surface as well as at early phases of its evolution compared to ns LPP. Moreover, the spatial extension of the plume emission in the visible region along the target normal is larger for fs LPP in comparison with ns LPP.

  8. Stellar Spectral Classification with Locality Preserving Projections and Support Vector Machine

    NASA Astrophysics Data System (ADS)

    Zhong-bao, Liu

    2016-06-01

    With the help of computer tools and algorithms, automatic stellar spectral classification has become an area of current interest. The process of stellar spectral classification mainly includes two steps: dimension reduction and classification. As a popular dimensionality reduction technique, Principal Component Analysis (PCA) is widely used in stellar spectra classification. Another dimensionality reduction technique, Locality Preserving Projections (LPP) has not been widely used in astronomy. The advantage of LPP is that it can preserve the local structure of the data after dimensionality reduction. In view of this, we investigate how to apply LPP+SVM in classifying the stellar spectral subclasses. In the comparative experiment, the performance of LPP is compared with PCA. The stellar spectral classification process is composed of the following steps. Firstly, PCA and LPP are respectively applied to reduce the dimension of spectra data. Then, Support Vector Machine (SVM) is used to classify the 4 subclasses of K-type and 3 subclasses of F-type spectra from Sloan Digital Sky Survey (SDSS). Lastly, the performance of LPP+SVM is compared with that of PCA+SVM in stellar spectral classification, and we found that LPP does better than PCA.

  9. Functional significance of the emotion-related late positive potential

    PubMed Central

    Brown, Stephen B. R. E.; van Steenbergen, Henk; Band, Guido P. H.; de Rover, Mischa; Nieuwenhuis, Sander

    2012-01-01

    The late positive potential (LPP) is an event-related potential (ERP) component over visual cortical areas that is modulated by the emotional intensity of a stimulus. However, the functional significance of this neural modulation remains elusive. We conducted two experiments in which we studied the relation between LPP amplitude, subsequent perceptual sensitivity to a non-emotional stimulus (Experiment 1) and visual cortical excitability, as reflected by P1/N1 components evoked by this stimulus (Experiment 2). During the LPP modulation elicited by unpleasant stimuli, perceptual sensitivity was not affected. In contrast, we found some evidence for a decreased N1 amplitude during the LPP modulation, a decreased P1 amplitude on trials with a relatively large LPP, and consistent negative (but non-significant) across-subject correlations between the magnitudes of the LPP modulation and corresponding changes in d-prime or P1/N1 amplitude. The results provide preliminary evidence that the LPP reflects a global inhibition of activity in visual cortex, resulting in the selective survival of activity associated with the processing of the emotional stimulus. PMID:22375117

  10. The effect of group training on pregnancy-induced lumbopelvic pain: systematic review and meta-analysis of randomized control trials.

    PubMed

    Fisseha, Berihu; Mishra, Prakash Kumar

    2016-02-01

    Since there is lack of up to date consensus exists as to whether group training is effective in improving lumbopelvic pain (LPP) after pregnancy, a review of the recent evidences is needed. To determine the effect of group exercise training for the management of LPP among pregnant women compared with usual antenatal care. An electronic database search for relevant randomized control trials published in English from 2006 to 2015 was conducted. Articles with outcome measures of self-reported LPP, visual analogue scale and sick leave due to LPP after pregnancy were included. Quality of the included articles was rated using Physiotherapy Evidence Database (PEDro) scale and the pooled effect of self-reported LPP was obtained by Review Manager (RevMan 5) software. Significant effect of group training was detected over usual antenatal care or no treatment with P=0.0035 (95% confidence interval, -0.2348 to -0.0044). The results of this systematic review proposed that group training reduces LPP significantly better than routine antenatal care for pregnant women suffered from LPP. PMID:26933655

  11. PP2A binds to the LIM domains of lipoma-preferred partner through its PR130/B″ subunit to regulate cell adhesion and migration.

    PubMed

    Janssens, Veerle; Zwaenepoel, Karen; Rossé, Carine; Petit, Marleen M R; Goris, Jozef; Parker, Peter J

    2016-04-15

    Here, we identify the LIM protein lipoma-preferred partner (LPP) as a binding partner of a specific protein phosphatase 2A (PP2A) heterotrimer that is characterised by the regulatory PR130/B″α1 subunit (encoded byPPP2R3A). The PR130 subunit interacts with the LIM domains of LPP through a conserved Zn(2+)-finger-like motif in the differentially spliced N-terminus of PR130. Isolated LPP-associated PP2A complexes are catalytically active. PR130 colocalises with LPP at multiple locations within cells, including focal contacts, but is specifically excluded from mature focal adhesions, where LPP is still present. An LPP-PR130 fusion protein only localises to focal adhesions upon deletion of the domain of PR130 that binds to the PP2A catalytic subunit (PP2A/C), suggesting that PR130-LPP complex formation is dynamic and that permanent recruitment of PP2A activity might be unfavourable for focal adhesion maturation. Accordingly, siRNA-mediated knockdown of PR130 increases adhesion of HT1080 fibrosarcoma cells onto collagen I and decreases their migration in scratch wound and Transwell assays. Complex formation with LPP is mandatory for these PR130-PP2A functions, as neither phenotype can be rescued by re-expression of a PR130 mutant that no longer binds to LPP. Our data highlight the importance of specific, locally recruited PP2A complexes in cell adhesion and migration dynamics. PMID:26945059

  12. Analysis of Lean Premixed/Prevaporized Combustion with KIVA-2

    NASA Technical Reports Server (NTRS)

    Deur, J. M.; Kundu, K. P.; Darling, D. D.; Cline, M. C.; Micklow, G. J.; Harper, M. R.; Simons, T. A.

    1994-01-01

    Requirements to reduce the emissions of pollutants from gas turbines used in aircraft propulsion and ground based power generation have led to consideration of lean premixed/prevaporized (LPP) combustion concept. This paper describes some of the LPP flame tube analyses performed at the NASA Research Center with KIVA-2, a well-known multi-dimensional CFD code for problems including sprays, turbulence, and combustion. Modifications to KIVA-2's boundary condition and chemistry treatments have been made to meet the needs of the present study. The study itself focuses on two key aspects of the LPP concept, low emissions and flame stability (including flashback and lean blowoff.

  13. Groups of adjacent contour segments for object detection.

    PubMed

    Ferrari, V; Fevrier, L; Jurie, F; Schmid, C

    2008-01-01

    We present a family of scale-invariant local shape features formed by chains of k connected, roughly straight contour segments (kAS), and their use for object class detection. kAS are able to cleanly encode pure fragments of an object boundary, without including nearby clutter. Moreover, they offer an attractive compromise between information content and repeatability, and encompass a wide variety of local shape structures. We also define a translation and scale invariant descriptor encoding the geometric configuration of the segments within a kAS, making kAS easy to reuse in other frameworks, for example as a replacement or addition to interest points. Software for detecting and describing kAS is released on lear.inrialpes.fr/software. We demonstrate the high performance of kAS within a simple but powerful sliding-window object detection scheme. Through extensive evaluations, involving eight diverse object classes and more than 1400 images, we 1) study the evolution of performance as the degree of feature complexity k varies and determine the best degree; 2) show that kAS substantially outperform interest points for detecting shape-based classes; 3) compare our object detector to the recent, state-of-the-art system by Dalal and Triggs [4]. PMID:18000323

  14. Insights from computational analysis of full-length β-ketoacyl-[ACP] synthase-II cDNA isolated from American and African oil palms

    PubMed Central

    Bhore, Subhash J.; Cha, Thye S.; Amelia, Kassim; Shah, Farida H.

    2014-01-01

    Background: Palm oil derived from fruits (mesocarp) of African oil palm (Elaeis guineensis Jacq. Tenera) and American oil palm (E. oleifera) is important for food industry. Due to high yield, Elaeis guineensis (Tenera) is cultivated on commercial scale, though its oil contains high (~54%) level of saturated fatty acids. The rate-limiting activity of beta-ketoacyl-[ACP] synthase-II (KAS-II) is considered mainly responsible for the high (44%) level of palmitic acid (C16:0) in the oil obtained from E. guineensis. Objective: The objective of this study was to annotate KAS-II cDNA isolated from American and African oil palms. Materials and Methods: The full-length E. oleifera KAS-II (EoKAS-II) cDNA clone was isolated using random method of gene isolation. Whereas, the E. guineensis KAS-II (EgTKAS-II) cDNA was isolated using reverse transcriptase polymerase chain reaction (RT-PCR) technique; and missing ends were obtained by employing 5’and 3’ RACE technique. Results: The results show that EoKAS-II and EgTKAS-II open reading frames (ORFs) are of 1689 and 1721 bp in length, respectively. Further analysis of the both EoKAS-II and EgTKAS-II predicted protein illustrates that they contains conserved domains for ‘KAS-I and II’, ‘elongating’ condensing enzymes, ‘condensing enzymes super-family’, and ‘3-oxoacyl-[ACP] synthase II’. The predicted protein sequences shows 95% similarity with each other. Consecutively, the three active sites (Cys, His, and His) were identified in both proteins. However, difference in positions of two active Histidine (His) residues was noticed. Conclusion: These insights may serve as the foundation in understanding the variable activity of KAS-II in American and African oil palms; and cDNA clones could be useful in the genetic engineering of oil palms. PMID:24678202

  15. Structure of 3-oxoacyl-(acyl-carrier protein) synthase II from Thermus thermophilus HB8

    SciTech Connect

    Bagautdinov, Bagautdin Ukita, Yoko; Miyano, Masashi; Kunishima, Naoki

    2008-05-01

    The crystal structure of 3-oxoacyl-(acyl-carrier protein) synthase II from T. thermophilus HB8 has been determined at 2.0 Å resolution and compared with the structures of β-keto-ACP synthases from other sources. The β-ketoacyl-(acyl carrier protein) synthases (β-keto-ACP synthases; KAS) catalyse the addition of two-carbon units to the growing acyl chain during the elongation phase of fatty-acid synthesis. As key regulators of bacterial fatty-acid synthesis, they are promising targets for the development of new antibacterial agents. The crystal structure of 3-oxoacyl-ACP synthase II from Thermus thermophilus HB8 (TtKAS II) has been solved by molecular replacement and refined at 2.0 Å resolution. The crystal is orthorhombic, space group P2{sub 1}2{sub 1}2, with unit-cell parameters a = 72.07, b = 185.57, c = 62.52 Å, and contains one homodimer in the asymmetric unit. The subunits adopt the well known α-β-α-β-α thiolase fold that is common to ACP synthases. The structural and sequence similarities of TtKAS II to KAS I and KAS II enzymes of known structure from other sources support the hypothesis of comparable enzymatic activity. The dimeric state of TtKAS II is important to create each fatty-acid-binding pocket. Closer examination of KAS structures reveals that compared with other KAS structures in the apo form, the active site of TtKAS II is more accessible because of the ‘open’ conformation of the Phe396 side chain.

  16. Recent advances in targeting the autotaxin-lysophosphatidate-lipid phosphate phosphatase axis in vivo.

    PubMed

    Benesch, Matthew G K; Tang, Xiaoyun; Venkatraman, Ganesh; Bekele, Raie T; Brindley, David N

    2016-07-01

    Extracellular lysophosphatidate (LPA) is a potent bioactive lipid that signals through six G-protein-coupled receptors. This signaling is required for embryogenesis, tissue repair and remodeling processes. LPA is produced from circulating lysophosphatidylcholine by autotaxin (ATX), and is degraded outside cells by a family of three enzymes called the lipid phosphate phosphatases (LPPs). In many pathological conditions, particularly in cancers, LPA concentrations are increased due to high ATX expression and low LPP activity. In cancers, LPA signaling drives tumor growth, angiogenesis, metastasis, resistance to chemotherapy and decreased efficacy of radiotherapy. Hence, targeting the ATX-LPA-LPP axis is an attractive strategy for introducing novel adjuvant therapeutic options. In this review, we will summarize current progress in targeting the ATX-LPA-LPP axis with inhibitors of autotaxin activity, LPA receptor antagonists, LPA monoclonal antibodies, and increasing low LPP expression. Some of these agents are already in clinical trials and have applications beyond cancer, including chronic inflammatory diseases. PMID:27533936

  17. Mechanisms of mindfulness: The dynamics of affective adaptation during open monitoring.

    PubMed

    Uusberg, Helen; Uusberg, Andero; Talpsep, Teri; Paaver, Marika

    2016-07-01

    Mindfulness - the nonjudgmental awareness of the present experience - is thought to facilitate affective adaptation through increased exposure to emotions and faster extinction of habitual responses. To test this framework, the amplification of the Late Positive Potential (LPP) by negative relative to neutral images was analyzed across stimulus repetitions while 37 novices performed an open monitoring mindfulness exercise. Compared to two active control conditions where attention was either diverted to a distracting task or the stimuli were attended without mindfulness instructions, open monitoring enhanced the initial LPP response to negative stimuli, indicating increased emotional exposure. Across successive repetitions, mindfulness reduced and ultimately removed the affective LPP amplification, suggesting extinction of habitual emotional reactions. This effect arose from reduced negative as well enlarged neutral LPPs. Unlike stimuli from control conditions, the images previously viewed with mindfulness instructions did not elicit affective LPP amplification during subsequent re-exposure, suggesting reconsolidation of stimulus meaning. PMID:27211913

  18. Emotional Modulation of the Late Positive Potential during Picture Free Viewing in Older and Young Adults.

    PubMed

    Renfroe, Jenna B; Bradley, Margaret M; Sege, Christopher T; Bowers, Dawn

    2016-01-01

    Hedonic bias during free viewing of novel emotional and neutral scenes was investigated in older adults and college students. A neurophysiological index of emotional picture processing-the amplitude of the centroparietal late positive potential (LPP)-was recorded from the scalp using a dense sensor array while participants (29 older adults; 21 college students) viewed emotionally engaging or mundane natural scenes that varied in specific content. Both students and older adults showed LPP enhancement when viewing affective, compared to neutral, scenes, and there was no difference in LPP amplitude between older individuals and college students when viewing neutral everyday scenes. However, compared to the college students, older individuals showed attenuated LPP amplitude when viewing emotional scenes, regardless of hedonic valence or specific content. Age related differences could be mediated by a reduction in reactive emotional arousal with age, possible mediated by repeated life exposure to emotional stimuli. PMID:27589393

  19. Recent advances in targeting the autotaxin-lysophosphatidate-lipid phosphate phosphatase axis in vivo

    PubMed Central

    Benesch, Matthew G.K.; Tang, Xiaoyun; Venkatraman, Ganesh; Bekele, Raie T.; Brindley, David N.

    2016-01-01

    Abstract Extracellular lysophosphatidate (LPA) is a potent bioactive lipid that signals through six G-protein-coupled receptors. This signaling is required for embryogenesis, tissue repair and remodeling processes. LPA is produced from circulating lysophosphatidylcholine by autotaxin (ATX), and is degraded outside cells by a family of three enzymes called the lipid phosphate phosphatases (LPPs). In many pathological conditions, particularly in cancers, LPA concentrations are increased due to high ATX expression and low LPP activity. In cancers, LPA signaling drives tumor growth, angiogenesis, metastasis, resistance to chemotherapy and decreased efficacy of radiotherapy. Hence, targeting the ATX-LPA-LPP axis is an attractive strategy for introducing novel adjuvant therapeutic options. In this review, we will summarize current progress in targeting the ATX-LPA-LPP axis with inhibitors of autotaxin activity, LPA receptor antagonists, LPA monoclonal antibodies, and increasing low LPP expression. Some of these agents are already in clinical trials and have applications beyond cancer, including chronic inflammatory diseases. PMID:27533936

  20. Synthesis of high efficient Ca{sub 2}SiO{sub 4}:Eu{sup 2+} green emitting phosphor by a liquid phase precursor method

    SciTech Connect

    Luo, Y.Y.; Jo, D.S.; Senthil, K.; Tezuka, S.; Kakihana, M.; Toda, K.; Masaki, T.; Yoon, D.H.

    2012-05-15

    Green emitting Eu{sup 2+}-doped Ca{sub 2}SiO{sub 4} phosphors were synthesized by three different methods (a conventional solid state reaction (SSR) method, a novel liquid phase precursor approach using SiO{sub 2} sol (LPP-SiO{sub 2}(sol)) and water-soluble silicon compound (LPP-WSS)). The obtained phosphors exhibited a broad excitation spectrum ranging from 225 to 450 nm and a strong green emission peak at 502 nm due to the 4f{sup 6}5d{sup 1}{yields}4f{sup 7}({sup 8}S{sub 7/2}) transition of Eu{sup 2+}. The highest luminescent intensity was obtained for the samples fired at 1100 Degree-Sign C. The dependence of luminescence properties on Eu{sup 2+} concentration for the phosphors synthesized using LPP-WSS method was also examined from 0.1 to 5.0 mol% and the maximum emission intensity was observed at 3.0 mol% Eu{sup 2+}. A detailed analysis using various characterizations revealed that phosphors produced by the LPP-WSS process exhibited more homogenous phase distribution and higher luminescence intensity than those from the other two processes, which suggested the potential application of Ca{sub 2}SiO{sub 4}:Eu{sup 2+} in white light-emitting diodes and fluorescence lamps. - Graphical abstract: The synthesis of Eu{sup 2+} doped Ca{sub 2}SiO{sub 4} green emitting phosphors were carried out using LPP-SiO{sub 2}(sol), LPP-WSS and SSR methods. The adequate reaction of starting materials base on solution mixing and cellulose impregnating during LPP-WSS procedure resulted in single crystalline structure as well as fine morphology, and finally determined a superior luminescent intensity. Highlights: Black-Right-Pointing-Pointer Ca{sub 2}SiO{sub 4}:Eu{sup 2+} phosphor was synthesized by three methods (SSR, LPP-SiO{sub 2} and LPP-WSS). Black-Right-Pointing-Pointer Effect of different processes on the property of phosphor was studied. Black-Right-Pointing-Pointer Phosphor produced by LPP-WSS showed better homogenous phase and fluorescent property. Black

  1. Further characterization of a highly attenuated Yersinia pestis CO92 mutant deleted for the genes encoding Braun lipoprotein and plasminogen activator protease in murine alveolar and primary human macrophages.

    PubMed

    van Lier, Christina J; Tiner, Bethany L; Chauhan, Sadhana; Motin, Vladimir L; Fitts, Eric C; Huante, Matthew B; Endsley, Janice J; Ponnusamy, Duraisamy; Sha, Jian; Chopra, Ashok K

    2015-03-01

    We recently characterized the Δlpp Δpla double in-frame deletion mutant of Yersinia pestis CO92 molecularly, biologically, and immunologically. While Braun lipoprotein (Lpp) activates toll-like receptor-2 to initiate an inflammatory cascade, plasminogen activator (Pla) protease facilitates bacterial dissemination in the host. The Δlpp Δpla double mutant was highly attenuated in evoking bubonic and pneumonic plague, was rapidly cleared from mouse organs, and generated humoral and cell-mediated immune responses to provide subsequent protection to mice against a lethal challenge dose of wild-type (WT) CO92. Here, we further characterized the Δlpp Δpla double mutant in two murine macrophage cell lines as well as in primary human monocyte-derived macrophages to gauge its potential as a live-attenuated vaccine candidate. We first demonstrated that the Δpla single and the Δlpp Δpla double mutant were unable to survive efficiently in murine and human macrophages, unlike WT CO92. We observed that the levels of Pla and its associated protease activity were not affected in the Δlpp single mutant, and, likewise, deletion of the pla gene from WT CO92 did not alter Lpp levels. Further, our study revealed that both Lpp and Pla contributed to the intracellular survival of WT CO92 via different mechanisms. Importantly, the ability of the Δlpp Δpla double mutant to be phagocytized by macrophages, to stimulate production of tumor necrosis factor-α and interleukin-6, and to activate the nitric oxide killing pathways of the host cells remained unaltered when compared to the WT CO92-infected macrophages. Finally, macrophages infected with either the WT CO92 or the Δlpp Δpla double mutant were equally efficient in their uptake of zymosan particles as determined by flow cytometric analysis. Overall, our data indicated that although the Δlpp Δpla double mutant of Y. pestis CO92 was highly attenuated, it retained the ability to elicit innate and subsequent acquired immune

  2. Lichen planopilaris is characterized by immune privilege collapse of the hair follicle's epithelial stem cell niche.

    PubMed

    Harries, Matthew J; Meyer, Katja; Chaudhry, Iskander; E Kloepper, Jennifer; Poblet, Enrique; Griffiths, Christopher Em; Paus, Ralf

    2013-10-01

    Lichen planopilaris (LPP) is a chronic inflammatory disease of unknown pathogenesis that leads to permanent hair loss. Whilst destruction of epithelial hair follicle stem cells (eHFSCs) that reside in an immunologically protected niche of the HF epithelium, the bulge, is a likely key event in LPP pathogenesis, this remains to be demonstrated. We have tested the hypotheses that bulge immune privilege (IP) collapse and inflammation-induced eHFSC death are key components in the pathogenesis of LPP. Biopsies of lesional and non-lesional scalp skin from adult LPP patients (n = 42) were analysed by quantitative (immuno)histomorphometry, real-time quantitative polymerase chain reaction (qRT-PCR), laser capture microdissection and microarray analysis, or skin organ culture. At both the protein and transcriptional level, lesional LPP HFs showed evidence for bulge IP collapse (ie increased expression of MHC class I and II, β2microglobulin; reduced TGFβ2 and CD200 expression). This was accompanied by a Th1-biased cytotoxic T cell response (ie increased CD8(+) GranzymeB(+) T cells and CD123(+) plasmacytoid dendritic cells, with increased CXCR3 expression) and increased expression of interferon-inducible chemokines (CXCL9/10/11). Interestingly, lesional LPP eHFSCs showed both increased proliferation and apoptosis in situ. Microarray analysis revealed a loss of eHFSC signatures and increased expression of T cell activation/binding markers in active LPP, while bulge PPARγ transcription was unaltered compared to non-lesional LPP HFs. In organ culture of non-lesional LPP skin, interferon-γ (IFNγ) induced bulge IP collapse. LPP is an excellent model disease for studying and preventing immune destruction of human epithelial stem cells in situ. These novel findings raise the possibility that LPP represents an autoimmune disease in whose pathogenesis IFNγ-induced bulge IP collapse plays an important role. Therapeutically, bulge IP protection/restoration may help to better manage

  3. Influence of Toothbrushing on the Antierosive Effect of Film-Forming Agents.

    PubMed

    Scaramucci, Taís; João-Souza, Samira Helena; Lippert, Frank; Eckert, George J; Aoki, Idalina V; Hara, Anderson T

    2016-01-01

    This study evaluated the influence of toothbrushing on the antierosive effect of solutions containing sodium fluoride (225 ppm/F), stannous chloride (800 ppm/Sn), sodium linear polyphosphate (2%/LPP), and their combinations, and deionized water as negative control (C). Solutions were tested in a 5-day erosion-remineralization-abrasion cycling model, using enamel and dentin specimens (n = 8). Erosion was performed 6 times/day for 5 min, exposure to the test solutions 3 times/day for 2min, and toothbrushing (or not) with toothpaste slurry 2 times/day for 2 min (45 strokes). Surface loss (SL) was determined by noncontact profilometry. Data were analyzed using three-way ANOVA (α = 0.05). Brushing caused more SL than no brushing for enamel (mean ± SD, in micrometers: 52.7 ± 6.6 and 33.0 ± 4.5, respectively), but not for dentin (28.2 ± 1.9 and 26.6 ± 1.8, respectively). For enamel without brushing, F+LPP+Sn showed the lowest SL (23.8 ± 3.4), followed by F+Sn (30.6 ± 4.9) and F+LPP (31.7 ± 1.7), which did not differ from each other. No differences were found between the other groups and C (37.8 ± 2.1). When brushing, F+LPP+Sn exhibited the lowest SL (36.7 ± 2.4), not differing from F+LPP (39.1 ± 1.8). F, F+Sn and LPP+Sn were similar (46.7 ± 2.9, 42.1 ± 2.8 and 45.3 ± 4.6, respectively) and better than C (52.7 ± 4.3). Sn (55.0 ± 2.4) and LPP (51.0 ± 4.3) did not differ from C. For dentin, neither groups differed from C, regardless of brushing. In conclusion, toothbrushing did not affect the antierosive effect of F+Sn, F+LPP and F+LPP+Sn on enamel, although overall it led to more erosion than nonbrushing. F and LPP+Sn showed a protective effect only under brushing conditions, whereas Sn and LPP did not exhibit any protection. For dentin, neither toothbrushing nor the test solutions influenced the development of erosion. PMID:26930495

  4. Allelic variation in the vacuolar TPK1 channel affects its calcium dependence and may impact on stomatal conductance.

    PubMed

    Hartley, Tom N; Maathuis, Frans J M

    2016-01-01

    Natural variation can be exploited to identify allelic variants of proteins. In this study, patch clamp was used to determine transport properties of two AtTPK1 alleles from Landsberg and Kas-2 ecotypes. No difference in conductance or ion selectivity was observed but the Kas version of TPK1 showed different Ca(2+) dependence in its open probability compared to Ler. Leaves from Kas showed lower rates of water loss than those of Ler, in either the absence or presence of ABA, an observation that is consistent with higher TPK1 channel activity at comparable cytoplasmic Ca(2+) concentrations. A model that explains the results is presented. PMID:26765783

  5. Quantitative proteomic analysis of drug-induced changes in mycobacteria.

    PubMed

    Hughes, Minerva A; Silva, Jeffrey C; Geromanos, Scott J; Townsend, Craig A

    2006-01-01

    A new approach for qualitative and quantitative proteomic analysis using capillary liquid chromatography and mass spectrometry to study the protein expression response in mycobacteria following isoniazid treatment is discussed. In keeping with known effects on the fatty acid synthase II pathway, proteins encoded by the kas operon (AcpM, KasA, KasB, Accd6) were significantly overexpressed, as were those involved in iron metabolism and cell division suggesting a complex interplay of metabolic events leading to cell death. PMID:16396495

  6. A Primary Cortical Input to Hippocampus Expresses a Pathway-Specific and Endocannabinoid-Dependent Form of Long-Term Potentiation

    PubMed Central

    Wang, Weisheng; Jia, Yousheng; Pham, Danielle T.; Karsten, Carley A.; Merrill, Collin B.; Gall, Christine M.; Piomelli, Daniele

    2016-01-01

    Abstract The endocannabinoid 2-arachidonoyl-sn-glycerol (2-AG), a key modulator of synaptic transmission in mammalian brain, is produced in dendritic spines and then crosses the synaptic junction to depress neurotransmitter release. Here we report that 2-AG-dependent retrograde signaling also mediates an enduring enhancement of glutamate release, as assessed with independent tests, in the lateral perforant path (LPP), one of two cortical inputs to the granule cells of the dentate gyrus. Induction of this form of long-term potentiation (LTP) involved two types of glutamate receptors, changes in postsynaptic calcium, and the postsynaptic enzyme that synthesizes 2-AG. Stochastic optical reconstruction microscopy confirmed that CB1 cannabinoid receptors are localized presynaptically to LPP terminals, while the inhibition or knockout of the receptors eliminated LPP-LTP. Suppressing the enzyme that degrades 2-AG dramatically enhanced LPP potentiation, while overexpressing it produced the opposite effect. Priming with a CB1 agonist markedly reduced the threshold for LTP. Latrunculin A, which prevents actin polymerization, blocked LPP-LTP when applied extracellularly but had no effect when infused postsynaptically into granule cells, indicating that critical actin remodeling resides in the presynaptic compartment. Importantly, there was no evidence for the LPP form of potentiation in the Schaffer-commissural innervation of field CA1 or in the medial perforant path. Peripheral injections of compounds that block or enhance LPP-LTP had corresponding effects on the formation of long-term memory for cues conveyed to the dentate gyrus by the LPP. Together, these results indicate that the encoding of information carried by a principal hippocampal afferent involves an unusual, regionally differentiated form of plasticity. PMID:27517090

  7. Graphs and matroids weighted in a bounded incline algebra.

    PubMed

    Lu, Ling-Xia; Zhang, Bei

    2014-01-01

    Firstly, for a graph weighted in a bounded incline algebra (or called a dioid), a longest path problem (LPP, for short) is presented, which can be considered the uniform approach to the famous shortest path problem, the widest path problem, and the most reliable path problem. The solutions for LPP and related algorithms are given. Secondly, for a matroid weighted in a linear matroid, the maximum independent set problem is studied. PMID:25126607

  8. Synthesis Process of Copper/Graphene Nanocomposite by the Liquid Phase Plasma Reduction Method.

    PubMed

    Kim, Sang-Chai; Park, Young-Kwon; Chung, Minchul; Ahn, Ho-Geun; Lee, Heon; Jung, Sang-Chul

    2016-02-01

    Liquid phase plasma (LPP) process was applied to the impregnation of copper nanoparticles onto graphene sheet. Approximately 30-50 nm sized tetragonal nanoparticles were dispersed uniformly on the surface of the two-dimensional graphene sheet. The amount of copper nanoparticles precipitated increased with increasing LPP process time. When combined with a subsequent process, the synthesized copper/graphene nanocomposites will be able to high-performance Li-ion batteries effectively. PMID:27433733

  9. A Primary Cortical Input to Hippocampus Expresses a Pathway-Specific and Endocannabinoid-Dependent Form of Long-Term Potentiation.

    PubMed

    Wang, Weisheng; Trieu, Brian H; Palmer, Linda C; Jia, Yousheng; Pham, Danielle T; Jung, Kwang-Mook; Karsten, Carley A; Merrill, Collin B; Mackie, Ken; Gall, Christine M; Piomelli, Daniele; Lynch, Gary

    2016-01-01

    The endocannabinoid 2-arachidonoyl-sn-glycerol (2-AG), a key modulator of synaptic transmission in mammalian brain, is produced in dendritic spines and then crosses the synaptic junction to depress neurotransmitter release. Here we report that 2-AG-dependent retrograde signaling also mediates an enduring enhancement of glutamate release, as assessed with independent tests, in the lateral perforant path (LPP), one of two cortical inputs to the granule cells of the dentate gyrus. Induction of this form of long-term potentiation (LTP) involved two types of glutamate receptors, changes in postsynaptic calcium, and the postsynaptic enzyme that synthesizes 2-AG. Stochastic optical reconstruction microscopy confirmed that CB1 cannabinoid receptors are localized presynaptically to LPP terminals, while the inhibition or knockout of the receptors eliminated LPP-LTP. Suppressing the enzyme that degrades 2-AG dramatically enhanced LPP potentiation, while overexpressing it produced the opposite effect. Priming with a CB1 agonist markedly reduced the threshold for LTP. Latrunculin A, which prevents actin polymerization, blocked LPP-LTP when applied extracellularly but had no effect when infused postsynaptically into granule cells, indicating that critical actin remodeling resides in the presynaptic compartment. Importantly, there was no evidence for the LPP form of potentiation in the Schaffer-commissural innervation of field CA1 or in the medial perforant path. Peripheral injections of compounds that block or enhance LPP-LTP had corresponding effects on the formation of long-term memory for cues conveyed to the dentate gyrus by the LPP. Together, these results indicate that the encoding of information carried by a principal hippocampal afferent involves an unusual, regionally differentiated form of plasticity. PMID:27517090

  10. Preparation and Characterization of Cobalt/Graphene Composites Using Liquid Phase Plasma System.

    PubMed

    Kim, Sang-Chai; Kim, Byung Hoon; Kim, Sun-Jae; Lee, Young-Seak; Kim, Hwan-Gi; Lee, Heon; Park, Sung Hoon; Jung, Sang-Chul

    2015-01-01

    Liquid phase plasma (LPP) method was applied, for the first time, to the impregnation of cabalt nanoparticles onto graphene. Nanoparticles were dispersed uniformly on the surface of the two-dimensional graphene sheet. The electron miocroscopy observation showed approximately 2-7 nm sized spherical nanoparticles deposited on the surface of graphene sheets. The XPS and EDX analyses revealed that both metal Co and CoO were present in the Co/graphene composites synthesized by the LPP method. PMID:26328336

  11. Application of Silver and Silver Oxide Nanoparticles Impregnated on Activated Carbon to the Degradation of Bromate.

    PubMed

    Choi, J S; Lee, H; Park, Y K; Kim, S J; Kim, B J; An, K H; Kim, B H; Jung, S C

    2016-05-01

    Silver and silver oxide nanoparticles were impregnated on the surface of powdered activated carbon (PAC) using a single-step liquid phase plasma (LPP) method. Spherical silver and silver oxide nanoparticles of 20 to 100 nm size were dipersed evenly on the surface of PAC. The impregnated PAC exhibited a higher activity for the decomposition of bromate than bare PAC. The XPS, Raman and EDX analyses showed that the Ag/PAC composites synthesized by the LPP process. PMID:27483780

  12. Randomized trial on the effectiveness of long- and short-term psychotherapy on psychosocial functioning and quality of life during a 5-year follow-up.

    PubMed

    Knekt, Paul; Heinonen, Erkki; Härkäpää, Kristiina; Järvikoski, Aila; Virtala, Esa; Rissanen, Julius; Lindfors, Olavi; Helsinki Psychotherapy Study Group

    2015-09-30

    Knowledge is incomplete on whether long-term psychotherapy is more effective than short-term therapy in treating mood and anxiety disorder, when measured by improvements in psychosocial functioning and life quality. In the Helsinki Psychotherapy Study, 326 outpatients with mood or anxiety disorder were randomized to solution-focused therapy (SFT), short-term psychodynamic psychotherapy (SPP), or long-term psychodynamic psychotherapy (LPP), and followed up for 5 years from the start of treatment. The outcome measures comprised 4 questionnaires on psychosocial functioning, assessing global social functioning (Social Adjustment Scale (SAS-SR), sense of coherence (Sense of Coherence Scale (SOC)), perceived competence (Self-Performance Survey), dispositional optimism (Life Orientation Test (LOT)), and 1 questionnaire assessing quality of life (Life Situation Survey (LSS)). Short-term therapies improved psychosocial functioning and quality of life more than LPP during the first year. The only exceptions were LOT and perceived competence, which did not differ between SPP and LPP. Later in the follow-up, SOC and perceived competence showed significantly more improvement in LPP than in the short-term therapy groups. No direct differences between SFT and SPP were noted. Short-term therapy has consistently more short-term effects on psychosocial functioning and quality of life than LPP, whereas LPP has some additional long-term benefits on psychosocial functioning. PMID:26162657

  13. Leak point pressure at different bladder volumes in stress urinary incontinence in women: Comparison between Valsalva and cough-induced leak point pressure

    PubMed Central

    Seo, Young Ho; Kim, Sun-Ouck; Yu, Ho Song; Kwon, Dongdeuk

    2016-01-01

    Introduction: We compared Valsalva leak point pressure (VLPP) in urodynamically proven stress urinary incontinence (SUI) in women at different bladder volumes; examined the relationship between VLPP and cough-induced leak point pressure (CLPP) compared by incontinence severity; and evaluated the influence of bladder volume on each leak point pressure (LPP). Methods: Women with urodynamically proven SUI who underwent serial VLPP and CLPP measurement at bladder volumes of 150, 200, 250, and 300 mL were included in this study (n=228). LPP determination was repeated two times in each subject after finishing one series of LPP measurement. LPP at different bladder volumes was compared by subjective symptom severity of Stamey grade. Results: Patients mean age was 51.3±7.6 years (range: 40–65 years). Stamey grade I, II, and III was assigned to 68 (29.8%), 102 (44.7%), and 58 (25.4%) patients, respectively. Mean CLPP was higher than VLPP (p=0.002) at every bladder volume. VLPP and CLPP were significantly decreased by the increase of bladder volume (p=0.001). The mean first positive LPPs were significantly lower at higher Stamey grade (p=0.004). Conclusions: LPP is more frequently induced by cough than by the Valsalva maneuver. VLPP and CLPP decreased significantly with bladder filling and those with severe symptoms of SUI are more likely to have low LPP. PMID:26858783

  14. Pediatric Lichen Planopilaris: Clinicopathologic Study of Four New Cases and a Review of the Literature.

    PubMed

    Christensen, Kevin N; Lehman, Julia S; Tollefson, Megha M

    2015-01-01

    Lichen planopilaris (LPP) is a rare form of cicatricial alopecia that has occasionally been reported in children. Because of the limited number of patients reported, little information is available about demographic characteristics, clinical presentation, or treatment options for these patients. A retrospective chart review of LPP cases in patients under 18 years of age from 1976 to 2013 was performed to further define clinicopathologic features of pediatric LPP. Four pediatric LPP patients ages 13 to 16 years were identified (three male, one female). One patient had scalp pruritus and one had other cutaneous findings of lichen planus (LP). Perifollicular scale and scarring were the most common physical examination findings, although changes mimicking those of alopecia areata were observed. Three patients were treated with topical or intralesional steroids. One patient was treated with minocycline. Histopathologic findings included perifollicular interface and perifollicular fibrosis in all cases. There was focal interfollicular interface in two cases and mild dermal mucin in one case. LPP is exceedingly rare in children. It may be misdiagnosed as alopecia areata in children because of the lack of symptoms and other features of LP. There should be a high index of suspicion for LPP in children with alopecia that is unresponsive to standard treatment or who have findings that are atypical for more common childhood alopecias. PMID:26058419

  15. Alterated integrin expression in lichen planopilaris

    PubMed Central

    d'Ovidio, Roberto; Sgarra, Concetta; Conserva, Anna; Angelotti, Umberto Filippo; Erriquez, Roberta; Foti, Caterina

    2007-01-01

    Background Lichen planopilaris (LPP) is an inflammatory disease characterized by a lymphomononuclear infiltrate surrounding the isthmus and infundibulum of the hair follicle of the scalp, that evolves into atrophic/scarring alopecia. In the active phase of the disease hairs are easily plucked with anagen-like hair-roots. In this study we focused on the expression of integrins and basement membrane components of the hair follicle in active LPP lesions. Methods Scalp biopsies were taken in 10 patients with LPP and in 5 normal controls. Using monoclonal antibodies against α3β1 and α6β4 integrins we showed the expression of these integrins and of the basement membrane components of the hair follicle in active LPP lesions and in healthy scalp skin. Results In the LPP involved areas, α3β1 was distributed in a pericellular pattern, the α6 subunit was present with a basolateral distribution while the β4 subunit showed discontinuous expression at the basal pole and occasionally, basolateral staining of the hair follicle. Conclusion: An altered distribution of the integrins in active LPP lesions can explain the phenomenon of easy pulling-out of the hair with a "gelatinous" root-sheath. PMID:17288588

  16. Psychosocial Intervention Is Associated with Altered Emotion Processing: An Event-Related Potential Study in At-Risk Adolescents

    PubMed Central

    Pincham, Hannah L.; Bryce, Donna; Kokorikou, Danae; Fonagy, Peter; Fearon, R. M. Pasco

    2016-01-01

    Emotion processing is vital for healthy adolescent development, and impaired emotional responses are associated with a number of psychiatric disorders. However, it is unclear whether observed differences between psychiatric populations and healthy controls reflect modifiable variations in functioning (and thus could be sensitive to changes resulting from intervention) or stable, non-modifiable, individual differences. The current study therefore investigated whether the Late Positive Potential (LPP; a neural index of emotion processing) can be used as a marker of therapeutic change following psycho-social intervention. At-risk male adolescents who had received less than four months intervention (minimal-intervention, N = 32) or more than nine months intervention (extended-intervention, N = 32) passively viewed emotional images whilst neural activity was recorded using electroencephalography. Significant differences in emotion processing, indicated by the LPP, were found between the two groups: the LPP did not differ according to valence in the minimal-intervention group, whereas the extended-intervention participants showed emotion processing in line with low risk populations (enhanced LPP for unpleasant images versus other images). Further, an inverse relationship between emotional reactivity (measured via the LPP) and antisocial behaviour was observed in minimal-intervention participants only. The data therefore provide preliminary cross-sectional evidence that abnormal neural responses to emotional information may be normalised following psychosocial intervention. Importantly, this study uniquely suggests that, in future randomised control trials, the LPP may be a useful biomarker to measure development and therapeutic change. PMID:26808519

  17. Caspofungin Injection

    MedlinePlus

    (kas'' poe fun' jin) ... hour once a day. The length of your treatment depends on your general health, the type of ... doctor about how you are feeling during your treatment.You should begin to feel better during the ...

  18. 50 CFR Table 14a to Part 679 - Port of Landing Codes 1, Alaska

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Kake 137 KAK Kaltag 310 KAL Kasilof 138 KAS Kenai 139 KEN Kenai River 139 KEN Ketchikan 141 KTN King... report a landing at an Alaska location not currently assigned a location code number, use “Other...

  19. 50 CFR Table 14a to Part 679 - Port of Landing Codes 1, Alaska

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Kake 137 KAK Kaltag 310 KAL Kasilof 138 KAS Kenai 139 KEN Kenai River 139 KEN Ketchikan 141 KTN King... report a landing at an Alaska location not currently assigned a location code number, use “Other...

  20. 50 CFR Table 14a to Part 679 - Port of Landing Codes 1, Alaska

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Kake 137 KAK Kaltag 310 KAL Kasilof 138 KAS Kenai 139 KEN Kenai River 139 KEN Ketchikan 141 KTN King... report a landing at an Alaska location not currently assigned a location code number, use “Other...

  1. 50 CFR Table 14a to Part 679 - Port of Landing Codes 1, Alaska

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Kake 137 KAK Kaltag 310 KAL Kasilof 138 KAS Kenai 139 KEN Kenai River 139 KEN Ketchikan 141 KTN King... report a landing at an Alaska location not currently assigned a location code number, use “Other...

  2. 50 CFR Table 14a to Part 679 - Port of Landing Codes 1, Alaska

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Kake 137 KAK Kaltag 310 KAL Kasilof 138 KAS Kenai 139 KEN Kenai River 139 KEN Ketchikan 141 KTN King... report a landing at an Alaska location not currently assigned a location code number, use “Other...

  3. Early Changes in Kidney Distribution under the New Allocation System.

    PubMed

    Massie, Allan B; Luo, Xun; Lonze, Bonnie E; Desai, Niraj M; Bingaman, Adam W; Cooper, Matthew; Segev, Dorry L

    2016-08-01

    The Kidney Allocation System (KAS), a major change to deceased donor kidney allocation, was implemented in December 2014. Goals of KAS included directing the highest-quality organs to younger/healthier recipients and increasing access to deceased donor kidney transplantation (DDKT) for highly sensitized patients and racial/ethnic minorities. Using national registry data, we compared kidney distribution, DDKT rates for waitlist registrants, and recipient characteristics between January 1, 2013, and December 3, 2014 (pre-KAS) with those between December 4, 2014, and August 31, 2015 (post-KAS). Regional imports increased from 8.8% pre-KAS to 12.5% post-KAS; national imports increased from 12.7% pre-KAS to 19.1% post-KAS (P<0.001). The proportion of recipients >30 years older than their donor decreased from 19.4% to 15.0% (P<0.001). The proportion of recipients with calculated panel-reactive antibody =100 increased from 1.0% to 10.3% (P<0.001). Overall DDKT rate did not change as modeled using exponential regression adjusting for candidate characteristics (P=0.07). However, DDKT rate (incidence rate ratio, 95% confidence interval) increased for black (1.19; 1.13 to 1.25) and Hispanic (1.13; 1.05 to 1.20) candidates and for candidates aged 18-40 (1.47; 1.38 to 1.57), but declined for candidates aged >50 (0.93; 0.87 to 0.98 for aged 51-60 and 0.90; 0.85 to 0.96 for aged >70). Delayed graft function in transplant recipients increased from 24.8% pre-KAS to 29.9% post-KAS (P<0.001). Thus, in the first 9 months under KAS, access to DDKT improved for minorities, younger candidates, and highly sensitized patients, but declined for older candidates. Delayed graft function increased substantially, possibly suggesting poorer long-term outcomes. PMID:26677865

  4. Mutual interaction between high and low stereo-regularity components for crystallization and melting behaviors of polypropylene blend fibers

    NASA Astrophysics Data System (ADS)

    Kawai, Kouya; Kohri, Youhei; Takarada, Wataru; Takebe, Tomoaki; Kanai, Toshitaka; Kikutani, Takeshi

    2016-03-01

    Crystallization and melting behaviors of blend fibers of two types of polypropylene (PP), i.e. high stereo-regularity/high molecular weight PP (HPP) and low stereo-regularity/low molecular weight PP (LPP), was investigated. Blend fibers consisting of various HPP/LPP compositions were prepared through the melt spinning process. Differential scanning calorimetry (DSC), temperature modulated DSC (TMDSC) and wide-angle X-ray diffraction (WAXD) analysis were applied for clarifying the crystallization and melting behaviors of individual components. In the DSC measurement of blend fibers with high LPP composition, continuous endothermic heat was detected between the melting peaks of LPP at around 40 °C and that of HPP at around 160 °C. Such endothermic heat was more distinct for the blend fibers with higher LPP composition indicating that the melting of LPP in the heating process was hindered because of the presence of HPP crystals. On the other hand, heat of crystallization was detected at around 90 °C in the case of blend fibers with LPP content of 30 to 70 wt%, indicating that the crystallization of HPP component was taking place during the heating of as-spun blend fibers in the DSC measurement. Through the TMDSC analysis, re-organization of the crystalline structure through the simultaneous melting and re-crystallization was detected in the cases of HPP and blend fibers, whereas re-crystallization was not detected during the melting of LPP fibers. In the WAXD analysis during the heating of fibers, amount of a-form crystal was almost constant up to the melting in the case of single component HPP fibers, whereas there was a distinct increase of the intensity of crystalline reflections from around 100 °C, right after the melting of LPP in the case of blend fibers. These results suggested that the crystallization of HPP in the spinning process as well as during the conditioning process after spinning was hindered by the presence of LPP.

  5. The influences of immigration on health information seeking behaviors among Korean Americans and Native Koreans.

    PubMed

    Oh, Kyeung Mi; Zhou, Qiuping Pearl; Kreps, Gary; Kim, Wonsun

    2014-04-01

    Korean Americans (KAs) have low screening rates for cancer and are often not well informed about their chronic diseases. Reduced access to health-related information is one reason for gaps in knowledge and the widening health disparities among minority populations. However, little research exists about KAs' health information seeking behaviors. Guided by the Structural Influence Model, this study examines the influence of immigration status on KAs' trust in health information sources and health information seeking behaviors. Cross-sectional surveys were conducted in the Washington, D.C., metropolitan area as well as in the Gwangju metropolitan city in South Korea during 2006-2007. Two hundred and fifty-four KAs and 208 native Koreans who were 40 years of age or older completed the surveys. When comparing native Koreans to KAs, we found KAs were 3 times more likely to trust health information from newspapers or magazines (odds ratio [OR] = 3.13; 95% confidence interval [CI] = 1.49-6.54) and 11 times more likely to read the health sections of newspapers or magazines (OR = 11.35; 95% CI = 3.92-32.91) in multivariate adjusted models. However, they were less likely to look for health information from TV (OR = 0.29; 95% CI = 0.12-0.72) than native Koreans. Our results indicate that immigration status has profound influences on KAs' health information seeking behaviors. Increasing the availability of reliable and valid health information from printed Korean language magazines or newspapers could have a positive influence on increasing awareness and promoting screening behaviors among KAs. PMID:23943681

  6. Retroactive application of the new kidney allocation system to renal transplants performed in the ECD/SCD era.

    PubMed

    Ramanathan, Rajesh; Gupta, Gaurav; Kim, Joohyun; Quinn, Keri; Behnke, Martha; Kang, Le; Sharma, Amit

    2015-12-01

    The kidney allocation system (KAS) aims to improve deceased donor kidney transplant outcomes by matching of donor allografts and kidney recipients using the kidney donor risk index (KDRI) and recipient estimated post-transplant survival (EPTS) indices. In this single-center study, KAS was retroactively applied to 573 adult deceased donor kidney transplants (2004-2012) performed in the extended criteria/standard criteria donor (ECD/SCD) era. Donor KDRI and recipient EPTS were calculated, and transplants were analyzed to identify KAS fits. These were defined as allocation of top 20% allografts to top 20% recipients and bottom 80% allografts to bottom 80% recipients. On retroactive calculation, 70.2% of all transplants fit the KAS. Transplants that fit the KAS had inferior 1- and 5-yr patient survival (95.5% vs. 98.8%, p = 0.048, and 83.4% vs. 91.7%, p = 0.018) and similar 1- and 5-yr graft survival compared to transplants that did not fit the KAS (91.3% vs. 94.1%, p = 0.276, and 72.7% vs. 73.9%, p = 0.561). While EPTS correlated with recipient survival (HR = 2.96, p < 0.001), KDRI correlated with both recipient (HR = 3.56, p < 0.001) and graft survival (HR = 3.23, p < 0.001). Overall, retroactive application of the KAS to transplants performed in the ECD/SCD era did not identify superior patient survival for kidneys allocated in accordance with the KAS. PMID:26436727

  7. A single membrane-bound enzyme catalyzes the conversion of 2,5-diketo-d-gluconate to 4-keto-d-arabonate in d-glucose oxidative fermentation by Gluconobacter oxydans NBRC 3292.

    PubMed

    Tazoe, Masaaki; Oishi, Hiromi; Kobayashi, Setsuko; Hoshino, Tatsuo

    2016-08-01

    4-Keto-d-arabonate synthase (4KAS), which converts 2,5-diketo-d-gluconate (DKGA) to 4-keto-d-arabonate (4KA) in d-glucose oxidative fermentation by some acetic acid bacteria, was solubilized from the Gluconobacter oxydans NBRC 3292 cytoplasmic membrane, and purified in an electrophoretically homogenous state. A single membrane-bound enzyme was found to catalyze the conversion from DKGA to 4KA. The 92-kDa 4KAS was a homodimeric protein not requiring O2 or a cofactor for the conversion, but was stimulated by Mn(2+). N-terminal amino acid sequencing of 4KAS, followed by gene homology search indicated a 1,197-bp open reading frame (ORF), corresponding to the GLS_c04240 locus, GenBank accession No. CP004373, encoding a 398-amino acid protein with a calculated molecular weight of 42,818 Da. An Escherichia coli transformant with the 4kas plasmid exhibited 4KAS activity. Furthermore, overexpressed recombinant 4KAS was purified in an electrophoretically homogenous state and had the same molecular size as the natural enzyme. PMID:27010909

  8. 3-Ketoacyl-acyl carrier protein synthase III from spinach (Spinacia oleracea) is not similar to other condensing enzymes of fatty acid synthase.

    PubMed Central

    Tai, H; Jaworski, J G

    1993-01-01

    A cDNA clone encoding spinach (Spinacia oleracea) 3-ketoacyl-acyl carrier protein synthase III (KAS III), which catalyzes the initial condensing reaction in fatty acid biosynthesis, was isolated. Based on the amino acid sequence of tryptic digests of purified spinach KAS III, degenerate polymerase chain reaction (PCR) primers were designed and used to amplify a 612-bp fragment from first-strand cDNA of spinach leaf RNA. A root cDNA library was probed with the PCR fragment, and a 1920-bp clone was isolated. Its deduced amino acid sequence matched the sequences of the tryptic digests obtained from the purified KAS III. Northern analysis confirmed that it was expressed in both leaf and root. The clone contained a 1218-bp open reading frame coding for 405 amino acids. The identity of the clone was confirmed by expression in Escherichia coli BL 21 as a glutathione S-transferase fusion protein. The deduced amino acid sequence was 48 and 45% identical with the putative KAS III of Porphyra umbilicalis and KAS III of E. coli, respectively. It also had a strong local homology to the plant chalcone synthases but had little homology with other KAS isoforms from plants, bacteria, or animals. PMID:8290632

  9. Expression of ABCB6 is related to resistance to 5-FU, SN-38 and vincristine.

    PubMed

    Minami, Kentaro; Kamijo, Youhei; Nishizawa, Yukihiko; Tabata, Sho; Horikuchi, Fumito; Yamamoto, Masatatsu; Kawahara, Kohich; Shinsato, Yoshinari; Tachiwada, Tokushi; Chen, Zhe-Sheng; Tsujikawa, Kazutake; Nakagawa, Masayuki; Seki, Naohiko; Akiyama, Shin-Ichi; Arima, Kazunari; Takeda, Yasuo; Furukawa, Tatsuhiko

    2014-09-01

    A previously established arsenite-resistant cell line, KAS, is also resistant to a variety of anticancer drugs. In order to understand responsible molecules for the multidrug resistance phenotype of KAS cells, we examined the expressions of ATP-binding cassette (ABC) transporters and found that the ABCB6 and ABCC1/ multidrug resistance protein 1 (ABCC1/MRP1) were increased. ABCC1/MRP1 was not completely responsible for the drug resistance spectrum of KAS cells and several reports have suggested that ABCB6 is related to anticancer drug and metal resistance. We, therefore, established and examined ABCB6-expressing KB cells and ABCB6-knockdown KAS cells. ABCB6 expression enhanced resistance to 5-fluorouracil (5-FU), SN-38 and vincristine (Vcr) but not to arsenite. Conversely, down-regulation of ABCB6 in KAS cells increased the sensitivity of KAS cells to 5-FU, SN-38 and Vcr, but not to arsenite. Our findings suggest that ABCB6 is involved in 5-FU, SN-38 and Vcr resistance. PMID:25202056

  10. The condensing activities of the Mycobacterium tuberculosis type II fatty acid synthase are differentially regulated by phosphorylation.

    PubMed

    Molle, Virginie; Brown, Alistair K; Besra, Gurdyal S; Cozzone, Alain J; Kremer, Laurent

    2006-10-01

    Phosphorylation of proteins by Ser/Thr protein kinases (STPKs) has recently become of major physiological importance because of its possible involvement in virulence of bacterial pathogens. Although Mycobacterium tuberculosis has eleven STPKs, the nature and function of the substrates of these enzymes remain largely unknown. In this work, we have identified for the first time STPK substrates in M. tuberculosis forming part of the type II fatty acid synthase (FAS-II) system involved in mycolic acid biosynthesis: the malonyl-CoA::AcpM transacylase mtFabD, and the beta-ketoacyl AcpM synthases KasA and KasB. All three enzymes were phosphorylated in vitro by different kinases, suggesting a complex network of interactions between STPKs and these substrates. In addition, both KasA and KasB were efficiently phosphorylated in M. bovis BCG each at different sites and could be dephosphorylated by the M. tuberculosis Ser/Thr phosphatase PstP. Enzymatic studies revealed that, whereas phosphorylation decreases the activity of KasA in the elongation process of long chain fatty acids synthesis, this modification enhances that of KasB. Such a differential effect of phosphorylation may represent an unusual mechanism of FAS-II system regulation, allowing pathogenic mycobacteria to produce full-length mycolates, which are required for adaptation and intracellular survival in macrophages. PMID:16873379

  11. Controlling the Emotional Bias: Performance, Late Positive Potentials, and the Effect of Anodal Transcranial Direct Current Stimulation (tDCS)

    PubMed Central

    Faehling, Florian; Plewnia, Christian

    2016-01-01

    Cognitive control of emotional processing is essential for adaptive human behavior. Biased attention toward emotionally salient information is critically linked with affective disorders and is discussed as a promising treatment target. Anodal (activity enhancing) transcranial direct current stimulation (tDCS) has been shown to increase healthy and impaired cognitive control over emotional distraction and is therefore widely used for the investigation and experimental treatment of this disorder. In this study, event-related potential (ERP) were recorded parallel to tDCS to track its online effects. Healthy volunteers (n = 87) performed a delayed working memory paradigm with emotional salient and neutral distractors during stimulation with different intensities (sham, 0.5, 1, 1.5 mA). Measuring the late positive potential (LPP), an ERP that indexes attention allocation, we found that a valence-specific increase of the early portion of the LPP (eLPP, 250–500 ms) was associated with less emotional distraction in the sham group. Of note, stimulation with tDCS exerted an intensity related effect on this correlation. The later part of the LPP (lLPP, 500–1000 ms) was found to be correlated with reaction time, regardless of valence. General effect of tDCS on LPPs and task performance were not observed. These findings demonstrate that ERP recordings parallel to tDCS are feasible to investigate the neuronal underpinnings of stimulation effects on executive functions. Furthermore, they support the notion that the LPP induced by a distractive stimulus during a working memory task mirrors the additional allocation of neuronal resources with a specific sensitivity of the early LPP for highly arousing negative stimuli. Finally, together with the variable magnitude and direction of the emotional bias, the lack of systematic modulations of LPPs and behavior by tDCS further underlines the important influence of the individual brain activity patterns on stimulation effects both on

  12. Effects of the inhaled treatment of liriope radix on an asthmatic mouse model.

    PubMed

    Kim, Ki-Suk; Cho, Dong-Hyuk; Yang, Hea Jung; Choi, Eun-Kyeong; Shin, Min Hee; Kim, Kang-Hoon; Ahn, Kwang Seok; Ha, In Jin; Na, Yun-Cheol; Um, Jae Young; Chung, Won Seok; Jung, Hee-Jae; Jung, Sung-Ki; Jang, Hyeung-Jin

    2015-01-01

    As a treatment for allergic asthma, inhaled treatments such as bronchodilators that contain β2-agonists have an immediate effect, which attenuates airway obstructions and decreases airway hypersensitivity. However, bronchodilators only perform on a one off basis, but not consistently. Asthma is defined as a chronic inflammatory disease of the airways accompanying the overproduction of mucus, airway wall remodeling, bronchial hyperreactivity and airway obstruction. Liriope platyphylla radix extract (LPP), a traditional Korean medicine, has been thoroughly studied and found to be an effective anti-inflammatory medicine. Here, we demonstrate that an inhaled treatment of LPP can attenuate airway hyperresponsiveness (AHR) in an ovalbumin-induced asthmatic mouse model, compared to the saline-treated group (p < 0.01). Moreover, LPP decreases inflammatory cytokine levels, such as eotaxin (p < 0.05), IL-5 (p < 0.05), IL-13 (p < 0.001), RANTES (p < 0.01), and TNF-α (p < 0.05) in the bronchoalveolar lavage (BAL) fluid of asthmatic mice. A histopathological study was carried out to determine the effects of LPP inhalation on mice lung tissue. We performed UPLC/ESI-QTOF-MS, LC/MS, and GC/MS analyses to analyze the chemical constituents of LPP, finding that these are ophiopogonin D, spicatoside A, spicatoside B, benzyl alcohol, and 5-hydroxymethylfurfural. This study demonstrates the effect of an inhaled LPP treatment both on airway AHR and on the inflammatory response in an asthmatic mouse model. Hence, LPP holds significant promise as a nasal inhalant for the treatment of asthmatic airway disease. PMID:25967662

  13. Laser-produced plasma sensor-probe system for in situ molten metal analysis. Final technical report

    SciTech Connect

    Kim, Y.W.

    1997-01-28

    The radically new methodology of in-situ laser-produced plasma (LPP) analysis of molten metals, as developed at Lehigh University, has been implemented into an LPP sensor-probe system, ready for deployment at steelmaking facilities. The system consists of an LPP sensor-probe head, which is immersed into the molten metal bath for the short duration of measurement, a control console, an umbilical cord connecting the above two units, and a support console providing coolants and pneumatic supports to the control console. The Department of Energy funding has supported Phase III-A and -B of the project in a joint sponsorship with AISI, CTU 5-2 Consortium, and Lehigh University. The objectives have been to: (1) implement the molten metal calibration protocol for the LPP analysis methodology; (2) implement the methodology in the form of a second-generation LPP sensor-probe system, which facilitates real-time process control by in-situ determination of elemental composition of molten steel alloys; (3) deploy such developmental systems in steelmaking facilities; (4) upgrade the systems to a third-generation design; and (5) effect technology transfer by selecting a manufacturer of commercial LPP sensor-probe systems. Four of the five objectives have been fully met. The deployment objective has been partially realized at present. The full LPP sensor-probe system has been put through trial immersion runs at a foundry, but its deployment at steelmaking facilities has progressed to a stage where various issues of financial and legal nature are being codified into a formal agreement between a host site and Lehigh University.

  14. Large Porous Particles for Sustained Release of a Decoy Oligonucelotide and Poly(ethylenimine): Potential for Combined Therapy of Chronic Pseudomonas aeruginosa Lung Infections.

    PubMed

    d'Angelo, Ivana; Perfetto, Brunella; Costabile, Gabriella; Ambrosini, Veronica; Caputo, Pina; Miro, Agnese; d'Emmanuele di Villa Bianca, Roberta; Sorrentino, Raffaella; Donnarumma, Giovanna; Quaglia, Fabiana; Ungaro, Francesca

    2016-05-01

    We have recently demonstrated that the specific inhibition of nuclear factor-κB by a decoy oligonucleotide (dec-ODN) delivered through inhalable large porous particles (LPP) made of poly(lactic-co-glycolic acid) (PLGA) may be highly beneficial for long-term treatment of lung inflammation. Nevertheless, besides chronic inflammation, multifunctional systems aimed to control also infection are required in chronic lung diseases, such as cystic fibrosis (CF). In this work, we tested the hypothesis that engineering PLGA-based LPP with branched poly(ethylenimine) (PEI) may improve LPP properties for pulmonary delivery of dec-ODN, with particular regard to the treatment of Pseudomonas aeruginosa lung infections. After getting insight into the role of PEI on the technological properties of PLGA-based LPP for delivery of dec-ODN, the putative synergistic effect of PEI free or PEI released from LPP on in vitro antimicrobial activity of tobramycin (Tb) and aztreonam (AZT) against P. aeruginosa was elucidated. Meanwhile, cytotoxicity studies on A549 cells were carried out. Results clearly demonstrate that the dry powders have promising aerosolization properties and afford a prolonged in vitro release of both dec-ODN and PEI. The encapsulation of PEI into LPP results in a 2-fold reduction of the minimum inhibitory concentration of AZT, while reducing the cytotoxic effect of PEI. Of note, the developed ODN/PLGA/PEI LPP persisted at lung at least for 14 days after intratracheal administration in rats where they can provide sustained and combined release of dec-ODN and PEI. dec-ODN will likely act as an anti-inflammatory drug, while PEI may enhance the therapeutic activity of inhaled antibiotics, which are commonly employed for the treatment of concomitant lung infections. PMID:27002689

  15. Lipid phosphate phosphatase inhibitors locally amplify lysophosphatidic acid LPA1 receptor signalling in rat brain cryosections without affecting global LPA degradation

    PubMed Central

    2012-01-01

    Background Lysophosphatidic acid (LPA) is a signalling phospholipid with multiple biological functions, mainly mediated through specific G protein-coupled receptors. Aberrant LPA signalling is being increasingly implicated in the pathology of common human diseases, such as arteriosclerosis and cancer. The lifetime of the signalling pool of LPA is controlled by the equilibrium between synthesizing and degradative enzymatic activity. In the current study, we have characterized these enzymatic pathways in rat brain by pharmacologically manipulating the enzymatic machinery required for LPA degradation. Results In rat brain cryosections, the lifetime of bioactive LPA was found to be controlled by Mg2+-independent, N-ethylmaleimide-insensitive phosphatase activity, attributed to lipid phosphate phosphatases (LPPs). Pharmacological inhibition of this LPP activity amplified LPA1 receptor signalling, as revealed using functional autoradiography. Although two LPP inhibitors, sodium orthovanadate and propranolol, locally amplified receptor responses, they did not affect global brain LPA phosphatase activity (also attributed to Mg2+-independent, N-ethylmaleimide-insensitive phosphatases), as confirmed by Pi determination and by LC/MS/MS. Interestingly, the phosphate analog, aluminium fluoride (AlFx-) not only irreversibly inhibited LPP activity thereby potentiating LPA1 receptor responses, but also totally prevented LPA degradation, however this latter effect was not essential in order to observe AlFx--dependent potentiation of receptor signalling. Conclusions We conclude that vanadate- and propranolol-sensitive LPP activity locally guards the signalling pool of LPA whereas the majority of brain LPA phosphatase activity is attributed to LPP-like enzymatic activity which, like LPP activity, is sensitive to AlFx- but resistant to the LPP inhibitors, vanadate and propranolol. PMID:22686545

  16. Low-frequency stimulation induces long-term depression and slow onset long-term potentiation at perforant path-dentate gyrus synapses in vivo.

    PubMed

    Gonzalez, Jossina; Morales, Isaiah S; Villarreal, Desiree M; Derrick, Brian E

    2014-03-01

    The expression of homosynaptic long-term depression (LTD) is thought to mediate a crucial role in sustaining memory function. Our in vivo investigations of LTD expression at lateral (LPP) and medial perforant path (MPP) synapses in the dentate gyrus (DG) corroborate prior demonstrations that PP-DG LTD is difficult to induce in intact animals. In freely moving animals, LTD expression occurred inconsistently among LPP-DG and MPP-DG responses. Interestingly, following acute electrode implantation in anesthetized rats, low-frequency stimulation (LFS; 900 pulses, 1 Hz) promotes slow-onset LTP at both MPP-DG and LPP-DG synapses that utilize distinct induction mechanisms. Systemic administration of the N-methyl-d-aspartate (NMDA) receptor antagonist (+/-)-cyclopiperidine-6-piperiperenzine (CPP; 10 mg/kg) 90 min before LFS selectively blocked MPP-DG but not LPP-DG slow onset LTP, suggesting MPP-DG synapses express a NMDA receptor-dependent slow onset LTP whereas LPP-DG slow onset LTP induction is NMDA receptor independent. In experiments where paired-pulse LFS (900 paired pulses, 200-ms paired-pulse interval) was used to induce LTD, paired-pulse LFS of the LPP resulted in rapid onset LTP of DG responses, whereas paired-pulse LFS of the MPP induced slow onset LTP of DG responses. Although LTD observations were very rare following acute electrode implantation in anesthetized rats, LPP-DG LTD was demonstrated in some anesthetized rats with previously implanted electrodes. Together, our data indicate in vivo PP-DG LTD expression is an inconsistent phenomenon that is primarily observed in recovered animals, suggesting perturbation of the dentate through surgery-related tissue trauma influences both LTD incidence and LTP induction at PP-DG synapses in vivo. PMID:24335215

  17. Stratum corneum lipid matrix: Location of acyl ceramide and cholesterol in the unit cell of the long periodicity phase.

    PubMed

    Mojumdar, E H; Gooris, G S; Groen, D; Barlow, D J; Lawrence, M J; Demé, B; Bouwstra, J A

    2016-08-01

    The extracellular lipid matrix in the skin's outermost layer, the stratum corneum, is crucial for the skin barrier. The matrix is composed of ceramides (CERs), cholesterol (CHOL) and free fatty acids (FFAs) and involves two lamellar phases: the short periodicity phase (SPP) and the long periodicity phase (LPP). To understand the skin barrier thoroughly, information about the molecular arrangement in the unit cell of these lamellar phases is paramount. Previously we examined the molecular arrangement in the unit cell of the SPP. Furthermore X-ray and neutron diffraction revealed a trilayer arrangement of lipids within the unit cell of the LPP [D. Groen et al., Biophysical Journal, 97, 2242-2249, 2009]. In the present study, we used neutron diffraction to obtain more details about the location of lipid (sub)classes in the unit cell of the LPP. The diffraction pattern revealed at least 8 diffraction orders of the LPP with a repeating unit of 129.6±0.5Å. To determine the location of lipid sub(classes) in the unit cell, samples were examined with either only protiated lipids or selectively deuterated lipids. The diffraction data obtained by means of D2O/H2O contrast variation together with a gradual replacement of one particular CER, the acyl CER, by its partly deuterated counterpart, were used to construct the scattering length density profiles. The acyl chain of the acyl CER subclass is located at a position of ~21.4±0.2Å from the unit cell centre of the LPP. The position and orientation of CHOL in the LPP unit cell were determined using tail and head-group deuterated forms of the sterol. CHOL is located with its head-group positioned ~26±0.2Å from the unit cell centre. This allows the formation of a hydrogen bond with the ester group of the acyl CER located in close proximity. Based on the positions of the deuterated moieties of the acyl CER, CHOL and the previously determined location of two other lipid subclasses [E.H. Mojumdar et al., Biophysical Journal

  18. Identification and physiological characterization of phosphatidic acid phosphatase enzymes involved in triacylglycerol biosynthesis in Streptomyces coelicolor

    PubMed Central

    2013-01-01

    Background Phosphatidic acid phosphatase (PAP, EC 3.1.3.4) catalyzes the dephosphorylation of phosphatidate yielding diacylglycerol (DAG), the lipid precursor for triacylglycerol (TAG) biosynthesis. Despite the importance of PAP activity in TAG producing bacteria, studies to establish its role in lipid metabolism have been so far restricted only to eukaryotes. Considering the increasing interest of bacterial TAG as a potential source of raw material for biofuel production, we have focused our studies on the identification and physiological characterization of the putative PAP present in the TAG producing bacterium Streptomyces coelicolor. Results We have identified two S. coelicolor genes, named lppα (SCO1102) and lppβ (SCO1753), encoding for functional PAP proteins. Both enzymes mediate, at least in part, the formation of DAG for neutral lipid biosynthesis. Heterologous expression of lppα and lppβ genes in E. coli resulted in enhanced PAP activity in the membrane fractions of the recombinant strains and concomitantly in higher levels of DAG. In addition, the expression of these genes in yeast complemented the temperature-sensitive growth phenotype of the PAP deficient strain GHY58 (dpp1lpp1pah1). In S. coelicolor, disruption of either lppα or lppβ had no effect on TAG accumulation; however, the simultaneous mutation of both genes provoked a drastic reduction in de novo TAG biosynthesis as well as in total TAG content. Consistently, overexpression of Lppα and Lppβ in the wild type strain of S. coelicolor led to a significant increase in TAG production. Conclusions The present study describes the identification of PAP enzymes in bacteria and provides further insights on the genetic basis for prokaryotic oiliness. Furthermore, this finding completes the whole set of enzymes required for de novo TAG biosynthesis pathway in S. coelicolor. Remarkably, the overexpression of these PAPs in Streptomyces bacteria contributes to a higher productivity of this single

  19. The impact of emotional involvement on online service buying decisions: an event-related potentials perspective.

    PubMed

    Zhao, Meina; Wang, Jing; Han, Weiwei

    2015-12-01

    When examining a buying process, changes in human brain signals and their event-related potential (ERP) components can be considered a reflection of the consumers' emotions. In this experiment, participants were shown 12 products and related services that were available for purchase. After recording ERP components, we used a questionnaire to measure the individuals' emotional involvement toward the services (i.e. the same services shown in the stimuli) of the 12 products to measure the emotional valence of the services. The emotional ERP components and the late positive potential (LPP) were elicited under the service conditions and distributed over the left frontal regions. We determined that the services may evoke an LPP and that services with a high emotional value may evoke a larger LPP, which suggests that positive emotion may be measured using the LPP amplitude in the left frontal regions. This result helps elucidate whether positive emotions are stimulated during the product-service system decision-making process and helps understand the emotional valences of different services. Our analysis of the emotional motivation of the consumer suggests that the LPP may be useful as an emotional indicator for measuring consumers' evaluation of services that provides a neural view of product-service system buying decisions. PMID:26457370

  20. The impact of emotional involvement on online service buying decisions: an event-related potentials perspective

    PubMed Central

    Wang, Jing; Han, Weiwei

    2015-01-01

    When examining a buying process, changes in human brain signals and their event-related potential (ERP) components can be considered a reflection of the consumers’ emotions. In this experiment, participants were shown 12 products and related services that were available for purchase. After recording ERP components, we used a questionnaire to measure the individuals’ emotional involvement toward the services (i.e. the same services shown in the stimuli) of the 12 products to measure the emotional valence of the services. The emotional ERP components and the late positive potential (LPP) were elicited under the service conditions and distributed over the left frontal regions. We determined that the services may evoke an LPP and that services with a high emotional value may evoke a larger LPP, which suggests that positive emotion may be measured using the LPP amplitude in the left frontal regions. This result helps elucidate whether positive emotions are stimulated during the product-service system decision-making process and helps understand the emotional valences of different services. Our analysis of the emotional motivation of the consumer suggests that the LPP may be useful as an emotional indicator for measuring consumers’ evaluation of services that provides a neural view of product-service system buying decisions. PMID:26457370

  1. Low NO(x) potential of gas turbine engines

    NASA Technical Reports Server (NTRS)

    Tacina, Robert R.

    1990-01-01

    The purpose is to correlate emission levels of gas turbine engines. The predictions of NO(x) emissions are based on a review of the literature of previous low NO(x) combustor programs and analytical chemical kinetic calculations. Concepts included in the literature review consisted of lean-premixed-prevaporized (LPP), rich burn/quick quench/lean burn (RQL), and direct injection. The NO(x) emissions were found to be an exponential function of adiabatic combustion temperature over a wide range of inlet temperatures, pressures and (lean) fuel-air ratios. A simple correlation of NO(x) formation with time was not found. The LPP and direct injection (using gaseous fuels) concepts have the lowest NO(x) emissions of the three concepts. The RQL data has higher values of NO(x) than the LPP concept, probably due to the stoichiometric temperatures and NO(x) production that occur during the quench step. Improvements in the quick quench step could reduce the NO(x) emissions to the LPP levels. The low NO(x) potential of LPP is offset by the operational disadvantages of its narrow stability limits and its susceptibility to autoignition/flashback. The Rich-Burn/Quick-Quench/Lean-Burn (RQL) and the direct injection concepts have the advantage of wider stability limits comparable to conventional combustors.

  2. Lichen planopilaris is associated with HLA DRB1*11 and DQB1*03 alleles.

    PubMed

    Pavlovsky, Lev; Israeli, Moshe; Sagy, Eti; Berg, Amy L; David, Michael; Shemer, Avner; Klein, Tirza; Hodak, Emmilia

    2015-02-01

    There are no studies of the possible association of the human leukocyte antigen (HLA) system with lichen planopilaris (LPP). To determine whether the HLA system is associated with LPP, 40 consecutive Jewish Israeli patients with LPP (study group) and 252 volunteers (controls) were typed for DRB1*and DQB1* loci by molecular methods. Compared with controls, the study group had a significantly higher frequency of the DRB1*11 allele (62% vs. 21%, corrected p-value (pc) = 0.001) owing to increased frequencies of DRB1*11: 01 and DRB1*11: 04. The DQB1*03 allele was also expressed at a significantly higher frequency in the study group (70% vs. 33%, pc = 0.0005); specifically, the frequency of DQB1*03: 01 was increased. The majority (82.5%) of the patients were of non-Ashkenazi origin. We conclude that LPP appears to be over-represented in non-Ashkenazi Jewish patients and is associated with an increased frequency of HLA DRB1*11 and DQB1*03 alleles. These findings suggest that immunogenetic factors play a role in LPP. PMID:24806356

  3. Laser-based microfocused x-ray source for mammography: feasibility study.

    PubMed

    Krol, A; Ikhlef, A; Kieffer, J C; Bassano, D A; Chamberlain, C C; Jiang, Z; Pépin, H; Prasad, S C

    1997-05-01

    A laser-produced plasma (LPP) x-ray source with possible application in mammography was created by focusing a laser beam on a Mo target. A Table-Top-Terawatt (TTT) laser operating at 1 J energy per pulse was employed. A dual pulse technique was used. Maximum energy transfer (approximately 10%) from laser light to hot electrons was reached at a 150 ps delay between pulses and the conversion efficiency (hard x-ray yield/laser energy input) was approximately 2 x 10(-4). The created LPP x-ray source is characterized by a very small focal spot size (tens of microns), Gaussian brightness distribution, and a very short pulse duration (a few ps). The spectral distribution of the generated x rays was measured. Images of the focal spot, using a pinhole camera, and images of a resolution pattern and a mammographic phantom were obtained. The LPP focal spot modulation transfer function for different magnification factors was calculated. We have shown that the LPP source in conjunction with a spherically bent, high throughput, crystal monochromator in a fixed-exit Rowland circle configuration can be used to created a narrow band tunable mammography system. Tunability to a specific patient breast tissue thickness and density would allow one to significantly improve contrast and resolution (exceeding 20 lp/mm) while lowering the exposure up to 50% for thicker breasts. The prospects for the LPP x-ray source for mammographic application are discussed. PMID:9167163

  4. Lichen planopilaris: update on pathogenesis and treatment.

    PubMed

    Baibergenova, Akerke; Donovan, Jeff

    2013-01-01

    Lichen planopilaris (LPP) is considered to be a follicular variant of lichen planus. Clinical variants include classic LPP, frontal fibrosing alopecia, and the Graham-Little-Piccardi-Lassueur syndrome. The pathogenesis of LPP remains to be fully elucidated, but like other cicatricial alopecias involves the irreversible destruction of hair follicle stem cells and loss of a hair follicle's capacity to regenerate itself In the early stages of LPP, patients may have scalp pruritus, burning, tenderness, and increased hair shedding. A scalp biopsy shows a lymphocytic infiltrate involving the isthmus and infundibulum. Apoptotic cells present in the external root sheath and concentric fibrosis surrounds the hair follicle. Treatment is prescribed with the goal to alleviate patient symptoms and to halt the progression of hair loss. Treatment involves use of potent topical corticosteroids and/or intralesional corticosteroids. Options for systemic treatment include anti-inflammatory agents such as hydroxychloroquine, tetracyclines, pioglitazones, and immunosuppressive medications such as cyclosporine, mycophenolate mofetil, or systemic corticosteroids. Hair transplantation may also be an option if the disease has been in clinical remission. The management of LPP can sometimes be challenging and additional research is needed to improve outcomes for patients. PMID:23930355

  5. Thermodynamic evaluation of the possibility to increase cogeneration turbine efficiency by using a heat pump operating with steam

    NASA Astrophysics Data System (ADS)

    Batenin, V. M.; Datsenko, V. V.; Zeigarnik, Yu. A.; Kosoi, A. S.; Sinkevich, M. V.

    2016-01-01

    Cogeneration turbines operate in different operation modes that considerably differ as to the working process conditions. In summer time, when heat demand is minimal, almost all steam flow passes through all turbine stages and enters into the condenser (condensing mode of operation). When heat supply is needed, the steam bleed-offs are used. The several last stages of the turbine (low-pressure part—LPP) have a control diaphragm at the inlet. When the heat supply is large, the diaphragm is maximally closed, and the entire steam flow, with an exception for a minimal ventilation flow is delivered to the steam bleed-offs (cogeneration mode). LPP flow path is designed for the optimal operation in the condensing mode. While running in cogeneration mode, the LPP operating conditions are far from optimal. Depending on the ventilation steam flow rate and outlet pressure, the LPP power can drop to zero or even become negative (ventilation mode). It is proposed to control an outlet steam pressure by using the heat pump that operates with steam. The heat pump energy consumption can be compensated and even exceeded by optimizing the steam expansion process in LPP. In this respect, operating conditions of cogeneration turbine LPPs during the cold season are analyzed. A brief description of a heat pump operating with steam is made. The possibility of increasing cogeneration turbine efficiency by using a steam heat pump is shown.

  6. Lichen Planopilaris in the Androgenetic Alopecia Area: A Pitfall for Hair Transplantation

    PubMed Central

    Baquerizo Nole, Katherine L.; Nusbaum, Bernard; Pinto, Giselle M.; Miteva, Mariya

    2015-01-01

    Background Classic lichen planopilaris (LPP) is a patchy form of primary lymphocytic cicatricial alopecia localized on the vertex of the scalp. It is important, however, to be aware of other, less recognized presentations that may be missed without dermatoscopy and pathology. Methods and Results We report 26 patients with LPP presenting with subtle erythema and scaling colocalized in the area of patterned thinning (androgenetic alopecia, AGA). All patients had been treated for seborrheic dermatitis in the past. Dermatoscopy showed the presence of 2-4 hairs emerging as a tuft from the same ostium surrounded by erythema, peripilar casts and interfollicular scaling associated with hair miniaturization. Histopathology obtained from those areas corresponded to LPP with concomitant follicular miniaturization. Conclusion Subtle or focal cases of LPP may be missed for seborrheic dermatitis when overlapping with AGA. Dermatoscopy-guided biopsy from the affected scalp is the best approach to make a timely diagnosis. This is particularly important in patients with AGA evaluated to undergo hair transplantation, as active LPP is a contraindication for these patients. PMID:27171849

  7. Reducing Auditory Hypersensitivities in Autistic Spectrum Disorder: Preliminary Findings Evaluating the Listening Project Protocol

    PubMed Central

    Porges, Stephen W.; Bazhenova, Olga V.; Bal, Elgiz; Carlson, Nancy; Sorokin, Yevgeniya; Heilman, Keri J.; Cook, Edwin H.; Lewis, Gregory F.

    2014-01-01

    Auditory hypersensitivities are a common feature of autism spectrum disorder (ASD). In the present study, the effectiveness of a novel intervention, the listening project protocol (LPP), was evaluated in two trials conducted with children diagnosed with ASD. LPP was developed to reduce auditory hypersensitivities. LPP is based on a theoretical “neural exercise” model that uses computer altered acoustic stimulation to recruit the neural regulation of middle ear muscles. Features of the intervention stimuli were informed by basic research in speech and hearing sciences that has identified the specific acoustic frequencies necessary to understand speech, which must pass through middle ear structures before being processed by other components of the auditory system. LPP was hypothesized to reduce auditory hypersensitivities by increasing the neural tone to the middle ear muscles to functionally dampen competing sounds in frequencies lower than human speech. The trials demonstrated that LPP, when contrasted to control conditions, selectively reduced auditory hypersensitivities. These findings are consistent with the polyvagal theory, which emphasizes the role of the middle ear muscles in social communication. PMID:25136545

  8. Comparative Analyses of Transcriptional Profiles in Mouse Organs Using a Pneumonic Plague Model after Infection with Wild-Type Yersinia pestis CO92 and Its Braun Lipoprotein Mutant

    PubMed Central

    Galindo, Cristi L.; Moen, Scott T.; Kozlova, Elena V.; Sha, Jian; Garner, Harold R.; Agar, Stacy L.; Chopra, Ashok K.

    2009-01-01

    We employed Murine GeneChips to delineate the global transcriptional profiles of the livers, lungs, and spleens in a mouse pneumonic plague infection model with wild-type (WT) Y. pestis CO92 and its Braun lipoprotein (Δlpp) mutant with reduced virulence. These organs showed differential transcriptional responses to infection with WT Y. pestis, but the overall host functional processes affected were similar across all three tissues. Gene expression alterations were found in inflammation, cytokine signaling, and apoptotic cell death-associated genes. Comparison of WT and Δlpp mutant-infected mice indicated significant overlap in lipopolysaccharide- (LPS-) associated gene expression, but the absence of Lpp perturbed host cell signaling at critical regulatory junctions resulting in altered immune response and possibly host cell apoptosis. We generated a putative signaling pathway including major inflammatory components that could account for the synergistic action of LPS and Lpp and provided the mechanistic basis of attenuation caused by deletion of the lpp gene from Y. pestis in a mouse model of pneumonic plague. PMID:20145715

  9. Dispositional mindfulness and the attenuation of neural responses to emotional stimuli

    PubMed Central

    Goodman, Robert J.; Inzlicht, Michael

    2013-01-01

    Considerable research has disclosed how cognitive reappraisals and the modulation of emotional responses promote successful emotion regulation. Less research has examined how the early processing of emotion-relevant stimuli may create divergent emotional response consequences. Mindfulness—a receptive, non-evaluative form of attention—is theorized to foster emotion regulation, and the present study examined whether individual differences in mindfulness would modulate neural responses associated with the early processing of affective stimuli. Focus was on the late positive potential (LPP) of the event-related brain potential to visual stimuli varying in emotional valence and arousal. This study first found, replicating past research, that high arousal images, particularly of an unpleasant type, elicited larger LPP responses. Second, the study found that more mindful individuals showed lower LPP responses to high arousal unpleasant images, even after controlling for trait attentional control. Conversely, two traits contrasting with mindfulness—neuroticism and negative affectivity—were associated with higher LPP responses to high arousal unpleasant images. Finally, mindfulness was also associated with lower LPP responses to motivationally salient pleasant images (erotica). These findings suggest that mindfulness modulates neural responses in an early phase of affective processing, and contribute to understanding how this quality of attention may promote healthy emotional functioning. PMID:22253259

  10. Keto Amphetamine Toxicity—Focus on the Redox Reactivity of the Cathinone Designer Drug Mephedrone

    PubMed Central

    den Hollander, Bjørnar; Sundström, Mira; Pelander, Anna; Ojanperä, Ilkka; Mervaala, Eero; Korpi, Esa Risto; Kankuri, Esko

    2014-01-01

    The β-keto amphetamine (cathinone, β-KA) designer drugs such as mephedrone (4-methylmethcathinone, 4-MMC) show a large degree of structural similarity to amphetamines like methamphetamine (METH). However, little is currently known about whether these substances also share the potential neurotoxic properties of their non-keto amphetamine counterparts, or what mechanisms could be involved. Here, we evaluate the cytotoxicity of β-KAs in SH-SY5Y cells using lactate dehydrogenase (LDH) assays, assess the redox potential of a range of β-KAs and non-keto amphetamines using the sensitive redox indicator 2-(4-Iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium (WST-1), and explore the effect of 4-MMC on the formation of protein adducts using ultra-high performance liquid chromatography/high-resolution time-of-flight mass spectrometry (UHPLC-HR-TOFMS) and on the mitochondrial respiratory chain using high-resolution respirometry. We show that treatment with β-KAs increases LDH release. Further, we demonstrate that even under physiological pH, β-KAs are effective and selective—as compared with their non-keto analogues—reductants in the presence of electron acceptors. Increased pH (range 7.6–8.0) greatly enhanced the reactivity up to sixfold. We found no evidence of protein adduct formation, suggesting the reactivity is due to direct electron transfer by the β-KAs. Finally, we show that 4-MMC and METH produce dissimilar effects on the respiratory chain. Our results indicate that β-KAs such as 4-MMC possess cytotoxic properties in vitro. Furthermore, in the presence of an electron-accepting redox partner, the ketone moiety of β-KAs is vital for pH-dependent redox reactivity. Further work is needed to establish the importance of β-KA redox properties and its potential toxicological importance in vivo. PMID:24913801

  11. 3D geological modeling of the Kasserine Aquifer System, Central Tunisia: New insights into aquifer-geometry and interconnections for a better assessment of groundwater resources

    NASA Astrophysics Data System (ADS)

    Hassen, Imen; Gibson, Helen; Hamzaoui-Azaza, Fadoua; Negro, François; Rachid, Khanfir; Bouhlila, Rachida

    2016-08-01

    The challenge of this study was to create a 3D geological and structural model of the Kasserine Aquifer System (KAS) in central Tunisia and its natural extension into north-east Algeria. This was achieved using an implicit 3D method, which honors prior geological data for both formation boundaries and faults. A current model is presented which provides defendable predictions for the spatial distribution of geology and water resources in aquifers throughout the model-domain. This work has allowed validation of regional scale geology and fault networks in the KAS, and has facilitated the first-ever estimations of groundwater resources in this region by a 3D method. The model enables a preliminary assessment of the hydraulic significance of the major faults by evaluating their influence and role on groundwater flow within and between four compartments of the multi-layered, KAS hydrogeological system. Thus a representative hydrogeological model of the study area is constructed. The possible dual nature of faults in the KAS is discussed in the context that some faults appear to be acting both as barriers to horizontal groundwater flow, and simultaneously as conduits for vertical flow. Also discussed is the possibility that two flow directions occur within the KAS, at a small syncline area of near Feriana. In summary, this work evaluates the influence of aquifer connectivity and the role of faults and geology in groundwater flow within the KAS aquifer system. The current KAS geological model can now be used to guide groundwater managers on the best placement for drilling to test and further refine the understanding of the groundwater system, including the faults connectivity. As more geological data become available, the current model can be easily edited and re-computed to provide an updated model ready for the next stage of investigation by numerical flow modeling.

  12. Isoniazid affects multiple components of the type II fatty acid synthase system of Mycobacterium tuberculosis.

    PubMed

    Slayden, R A; Lee, R E; Barry, C E

    2000-11-01

    Genetic and biochemical evidence has implicated two different target enzymes for isoniazid (INH) within the unique type II fatty acid synthase (FAS) system involved in the production of mycolic acids. These two components are an enoyl acyl carrier protein (ACP) reductase, InhA, and a beta-ketoacyl-ACP synthase, KasA. We compared the consequences of INH treatment of Mycobacterium tuberculosis (MTB) with two inhibitors having well-defined targets: triclosan (TRC), which inhibits InhA; and thiolactomycin (TLM), which inhibits KasA. INH and TLM, but not TRC, upregulate the expression of an operon containing five FAS II components, including kasA and acpM. Although all three compounds inhibit mycolic acid synthesis, treatment with INH and TLM, but not with TRC, results in the accumulation of ACP-bound lipid precursors to mycolic acids that were 26 carbons long and fully saturated. TLM-resistant mutants of MTB were more cross-resistant to INH than TRC-resistant mutants. Overexpression of KasA conferred more resistance to TLM and INH than to TRC. Overexpression of InhA conferred more resistance to TRC than to INH and TLM. Co-overexpression of both InhA and KasA resulted in strongly enhanced levels of INH resistance, in addition to cross-resistance to both TLM and TRC. These results suggest that these components of the FAS II complex are not independently regulated and that alterations in the expression level of InhA affect expression levels of KasA. Nonetheless, INH appeared to resemble TLM more closely in overall mode of action, and KasA levels appeared to be tightly correlated with INH sensitivity. PMID:11069675

  13. The supportive effect of supplementation with α-keto acids on physical training in type 2 diabetes mellitus.

    PubMed

    Liu, Y; Spreng, T; Lehr, M; Yang, B; Karau, A; Gebhardt, H; Steinacker, J M

    2015-07-01

    The maintenance of physical activity is crucial for the prevention and management of type 2 diabetes (T2D), and exercise induced changes including production of metabolites like ammonia can result in fatigue and exercise intolerance. Nutritional supplements may serve as an effective measure in supporting patients undergoing physical training by acting on their metabolism. This study investigates the effects of supplementation with α-keto acids (KAS) on exercise tolerance and glucose control in T2D patients. In a double-blind, placebo-controlled, randomized study 28 T2D patients underwent 6 weeks training on a cycle ergometer while they were supplemented with either a placebo or KAS (0.2 g kg(-1) body weight each day). The weekly training volume, power output at maximum and lactic threshold, leg muscle torque, the plasma concentration and 8 h urinary discharge of glucose, ammonia and urea were determined before and after the training as well as after one week of recovery. With KAS the patients did significantly more voluntary exercise (213 vs. 62 min, P < 0.01), reached a higher VO2max (27.3 vs. 24.8 ml min(-1) kg(-1)), higher power output (224 vs. 193 watts, P < 0.05) and greater endurance capacity (108 vs. 96 watts at lactic threshold, P < 0.05). Although the patients without KAS improved their glucose control after the training (P < 0.05), this effect could not be maintained after recovery as it was in the KAS group, where there was a prolonged benefit in glucose control. KAS also affected the ammonia and urea metabolism. KAS delivered supportive effects on the physical training along with a prolonged benefit in glucose control in T2D patients. PMID:26068548

  14. Transcript Abundance of Putative Lipid Phosphate Phosphatases During Development of Trypanosoma brucei in the Tsetse Fly.

    PubMed

    Alves e Silva, Thiago Luiz; Savage, Amy F; Aksoy, Serap

    2016-04-01

    African trypanosomes (Trypanosoma brucei spp.) cause devastating diseases in sub-Saharan Africa. Trypanosomes differentiate repeatedly during development in tsetse flies before gaining mammalian infectivity in fly salivary glands. Lipid phosphate phosphatases (LPPs) are involved in diverse biological processes, such as cell differentiation and cell migration. Gene sequences encoding two putative T. brucei LPP proteins were used to search the T. brucei genome, revealing two additional putative family members. Putative structural features and transcript abundance during parasite development in tsetse fly were characterized. Three of the four LPP proteins are predicted to have six transmembrane domains, while the fourth shows only one. Semiquantitative gene expression revealed differential regulation of LPPs during parasite development. Transcript abundance for three of the four putative LPP genes was elevated in parasites infecting salivary glands, but not mammalian-infective metacyclic cells in fly saliva, indicating a potential role of this family in parasite establishment in tsetse salivary glands. PMID:26856918

  15. Age-related changes in emotional face processing across childhood and into young adulthood: Evidence from event-related potentials.

    PubMed

    MacNamara, Annmarie; Vergés, Alvaro; Kujawa, Autumn; Fitzgerald, Kate D; Monk, Christopher S; Phan, K Luan

    2016-01-01

    Socio-emotional processing is an essential part of development, and age-related changes in its neural correlates can be observed. The late positive potential (LPP) is a measure of motivated attention that can be used to assess emotional processing; however, changes in the LPP elicited by emotional faces have not been assessed across a wide age range in childhood and young adulthood. We used an emotional face matching task to examine behavior and event-related potentials (ERPs) in 33 youth aged 7-19 years old. Younger children were slower when performing the matching task. The LPP elicited by emotional faces but not control stimuli (geometric shapes) decreased with age; by contrast, an earlier ERP (the P1) decreased with age for both faces and shapes, suggesting increased efficiency of early visual processing. Results indicate age-related attenuation in emotional processing that may stem from greater efficiency and regulatory control when performing a socio-emotional task. PMID:26220144

  16. Comparative study of laser produced Li plasma plumes from thin film and solid target

    NASA Astrophysics Data System (ADS)

    Kumar, Ajai; Singh, R. K.; Prahlad, V.; Joshi, H. C.

    2008-11-01

    The evolution features of lithium ions and neutrals generated by two different schemes viz. the laser-blow-off (LBO) of multicomponent LiF-C thin film and conventional laser ablation (referred here as LPP) from solid lithium have been studied using optical emission spectroscopic technique. The optical signal emitted by Li I (at 670.8 nm) and Li II (548.4 nm) was monitored as a function of laser fluence, ambient gas pressure, and distance "z" from the target. Apart from their similarities, some interesting differences were noticed in temporal profiles of the plumes generated by LPP and LBO both in vacuum as well as in the presence of the ambient gas. A comparative analysis of experimental results indicates that the ablation mechanism and subsequent laser-plume interaction were responsible for the observed differences in LPP and LBO plumes. Expansion features of the plume are discussed in the light of two different models.

  17. 100W EUV light-source key component technology update for HVM

    NASA Astrophysics Data System (ADS)

    Hori, Tsukasa; Kawasuji, Yasufumi; Tanaka, Hiroshi; Watanabe, Yukio; Shiraishi, Yutaka; Abe, Tamotsu; Okamoto, Takeshi; Kodama, Takeshi; Nakarai, Hiroaki; Yamazaki, Taku; Okazaki, Shinji; Saitou, Takashi; Mizoguchi, Hakaru

    2016-03-01

    Gigaphoton Inc. develops a high-power laser produced plasma extreme ultraviolet (LPP EUV) light source for high volume manufacturing which enables sub-10nm critical layer patterning for semiconductor device fabrication. A technology update of key components of a 100 W LPP-EUV light source is given in this paper. The key components efficiently produce a stable plasma and evacuate the tin debris from the EUV vessel with a magnetic debris mitigation system. The chosen technology guarantees therefore a high-power and long-life EUV light source system. Each component is described with updated data. The latest system performance results are also presented. They were obtained from our proto LPP-EUV light systems which support 100 W output power.

  18. Observations on the Occurrence, Distribution, and Seasonal Incidence of Blue-green Algal Viruses

    PubMed Central

    Safferman, Robert S.; Morris, Mary E.

    1967-01-01

    Phycovirus populations were found in 11 of the 12 waste stabilization ponds studied. These populations were comprised solely of blue-green algal (BGA) viruses. Two virus types were observed, one of which was related to the previously reported LPP-1 virus. The incidence and magnitude of the LPP group indicated that several of the ponds supported well-established BGA virus populations of this type. Counts as high as 270 plaque-forming units/ml were noted; however, marked differences in the nature and magnitude of these BGA viruses were apparent even in geographically related ponds of similar design. Of the algal strains found dominant in these ponds, none was of the type reported susceptible to the LPP viruses. PMID:16349731

  19. Observations on the Occurrence, Distribution, and Seasonal Incidence of Blue-green Algal Viruses.

    PubMed

    Safferman, R S; Morris, M E

    1967-09-01

    Phycovirus populations were found in 11 of the 12 waste stabilization ponds studied. These populations were comprised solely of blue-green algal (BGA) viruses. Two virus types were observed, one of which was related to the previously reported LPP-1 virus. The incidence and magnitude of the LPP group indicated that several of the ponds supported well-established BGA virus populations of this type. Counts as high as 270 plaque-forming units/ml were noted; however, marked differences in the nature and magnitude of these BGA viruses were apparent even in geographically related ponds of similar design. Of the algal strains found dominant in these ponds, none was of the type reported susceptible to the LPP viruses. PMID:16349731

  20. Effect of a Multi-Level Education Intervention Model on Knowledge and Attitudes of Accidental Injuries in Rural Children in Zunyi, Southwest China

    PubMed Central

    Cao, Bo-Ling; Shi, Xiu-Quan; Qi, Yong-Hong; Hui, Ya; Yang, Hua-Jun; Shi, Shang-Peng; Luo, Li-Rong; Zhang, Hong; Wang, Xin; Yang, Ying-Ping

    2015-01-01

    Objective: To explore the effect of a school-family-individual (SFI) multi-level education intervention model on knowledge and attitudes about accidental injuries among school-aged children to improve injury prevention strategies and reduce the incidence of pediatric injuries. Methods: The random sample of rural school-aged children were recruited by using a multistage, stratified, cluster sampling method in Zunyi, Southwest China from 2012 to 2014, and 2342 children were randomly divided into intervention and control groups. Then children answered a baseline survey to collect knowledge and attitude scores (KAS) of accidental injuries. In the intervention group, children, their parents/guardians and the school received a SFI multi-level education intervention, which included a children’s injury-prevention poster at schools, an open letter about security instruction for parents/guardians and multiple-media health education (Microsoft PowerPoint lectures, videos, handbooks, etc.) to children. Children in the control group were given only handbook education. After 16 months, children answered a follow-up survey to collect data on accidental injury types and accidental injury-related KAS for comparing the intervention and control groups and baseline and follow-up data. Results: The distribution of gender was not significantly different while age was different between the baseline and follow-up survey. At baseline, the mean KAS was lower for the intervention than control group (15.37 ± 3.40 and 18.35 ± 5.01; p < 0.001). At follow-up, the mean KAS was higher for the intervention than control group (21.16 ± 3.05 and 20.02 ± 3.40; p < 0.001). The increase in KAS in the intervention and control groups was significant (p < 0.001; KAS: 5.79 vs. 1.67) and suggested that children’s injury-related KAS improved in the intervention group. Moreover, the KAS between the groups differed for most subtypes of incidental injuries (based on International Classification of

  1. Motivated Attention to Cocaine and Emotional Cues in Abstinent and Current Cocaine Users: An ERP Study

    PubMed Central

    Dunning, Jonathan P.; Parvaz, Muhammad A.; Hajcak, Greg; Maloney, Thomas; Alia-Klein, Nelly; Woicik, Patricia A.; Telang, Frank; Wang, Gene-Jack; Volkow, Nora D.; Goldstein, Rita Z.

    2011-01-01

    Event-related potentials (ERPs) are a direct measure of neural activity and are ideally suited to study the time-course of attentional engagement with emotional and drug-related stimuli in addiction. In particular, the late positive potential (LPP) appears enhanced following cocaine-related compared to neutral stimuli in individuals with cocaine use disorders (CUD). However, previous studies have not directly compared cocaine-related to emotional stimuli while examining potential differences between abstinent and current cocaine users. The present study examined ERPs in 55 CUD (27 abstinent and 28 current users) and 29 matched healthy controls while they passively viewed pleasant, unpleasant, neutral, and cocaine-related pictures. To examine the time-course of attention to these stimuli, we analyzed both an early and later window in the LPP as well as the early posterior negativity (EPN), established in assessing motivated attention. Cocaine pictures elicited increased electrocortical measures of motivated attention in ways similar to affectively pleasant and unpleasant pictures in all CUD, an effect that was no longer discernible during the late LPP window for the current users. This group also exhibited deficient processing of the other emotional stimuli (early LPP window: pleasant pictures; late LPP window: pleasant and unpleasant pictures). Results were unique to the LPP and not EPN. Taken together, results support a relatively early attention bias to cocaine stimuli in cocaine addicted individuals further suggesting that recent cocaine use decreases such attention bias during later stages of processing but at the expense of deficient processing of other emotional stimuli. PMID:21450043

  2. Electrophysiological Correlates of Aberrant Motivated Attention and Salience Processing in Unaffected Relatives of Schizophrenia Patients.

    PubMed

    Andersen, Elizabeth H; Campbell, Alana M; Schipul, Sarah E; Bellion, Carolyn M; Donkers, Franc C L; Evans, Anna M; Belger, Aysenil

    2016-01-01

    Patients with schizophrenia (SCZ) exhibit debilitating deficits in attention and affective processing, which are often resistant to treatment and associated with poor functional outcomes. Impaired orientation to task-relevant target information has been indexed by diminished P3b event-related potentials in patients, as well as their unaffected first-degree relatives, suggesting that P3b may be a vulnerability marker for schizophrenia. Despite intact affective valence processing, patients are unable to employ cognitive change strategies to reduce electrophysiological responses to aversive stimuli. Less is known about the attentional processing of emotionally salient task-irrelevant information in patients and unaffected first-degree relatives. The goal of the present study was to examine the neural correlates of salience processing, as indexed by the late positive potential (LPP), during the processing of emotionally salient distractor stimuli in 31 patients with SCZ, 28 first-degree relatives, and 47 control participants using an oddball paradigm. Results indicated that despite intact novelty detection (P3a), both SCZ and first-degree relatives demonstrated deficiencies in attentional processing, reflected in attenuated target-P3b, and aberrant motivated attention, with reduced early-LPP amplitudes for aversive stimuli relative to controls. First-degree relatives revealed a unique enhancement of the late-LPP response, possibly underlying an exaggerated evaluation of salient information and a compensatory engagement of neural circuitry. Furthermore, reduced early-LPP and target-P3b amplitudes were associated with enhanced symptom severity. These findings suggest that, in addition to P3b, LPP may be useful for monitoring clinical state. Future studies will explore the value of P3 and LPP responses as vulnerability markers for early detection and prediction of psychopathology. PMID:26251457

  3. Personality and emotional processing: A relationship between extraversion and the late positive potential in adolescence.

    PubMed

    Speed, Brittany C; Nelson, Brady D; Perlman, Greg; Klein, Daniel N; Kotov, Roman; Hajcak, Greg

    2015-08-01

    Neuroticism and extraversion are multifaceted affective-laden personality traits that have been associated with major depressive disorder (MDD). Research and theory have argued that extraversion, and particularly its facet positive emotionality, is specific to MDD, while neuroticism is common across internalizing disorders. Converging evidence has suggested that MDD is associated with reduced engagement with emotional stimuli, but it remains unclear whether either extraversion, neuroticism, or both modulate reactivity to emotional cues. The late positive potential (LPP) is an event-related brain potential that is uniquely suited to assess engagement with emotional stimuli because it reflects sustained attention toward emotional content. The current study examined the LPP in relation to personality traits that may confer risk for depression by examining the relationship between the LPP and both neuroticism and extraversion in never-depressed adolescent girls. Specifically, 550 girls aged 13.5-15.5 with no lifetime history of depression completed an emotional picture-viewing task, and the LPP was measured in response to neutral, pleasant, and unpleasant pictures. Personality traits were gathered via self- and informant report. Results indicated that high extraversion was associated with a potentiated LPP to emotional pictures-and this effect was accounted for by positive emotionality in particular. In contrast, there was no association between the LPP and neuroticism or its facets. The present study is one of the first to demonstrate that extraversion is associated with variation in neural indices of emotional picture processing, similar to what has been observed among individuals with depression and at high risk for depression. PMID:25847353

  4. Link Protein N-terminal Peptide Binds to Bone Morphogenetic Protein (BMP) Type II Receptor and Drives Matrix Protein Expression in Rabbit Intervertebral Disc Cells*

    PubMed Central

    Wang, Zili; Weitzmann, M. Neale; Sangadala, Sreedhara; Hutton, William C.; Yoon, S. Tim

    2013-01-01

    Intervertebral disc (IVD) degeneration and associated spinal disorders are leading sources of morbidity, and they can be responsible for chronic low back pain. Treatments for degenerative disc diseases continue to be a challenge. Intensive research is now focusing on promoting regeneration of degenerated discs by stimulating production of the disc matrix. Link protein N-terminal peptide (LPP) is a proteolytic fragment of link protein, an important cross-linker and stabilizer of the major structural components of cartilage, aggrecan and hyaluronan. In this study we investigated LPP action in rabbit primary intervertebral disc cells cultured ex vivo in a three-dimensional alginate matrix. Our data reveal that LPP promotes disc matrix production, which was evidenced by increased expression of the chondrocyte-specific transcription factor SOX9 and the extracellular matrix macromolecules aggrecan and collagen II. Using colocalization and pulldown studies we further document a noggin-insensitive direct peptide-protein association between LPP and BMP-RII. This association mediated Smad signaling that converges on BMP genes leading to expression of BMP-4 and BMP-7. Furthermore, through a cell-autonomous loop BMP-4 and BMP-7 intensified Smad1/5 signaling though a feedforward circuit involving BMP-RI, ultimately promoting expression of SOX9 and downstream aggrecan and collagen II genes. Our data define a complex regulatory signaling cascade initiated by LPP and suggest that LPP may be a useful therapeutic substitute for direct BMP administration to treat IVD degeneration and to ameliorate IVD-associated chronic low back pain. PMID:23940040

  5. Identification of carbonylated lipids from different phospholipid classes by shotgun and LC-MS lipidomics.

    PubMed

    Ni, Zhixu; Milic, Ivana; Fedorova, Maria

    2015-07-01

    Oxidized lipids play a significant role in the pathogenesis of numerous oxidative stress-related human disorders, such as atherosclerosis, obesity, inflammation, and autoimmune diseases. Lipid peroxidation, induced by reactive oxygen and nitrogen species, yields a high variety of modified lipids. Among them, carbonylated lipid peroxidation products (oxoLPP), formed by oxidation of the fatty acid moiety yielding aldehydes or ketones (carbonyl groups), are electrophilic compounds that are able to modify nucleophilic substrates like proteins, nucleic acid, and aminophospholipids. Some carbonylated phosphatidylcholines possess even pro-inflammatory activities. However, little is known about oxoLPP derived from other phospholipid (PL) classes. Here, we present a new analytical strategy based on the mass spectrometry (MS) of PL-oxoLPP derivatized with 7-(diethylamino)coumarin-3-carbohydrazide (CHH). Shotgun MS revealed many oxoLPP derived from in vitro oxidized glycerophosphatidylglycerols (PG, 31), glycerophosphatidylcholine (PC, 23), glycerophosphatidylethanolamine (PE, 34), glycerophosphatidylserines (PS, 7), glycerophosphatidic acids (PA, 17), and phosphatidylinositiolphosphates (PIP, 6) vesicles. This data were used to optimize LipidXplorer-assisted identification, and a python-based post-processing script was developed to increase both throughput and accuracy. When applied to full lipid extracts from rat primary cardiomyocytes treated with peroxynitrite donor SIN-1, ten PL-bound oxoLPP were unambiguously identified by LC-MS, including two PC-, two PE-, one PG-, two PS-, and three PA-derived species. Some of the well-known carbonylated PC were detected, while most PL-oxoLPP were shown for the first time. PMID:25701423

  6. Diversion of phagosome trafficking by pathogenic Rhodococcus equi depends on mycolic acid chain length.

    PubMed

    Sydor, Tobias; von Bargen, Kristine; Hsu, Fong-Fu; Huth, Gitta; Holst, Otto; Wohlmann, Jens; Becken, Ulrike; Dykstra, Tobias; Söhl, Kristina; Lindner, Buko; Prescott, John F; Schaible, Ulrich E; Utermöhlen, Olaf; Haas, Albert

    2013-03-01

    Rhodococcus equi is a close relative of Mycobacterium spp. and a facultative intracellular pathogen which arrests phagosome maturation in macrophages before the late endocytic stage. We have screened a transposon mutant library of R. equi for mutants with decreased capability to prevent phagolysosome formation. This screen yielded a mutant in the gene for β-ketoacyl-(acyl carrier protein)-synthase A (KasA), a key enzyme of the long-chain mycolic acid synthesizing FAS-II system. The longest kasA mutant mycolic acid chains were 10 carbon units shorter than those of wild-type bacteria. Coating of non-pathogenic E. coli with purified wild-type trehalose dimycolate reduced phagolysosome formation substantially which was not the case with shorter kasA mutant-derived trehalose dimycolate. The mutant was moderately attenuated in macrophages and in a mouse infection model, but was fully cytotoxic.Whereas loss of KasA is lethal in mycobacteria, R. equi kasA mutant multiplication in broth was normal proving that long-chain mycolic acid compounds are not necessarily required for cellular integrity and viability of the bacteria that typically produce them. This study demonstrates a central role of mycolic acid chain length in diversion of trafficking by R. equi. PMID:23078612

  7. Intramuscular Immunization of Mice with a Live-Attenuated Triple Mutant of Yersinia pestis CO92 Induces Robust Humoral and Cell-Mediated Immunity To Completely Protect Animals against Pneumonic Plague.

    PubMed

    Tiner, Bethany L; Sha, Jian; Ponnusamy, Duraisamy; Baze, Wallace B; Fitts, Eric C; Popov, Vsevolod L; van Lier, Christina J; Erova, Tatiana E; Chopra, Ashok K

    2015-12-01

    Earlier, we showed that the Δlpp ΔmsbB Δail triple mutant of Yersinia pestis CO92 with deleted genes encoding Braun lipoprotein (Lpp), an acyltransferase (MsbB), and the attachment invasion locus (Ail), respectively, was avirulent in a mouse model of pneumonic plague. In this study, we further evaluated the immunogenic potential of the Δlpp ΔmsbB Δail triple mutant and its derivative by different routes of vaccination. Mice were immunized via the subcutaneous (s.c.) or the intramuscular (i.m.) route with two doses (2 × 10(6) CFU/dose) of the above-mentioned triple mutant with 100% survivability of the animals. Upon subsequent pneumonic challenge with 70 to 92 50% lethal doses (LD(50)) of wild-type (WT) strain CO92, all of the mice survived when immunization occurred by the i.m. route. Since Ail has virulence and immunogenic potential, a mutated version of Ail devoid of its virulence properties was created, and the genetically modified ail replaced the native ail gene on the chromosome of the Δlpp ΔmsbB double mutant, creating a Δlpp ΔmsbB::ailL2 vaccine strain. This newly generated mutant was attenuated similarly to the Δlpp ΔmsbB Δail triple mutant when administered by the i.m. route and provided 100% protection to animals against subsequent pneumonic challenge. Not only were the two above-mentioned mutants cleared rapidly from the initial i.m. site of injection in animals with no histopathological lesions, the immunized mice did not exhibit any disease symptoms during immunization or after subsequent exposure to WT CO92. These two mutants triggered balanced Th1- and Th2-based antibody responses and cell-mediated immunity. A substantial increase in interleukin-17 (IL-17) from the T cells of vaccinated mice, a cytokine of the Th17 cells, further augmented their vaccine potential. Thus, the Δlpp ΔmsbB Δail and Δlpp ΔmsbB::ailL2 mutants represent excellent vaccine candidates for plague, with the latter mutant still retaining Ail immunogenicity but

  8. Intramuscular Immunization of Mice with a Live-Attenuated Triple Mutant of Yersinia pestis CO92 Induces Robust Humoral and Cell-Mediated Immunity To Completely Protect Animals against Pneumonic Plague

    PubMed Central

    Tiner, Bethany L.; Ponnusamy, Duraisamy; Baze, Wallace B.; Fitts, Eric C.; Popov, Vsevolod L.; van Lier, Christina J.; Erova, Tatiana E.

    2015-01-01

    Earlier, we showed that the Δlpp ΔmsbB Δail triple mutant of Yersinia pestis CO92 with deleted genes encoding Braun lipoprotein (Lpp), an acyltransferase (MsbB), and the attachment invasion locus (Ail), respectively, was avirulent in a mouse model of pneumonic plague. In this study, we further evaluated the immunogenic potential of the Δlpp ΔmsbB Δail triple mutant and its derivative by different routes of vaccination. Mice were immunized via the subcutaneous (s.c.) or the intramuscular (i.m.) route with two doses (2 × 106 CFU/dose) of the above-mentioned triple mutant with 100% survivability of the animals. Upon subsequent pneumonic challenge with 70 to 92 50% lethal doses (LD50) of wild-type (WT) strain CO92, all of the mice survived when immunization occurred by the i.m. route. Since Ail has virulence and immunogenic potential, a mutated version of Ail devoid of its virulence properties was created, and the genetically modified ail replaced the native ail gene on the chromosome of the Δlpp ΔmsbB double mutant, creating a Δlpp ΔmsbB::ailL2 vaccine strain. This newly generated mutant was attenuated similarly to the Δlpp ΔmsbB Δail triple mutant when administered by the i.m. route and provided 100% protection to animals against subsequent pneumonic challenge. Not only were the two above-mentioned mutants cleared rapidly from the initial i.m. site of injection in animals with no histopathological lesions, the immunized mice did not exhibit any disease symptoms during immunization or after subsequent exposure to WT CO92. These two mutants triggered balanced Th1- and Th2-based antibody responses and cell-mediated immunity. A substantial increase in interleukin-17 (IL-17) from the T cells of vaccinated mice, a cytokine of the Th17 cells, further augmented their vaccine potential. Thus, the Δlpp ΔmsbB Δail and Δlpp ΔmsbB::ailL2 mutants represent excellent vaccine candidates for plague, with the latter mutant still retaining Ail immunogenicity but with

  9. Lysophosphatidic acid metabolism and elimination in cardiovascular disease

    NASA Astrophysics Data System (ADS)

    Salous, Abdelghaffar Kamal

    The bioactive lipids lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) are present in human and mouse plasma at a concentration of ~0.1-1 microM and regulate physiological and pathophysiological processes in the cardiovascular system including atherothrombosis, intimal hyperplasia, and immune function, edema formation, and permeability. PPAP2B, the gene encoding LPP3, a broad activity integral membrane enzyme that terminates LPA actions in the vasculature, has a single nucleotide polymorphism that been recently associated with coronary artery disease risk. The synthesis and signaling of LPA and S1P in the cardiovascular system have been extensively studied but the mechanisms responsible for their elimination are less well understood. The broad goal of this research was to examine the role of LPP3 in the termination of LPA signaling in models of cardiovascular disease involving vascular wall cells, investigate the role of LPP3 in the elimination of plasma LPA, and further characterize the elimination of plasma LPA. The central hypothesis is that LPP3 plays an important role in attenuating the pathological responses to LPA signaling and that it mediates the elimination of exogenously applied bioactive lipids from the plasma. These hypotheses were tested using molecular biological approaches, in vitro studies, synthetic lysophospholipid mimetics, modified surgical procedures, and mass spectrometry assays. My results indicated that LPP3 played a critical role in attenuating LPA signaling mediating the pathological processes of intimal hyperplasia and vascular leak in mouse models of disease. Additionally, enzymatic inactivation of lysophospholipids by LPP and PLA enzymes in the plasma was not a primary mechanism for the rapid elimination of plasma LPA and S1P. Instead, evidence strongly suggested a transcellular uptake mechanism by hepatic non-parenchymal cells as the predominant mechanism for elimination of these molecules. These results support a model in

  10. Effects of harmonics on aesthetic judgments of music: an ERP study involving laypersons and experts.

    PubMed

    Jaśkiewicz, Marta; Francuz, Piotr; Zabielska-Mendyk, Emilia; Zapała, Dariusz; Augustynowicz, Paweł

    2016-01-01

    The purpose of the study was to test whether aesthetic judgments of music are affected by expertise or harmonic violation of musical sequences. The participants were 14 musical experts and 13 laypersons; they were asked to judge the beauty and correctness of extracts from J. S. Bach's chorales. Experts and laypersons showed different late positive potential (LPP) responses to the appraisal of correctness. LPP also proved to be sensitive to the extent to which the extracts violated harmonic expectations. The relationship between the early right anterior negativity potential (ERAN) and the harmonic correctness of chords was similar in laypersons and experts. PMID:27373951

  11. LACIE performance predictor final operational capability program description, volume 3

    NASA Technical Reports Server (NTRS)

    1976-01-01

    The requirements and processing logic for the LACIE Error Model program (LEM) are described. This program is an integral part of the Large Area Crop Inventory Experiment (LACIE) system. LEM is that portion of the LPP (LACIE Performance Predictor) which simulates the sample segment classification, strata yield estimation, and production aggregation. LEM controls repetitive Monte Carlo trials based on input error distributions to obtain statistical estimates of the wheat area, yield, and production at different levels of aggregation. LEM interfaces with the rest of the LPP through a set of data files.

  12. Genes involved in forebrain development in the zebrafish, Danio rerio.

    PubMed

    Heisenberg, C P; Brand, M; Jiang, Y J; Warga, R M; Beuchle, D; van Eeden, F J; Furutani-Seiki, M; Granato, M; Haffter, P; Hammerschmidt, M; Kane, D A; Kelsh, R N; Mullins, M C; Odenthal, J; Nusslein-Volhard, C

    1996-12-01

    We identified four zebrafish mutants with defects in forebrain induction and patterning during embryogenesis. The four mutants define three genes: masterblind (mbl), silberblick (slb), and knollnase (kas). In mbl embryos, the anterior forebrain acquires posterior forebrain characteristics: anterior structures such as the eyes, olfactory placodes and the telencephalon are missing, whereas the epiphysis located in the posterior forebrain is expanded. In slb embryos, the extension of the embryonic axis is initially delayed and eventually followed by a partial fusion of the eyes. Finally, in kas embryos, separation of the telencephalic primordia is incomplete and dorsal midline cells fail to form a differentiated roof plate. Analysis of the mutant phenotypes indicates that we have identified genes essential for the specification of the anterior forebrain (mbl), positioning of the eyes (slb) and differentiation of the roof plate (kas). In an appendix to this study we list mutants showing alterations in the size of the eyes and abnormal differentiation of the lenses. PMID:9007240

  13. Apamin-Sensitive Small Conductance Calcium-Activated Potassium Channels were Negatively Regulated by Captopril in Volume-Overload Heart Failure Rats.

    PubMed

    Hongyuan, Bai; Xin, Dong; Jingwen, Zhang; Li, Gao; Yajuan, Ni

    2016-08-01

    In heart failure (HF), the malignant arrhythmias occur frequently; a study demonstrated that upregulation of I KAS resulted in recurrent spontaneous ventricular fibrillation in HF. However, the regulation of SK channels was poorly understood. The activation of SK channels depended on [Ca(2+)]i and PP2A; studies suggested that angiotensin II can regulate them. So, we hypothesized that in HF, the excess of angiotensin may regulate the SK channels and result in the remodeling of SK channels. To test the hypothesis, we used volume-overload-induced HF rat model, treated with captopril, performed whole-cell patch clamp to record apamin-sensitive currents (I KAS), and I-V curve was studied. The sensitivity of I KAS to [Ca(2+)]i was also explored by setting various [Ca(2+)]i (10, 100, 500, 900, 1000, and 10,000 nM), and the steady-state Ca(2+) response of I KAS was attained and performed Hill fitting with the equation (y = 1/[1 + (EC50/x) (n) ]). Immunofluorescent staining, real-time PCR, Western blot were also carried out to furtherly investigate the underlying molecular mechanisms of the regulation. Captopril significantly decreased the mean density of I KAS when [Ca(2+)]i was 500, 900, 1000, and 10000 nM. The Hill fitting showed significantly different EC50 values and the Hill coefficients and showed captopril significantly shifted rightward the steady-state Ca(2+) response of I KAS. The results of real-time PCR and Western blot demonstrated captopril decreased the mRNA and protein expression of SK3 channels. Captopril significantly downregulated the sensitivity of SK channels to [Ca(2+)]i and the SK3 channels expression in HF, and reversed the SK channels remodeling. PMID:26924798

  14. Keratoacanthoma and Keratoacanthoma-Like Squamous Cell Carcinoma: Similar Morphology but Different Pathogenesis.

    PubMed

    Watanabe, Isabela C; Magalhães, Renata F; de Moraes, Aparecida M; Stelini, Rafael F; Cintra, Geórgia F; Metze, Konradin; Cintra, Maria L

    2015-06-01

    Differential diagnosis between keratoacanthoma (KA) and squamous cell carcinoma (SCC) is difficult due to their similarities. The mechanisms that drive their distinct biological behavior are poorly understood. To investigate whether the assessment of microvessel density (MVD) could be helpful in KA and SCC differential diagnosis and to gain insight into the pathogenesis of KA-like neoplasms, we compared the density of CD105- and CD34-stained vessels in KAs and SCCs and their relation to the expression of the p53 oncoprotein and proliferation marker Ki67. This is an observational retrospective cohort study. Forty lesions with clinical appearance of KAs (29 KAs and 11 SCCs) entered the study. A biopsy was taken from each lesion at presentation and the natural clinical course was monitored for at least 1 month. Growing or minimally regressing lesions were submitted to complete surgical excision. The diagnoses were established on combined clinical, histological, and follow-up evaluations. The MVD and p53 or Ki67 expression in neoplastic cells were assessed through morphometry. The MVD did not show discriminating power between KAs and SCCs. The Ki67 proliferation rate was significantly higher in SCCs. Although neoangiogenesis (CD105-MVD) in KAs was associated with cell proliferation, in SCCs it was not. There was significant correlation between p53 expression and neoplasia size in SCCs but not in KAs. From our results, we may conclude that KA and SCC have similarities, as CD105- and CD34-MVD. However, the low Ki67 proliferation index and the positive correlation between Ki-67 index and neovascularization in KA suggest a dependence in neovascularization to grow in KA, pointing to involvement of distinct pathogenesis. PMID:26061320

  15. Keratoacanthoma and Keratoacanthoma-Like Squamous Cell Carcinoma

    PubMed Central

    Watanabe, Isabela C.; Magalhães, Renata F.; de Moraes, Aparecida M.; Stelini, Rafael F.; Cintra, Geórgia F.; Metze, Konradin; Cintra, Maria L.

    2015-01-01

    Abstract Differential diagnosis between keratoacanthoma (KA) and squamous cell carcinoma (SCC) is difficult due to their similarities. The mechanisms that drive their distinct biological behavior are poorly understood. To investigate whether the assessment of microvessel density (MVD) could be helpful in KA and SCC differential diagnosis and to gain insight into the pathogenesis of KA-like neoplasms, we compared the density of CD105- and CD34-stained vessels in KAs and SCCs and their relation to the expression of the p53 oncoprotein and proliferation marker Ki67. This is an observational retrospective cohort study. Forty lesions with clinical appearance of KAs (29 KAs and 11 SCCs) entered the study. A biopsy was taken from each lesion at presentation and the natural clinical course was monitored for at least 1 month. Growing or minimally regressing lesions were submitted to complete surgical excision. The diagnoses were established on combined clinical, histological, and follow-up evaluations. The MVD and p53 or Ki67 expression in neoplastic cells were assessed through morphometry. The MVD did not show discriminating power between KAs and SCCs. The Ki67 proliferation rate was significantly higher in SCCs. Although neoangiogenesis (CD105-MVD) in KAs was associated with cell proliferation, in SCCs it was not. There was significant correlation between p53 expression and neoplasia size in SCCs but not in KAs. From our results, we may conclude that KA and SCC have similarities, as CD105- and CD34-MVD. However, the low Ki67 proliferation index and the positive correlation between Ki-67 index and neovascularization in KA suggest a dependence in neovascularization to grow in KA, pointing to involvement of distinct pathogenesis. PMID:26061320

  16. MCCE2: Improving Protein pKa Calculations with Extensive Side Chain Rotamer Sampling

    PubMed Central

    SONG, YIFAN; MAO, JUNJUN; GUNNER, M. R.

    2009-01-01

    Multiconformation continuum electrostatics (MCCE) explores different conformational degrees of freedom in Monte Carlo calculations of protein residue and ligand pKas. Explicit changes in side chain conformations throughout a titration create a position dependent, heterogeneous dielectric response giving a more accurate picture of coupled ionization and position changes. The MCCE2 methods for choosing a group of input heavy atom and proton positions are described. The pKas calculated with different isosteric conformers, heavy atom rotamers and proton positions, with different degrees of optimization are tested against a curated group of 305 experimental pKas in 33 proteins. QUICK calculations, with rotation around Asn and Gln termini, sampling His tautomers and torsion minimum hydroxyls yield an RMSD of 1.34 with 84% of the errors being <1.5 pH units. FULL calculations adding heavy atom rotamers and side chain optimization yield an RMSD of 0.90 with 90% of the errors <1.5 pH unit. Good results are also found for pKas in the membrane protein bacteriorhodopsin. The inclusion of extra side chain positions distorts the dielectric boundary and also biases the calculated pKas by creating more neutral than ionized conformers. Methods for correcting these errors are introduced. Calculations are compared with multiple X-ray and NMR derived structures in 36 soluble proteins. Calculations with X-ray structures give significantly better pKas. Results with the default protein dielectric constant of 4 are as good as those using a value of 8. PMID:19274707

  17. The biosynthesis of mycolic acids in Mycobacterium tuberculosis relies on multiple specialized elongation complexes interconnected by specific protein-protein interactions.

    PubMed

    Veyron-Churlet, Romain; Bigot, Sarah; Guerrini, Olivier; Verdoux, Sébastien; Malaga, Wladimir; Daffé, Mamadou; Zerbib, Didier

    2005-11-01

    Tuberculosis kills about two million people every year and remains one of the leading causes of mortality worldwide. As a result of the increasing antibiotic resistance of Mycobacterium tuberculosis (Mtb) strains, there is an urgent need for new antitubercular drugs. Several efficient antibiotics, including isoniazid, specifically target the fatty acid synthase-II (FAS-II) complex of mycolic acid biosynthesis. We have previously shown that there are protein-protein interactions between the components of FAS-II that are essential for mycobacterial survival. We have now looked at the potential partners of FAS-II, mtFabD, the methyltransferases MmaAs, and Pks13. A combination of yeast two-hybrid and co-immunoprecipitation experiments showed that mtFabD interacts with each beta-ketoacyl-synthase (KasA, KasB and mtFabH) and with the core of FAS-II (InhA and MabA). The methyltransferases have a greater affinity for KasA and KasB than for mtFabH, suggesting that modifications on the meromycolic chains may occur during their elongation. Finally, Pks13, which catalyzes the final Claisen condensation of mycolic acids, interacts specifically with KasB. These data allowed us to determine the architecture of the multiple specialized FAS-II complexes, giving us insights into the organization of the complete mycolic acids biosynthesis. Our studies suggest a new and crucial interaction (KasB-Pks13) as a putative target for peptidomimetic antibiotics. PMID:16213523

  18. Slow onset inhibition of bacterial beta-ketoacyl-acyl carrier protein synthases by thiolactomycin.

    PubMed

    Machutta, Carl A; Bommineni, Gopal R; Luckner, Sylvia R; Kapilashrami, Kanishk; Ruzsicska, Bela; Simmerling, Carlos; Kisker, Caroline; Tonge, Peter J

    2010-02-26

    Thiolactomycin (TLM), a natural product thiolactone antibiotic produced by species of Nocardia and Streptomyces, is an inhibitor of the beta-ketoacyl-acyl carrier protein synthase (KAS) enzymes in the bacterial fatty acid synthase pathway. Using enzyme kinetics and direct binding studies, TLM has been shown to bind preferentially to the acyl-enzyme intermediates of the KASI and KASII enzymes from Mycobacterium tuberculosis and Escherichia coli. These studies, which utilized acyl-enzyme mimics in which the active site cysteine was replaced by a glutamine, also revealed that TLM is a slow onset inhibitor of the KASI enzymes KasA and ecFabB but not of the KASII enzymes KasB and ecFabF. The differential affinity of TLM for the acyl-KAS enzymes is proposed to result from structural change involving the movement of helices alpha5 and alpha6 that prepare the enzyme to bind malonyl-AcpM or TLM and that is initiated by formation of hydrogen bonds between the acyl-enzyme thioester and the oxyanion hole. The finding that TLM is a slow onset inhibitor of ecFabB supports the proposal that the long residence time of TLM on the ecFabB homologues in Serratia marcescens and Klebsiella pneumonia is an important factor for the in vivo antibacterial activity of TLM against these two organisms despite the fact that the in vitro MIC values are only 100-200 microg/ml. The mechanistic data on the interaction of TLM with KasA will provide an important foundation for the rational development of high affinity KasA inhibitors based on the thiolactone skeleton. PMID:20018879

  19. Thiolactomycin-Based Inhibitors of Bacterial β-Ketoacyl-ACP Synthases with in Vivo Activity.

    PubMed

    Bommineni, Gopal R; Kapilashrami, Kanishk; Cummings, Jason E; Lu, Yang; Knudson, Susan E; Gu, Chendi; Walker, Stephen G; Slayden, Richard A; Tonge, Peter J

    2016-06-01

    β-Ketoacyl-ACP synthases (KAS) are key enzymes involved in the type II bacterial fatty acid biosynthesis (FASII) pathway and are putative targets for antibacterial discovery. Several natural product KAS inhibitors have previously been reported, including thiolactomycin (TLM), which is produced by Nocardia spp. Here we describe the synthesis and characterization of optically pure 5R-thiolactomycin (TLM) analogues that show improved whole cell activity against bacterial strains including methicillin-resistant Staphylococcus aureus (MRSA) and priority pathogens such as Francisella tularensis and Burkholderia pseudomallei. In addition, we identify TLM analogues with in vivo efficacy against MRSA and Klebsiella pneumoniae in animal models of infection. PMID:27187871

  20. "In Practice It Doesn't Always Work out Like That." Undergraduate Experiences in a Research Community of Practice

    ERIC Educational Resources Information Center

    John, Joanna; Creighton, John

    2013-01-01

    This paper examines the extent to which a structured undergraduate research intervention, UROP, permits undergraduate students early access to legitimate peripheral participation (LPP) in a research community of practice. Accounts of placement experiences suggest that UROP affords rich possibilities for engagement with research practice.…

  1. Do reward-processing deficits in schizophrenia-spectrum disorders promote cannabis use? An investigation of physiological response to natural rewards and drug cues

    PubMed Central

    Cassidy, Clifford M.; Brodeur, Mathieu B.; Lepage, Martin; Malla, Ashok

    2014-01-01

    Background Dysfunctional reward processing is present in individuals with schizophrenia-spectrum disorders (SSD) and may confer vulnerability to addiction. Our objective was to identify a deficit in patients with SSD on response to rewarding stimuli and determine whether this deficit predicts cannabis use. Methods We divided a group of patients with SSD and nonpsychotic controls into cannabis users and nonusers. Response to emotional and cannabis-associated visual stimuli was assessed using self-report, event-related potentials (using the late positive potential [LPP]), facial electromyography and skin-conductance response. Results Our sample comprised 35 patients with SSD and 35 nonpsychotic controls. Compared with controls, the patients with SSD showed blunted LPP response to pleasant stimuli (p = 0.003). Across measures, cannabis-using controls showed greater response to pleasant stimuli than to cannabis stimuli whereas cannabis-using patients showed little bias toward pleasant stimuli. Reduced LPP response to pleasant stimuli was predictive of more frequent subsequent cannabis use (β = −0.24, p = 0.034). Limitations It is not clear if the deficit associated with cannabis use is specific to rewarding stimuli or nonspecific to any kind of emotionally salient stimuli. Conclusion The LPP captures a reward-processing deficit in patients with SSD and shows potential as a biomarker for identifying patients at risk of heavy cannabis use. PMID:24913137

  2. Influence of pulse width on the laser ablation of zinc in nitrogen ambient

    NASA Astrophysics Data System (ADS)

    Smijesh, N.; Rao, Kavya H.; Philip, Reji

    2016-04-01

    Time-resolved spectroscopic measurements of expanding plasma plumes generated by irradiating a solid zinc target with laser pulses of 7 ns and 100 fs durations are carried out in the ambient pressure range of 0.05-200 Torr of nitrogen. At the relatively high input fluence of ~16 J/cm2, fast and slow atomic species are found to appear at different times in the optical time-of-flight (OTOF) spectra, the dynamics of which is primarily determined by the pulse duration of the excitation laser. In fs LPP, the average speed of fast species is unaffected by an increase in ambient pressure, while in ns LPP, the speed is found to reduce with pressure. The slow species shows a sharp peak in the OTOF spectra with a narrow velocity distribution for fs LPP, indicating a large number density and low electron temperature, which is consistent with optical emission spectroscopic (OES) studies. On the other hand, for ns LPP, the OTOF of slow species shows a more broadened profile which can be attributed to strong plume-laser interaction. The dynamics of slow species is heavily influenced by the presence of shock waves, which leads to the occurrence of much slower species at larger pressures.

  3. Characterization of Bimetallic Fe-Ru Oxide Nanoparticles Prepared by Liquid-Phase Plasma Method

    NASA Astrophysics Data System (ADS)

    Lee, Sung-Jin; Lee, Heon; Jeon, Ki-Joon; Park, Hyunwoong; Park, Young-Kwon; Jung, Sang-Chul

    2016-07-01

    The bimetallic Fe-Ru oxide nanoparticles were synthesized in the liquid-phase plasma (LPP) method which employed iron chloride and ruthenium chloride as precursors. The active species (OH·, Hα, Hβ, and OI) and the iron and ruthenium ions were observed in the plasma field created by the LPP process. The spherical-shaped bimetallic Fe-Ru oxide nanoparticles were synthesized by the LPP reaction, and the size of the particles was growing along with the progression of the LPP reaction. The synthesized bimetallic Fe-Ru oxide nanoparticles were comprised of Fe2O3, Fe3O4, RuO, and RuO2. Ruthenium had a higher reduction potential than iron and resulted in higher ruthenium composition in the synthesized bimetallic nanoparticles. The control of the molar ratio of the precursors in the reactant solution was found to be employed as a means to control the composition of the elements in bimetallic nanoparticles.

  4. The Sex Differences in Regulating Unpleasant Emotion by Expressive Suppression: Extraversion Matters

    PubMed Central

    Cai, Ayan; Lou, Yixue; Long, Quanshan; Yuan, Jiajin

    2016-01-01

    Males are known for more suppression of emotional displays than females. However, when the emotion regulation effect of expressive suppression is greater in males, and how this sex difference varies with emotion display-related personality (e.g., extraversion), are undetermined. Event-related potentials were recorded while male and female participants different in extraversion were required to attend to or suppress emotional expression to negative pictures. Sex and extraversion did not modulate self-reported emotional experience. However, late positive potential (LPP) amplitudes showed an extraversion-moderated sex difference in the 2000–3000 ms and the 3000–4000 ms time epochs. LPP amplitudes were decreased during suppression versus viewing conditions in ambivert males, while this effect was absent in ambivert females. However, the LPP amplitudes of extraverts were similar for suppression and viewing conditions, irrespective of sex and timing. Regardless of early, middle, or late time windows, LPP amplitudes were positively related to self-reported emotion. These results suggest a male advantage for using expressive suppression for emotion regulation in non-extraverted, ambivert individuals. PMID:27458408

  5. CELL-SURFACE DISPLAY OF SYNTHETIC PHYTOCHELATINS USING ICE NUCLEATION PROTEIN FOR ENHANCED HEAVY-METAL BIOACCUMULATION. (R827227)

    EPA Science Inventory

    Synthetic phytochelatins (ECs) composed of (Glu–Cys)nGly are protein analogs of phytochelatin that exhibit improved metal-binding capacity over metallothioneins (MTs). Expression of EC20 on the surface of E. coli using the Lpp-OmpA anchor resulted in i...

  6. This person is saying bad things about you: The influence of physically and socially threatening context information on the processing of inherently neutral faces.

    PubMed

    Klein, Fabian; Iffland, Benjamin; Schindler, Sebastian; Wabnitz, Pascal; Neuner, Frank

    2015-12-01

    Recent studies have shown that the perceptual processing of human faces is affected by context information, such as previous experiences and information about the person represented by the face. The present study investigated the impact of verbally presented information about the person that varied with respect to affect (neutral, physically threatening, socially threatening) and reference (self-referred, other-referred) on the processing of faces with an inherently neutral expression. Stimuli were presented in a randomized presentation paradigm. Event-related potential (ERP) analysis demonstrated a modulation of the evoked potentials by reference at the EPN (early posterior negativity) and LPP (late positive potential) stage and an enhancing effect of affective valence on the LPP (700-1000 ms) with socially threatening context information leading to the most pronounced LPP amplitudes. We also found an interaction between reference and valence with self-related neutral context information leading to more pronounced LPP than other related neutral context information. Our results indicate an impact of self-reference on early, presumably automatic processing stages and also a strong impact of valence on later stages. Using a randomized presentation paradigm, this study confirms that context information affects the visual processing of faces, ruling out possible confounding factors such as facial configuration or conditional learning effects. PMID:25967930

  7. Language, Faith and Identity: A Historical Insight into Discourses of Language Ideology and Planning by the Lutheran Church of Australia

    ERIC Educational Resources Information Center

    Hatoss, Aniko

    2012-01-01

    While most language-planning and policy (LPP) studies have focussed on language decisions made by government bodies, in recent years there has been an increased interest in micro-level language planning in immigrant contexts. Few studies, however, have used this framework to retrospectively examine the planning decisions of religious institutions,…

  8. Actors and Agency in Academic Language Policy and Planning

    ERIC Educational Resources Information Center

    Fenton-Smith, Ben; Gurney, Laura

    2016-01-01

    Nearly two decades have passed since Kaplan and Baldauf [1997. "Language planning from practice to theory." Clevedon: Multilingual Matters] drew attention to the dearth of language policy and planning (LPP) in higher education. Despite the continuing inflow of English as an additional language students into Anglophone universities, and a…

  9. Stop laughing! Humor perception with and without expressive suppression.

    PubMed

    Korb, Sebastian; Grandjean, Didier; Samson, Andrea C; Delplanque, Sylvain; Scherer, Klaus R

    2012-01-01

    The neurophysiological study of emotion regulation focused on the strategy of reappraisal-i.e., the cognitive reinterpretation of a stimulus. Reappraisal reduces emotional expression, the experience of both negative and positive feelings, and the amplitude of an event-related potential (ERP)-the late positive potential (LPP). In contrast, the strategy of expressive suppression (ES), being the inhibition of emotional expression, has been reported to reduce subjective feelings of positive, but not negative emotion, and has not yet been investigated with ERPs. We focused on the LPP to assess the correlates of ES in the context of humor perception. Twenty-two female participants rated sequences of humorous (H) and non-humorous (NH) pictures, while their zygomaticus muscle was recorded. A spontaneous (SP) condition, in which participants attended naturally to the pictures, resulted in higher ratings of funniness, increased smiling, and increased LPP amplitude for H compared to NH stimuli. An ES condition, in which participants suppressed their facial reactions, resulted in reduced smiling, without affecting subjective ratings. LPP amplitude did not differ between H and NH stimuli during ES, suggesting equal allocation of processing resources to both stimuli. These results suggest that, similarly to reappraisal, ES modifies the way the brain processes positive emotional stimuli. PMID:22369232

  10. Language Policy and Planning in Language Education: Legacies, Consequences, and Possibilities

    ERIC Educational Resources Information Center

    Wiley, Terrence G.; García, Ofelia

    2016-01-01

    This article considers the relevance of language policy and planning (LPP) for language education in the United States in relation to the country's longstanding and continuing multilingualism. In reflecting on the U.S. context, one striking feature is the absence of a guiding overarching explicit national educational language policy. Language…

  11. Optimization of extreme ultraviolet photons emission and collection in mass-limited laser produced plasmas for lithography application

    SciTech Connect

    Sizyuk, T.; Hassanein, A.

    2012-08-01

    The progress in development of commercial system for next generation EUV lithography requires, among other factors, significant improvement in EUV photon sources such as discharge produced plasma (DPP) and laser produced plasma (LPP) devices. There are still many uncertainties in determining the optimum device since there are many parameters for the suitable and efficient energy source and target configuration and size. Complex devices with trigger lasers in DPP or with pre-pulsing in LPP provide wide area for optimization in regards to conversion efficiency (CE) and components lifetime. We considered in our analysis a promising LPP source configuration using 10-30 {mu}m tin droplet targets, and predicted conditions for the most efficient EUV radiation output and collection as well as calculating photons source location and size. We optimized several parameters of dual-beam lasers and their relationship to target size. We used our HEIGHTS comprehensive and integrated full 3D simulation package to study and optimize LPP processes with various target sizes to maximize the CE of the system.

  12. Characterization of Bimetallic Fe-Ru Oxide Nanoparticles Prepared by Liquid-Phase Plasma Method.

    PubMed

    Lee, Sung-Jin; Lee, Heon; Jeon, Ki-Joon; Park, Hyunwoong; Park, Young-Kwon; Jung, Sang-Chul

    2016-12-01

    The bimetallic Fe-Ru oxide nanoparticles were synthesized in the liquid-phase plasma (LPP) method which employed iron chloride and ruthenium chloride as precursors. The active species (OH·, Hα, Hβ, and O(I)) and the iron and ruthenium ions were observed in the plasma field created by the LPP process. The spherical-shaped bimetallic Fe-Ru oxide nanoparticles were synthesized by the LPP reaction, and the size of the particles was growing along with the progression of the LPP reaction. The synthesized bimetallic Fe-Ru oxide nanoparticles were comprised of Fe2O3, Fe3O4, RuO, and RuO2. Ruthenium had a higher reduction potential than iron and resulted in higher ruthenium composition in the synthesized bimetallic nanoparticles. The control of the molar ratio of the precursors in the reactant solution was found to be employed as a means to control the composition of the elements in bimetallic nanoparticles. PMID:27456502

  13. A hemispherical Langmuir probe array detector for angular resolved measurements on droplet-based laser-produced plasmas

    SciTech Connect

    Gambino, Nadia Brandstätter, Markus; Rollinger, Bob; Abhari, Reza

    2014-09-15

    In this work, a new diagnostic tool for laser-produced plasmas (LPPs) is presented. The detector is based on a multiple array of six motorized Langmuir probes. It allows to measure the dynamics of a LPP in terms of charged particles detection with particular attention to droplet-based LPP sources for EUV lithography. The system design permits to temporally resolve the angular and radial plasma charge distribution and to obtain a hemispherical mapping of the ions and electrons around the droplet plasma. The understanding of these dynamics is fundamental to improve the debris mitigation techniques for droplet-based LPP sources. The device has been developed, built, and employed at the Laboratory for Energy Conversion, ETH Zürich. The experimental results have been obtained on the droplet-based LPP source ALPS II. For the first time, 2D mappings of the ion kinetic energy distribution around the droplet plasma have been obtained with an array of multiple Langmuir probes. These measurements show an anisotropic expansion of the ions in terms of kinetic energy and amount of ion charge around the droplet target. First estimations of the plasma density and electron temperature were also obtained from the analysis of the probe current signals.

  14. Cognitive load and emotional processing in Generalized Anxiety Disorder: Electrocortical evidence for increased distractibility

    PubMed Central

    MacNamara, Annmarie; Proudfit, Greg Hajcak

    2014-01-01

    Generalized Anxiety Disorder (GAD) may be characterized by emotion regulation deficits attributable to an imbalance between top-down (i.e., goal-driven) and bottom-up (i.e., stimulus-driven) attention. In prior work, these attentional processes were examined by presenting unpleasant and neutral pictures within a working memory paradigm. The late positive potential (LPP) measured attention toward task-irrelevant pictures. Results from this prior work showed that working memory load reduced the LPP across participants; however, this effect was attenuated for individuals with greater self-reported state anxiety, suggesting reduced top-down control. In the current study, the same paradigm was used with 106 medication-free, female participants – 71 with GAD and 35 without GAD. Unpleasant pictures elicited larger LPPs, and working memory load reduced the picture-elicited LPP. Compared to healthy controls, participants with GAD showed large LPPs to unpleasant pictures presented under high working memory load. Self-reported symptoms of anhedonic depression were related to a reduced effect of working memory load on the LPP elicited by neutral pictures. These results indicate that individuals with GAD show less flexible modulation of attention when confronted with unpleasant stimuli. Furthermore, among those with GAD, anhedonic depression may broaden attentional deficits to neutral distracters. PMID:24933276

  15. Existential neuroscience: neurophysiological correlates of proximal defenses against death-related thoughts

    PubMed Central

    Jonas, Eva; Kronbichler, Martin

    2013-01-01

    A great deal of evidence suggests that reminders of mortality increase ingroup support and worldview defense, presumably in order to deal with the potential for anxiety that roots in the knowledge that death is inevitable. Interestingly, these effects are obtained solely when thoughts of death are not in the focus of consciousness. When conscious, death-related thoughts are usually defended against using proximal defenses, which entail distraction or suppression. The present study aimed at demonstrating neurophysiological correlates of proximal defenses. We focused on the late positive potential (LPP), which is thought to reflect an increased allocation of attention toward, and processing of, motivationally relevant stimuli. Our prediction was that the LPP should be increased for death-related relative to death-unrelated, but equally unpleasant stimulus words. In Experiment 1, this prediction was confirmed. This finding was replicated in Experiment 2, which used a target word detection task. In Experiment 2, both death-related and pleasant words elicited an enhanced LPP, presumably because during the less demanding task, people might have distracted themselves from the mortality reminders by focusing on pleasant words. To summarize, we were able to identify a plausible neurophysiological marker of proximal defenses in the form of an increased LPP to death-related words. PMID:22267519

  16. Lipid phosphate phosphatases regulate lysophosphatidic acid production and signaling in platelets: studies using chemical inhibitors of lipid phosphate phosphatase activity.

    PubMed

    Smyth, Susan S; Sciorra, Vicki A; Sigal, Yury J; Pamuklar, Zehra; Wang, Zuncai; Xu, Yong; Prestwich, Glenn D; Morris, Andrew J

    2003-10-31

    Blood platelets play an essential role in ischemic heart disease and stroke contributing to acute thrombotic events by release of potent inflammatory agents within the vasculature. Lysophosphatidic acid (LPA) is a bioactive lipid mediator produced by platelets and found in the blood and atherosclerotic plaques. LPA receptors on platelets, leukocytes, endothelial cells, and smooth muscle cells regulate growth, differentiation, survival, motility, and contractile activity. Definition of the opposing pathways of synthesis and degradation that control extracellular LPA levels is critical to understanding how LPA bioactivity is regulated. We show that intact platelets and platelet membranes actively dephosphorylate LPA and identify the major enzyme responsible as lipid phosphate phosphatase 1 (LPP1). Localization of LPP1 to the platelet surface is increased by exposure to LPA. A novel receptor-inactive sn-3-substituted difluoromethylenephosphonate analog of phosphatidic acid that is a potent competitive inhibitor of LPP1 activity potentiates platelet aggregation and shape change responses to LPA and amplifies LPA production by agonist-stimulated platelets. Our results identify LPP1 as a pivotal regulator of LPA signaling in the cardiovascular system. These findings are consistent with genetic and cell biological evidence implicating LPPs as negative regulators of lysophospholipid signaling and suggest that the mechanisms involve both attenuation of lysophospholipid actions at cell surface receptors and opposition of lysophospholipid production. PMID:12909631

  17. 76 FR 55699 - Proposed Establishment of Everglades Headwaters National Wildlife Refuge and Conservation Area

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-08

    ...We, the Fish and Wildlife Service (Service), propose to establish a national wildlife refuge and conservation area in Polk, Osceola, Highlands, and Okeechobee Counties, in central and south Florida. A draft Land Protection Plan (LPP) and Environmental Assessment (EA) for the establishment of the proposed refuge and conservation area were prepared with input from Federal, State, and local......

  18. TESOL and Policy Enactments: Perspectives from Practice

    ERIC Educational Resources Information Center

    Ramanathan, Vaidehi; Morgan, Brian

    2007-01-01

    Prior research in the area of language policy and planning (LPP) has been focused primarily on macro decision-making and the impact of national, local, and institutional policies in educational settings. Only recently have scholars begun examining the everyday contexts in which policies are interpreted and negotiated in ways that reflect local…

  19. Genome-wide analysis suggests divergent evolution of lipid phosphotases/phosphotransferase genes in plants.

    PubMed

    Wang, Peng; Chen, Zhenxi; Kasimu, Rena; Chen, Yinhua; Zhang, Xiaoxiao; Gai, Jiangtao

    2016-08-01

    Genes of the LPPT (lipid phosphatase/phosphotransferase) family play important roles in lipid phosphorous transfer and triacylglycerol accumulation in plants. To provide overviews of the plant LPPT family and their overall relationships, here we carried out genome-wide identifications and analyses of plant LPPT family members. A total of 643 putative LPPT genes were identified from 48 sequenced plant genomes, among which 205 genes from 14 plants were chosen for further analyses. Plant LPPT genes belonged to three distinctive groups, namely the LPT (lipid phosphotransfease), LPP (lipid phosphatase), and pLPP (plastidic lipid phosphotransfease) groups. Genes of the LPT group could be further partitioned into three groups, two of which were only identified in terrestrial plants. Genes in the LPP and pLPP groups experienced duplications in early stages of plant evolution. Among 17 Zea mays LPPT genes, divergence of temporal-spatial expression patterns was revealed based on microarray data analysis. Peptide sequences of plant LPPT genes harbored different conserved motifs. A test of Branch Model versus One-ratio Model did not support significant selective pressures acting on different groups of LPPT genes, although quite different nonsynonymous evolutionary rates and selective pressures were observed. The complete picture of the plant LPPT family provided here should facilitate further investigations of plant LPPT genes and offer a better understanding of lipid biosynthesis in plants. PMID:27501416

  20. Low NOx, Lean Direct Wall Injection Combustor Concept Developed

    NASA Technical Reports Server (NTRS)

    Tacina, Robert R.; Wey, Changlie; Choi, Kyung J.

    2003-01-01

    The low-emissions combustor development at the NASA Glenn Research Center is directed toward advanced high-pressure aircraft gas turbine applications. The emphasis of this research is to reduce nitrogen oxides (NOx) at high-power conditions and to maintain carbon monoxide and unburned hydrocarbons at their current low levels at low-power conditions. Low-NOx combustors can be classified into rich burn and lean burn concepts. Lean burn combustors can be further classified into lean-premixed-prevaporized (LPP) and lean direct injection (LDI) combustors. In both concepts, all the combustor air, except for liner cooling flow, enters through the combustor dome so that the combustion occurs at the lowest possible flame temperature. The LPP concept has been shown to have the lowest NOx emissions, but for advanced high-pressure-ratio engines, the possibly of autoignition or flashback precludes its use. LDI differs from LPP in that the fuel is injected directly into the flame zone and, thus, does not have the potential for autoignition or flashback and should have greater stability. However, since it is not premixed and prevaporized, the key is good atomization and mixing of the fuel quickly and uniformly so that flame temperatures are low and NOx formation levels are comparable to those of LPP.

  1. Impaired Emotion Regulation in Schizophrenia: Evidence From Event-Related Potentials

    PubMed Central

    Horan, William P.; Hajcak, Greg; Wynn, Jonathan K.; Green, Michael F.

    2014-01-01

    Background Although several aspects of emotion appear intact in schizophrenia, there is emerging evidence that patients show an impaired ability to adaptively regulate their emotions. This ERP study examined whether schizophrenia is associated with impaired neural responses to appraisal frames – i.e., when negative stimuli are presented in a less negative context. Methods 31 schizophrenia outpatients and 27 healthy controls completed a validated picture viewing task with three conditions: 1) Neutral pictures preceded by neutral descriptions (“Neutral”), 2) Unpleasant pictures preceded by negative descriptions (“Preappraised negative”), 3) Unpleasant pictures preceded by more neutral descriptions (“Preappraised neutral”). Analyses focused on the Late Positive Potential (LPP), an index of facilitated attention to emotional stimuli that is reduced following cognitive emotion regulation strategies, during four time windows from 300 – 2000 ms post picture onset. Results Replicating prior studies, controls showed smaller LPP in Preappraised neutral and Neutral vs. Preappraised negative conditions throughout 300 – 2000 ms. In contrast, patients showed (a) larger LPP in Preappraised neutral and Preappraised negative vs. Neutral conditions in the initial period (300 – 600 ms) and (b) an atypical pattern of larger LPP to Preappraised neutral vs. Preappraised negative and Neutral conditions in the 600–1500 ms epochs. Conclusions Modulation of neural responses by a cognitive emotion regulation strategy appears impaired in schizophrenia during the first two seconds after exposure to unpleasant stimuli. PMID:23360592

  2. Language Policy as a Sociocultural Tool: Insights from the University of Cape Town

    ERIC Educational Resources Information Center

    Karjalainen, Magda

    2016-01-01

    This theoretically oriented article draws on the author's previous research, which examined language policy and planning (LPP) of the University of Cape Town within the context of post-apartheid transformation driven by need to redress inequalities of the past, and demands of globalization. Drawing on critical linguistics, but indicating…

  3. BIODEGRADATION OF ORGANOPHOSPHORUS PESTICIDES BY SURFACE-EXPRESSED ORGANOPHOSPHORUS HYDROLASE. (R823663)

    EPA Science Inventory

    Organophosphorus hydrolase (OPH) was displayed and anchored onto the surface of
    Escherichia coli using an Lpp-OmpA fusion system. Production of the fusion proteins in membrane
    fractions was verified by immunoblotting with OmpA antisera. inclusion of the organophosphorus
    ...

  4. Slicing the Onion Ethnographically: Layers and Spaces in Multilingual Language Education Policy and Practice

    ERIC Educational Resources Information Center

    Hornberger, Nancy H.; Johnson, David Cassels

    2007-01-01

    In this article, we take up the call for more multilayered and ethnographic approaches to language policy and planning (LPP) research by sharing two examples of how ethnography can illuminate local interpretation and implementation. We offer ethnographic data collected in two very different institutions--the School District of Philadelphia and the…

  5. An electrocortical investigation of voluntary emotion regulation in combat-related posttraumatic stress disorder.

    PubMed

    Fitzgerald, Jacklynn M; MacNamara, Annmarie; DiGangi, Julia A; Kennedy, Amy E; Rabinak, Christine A; Patwell, Ryan; Greenstein, Justin E; Proescher, Eric; Rauch, Sheila A M; Hajcak, Greg; Phan, K Luan

    2016-03-30

    Posttraumatic stress disorder (PTSD) - a debilitating disorder characterized by severe deficits in emotion regulation - is prevalent among U.S. military veterans. Research into the pathophysiology of PTSD has focused primarily on emotional reactivity, showing evidence of heightened neural response during negative affect provocation. By comparison, studies of brain functioning during the voluntary regulation of negative affect are limited. In the current study, combat-exposed U.S. military veterans with (n=25) and without (n=25) PTSD performed an emotion regulation task during electroencephalographic (EEG) recording. The late positive potential (LPP) was used as a measure of sustained attention toward, and processing of, negative and neutral pictures, and was scored prior to and after instructions to either maintain or down-regulate emotional response using the strategy of cognitive reappraisal. Results showed that groups did not differ in picture-elicited LPP amplitude either prior to or during cognitive reappraisal; reappraisal reduced the LPP in both groups over time. Time-dependent increases in LPP amplitude as a function of emotional reactivity maintenance were evident in the non-PTSD group only. This latter finding may signal PTSD-related deficits in sustained engagement with emotion-processing over the course of several seconds. PMID:26922156

  6. Synthesis of high efficient Ca2SiO4:Eu2+ green emitting phosphor by a liquid phase precursor method

    NASA Astrophysics Data System (ADS)

    Luo, Y. Y.; Jo, D. S.; Senthil, K.; Tezuka, S.; Kakihana, M.; Toda, K.; Masaki, T.; Yoon, D. H.

    2012-05-01

    Green emitting Eu2+-doped Ca2SiO4 phosphors were synthesized by three different methods (a conventional solid state reaction (SSR) method, a novel liquid phase precursor approach using SiO2 sol (LPP-SiO2(sol)) and water-soluble silicon compound (LPP-WSS)). The obtained phosphors exhibited a broad excitation spectrum ranging from 225 to 450 nm and a strong green emission peak at 502 nm due to the 4f65d1→4f7(8S7/2) transition of Eu2+. The highest luminescent intensity was obtained for the samples fired at 1100 °C. The dependence of luminescence properties on Eu2+ concentration for the phosphors synthesized using LPP-WSS method was also examined from 0.1 to 5.0 mol% and the maximum emission intensity was observed at 3.0 mol% Eu2+. A detailed analysis using various characterizations revealed that phosphors produced by the LPP-WSS process exhibited more homogenous phase distribution and higher luminescence intensity than those from the other two processes, which suggested the potential application of Ca2SiO4:Eu2+ in white light-emitting diodes and fluorescence lamps.

  7. Somatomotor and sensory urethral control of micturition in female rats

    PubMed Central

    Cruz, Yolanda; Pastelín, César; Balog, Brian M.; Zaszczurynski, Paul J.

    2014-01-01

    In rats, axons of external urethral sphincter (EUS) motoneurons travel through the anastomotic branch of the pudendal nerve (ABPD) and anastomotic branch of the lumbosacral trunk (ABLT) and converge in the motor branch of the sacral plexus (MBSP). The aim of the present study was to determine in female rats the contribution of these somatomotor pathways and urethral sensory innervation from the dorsal nerve of the clitoris on urinary continence and voiding. EUS electromyographic (EMG) activity during cystometry, leak point pressure (LPP), and voiding efficiency (VE) were assessed in anesthetized virgin Sprague-Dawley female rats before and after transection of the above nerve branches. Transection of the MBSP eliminated EUS EMG, decreased LPP by 50%, and significantly reduced bladder contraction duration, peak pressure, intercontraction interval, and VE. Transection of the ABPD or ABLT decreased EUS EMG discharge and LPP by 25% but did not affect VE. Transection of the dorsal nerve of the clitoris did not affect LPP but reduced contraction duration, peak pressure, intercontraction interval, and VE. We conclude that somatomotor control of micturition is provided by the MBSP with axons travelling through the ABPD and ABLT. Partial somatomotor urethral denervation induces mild urinary incontinence, whereas partial afferent denervation induces voiding dysfunction. ABPD and ABLT pathways could represent a safeguard ensuring innervation to the EUS in case of upper nerve damage. Detailed knowledge of neuroanatomy and functional innervation of the urethra will enable more accurate animal models of neural development, disease, and dysfunction in the future. PMID:25339694

  8. The neural and psychological basis of herding in purchasing books online: an event-related potential study.

    PubMed

    Chen, Mingliang; Ma, Qingguo; Li, Minle; Dai, Shenyi; Wang, Xiaoyi; Shu, Liangchao

    2010-06-01

    In this study, event-related brain potentials (ERPs) were used to investigate the neural and psychological bases of consumer herding decision in purchasing books online. Sixteen participants were asked to decide as quickly as possible whether to buy a book on the basis of its title keywords and the numbers of positive and negative reviews in stimulus. The given title keywords were very similar, and participants did not have special preference for any particular one. Hence, they were forced to adopt the strategy of herding decision: choosing to buy the book when there were consistent positive reviews, choosing not to buy when there were consistent negative reviews, randomly choosing to buy or not to buy when there were no consistent reviews. The herding decision triggers a categorical processing of the consistency level of customer reviews. Remarkable late positive potential (LPP), a component of ERP sensitive to categorization processes, was elicited. The LPP amplitudes varied as a function of review consistency. The LPP amplitudes for three categories of review consistency were significantly different, and their order is such that absolute consistent review was greater than relative consistent review, which was greater than inconsistent review. In addition, behavioral data revealed that the higher the consistency of the customer reviews, the higher the herd rate. It is possible that customer reviews with higher consistency let participants make herding decisions more resolutely. The present results suggest that the LPP may be regarded as an endogenous neural signal of the herding mechanism in a sense and that the LPP amplitude is potentially a measure of consumers' herd tendency in purchase decisions. PMID:20557253

  9. A type IV translocated Legionella cysteine phytase counteracts intracellular growth restriction by phytate.

    PubMed

    Weber, Stephen; Stirnimann, Christian U; Wieser, Mara; Frey, Daniel; Meier, Roger; Engelhardt, Sabrina; Li, Xiaodan; Capitani, Guido; Kammerer, Richard A; Hilbi, Hubert

    2014-12-01

    The causative agent of Legionnaires' pneumonia, Legionella pneumophila, colonizes diverse environmental niches, including biofilms, plant material, and protozoa. In these habitats, myo-inositol hexakisphosphate (phytate) is prevalent and used as a phosphate storage compound or as a siderophore. L. pneumophila replicates in protozoa and mammalian phagocytes within a unique "Legionella-containing vacuole." The bacteria govern host cell interactions through the Icm/Dot type IV secretion system (T4SS) and ∼300 different "effector" proteins. Here we characterize a hitherto unrecognized Icm/Dot substrate, LppA, as a phytate phosphatase (phytase). Phytase activity of recombinant LppA required catalytically essential cysteine (Cys(231)) and arginine (Arg(237)) residues. The structure of LppA at 1.4 Å resolution revealed a mainly α-helical globular protein stabilized by four antiparallel β-sheets that binds two phosphate moieties. The phosphates localize to a P-loop active site characteristic of dual specificity phosphatases or to a non-catalytic site, respectively. Phytate reversibly abolished growth of L. pneumophila in broth, and growth inhibition was relieved by overproduction of LppA or by metal ion titration. L. pneumophila lacking lppA replicated less efficiently in phytate-loaded Acanthamoeba castellanii or Dictyostelium discoideum, and the intracellular growth defect was complemented by the phytase gene. These findings identify the chelator phytate as an intracellular bacteriostatic component of cell-autonomous host immunity and reveal a T4SS-translocated L. pneumophila phytase that counteracts intracellular bacterial growth restriction by phytate. Thus, bacterial phytases might represent therapeutic targets to combat intracellular pathogens. PMID:25339170

  10. The relationship between plasmapause, solar wind and geomagnetic activity between 2007 and 2011

    NASA Astrophysics Data System (ADS)

    Verbanac, G.; Pierrard, V.; Bandić, M.; Darrouzet, F.; Rauch, J.-L.; Décréau, P.

    2015-10-01

    Taking advantage of the Cluster satellite mission and especially the observations made by the instrument WHISPER to deduce the electron number density along the orbit of the satellites, we studied the relationships between the plasmapause positions (LPP) and the following LPP indicators: (a) solar wind coupling functions Bz (Z component of the interplanetary magnetic field vector, B, in GSM system), BV (related to the interplanetary electric field; B is the magnitude of the interplanetary magnetic field vector, V is solar wind velocity), and dΦmp/dt (which combines different physical processes responsible for the magnetospheric activity) and (b) geomagnetic indices Dst, Ap and AE. The analysis is performed separately for three magnetic local time (MLT) sectors (Sector1 - night sector (01:00-07:00 MLT); Sector2 - day sector (07:00-16:00 MLT); Sector3 - evening sector (16:00-01:00 MLT)) and for all MLTs taken together. All LPP indicators suggest the faster plasmapause response in the postmidnight sector. Delays in the plasmapause responses (hereafter time lags) are approximately 2-27 h, always increasing from Sector1 to Sector3. The obtained fits clearly resolve the MLT structures. The variability in the plasmapause is the largest for low values of LPP indicators, especially in Sector2. At low activity levels,LPP exhibits the largest values on the dayside (in Sector2) and the smallest on the postmidnight side (Sector1). Displacements towards larger values on the evening side (Sector3) and towards lower values on the dayside (Sector2) are identified for enhanced magnetic activity. Our results contribute to constraining the physical mechanisms involved in the plasmapause formation and to further study the still not well understood related issues.