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Sample records for kas lpp kaosele

  1. 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.

  2. 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.

  3. Driver fatigue recognition based on supervised LPP and MKSVM

    NASA Astrophysics Data System (ADS)

    Huang, Wei; Zhang, Wei

    2011-06-01

    Driver fatigue is a significant factor in many traffic accidents. In this paper, a novel approach is proposed to recognize driver fatigue. First of all, in order to extract effective feature of fatigue expression from face images, supervised locality preserving projections (SLPP) is adopted, which can solve the problem that LPP ignores the within-class local structure by adopting prior class label information. And then multiple kernels support vector machines (MKSVM) is employed to recognizing fatigue expression, Compared to SVM, which can improve the interpretability of decision function and performance of fatigue recognition. Experimental results are shown to demonstrate the effectiveness of the proposed method.

  4. Utilizing the Learning Promotion Potential (LPP) Framework to Facilitate Application of Higher-Order Cognitive Skills

    ERIC Educational Resources Information Center

    Odiemo, Luke Okunya

    2009-01-01

    Introduction: Different authors have proposed LPP as a pedagogical theorization framework to facilitate the linkage of psychological theory to teaching practice because it is useful for designing and assessing the effectiveness of pedagogical practice. This study aimed at testing the utility of the LPP-based theory-informed strategy at promoting…

  5. 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.

  6. Antigenic and Genetic Characterization of Lipoprotein LppQ from Mycoplasma mycoides subsp. mycoides SC

    PubMed Central

    Abdo, El-Mostafa; Nicolet, Jacques; Frey, Joachim

    2000-01-01

    Lipoprotein LppQ, a predominant 48-kDa antigen, and its corresponding gene, lppQ, were characterized in Mycoplasma mycoides subsp. mycoides SC, the etiological agent of contagious bovine pleuropneumonia. The lppQ gene is specific to M. mycoides subsp. mycoides SC and was found in the type strain and in field strains isolated in Europe, Africa, and Australia, as well as in vaccinal strains. LppQ is encoded as a precursor with a consensus sequence for prokaryotic signal peptidase II and a lipid attachment site. The leader sequence shows significant prominent transmembrane helix structure with a predicted outside-to-inside helix formation capacity. The N-terminal domain of the mature LppQ was shown to be surface exposed. It induced a strong, specific, early, and persistent immune response in naturally and experimentally infected animals. The C-terminal domain of LppQ possesses an integral membrane structure built up of repeated units, rich in hydrophobic and aromatic amino acids, which have a pore formation potential. A recombinant peptide representing the N-terminal domain of LppQ was obtained by site-directed mutagenesis of nine Mycoplasma-specific TGA (Trp) codons into universal TGG (Trp) codons and expression in Escherichia coli hosts. It was used for serodetection of cattle infected with M. mycoides subsp. mycoides SC, in which it was detected postinfection for significantly longer than conventional serological test reactions. PMID:10882657

  7. Performance of 100-W HVM LPP-EUV source

    NASA Astrophysics Data System (ADS)

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

    2015-08-01

    At Gigaphoton Inc., we have developed unique and original technologies for a carbon dioxide laser-produced tin plasma extreme ultraviolet (CO2-Sn-LPP EUV) light source, which is the most promising solution for high-power high-volume manufacturing (HVM) EUV lithography at 13.5 nm. Our unique technologies include the combination of a pulsed CO2 laser with Sn droplets, the application of dual-wavelength laser pulses for Sn droplet conditioning, and subsequent EUV generation and magnetic field mitigation. Theoretical and experimental data have clearly shown the advantage of our proposed strategy. Currently, we are developing the first HVM light source, `GL200E'. This HVM light source will provide 250-W EUV power based on a 20-kW level pulsed CO2 laser. The preparation of a high average-power CO2 laser (more than 20 kW output power) has been completed in cooperation with Mitsubishi Electric Corporation. Recently, we achieved 140 W at 50 kHz and 50% duty cycle operation as well as 2 h of operation at 100 W of power level. Further improvements are ongoing. We will report the latest status and the challenge to reach stable system operation of more than 100 W at about 4% conversion efficiency with 20-μm droplets and magnetic mitigation.

  8. Performance of one hundred watt HVM LPP-EUV source

    NASA Astrophysics Data System (ADS)

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

    2015-03-01

    We have been developing CO2-Sn-LPP EUV light source which is the most promising solution as the 13.5nm high power light source for HVM EUVL. Unique and original technologies such as: combination of pulsed CO2 laser and Sn droplets, dual wavelength laser pulses shooting, and mitigation with magnetic field, have been developed in Gigaphoton Inc. The theoretical and experimental data have clearly showed the advantage of our proposed strategy. Based on these data we are developing first practical source for HVM - "GL200E". This data means 250W EUV power will be able to realize around 20kW level pulsed CO2 laser. We have reported engineering data from our recent test such around 43W average clean power, CE=2.0%, with 100kHz operation and other data 19). We have already finished preparation of higher average power CO2 laser more than 20kW at output power cooperate with Mitsubishi Electric Corporation 14). Recently we achieved 92W with 50kHz, 50% duty cycle operation 20). We have reported component technology progress of EUV light source system. We report promising experimental data and result of simulation of magnetic mitigation system in Proto #1 system. We demonstrated several data with Proto #2 system: (1) emission data of 140W in burst under 70kHz 50% duty cycle during 10 minutes. (2) emission data of 118W in burst under 60kHz 70% duty cycle during 10 minutes. (3) emission data of 42W in burst under 20kHz 50% duty cycle (10000pls/0.5ms OFF) during 3 hours (110Mpls). Also we report construction of Pilot #1 system. Final target is week level operation with 250W EUV power with CE=4%, more than 27kW CO2 laser power by the end of Q2 of 2015.

  9. Domain analysis of lipoprotein LppQ in Mycoplasma mycoides subsp. mycoides SC

    PubMed Central

    Bonvin-Klotz, Laetitia; Kühni-Boghenbor, Kathrin; Kapp, Nadine; Frey, Joachim; Stoffel, Michael H.

    2007-01-01

    The lipoprotein LppQ is the most prominent antigen of Mycoplasma mycoides subsp. mycoides small colony type (SC) during infection of cattle. This pathogen causes contagious bovine pleuropneumonia (CBPP), a devastating disease of considerable socio-economic importance in many countries worldwide. The dominant antigenicity and high specificity for M. mycoides subsp. mycoides SC of lipoprotein LppQ have been exploited for serological diagnosis and for epidemiological investigations of CBPP. Scanning electron microscopy and immunogold labelling were used to provide ultrastructural evidence that LppQ is located to the cell membrane at the outer surface of M. mycoides subsp. mycoides SC. The selectivity and specificity of this method were demonstrated through discriminating localization of extracellular (i.e., in the zone of contact with host cells) vs. integral membrane domains of LppQ. Thus, our findings support the suggestion that the accessible N-terminal domain of LppQ is surface exposed and such surface localization may be implicated in the pathogenesis of CBPP. PMID:17674137

  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. The large universal Pantoea plasmid LPP-1 plays a major role in biological and ecological diversification

    PubMed Central

    2012-01-01

    Background Pantoea spp. are frequently isolated from a wide range of ecological niches and have various biological roles, as plant epi- or endophytes, biocontrol agents, plant-growth promoters or as pathogens of both plant and animal hosts. This suggests that members of this genus have undergone extensive genotypic diversification. One means by which this occurs among bacteria is through the acquisition and maintenance of plasmids. Here, we have analyzed and compared the sequences of a large plasmid common to all sequenced Pantoea spp. Results and discussion The Large PantoeaPlasmids (LPP-1) of twenty strains encompassing seven different Pantoea species, including pathogens and endo-/epiphytes of a wide range of plant hosts as well as insect-associated strains, were compared. The LPP-1 plasmid sequences range in size from ~281 to 794 kb and carry between 238 and 750 protein coding sequences (CDS). A core set of 46 proteins, encompassing 2.2% of the total pan-plasmid (2,095 CDS), conserved among all LPP-1 plasmid sequences, includes those required for thiamine and pigment biosynthesis. Phylogenetic analysis reveals that these plasmids have arisen from an ancestral plasmid, which has undergone extensive diversification. Analysis of the proteins encoded on LPP-1 also showed that these plasmids contribute to a wide range of Pantoea phenotypes, including the transport and catabolism of various substrates, inorganic ion assimilation, resistance to antibiotics and heavy metals, colonization and persistence in the host and environment, pathogenesis and antibiosis. Conclusions LPP-1 is universal to all Pantoea spp. whose genomes have been sequenced to date and is derived from an ancestral plasmid. LPP-1 encodes a large array of proteins that have played a major role in the adaptation of the different Pantoea spp. to their various ecological niches and their specialization as pathogens, biocontrol agents or benign saprophytes found in many diverse environments. PMID:23151240

  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. 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.

  16. Genetic and Serological Analysis of Lipoprotein LppA in Mycoplasma mycoides subsp. mycoides LC and Mycoplasma mycoides subsp. capri

    PubMed Central

    Monnerat, Marie-Pierre; Thiaucourt, François; Poveda, Jose B.; Nicolet, Jacques; Frey, Joachim

    1999-01-01

    The genes encoding the 62-kDa lipoproteins from the Mycoplasma mycoides subsp. mycoides large-colony type (LC) strain Y-goat and the M. mycoides subsp. capri strain PG3 were cloned and analyzed by sequencing. These two lipoproteins have been named LppA[MmymyLC] and LppA[Mmyca], and their corresponding genes have been named lppA[MmymyLC] and lppA[Mmyca], respectively. The nucleotide and deduced amino acid sequences of these two lipoproteins showed a very high degree of similarity between these two mycoplasmas. Given the sequence data, LppA seems to fulfill the same structural functions as the previously described major lipoproteins P72 of M. mycoides subsp. mycoides small-colony type and P67 of the Mycoplasma species bovine group 7. Based on lppA gene sequences of M. mycoides subsp. mycoides LC and M. mycoides subsp. capri type strains, a specific PCR assay was developed so that it amplified this gene in all field strains of the two species analyzed in this study but not in the other members of the M. mycoides cluster. Analysis of the PCR-amplified lppA genes with frequently cutting restriction enzymes showed a certain degree of genetic variability which, however, did not cluster the two subspecies. This PCR therefore allows a rapid identification of M. mycoides subsp. mycoides LC and M. mycoides subsp. capri but does not distinguish between these two closely related subspecies. LppA was expressed in Escherichia coli K-12 and used for the production of polyclonal mouse antiserum. Antibodies against recombinant LppA[MmymyLC] reacted with a 62-kDa protein in all M. mycoides subsp. mycoides LC and M. mycoides subsp. capri type strains and field strains tested but not with the other members of the M. mycoides cluster, thus showing the antigenic specificity of LppA and further supporting the concept that a close relationship exists between these two mycoplasmas. PMID:10066658

  17. 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

  18. Expression of LPP3 in Bergmann glia is required for proper cerebellar sphingosine-1-phosphate metabolism/signaling and development

    PubMed Central

    López-Juárez, Alejandro; Morales-Lázaro, Sara; Sánchez-Sánchez, Roberto; Sunkara, Manjula; Lomelí, Hilda; Velasco, Iván; Morris, Andrew J.; Escalante-Alcalde, Diana

    2011-01-01

    Bioactive lipids serve as intracellular and extracellular mediators in cell signaling in normal and pathological conditions. Here we describe that an important regulator of some of these lipids, the lipid phosphate phosphatase-3 (LPP3), is abundantly expressed in specific plasma membrane domains of Bergmann glia (BG), a specialized type of astrocyte with key roles in cerebellum development and physiology. Mice selectively lacking expression of LPP3/Ppap2b in the nervous system are viable and fertile but exhibit defects in postnatal cerebellum development and modifications in the cytoarchitecture and arrangement of BG with a mild non-progressive motor coordination defect. Lipid and gene profiling studies in combination with pharmacological treatments suggest that most of these effects are associated with alterations in sphingosine-1-phosphate (S1P) metabolism and signaling. Altogether our data indicate that LPP3 participates in several aspects of neuron-glia communication required for proper cerebellum development. PMID:21319224

  19. Expression of LPP3 in Bergmann glia is required for proper cerebellar sphingosine-1-phosphate metabolism/signaling and development.

    PubMed

    López-Juárez, Alejandro; Morales-Lázaro, Sara; Sánchez-Sánchez, Roberto; Sunkara, Manjula; Lomelí, Hilda; Velasco, Iván; Morris, Andrew J; Escalante-Alcalde, Diana

    2011-04-01

    Bioactive lipids serve as intracellular and extracellular mediators in cell signaling in normal and pathological conditions. Here we describe that an important regulator of some of these lipids, the lipid phosphate phosphatase-3 (LPP3), is abundantly expressed in specific plasma membrane domains of Bergmann glia (BG), a specialized type of astrocyte with key roles in cerebellum development and physiology. Mice selectively lacking expression of LPP3/Ppap2b in the nervous system are viable and fertile but exhibit defects in postnatal cerebellum development and modifications in the cytoarchitecture and arrangement of BG with a mild non-progressive motor coordination defect. Lipid and gene profiling studies in combination with pharmacological treatments suggest that most of these effects are associated with alterations in sphingosine-1-phosphate (S1P) metabolism and signaling. Altogether our data indicate that LPP3 participates in several aspects of neuron-glia communication required for proper cerebellum development.

  20. 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

  1. 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

  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. 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

  4. Severe neural tube defects in the loop-tail mouse result from mutation of Lpp1, a novel gene involved in floor plate specification.

    PubMed

    Murdoch, J N; Doudney, K; Paternotte, C; Copp, A J; Stanier, P

    2001-10-15

    Neural tube defects (NTD) are clinically important congenital malformations whose molecular mechanisms are poorly understood. The loop-tail (Lp) mutant mouse provides a model for the most severe NTD, craniorachischisis, in which the brain and spinal cord remain open. During a positional cloning approach, we have identified a mutation in a novel gene, Lpp1, in the Lp mouse, providing a strong candidate for the genetic causation of craniorachischisis in LP: Lpp1 encodes a protein of 521 amino acids, with four transmembrane domains related to the Drosophila protein strabismus/van gogh (vang). The human orthologue, LPP1, shares 89% identity with the mouse gene at the nucleotide level and 99% identity at the amino acid level. Lpp1 is expressed in the ventral part of the developing neural tube, but is excluded from the floor plate where Sonic hedgehog (Shh) is expressed. Embryos lacking Shh express Lpp1 throughout the ventral neural tube, suggesting negative regulation of Lpp1 by SHH: Our findings suggest that the mutual interaction between Lpp1 and Shh may define the lateral boundary of floor plate differentiation. Loss of Lpp1 function disrupts neurulation by permitting more extensive floor plate induction by Shh, thereby inhibiting midline bending of the neural plate during initiation of neurulation.

  5. 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

  6. Acute Stress Dysregulates the LPP ERP Response to Emotional Pictures and Impairs Sustained Attention: Time-Sensitive Effects.

    PubMed

    Alomari, Rima A; Fernandez, Mercedes; Banks, Jonathan B; Acosta, Juliana; Tartar, Jaime L

    2015-05-20

    Stress can increase emotional vigilance at the cost of a decrease in attention towards non-emotional stimuli. However, the time-dependent effects of acute stress on emotion processing are uncertain. We tested the effects of acute stress on subsequent emotion processing up to 40 min following an acute stressor. Our measure of emotion processing was the late positive potential (LPP) component of the visual event-related potential (ERP), and our measure of non-emotional attention was the sustained attention to response task (SART). We also measured cortisol levels before and after the socially evaluated cold pressor test (SECPT) induction. We found that the effects of stress on the LPP ERP emotion measure were time sensitive. Specifically, the LPP ERP was only altered in the late time-point (30-40 min post-stress) when cortisol was at its highest level. Here, the LPP no longer discriminated between the emotional and non-emotional picture categories, most likely because neutral pictures were perceived as emotional. Moreover, compared to the non-stress condition, the stress-condition showed impaired performance on the SART. Our results support the idea that a limit in attention resources after an emotional stressor is associated with the brain incorrectly processing non-emotional stimuli as emotional and interferes with sustained attention.

  7. Acute Stress Dysregulates the LPP ERP Response to Emotional Pictures and Impairs Sustained Attention: Time-Sensitive Effects

    PubMed Central

    Alomari, Rima A.; Fernandez, Mercedes; Banks, Jonathan B.; Acosta, Juliana; Tartar, Jaime L.

    2015-01-01

    Stress can increase emotional vigilance at the cost of a decrease in attention towards non-emotional stimuli. However, the time-dependent effects of acute stress on emotion processing are uncertain. We tested the effects of acute stress on subsequent emotion processing up to 40 min following an acute stressor. Our measure of emotion processing was the late positive potential (LPP) component of the visual event-related potential (ERP), and our measure of non-emotional attention was the sustained attention to response task (SART). We also measured cortisol levels before and after the socially evaluated cold pressor test (SECPT) induction. We found that the effects of stress on the LPP ERP emotion measure were time sensitive. Specifically, the LPP ERP was only altered in the late time-point (30–40 min post-stress) when cortisol was at its highest level. Here, the LPP no longer discriminated between the emotional and non-emotional picture categories, most likely because neutral pictures were perceived as emotional. Moreover, compared to the non-stress condition, the stress-condition showed impaired performance on the SART. Our results support the idea that a limit in attention resources after an emotional stressor is associated with the brain incorrectly processing non-emotional stimuli as emotional and interferes with sustained attention. PMID:26010485

  8. Acute Stress Dysregulates the LPP ERP Response to Emotional Pictures and Impairs Sustained Attention: Time-Sensitive Effects.

    PubMed

    Alomari, Rima A; Fernandez, Mercedes; Banks, Jonathan B; Acosta, Juliana; Tartar, Jaime L

    2015-01-01

    Stress can increase emotional vigilance at the cost of a decrease in attention towards non-emotional stimuli. However, the time-dependent effects of acute stress on emotion processing are uncertain. We tested the effects of acute stress on subsequent emotion processing up to 40 min following an acute stressor. Our measure of emotion processing was the late positive potential (LPP) component of the visual event-related potential (ERP), and our measure of non-emotional attention was the sustained attention to response task (SART). We also measured cortisol levels before and after the socially evaluated cold pressor test (SECPT) induction. We found that the effects of stress on the LPP ERP emotion measure were time sensitive. Specifically, the LPP ERP was only altered in the late time-point (30-40 min post-stress) when cortisol was at its highest level. Here, the LPP no longer discriminated between the emotional and non-emotional picture categories, most likely because neutral pictures were perceived as emotional. Moreover, compared to the non-stress condition, the stress-condition showed impaired performance on the SART. Our results support the idea that a limit in attention resources after an emotional stressor is associated with the brain incorrectly processing non-emotional stimuli as emotional and interferes with sustained attention. PMID:26010485

  9. 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

  10. 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

  11. 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

  12. Physiological alterations in Bradybaena similaris (Stylommatophora: Bradybaenidae) induced by the entomopathogenic nematode Heterorhabditis indica (Rhabditida: Heterorhabditidae) strain LPP1.

    PubMed

    Tunholi, Victor Menezes; Monteiro, Caio Oliveira; Cristina da Silva, Lidiane; Dolinski, Claudia de Melo; José dos Santos, Marcos Antônio; Rodrigues, Maria de Lurdes de Azevedo; Bittencourt, Vânia Rita Elias Pinheiro; Pinheiro, Jairo; Tunholi-Alves, Vinícius Menezes

    2014-04-01

    Heterorhabditis is a nematode found in the soil that is used as an important biological control agent against various organisms. However, few studies have been performed of its use against snails and the present study is the first to investigate the effect of experimental exposure of Bradybaena similaris to Heterorhabditis indica LPP1. Two groups of 16 snails were formed: the control group (not exposed) and the treatment, which was exposed for three weeks to infective juveniles (J3) of H. indica LPP1. The entire experiment was conducted in duplicate, using a total of 64 snails. After this period, the snails were dissected to collect the hemolymph to evaluate the possible physiological alterations, namely total proteins, uric acid and hemolymph urea, as well as the activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) as a result of the infection. The terrariums were analyzed on alternate days throughout the experiment to count the dead snails. Intense proteolysis was observed in the infected snails. An increase in the level of uric acid and reduction of the hemolymph urea content indicated that the infection by H. indica results in the inversion of the excretion pattern of the host snail. Variations in the aminotransferase activities were also observed, with the infected group presenting significantly higher values (p<0.05) than the control group for both ALT and AST. The exposure to H. indica LPP1 caused 55% mortality, with the highest rate observed in the first week after exposure (30%). These results suggest that the use of H. indica LPP1 is a feasible alternative for the biological control of B. similaris.

  13. Comparison of the organophosphorus hydrolase surface display using InaVN and Lpp-OmpA systems in Escherichia coli.

    PubMed

    Karami, Ali; Latifi, Ali Mohammad; Khodi, Samaneh

    2014-03-28

    The purpose of this study was to compare the ability of an engineered Escherichia coli to degrade chlorpyrifos (Cp) using an organophosphorus hydrolase enzyme by employing the Lpp-OmpA chimera and the N-terminal domain of the ice nucleation protein as anchoring motifs. Tracing of the expression location of the recombinant protein using SDS-PAGE showed the presentation of OPH by both anchors on the outer membrane. This is the first report on the presentation of OPH on the cell surface by Lpp-OmpA under the control of the T7 promoter. The results showed cell growth in the presence of Cp as the sole source of energy, without growth inhibition, and with higher whole-cell activity for both cells harboring plasmids pENVO and pELMO, at approximately 10,342.85 and 10,857.14 U/mg, respectively. Noticeably, the protein displayed by pELMO was lower than the protein displayed by pENVO. It can be concluded that Lpp-OmpA can display less protein, but more functional OPH protein. These results highlight the high potential, of both engineered bacteria, for use in the bioremediation of pesticide-contaminated sources in the environment. PMID:24150492

  14. 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

  15. High average power CO II laser MOPA system for Tin target LPP EUV light source

    NASA Astrophysics Data System (ADS)

    Ariga, Tatsuya; Hoshino, Hideo; Endo, Akira

    2007-02-01

    Extreme ultraviolet lithography (EUVL) is the candidate for next generation lithography to be introduced by the semiconductor industry to HVM (high volume manufacturing) in 2013. The power of the EUVL light source has to be at least 115W at a wavelength of 13.5nm. A laser produced plasma (LPP) is the main candidate for this light source but a cost effective laser driver is the key requirement for the realization of this concept. We are currently developing a high power and high repetition rate CO II laser system to achieve 50 W intermediate focus EUV power with a Tin droplet target. We have achieved CE of 2.8% with solid Tin wire target by a transversely excited atmospheric (TEA) CO II laser MOPA system with pulse width, pulse energy and pulse repetition rate as 10~15 ns, 30 mJ and 10 Hz, respectively. A CO II laser system with a short pulse length less than 15 ns, a nominal average power of a few kW, and a repetition rate of 100 kHz, based on RF-excited, fast axial flow CO II laser amplifiers is under development. Output power of about 3 kW has been achieved with a pulse length of 15 ns at 130 kHz repletion rate in a small signal amplification condition with P(20) single line. The phase distortion of the laser beam after amplification is negligible and the beam can be focused to about 150μm diameter in 1/e2. The CO II laser system is reported on short pulse amplification performance using RF-excited fast axial flow lasers as amplifiers. And the CO II laser average output power scaling is shown towards 5~10 kW with pulse width of 15 ns from a MOPA system.

  16. Prevalence and Associated Factors of Prehypertension and Hypertension in Iranian Population: The Lifestyle Promotion Project (LPP)

    PubMed Central

    Tabrizi, Jafar Sadegh; Sadeghi-Bazargani, Homayoun; Farahbakhsh, Mostafa; Nikniaz, Leila; Nikniaz, Zeinab

    2016-01-01

    Background This population-based study aimed at investigating the prevalence and associated factors of prehypertension/hypertension in Iran. Methods and Findings The data (n = 2818) for this study were collected in 2015 as a part of the major Lifestyle Promotion Project (LPP) conducted in East Azerbaijan (urban and regional parts). The data for socio-demographic status, dietary information, and physical activity and anxiety levels were collected through validated questionnaires. Then, physical examination including systolic and diastolic blood pressure (SBP, DBP), body mass index (BMI) and conicity index was performed. First-morning spot urine (SU) sample was collected to assume salt intake. The One-way ANOVA, logistic regression, chi-square test and independent t-test were used for statistical analysis. The prevalence of prehypertension, stage I and stage II hypertension, and overall hypertension was 47.3%, 13.6%, 5.45% and 22.6% respectively. The mean systolic (p = 0.004) and diastolic (p<0.001) blood pressure in men were significantly higher than women. Results of logistic regression analysis showed that in both sexes, family history of hypertension, obesity, abdominal obesity, anxiety and having high levels of sodium intake were associated with high blood pressure (p< 0.05). Additionally, 45.8% of the hypertensive patients were aware of their disease, 10.0% of the aware patients, and 44.5% of everyone with high blood pressure were receiving antihypertensive medication. Conclusions Our data showed that prehypertension/hypertension is a major health problem in Iran. Focusing on identifying risk factors to hypertension, regular drug intake, good nutrition, physical activity, and changing lifestyles of patients with hypertension are essential. PMID:27783691

  17. 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

  18. 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

  19. 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

  20. A Celiac Cellular Phenotype, with Altered LPP Sub-Cellular Distribution, Is Inducible in Controls by the Toxic Gliadin Peptide P31-43

    PubMed Central

    Nanayakkara, Merlin; Kosova, Roberta; Lania, Giuliana; Sarno, Marco; Gaito, Alessandra; Galatola, Martina; Greco, Luigi; Cuomo, Marialaura; Troncone, Riccardo; Auricchio, Salvatore

    2013-01-01

    Celiac disease (CD) is a frequent inflammatory intestinal disease, with a genetic background, caused by gliadin-containing food. Undigested gliadin peptides P31-43 and P57-68 induce innate and adaptive T cell-mediated immune responses, respectively. Alterations in the cell shape and actin cytoskeleton are present in celiac enterocytes, and gliadin peptides induce actin rearrangements in both the CD mucosa and cell lines. Cell shape is maintained by the actin cytoskeleton and focal adhesions, sites of membrane attachment to the extracellular matrix. The locus of the human Lipoma Preferred Partner (LPP) gene was identified as strongly associated with CD using genome-wide association studies (GWAS). The LPP protein plays an important role in focal adhesion architecture and acts as a transcription factor in the nucleus. In this study, we examined the hypothesis that a constitutive alteration of the cell shape and the cytoskeleton, involving LPP, occurs in a cell compartment far from the main inflammation site in CD fibroblasts from skin explants. We analyzed the cell shape, actin organization, focal adhesion number, focal adhesion proteins, LPP sub-cellular distribution and adhesion to fibronectin of fibroblasts obtained from CD patients on a Gluten-Free Diet (GFD) and controls, without and with treatment with A-gliadin peptide P31-43. We observed a “CD cellular phenotype” in these fibroblasts, characterized by an altered cell shape and actin organization, increased number of focal adhesions, and altered intracellular LPP protein distribution. The treatment of controls fibroblasts with gliadin peptide P31-43 mimics the CD cellular phenotype regarding the cell shape, adhesion capacity, focal adhesion number and LPP sub-cellular distribution, suggesting a close association between these alterations and CD pathogenesis. PMID:24278174

  1. The CsgA and Lpp Proteins of an Escherichia coli O157:H7 Strain Affect HEp-2 Cell Invasion, Motility, and Biofilm Formation ▿

    PubMed Central

    Uhlich, Gaylen A.; Gunther, Nereus W.; Bayles, Darrell O.; Mosier, Derek A.

    2009-01-01

    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 biofilms on solid surfaces, invades cultured epithelial cells, and is more virulent in mice than strain 43895. In this study we compared the formic acid-soluble proteins expressed by strains 43895OR and 43895 using one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis and identified two differentially expressed proteins. A 17-kDa protein unique to strain 43895OR was identified from matrix-assisted laser desorption ionization-time of flight analysis combined with mass spectrometry (MS) and tandem MS (MS/MS) as the curli subunit encoded by csgA. A <10-kDa protein, more highly expressed in strain 43895, was identified as the Lpp lipoprotein. Mutants of strain 43895OR with disruption of lpp, csgA, or both lpp and csgA were created and tested for changes in phenotype and function. The results of this study show that both Lpp and CsgA contribute to the observed colony morphology, Congo red binding, motility, and biofilm formation. We also show that both CsgA and Lpp are required by strain 43895OR for the invasion of cultured HEp-2 cells. These studies suggest that in strain 43895OR, the murein lipoprotein Lpp indirectly regulates CsgA expression through the CpxAR system by a posttranscriptional mechanism. PMID:19179421

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

    PubMed Central

    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

  3. 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

  4. 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.

  5. 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

  6. 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.

  7. Mechanical Properties of the Extracellular Matrix Alter Expression of Smooth Muscle Protein LPP and its Partner Palladin; Relationship to Early Atherosclerosis and Vascular Injury

    PubMed Central

    Jin, Li; Hastings, Nicole E.; Blackman, Brett R.; Somlyo, Avril V.

    2010-01-01

    Lipoma preferred partner (LPP) localizes to focal adhesions/dense bodies, is selectively expressed in smooth muscle cells (SMC) and enhances cell migration. SMCs cultured on denatured collagen or on a rigid substrate, up regulated expression of LPP, its partner palladin, tenascin C (TN-C), phosphorylated focal adhesion kinase (pFAK) and exhibited robust stress fibers. In an endothelial (EC) /SMC hemodynamic flow system, shear stress waveforms mimicking atheroprone flow, applied to the EC layer, significantly decreased expression of SMC LPP and palladin. They were also down regulated with TN-C, in an ApoE murine model of atherosclerosis and with oxidative stress but up regulated in an arterial injury model in response to upstream sequential changes in pFAK, Prx1 and TN-C. In conclusion, expression of LPP and palladin are modulated by a mix of mechanical cues, oxidative stress and substrate composition which translate into their up or down regulation in vessel wall injury and early atherogenesis. PMID:19205907

  8. 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

  9. 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.

  10. 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

  11. Theoretical determination of the p Kas of the 8-hydroxyquinoline-5-sulfonic acid: A DFT based approach

    NASA Astrophysics Data System (ADS)

    Le Bahers, Tangui; Adamo, Carlo; Ciofini, Ilaria

    2009-04-01

    The three acid dissociation constants (p Kas) of the 8-hydroxyquinoline-5-sulfonic acid were computed using a computational protocol based on Density Functional Theory. A hybrid exchange correlation functional was applied and bulk solvent effects were treated within the framework of the Polarizable Continuum Model. Direct solute-solvent interactions were taken into account adding explicit water molecules. The computed p Kas are in line with the experimental data and allow better defining the first p Ka, confirmed to be negative. From the calculated p Kas, 'ab initio' distribution diagrams of the relative concentration of the different species in solution as a function of pH were drawn.

  12. 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

  13. 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

  14. The Legionella pneumophila F-box protein Lpp2082 (AnkB) modulates ubiquitination of the host protein parvin B and promotes intracellular replication.

    PubMed

    Lomma, M; Dervins-Ravault, D; Rolando, M; Nora, T; Newton, H J; Sansom, F M; Sahr, T; Gomez-Valero, L; Jules, M; Hartland, E L; Buchrieser, C

    2010-09-01

    The environmental pathogen Legionella pneumophila encodes three proteins containing F-box domains and additional protein-protein interaction domains, reminiscent of eukaryotic SCF ubiquitin-protein ligases. Here we show that the F-box proteins of L. pneumophila strain Paris are Dot/Icm effectors involved in the accumulation of ubiquitinated proteins associated with the Legionella-containing vacuole. Single, double and triple mutants of the F-box protein encoding genes were impaired in infection of Acanthamoeba castellanii, THP-1 macrophages and human lung epithelial cells. Lpp2082/AnkB was essential for infection of the lungs of A/J mice in vivo, and bound Skp1, the interaction partner of the SCF complex in mammalian cells, similar to AnkB from strain AA100/130b. Using a yeast two-hybrid screen and co-immunoprecipitation analysis we identified ParvB a protein present in focal adhesions and in lamellipodia, as a target. Immunofluorescence analysis confirmed that ectopically expressed Lpp2082/AnkB colocalized with ParvB at the periphery of lamellipodia. Unexpectedly, ubiquitination tests revealed that Lpp2082/AnkB diminishes endogenous ubiquitination of ParvB. Based on these results we propose that L. pneumophila modulates ubiquitination of ParvB by competing with eukaryotic E3 ligases for the specific protein-protein interaction site of ParvB, thereby revealing a new mechanism by which L. pneumophila may employ translocated effector proteins to promote bacterial survival.

  15. Thiolactomycin-based β-Ketoacyl-AcpM Synthase A (KasA) Inhibitors

    PubMed Central

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

    2013-01-01

    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

  16. 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

  17. 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

  18. 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

  19. Synthesis of arbitrary pulse waveforms in QCL-seeded ns-pulse CO2 laser for optimization of an LPP EUV source.

    PubMed

    Nowak, Krzysztof M; Kurosawa, Yoshiaki; Suganuma, Takashi; Kawasuji, Yasufumi; Nakarai, Hiroaki; Saito, Takashi; Fujimoto, Junichi; Mizoguchi, Hakaru

    2016-07-01

    One of the unique features of the quantum-cascade-laser-seeded, nanosecond-pulse CO2 laser, invented for the purpose of generation of extreme UV by laser-produced-plasma, is a robust synthesis of arbitrary pulse waveforms. In the present Letter we report on experimental results that are, to our best knowledge, the first demonstration of such functionality obtainable from nanosecond-pulse CO2 laser technology. An online pulse duration adjustment within 10-40 ns was demonstrated, and a few exemplary pulse waveforms were synthesized, such as "tophat," "tailspike," and "leadspike" shapes. Such output characteristics may be useful to optimize the performance of LPP EUV source. PMID:27367116

  20. Synthesis of arbitrary pulse waveforms in QCL-seeded ns-pulse CO2 laser for optimization of an LPP EUV source.

    PubMed

    Nowak, Krzysztof M; Kurosawa, Yoshiaki; Suganuma, Takashi; Kawasuji, Yasufumi; Nakarai, Hiroaki; Saito, Takashi; Fujimoto, Junichi; Mizoguchi, Hakaru

    2016-07-01

    One of the unique features of the quantum-cascade-laser-seeded, nanosecond-pulse CO2 laser, invented for the purpose of generation of extreme UV by laser-produced-plasma, is a robust synthesis of arbitrary pulse waveforms. In the present Letter we report on experimental results that are, to our best knowledge, the first demonstration of such functionality obtainable from nanosecond-pulse CO2 laser technology. An online pulse duration adjustment within 10-40 ns was demonstrated, and a few exemplary pulse waveforms were synthesized, such as "tophat," "tailspike," and "leadspike" shapes. Such output characteristics may be useful to optimize the performance of LPP EUV source.

  1. 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

  2. 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

  3. 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

  4. 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.

  5. 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.

  6. 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

  7. Docking studies of flavonoid compounds as inhibitors of β-ketoacyl acyl carrier protein synthase I (Kas I) of Escherichia coli.

    PubMed

    Sabbagh, Ghalia; Berakdar, Noura

    2015-09-01

    Escherichia coli is one of the most frequent causes of many common bacterial infections, including cholecystitis, bacteremia, cholangitis, urinary tract infection (UTI), traveler's diarrhea and other clinical infections such as neonatal meningitis and pneumonia. The fatty acid biosynthesis is essential for the bacterial viability and growth. There are three types of β-ketoacyl acyl carrier protein synthase (KAS) which are important for overcoming the bacterial resistance problem. β-ketoacyl acyl carrier protein synthase I (KAS I) is member of the condensing enzyme family, which is a key catalyst in bacterial fatty acid biosynthesis, and thus an attractive target for novel antibioticsis related to the elongation of unsaturated fatty acids in bacterial fatty acid synthesis and can be a good therapeutic target of designing novel antibiotics. In this report, we performed docking study of E. coli (KAS I) and 50 flavonoids. Out of these 50 flavonoids, there are two compounds, genistein and isorhamnetin, that showed the superior binding energy while fully satisfying the conditions of drug likeliness. The predicted binding energy of genistein and isorhamnetin toward KAS I are -135.76kcal/mol and -132.42kcal/mol, respectively. These energies favorably compare to the biding energy of known drugs thiolactomicin and cerulenin that are -90.26kcal/mol and -99.64kcal/mol, respectively. The method used was docking with the selected E. coli (KAS I-PDB ID-1FJ4) using iGemdock. This was also found to obey the Lipinski's guidelines of five and to show the drug likeliness and bioavailability. PMID:26292066

  8. 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

  9. Mitochondrial Protein Lipoylation Does Not Exclusively Depend on the mtKAS Pathway of de Novo Fatty Acid Synthesis in Arabidopsis1[W][OA

    PubMed Central

    Ewald, Ralph; Kolukisaoglu, Üner; Bauwe, Ursula; Mikkat, Stefan; Bauwe, Hermann

    2007-01-01

    The photorespiratory Arabidopsis (Arabidopsis thaliana) mutant gld1 (now designated mtkas-1) is deficient in glycine decarboxylase (GDC) activity, but the exact nature of the genetic defect was not known. We have identified the mtkas-1 locus as gene At2g04540, which encodes β-ketoacyl-[acyl carrier protein (ACP)] synthase (mtKAS), a key enzyme of the mitochondrial fatty acid synthetic system. One of its major products, octanoyl-ACP, is regarded as essential for the intramitochondrial lipoylation of several proteins including the H-protein subunit of GDC and the dihydrolipoamide acyltransferase (E2) subunits of two other essential multienzyme complexes, pyruvate dehydrogenase and α-ketoglutarate dehydrogenase. This view is in conflict with the fact that the mtkas-1 mutant and two allelic T-DNA knockout mutants grow well under nonphotorespiratory conditions. Although on a very low level, the mutants show residual lipoylation of H protein, indicating that the mutation does not lead to a full functional knockout of GDC. Lipoylation of the pyruvate dehydrogenase and α-ketoglutarate dehydrogenase E2 subunits is distinctly less reduced than that of H protein in leaves and remains unaffected from the mtKAS knockout in roots. These data suggest that mitochondrial protein lipoylation does not exclusively depend on the mtKAS pathway of lipoate biosynthesis in leaves and may occur independently of this pathway in roots. PMID:17616510

  10. 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

  11. 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

  12. Virus-induced silencing of Comt, pAmt and Kas genes results in a reduction of capsaicinoid accumulation in chili pepper fruits.

    PubMed

    del Rosario Abraham-Juárez, Ma; del Carmen Rocha-Granados, Ma; López, Mercedes G; Rivera-Bustamante, Rafael Francisco; Ochoa-Alejo, Neftalí

    2008-02-01

    Capsaicinoids are responsible for the pungent taste of chili pepper fruits of Capsicum species. Capsaicinoids are biosynthesized through both the phenylpropanoid and the branched-fatty acids pathways. Fragments of Comt (encoding a caffeic acid O-methyltransferase), pAmt (a putative aminotransferase), and Kas (a beta-keto-acyl-[acyl-carrier-protein] synthase) genes, that are differentially expressed in placenta tissue of pungent chili pepper, were individually inserted into a Pepper huasteco yellow veins virus (PHYVV)-derived vector to determine, by virus-induced gene silencing, irrespective of whether these genes are involved in the biosynthesis of capsaicinoids. Reduction of the respective mRNA levels as well as the presence of related siRNAs confirmed the silencing of these three genes. Morphological alterations were evident in plants inoculated with PHYVV::Comt and PHYVV::Kas constructs; however, plants inoculated with PHYVV::pAmt showed no evident alterations. On the other hand, fruit setting was normal in all cases. Biochemical analysis of placenta tissues showed that, indeed, independent silencing of all three genes led to a dramatic reduction in capsaicinoid content in the fruits demonstrating the participation of these genes in capsaicinoid biosynthesis. Using this approach it was possible to generate non-pungent chili peppers at high efficiency.

  13. 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

  14. [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

  15. 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…

  16. Progress in LPP EUV source development at Osaka University

    NASA Astrophysics Data System (ADS)

    Miyanaga, Noriaki; Nishimura, Hiroaki; Fujioka, Shinsuke; Aota, Tatsuya; Uchida, Shigeaki; Yamaura, Michiteru; Shimada, Yoshinori; Hashimoto, Kazuhisa; Nagai, Keiji; Norimatsu, Takayoshi; Nishihara, Katsunobu; Murakami, Masakatsu; Zhakhovskii, Vasilli; Kang, Young G.; Sunahara, Atsushi; Furukawa, Hiroyuki; Sasaki, Akira; Nishikawa, Takeshi; Nakatsuka, Massahiro; Fujita, Hisanori; Tsubakimoto, Koji; Yoshida, Hidetsugu; Izawa, Yasukazu; Mima, Kunioki

    2006-03-01

    For EUV lithography the generation of clean and efficient light source and the high-power laser technology are key issues. Theoretical understanding with modeling and simulation of laser-produced EUV source based on detailed experimental database gives us the prediction of optimal plasma conditions and their suitable laser conditions for different target materials (tin, xenon and lithium). With keeping etendue limit the optimal plasma size is determined by an appropriate optical depth which can be controlled by the combination of laser wavelength and pulse width. The most promising candidate is tin (Sn) plasma heated by Nd:YAG laser with a pulse width of a few ns. Therefore the generation technology of clean Sn plasma is a current important subject to be resolved for practical use. For this purpose we have examined the feasibility of laser-driven rocket-like injection of extremely mass-limited Sn or SnO II (punched-out target) with a speed exceeding 100m/s. Such a mass-limited low-density target is most preferable for substantial reduction of ion energy compared with usual bulk target. For high average power EUV generation we are developing a laser system which is CW laser diode pumped Nd:YAG ceramic laser (master oscillator and power amplifier system) operating at 5-10 kHz repetition rate. The design of practical laser for EUV source is being carried out based on the recent performance of >1 kW output power.

  17. 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.

  18. 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

  19. 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.

  20. Distributed database kriging for adaptive sampling (D²KAS)

    DOE PAGES

    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

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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.

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

    SciTech Connect

    Kristin Persson

    2014-07-09

    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

  7. 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.

  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. Global gene expression of a murein (Braun) lipoprotein mutant of Salmonella enterica serovar Typhimurium by microarray analysis.

    PubMed

    Fadl, A A; Galindo, C L; Sha, J; Klimpel, G R; Popov, V L; Chopra, A K

    2006-06-01

    Braun/murein lipoprotein (Lpp) is one of the major outer membrane components of gram-negative enteric bacteria involved in inflammatory responses and septic shock. In previous studies, we reported that two copies of the lipoprotein (lpp) gene (designated as lppA and lppB) existed on the chromosome of Salmonella enterica serovar Typhimurium. Deletion of both lppA and lppB genes rendered Salmonella defective in invasion, motility, induction of cytotoxicity, and production of inflammatory cytokines/chemokines. The lppAB double-knockout (DKO) mutant was attenuated in mice, and animals immunized with this mutant were protected against subsequent challenge with lethal doses of wild-type (wt) S. Typhimurium. To better understand how deletion of the lpp gene might affect Salmonella virulence, we performed global transcriptional profiling of the genes in the wt and the lppAB DKO mutant of S. Typhimurium using microarrays. Our data revealed alterations in the expression of flagellar genes, invasion-associated type III secretion system genes, and transcriptional virulence gene regulators in the lppAB DKO mutant compared to wt S. Typhimurium. These data correlated with the lppAB DKO mutant phenotype and provided possible mechanism(s) of Lpp-associated attenuation in S. Typhimurium. Although these studies were performed in in vitro grown bacteria, our future research will be targeted at global transcriptional profiling of the genes in in vivo grown wt S. Typhimurium and its Lpp mutant.

  11. Comments on "globally maximizing, locally minimizing: unsupervised discriminant projection with application to face and palm biometrics".

    PubMed

    Deng, Weihong; Hu, Jiani; Guo, Jun; Zhang, Honggang; Zhang, Chuang

    2008-08-01

    In [1], UDP is proposed to address the limitation of LPP for the clustering and classification tasks. In this communication, we show that the basic ideas of UDP and LPP are identical. In particular, UDP is just a simplified version of LPP on the assumption that the local density is uniform.

  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. The two murein lipoproteins of Salmonella enterica serovar Typhimurium contribute to the virulence of the organism.

    PubMed

    Sha, J; Fadl, A A; Klimpel, G R; Niesel, D W; Popov, V L; Chopra, A K

    2004-07-01

    Septic shock due to Salmonella and other gram-negative enteric pathogens is a leading cause of death worldwide. The role of lipopolysaccharide in sepsis is well studied; however, the contribution of other bacterial outer membrane components, such as Braun (murein) lipoprotein (Lpp), is not well defined. The genome of Salmonella enterica serovar Typhimurium harbors two copies of the lipoprotein (lpp) gene. We constructed a serovar Typhimurium strain with deletions in both copies of the lpp gene (lpp1 and lpp2) by marker exchange mutagenesis. The integrity of the cell membrane and the secretion of the effector proteins through the type III secretion system were not affected in the lpp double-knockout mutant. Subsequently, the virulence potential of this mutant was examined in a cell culture system using T84 intestinal epithelial and RAW264.7 macrophage cell lines and a mouse model of salmonellosis. The lpp double-knockout mutant was defective in invading and inducing cytotoxic effects in T84 and RAW264.7 cells, although binding of the mutant to the host cell was not affected when compared to the wild-type (WT) serovar Typhimurium. The motility of the mutant was impaired, despite the finding that the number of flagella was similar in the lpp double knockout mutant and the WT serovar Typhimurium. Deletion in the lpp genes did not affect the intracellular survival and replication of Salmonella in macrophages and T84 cells. Induction of the proinflammatory cytokines tumor necrosis factor alpha and interleukin-8 (IL-8) was significantly reduced in macrophages and T84 cells infected with the lpp double-knockout mutant. The levels of IL-8 remained unaffected in T84 cells when infected with either live or heat-killed WT and lpp mutant, indicating that invasion was not required for IL-8 production and that Toll-like receptor 2 signaling might be affected in the Lpp double-knockout mutant. These effects of the Lpp protein could be restored by complementation of the isogenic

  14. 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

  15. Murein lipoprotein is a critical outer membrane component involved in Salmonella enterica serovar typhimurium systemic infection.

    PubMed

    Fadl, A A; Sha, J; Klimpel, G R; Olano, J P; Niesel, D W; Chopra, A K

    2005-02-01

    Lipopolysaccharide (LPS) and Braun (murein) lipoprotein (Lpp) are major components of the outer membrane of gram-negative enteric bacteria that function as potent stimulators of inflammatory and immune responses. In a previous paper, we provided evidence that two functional copies of the lipoprotein gene (lppA and lppB) located on the chromosome of Salmonella enterica serovar Typhimurium contributed to bacterial virulence. In this study, we characterized lppA and lppB single-knockout (SKO) mutants and compared them with an lpp double-knockout (DKO) mutant using in vitro and in vivo models. Compared to the lpp DKO mutant, which was nonmotile, the motility of the lpp SKO mutants was significantly increased (73 to 77%), although the level of motility did not reach the level of wild-type (WT) S. enterica serovar Typhimurium. Likewise, the cytotoxicity was also significantly increased when T84 human intestinal epithelial cells and RAW264.7 murine macrophages were infected with the lpp SKO mutants compared to the cytotoxicity when cells were infected with the lpp DKO mutant. The level of interleukin-8 (IL-8) in polarized T84 cells infected with the lppB SKO mutant was significantly higher (two- to threefold higher), reaching the level in cells infected with WT S. enterica serovar Typhimurium, than the level in host cells infected with the lppA SKO mutant. The lpp DKO mutant induced minimal levels of IL-8. Similarly, sera from mice infected with the lppB SKO mutant contained 4.5- to 10-fold-higher levels of tumor necrosis factor-alpha and IL-6; the levels of these cytokines were 1.7- to 3.0-fold greater in the lppA SKO mutant-infected mice than in animals challenged with the lpp DKO mutant. The increased cytokine levels observed with the lppB SKO mutant in mice correlated with greater tissue damage in the livers and spleens of these mice than in the organs of animals infected with the lppA SKO and lpp DKO mutants. Moreover, the lppB SKO mutant-infected mice had increased

  16. 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

  17. Lichen Planopilaris Versus Discoid Lupus Erythematosus: A Trichoscopic Perspective

    PubMed Central

    Ankad, Balachandra S; Beergouder, Savitha L; Moodalgiri, Vishnu M

    2013-01-01

    Trichoscopy enables visualization of subsurface structures and color patterns of scalp and hair. Recently, its applications expanded to diagnose inflammatory conditions such as lichen planopilaris (LPP), scalp psoriasis, and discoid lupus erythematosus (DLE). Clinically, both LPP and DLE appear similar as cicatricial alopecia on the scalp making the diagnosis difficult. Here, we report the utility of trichoscopy in the clinical diagnosis of LPP and DLE. Clinically, suspected lesions of DLE and LPP on the scalp of each patient were observed under trichoscopy. Histopathology of lesions confirmed the clinical diagnosis. Authors observed characteristic trichoscopic features in LPP as well as in DLE proving the clinical diagnosis. Hence, trichoscopy can be used to diagnose LPP and DLE clinically avoiding skin biopsy. PMID:24778533

  18. Narrowband UVB-induced lichen planus pemphigoide

    PubMed Central

    Mandy Chan, Wai Man; See Lee, Joyce Siong; Thiam Theng, Colin Seng; Chua, Sze Hon; Boon Oon, Hazel Hwee

    2011-01-01

    Lichen planus pemphigoides (LPP) is an autoimmune disease characterised by evolution of subepidermal blisters on normal and lichen planus affected skin. We describe a case of LPP in a 54-year-old Chinese woman. The patient presented with psoriasiform plaques and was diagnosed with guttate psoriasis. Narrowband ultraviolet B (NBUVB) therapy was commenced, and she experienced a generalised eruption of violaceous papules, bullae over the lower limbs, and Wickham's striae over the buccal mucosa. Histology from a plaque revealed interface dermatitis, while a specimen from a blister showed subepidermal bulla. Direct immunofluorescence showed linear deposition of IgG and C3 along the basement membrane. A diagnosis of LPP was made on clinicopathological grounds. This is the first case report of NBUVB alone in unmasking LPP. In this case report, we describe the pathological mechanism of NBUVB in the development of LPP and key features distinguishing LPP from bullous lupus erythematosus, bullous lichen planus, bullous pemphigoid, and psoriasis. PMID:25386295

  19. 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

  20. 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

  1. 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

  2. An Engineered Strong Promoter for Streptomycetes

    PubMed Central

    Wang, Weishan; Li, Xiao; Wang, Juan; Xiang, Sihai; Feng, Xiaozhou

    2013-01-01

    Well-characterized promoters are essential tools for metabolic engineering and synthetic biology. In Streptomyces coelicolor, the native kasOp is a temporally expressed promoter strictly controlled by two regulators, ScbR and ScbR2. In this work, first, kasOp was engineered to remove a common binding site of ScbR and ScbR2 upstream of its core region, thus generating a stronger promoter, kasOp3. Second, another ScbR binding site internal to the kasOp3 core promoter region was abolished by random mutation and screening of the mutant library to obtain the strongest promoter, kasOp* (where the asterisk is used to distinguish the engineered promoter from the native promoter). The activities of kasOp* were compared with those of two known strong promoters, ermEp* and SF14p, in three Streptomyces species. kasOp* showed the highest activity at the transcription and protein levels in all three hosts. Furthermore, relative to ermEp* and SF14p, kasOp* was shown to confer the highest actinorhodin production level when used to drive the expression of actII-ORF4 in S. coelicolor. Therefore, kasOp* is a simple and well-defined strong promoter useful for gene overexpression in streptomycetes. PMID:23686264

  3. 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…

  4. 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,…

  5. 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…

  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. Quantification of neurological and other contributors to continence in female rats

    PubMed Central

    Jiang, Hai-Hong; Salcedo, Levilester B.; Damaser, Margot S.

    2011-01-01

    Smooth muscle, striated muscle, their central and peripheral innervations and control, and mucosal coaptation contribute to maintenance of continence. We used manual leak point pressure (mLPP) testing and electrical stimulation LPP (eLPP) testing in female rats to quantify the contribution of these factors to urethral resistance, a measure of continence. Abdominal muscles were electrically stimulated to induce leakage for eLPP. A Crede maneuver was applied for mLPP. These were repeated after complete T8 spinal cord injury (SCI) and/or bilateral pudendal nerve transection (PNT). After euthanasia, mLPP was repeated. MLPP was not significantly affected by opening the abdomen, suggesting that intra-abdominal pressure transmission contributes little to continence during slow pressure changes. ELPP was significantly higher than mLPP in intact rats, after PNT, and after SCI+PNT, suggesting that abdominal pressure transmission contributes to continence during rapid increases in intra-abdominal pressure. MLPP decreased significantly after PNT, indicating that urethral striated muscles contribute significantly to continence. ELPP decreased significantly after PNT with and without SCI, suggesting that supraspinal control significantly affects continence during rapid pressure changes, but not during slow pressure changes. MLPP after euthanasia was significantly decreased compared to mLPP after SCI+PNT, suggesting that urethral mucosal seal coaptation and tissue elasticity also contribute to continence. The urethra is a complex organ that maintains continence via a highly organized and hierarchical system involving both the central and peripheral nervous systems. PMID:21295013

  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. Transient tasks and enduring emotions: the impacts of affective content, task relevance, and picture duration on the sustained late positive potential.

    PubMed

    Gable, Philip A; Adams, David L; Proudfit, Greg Hajcak

    2015-03-01

    The present experiments were designed to examine the influences of picture duration, task relevance, and affective content on neural measures of sustained engagement, as indexed by the late positive potential (LPP). Much prior work has shown that the event-related potential in and around the P3-here referred to as the early LPP-is modulated by affective content, nonaffective task relevance, and stimulus duration. However, later portions of the LPP (>1,000 ms) may represent either a return to baseline or a continued physiological process related to motivational engagement. In the present experiments, we tested whether modulation of the later LPP depends on varying motivational engagement using stimulus duration, affective content, and task relevance. The results of Experiment 1 revealed that stimulus duration modulates the sustained LPP (i.e., 1,000-2,000 ms) in response to affective, but not task-relevant, stimuli from a modified counting oddball task. The results of Experiment 2 revealed that the sustained increase in the LPP is sensitive to both emotional content and task relevance when the task requires sustained engagement with target stimuli (e.g., determining the duration of stimulus presentation). The impacts of emotional content and task relevance had additive effects on the later portion of the LPP. In sum, both emotional content and task relevance can result in a protracted increase in the later LPP. These data suggest that affective content automatically sustains engagement, whereas task relevance only prolongs engagement when it is necessary for task completion.

  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. 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

  12. Evaluation of Staphylococcus aureus Lipoproteins: Role in Nutritional Acquisition and Pathogenicity

    PubMed Central

    Shahmirzadi, Shideh V.; Nguyen, Minh-Thu; Götz, Friedrich

    2016-01-01

    Bacterial lipoproteins (Lpp) represent a major class of membrane proteins. They are distinguished by a lipid moiety at the N-terminus by which they are anchored either in the outer leaflet of the cytoplasmic membrane or, in Gram-negative bacteria, also in the inner leaflet of the outer membrane. In Gram-positive bacteria Lpp significantly contribute to nutrient transport, Toll-like receptor 2 activation and pathogenicity. Here we examine the Lpp of Staphylococcus aureus USA300, as a prototype for a multiple antibiotic resistant and community-acquired pathogen that is rapidly spreading worldwide. The compiled Lpp were grouped according to the postulated function and dissemination of homologs in the genus Staphylococcus and beyond. Based on this evaluation we also point out Lpp as promising vaccine candidates.

  13. Evaluation of Staphylococcus aureus Lipoproteins: Role in Nutritional Acquisition and Pathogenicity

    PubMed Central

    Shahmirzadi, Shideh V.; Nguyen, Minh-Thu; Götz, Friedrich

    2016-01-01

    Bacterial lipoproteins (Lpp) represent a major class of membrane proteins. They are distinguished by a lipid moiety at the N-terminus by which they are anchored either in the outer leaflet of the cytoplasmic membrane or, in Gram-negative bacteria, also in the inner leaflet of the outer membrane. In Gram-positive bacteria Lpp significantly contribute to nutrient transport, Toll-like receptor 2 activation and pathogenicity. Here we examine the Lpp of Staphylococcus aureus USA300, as a prototype for a multiple antibiotic resistant and community-acquired pathogen that is rapidly spreading worldwide. The compiled Lpp were grouped according to the postulated function and dissemination of homologs in the genus Staphylococcus and beyond. Based on this evaluation we also point out Lpp as promising vaccine candidates. PMID:27679612

  14. Evaluation of Staphylococcus aureus Lipoproteins: Role in Nutritional Acquisition and Pathogenicity.

    PubMed

    Shahmirzadi, Shideh V; Nguyen, Minh-Thu; Götz, Friedrich

    2016-01-01

    Bacterial lipoproteins (Lpp) represent a major class of membrane proteins. They are distinguished by a lipid moiety at the N-terminus by which they are anchored either in the outer leaflet of the cytoplasmic membrane or, in Gram-negative bacteria, also in the inner leaflet of the outer membrane. In Gram-positive bacteria Lpp significantly contribute to nutrient transport, Toll-like receptor 2 activation and pathogenicity. Here we examine the Lpp of Staphylococcus aureus USA300, as a prototype for a multiple antibiotic resistant and community-acquired pathogen that is rapidly spreading worldwide. The compiled Lpp were grouped according to the postulated function and dissemination of homologs in the genus Staphylococcus and beyond. Based on this evaluation we also point out Lpp as promising vaccine candidates. PMID:27679612

  15. 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

  16. 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…

  17. 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)

  18. 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

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. 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

  4. Lipoproteins of Gram-Positive Bacteria: Key Players in the Immune Response and Virulence.

    PubMed

    Nguyen, Minh Thu; Götz, Friedrich

    2016-09-01

    Since the discovery in 1973 of the first of the bacterial lipoproteins (Lpp) in Escherichia coli, Braun's lipoprotein, the ever-increasing number of publications indicates the importance of these proteins. Bacterial Lpp belong to the class of lipid-anchored proteins that in Gram-negative bacteria are anchored in both the cytoplasmic and outer membranes and in Gram-positive bacteria are anchored only in the cytoplasmic membrane. In contrast to the case for Gram-negative bacteria, in Gram-positive bacteria lipoprotein maturation and processing are not vital. Physiologically, Lpp play an important role in nutrient and ion acquisition, allowing particularly pathogenic species to better survive in the host. Bacterial Lpp are recognized by Toll-like receptor 2 (TLR2) of the innate immune system. The important role of Lpp in Gram-positive bacteria, particularly in the phylum Firmicutes, as key players in the immune response and pathogenicity has emerged only in recent years. In this review, we address the role of Lpp in signaling and modulating the immune response, in inflammation, and in pathogenicity. We also address the potential of Lpp as promising vaccine candidates.

  5. 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.

  6. 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.

  7. 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.

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

    PubMed Central

    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

  9. 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

  10. 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

  11. 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

  12. 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.

  13. 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

  14. 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

  15. 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

  16. Deletion of the Braun lipoprotein-encoding gene and altering the function of lipopolysaccharide attenuate the plague bacterium.

    PubMed

    Sha, Jian; Kirtley, Michelle L; van Lier, Christina J; Wang, Shaofei; Erova, Tatiana E; Kozlova, Elena V; Cao, Anthony; Cong, Yingzi; Fitts, Eric C; Rosenzweig, Jason A; Chopra, Ashok K

    2013-03-01

    Braun (murein) lipoprotein (Lpp) and lipopolysaccharide (LPS) are major components of the outer membranes of Enterobacteriaceae family members that are capable of triggering inflammatory immune responses by activating Toll-like receptors 2 and 4, respectively. Expanding on earlier studies that demonstrated a role played by Lpp in Yersinia pestis virulence in mouse models of bubonic and pneumonic plague, we characterized an msbB in-frame deletion mutant incapable of producing an acyltransferase that is responsible for the addition of lauric acid to the lipid A moiety of LPS, as well as a Δlpp ΔmsbB double mutant of the highly virulent Y. pestis CO92 strain. Although the ΔmsbB single mutant was minimally attenuated, the Δlpp single mutant and the Δlpp ΔmsbB double mutant were significantly more attenuated than the isogenic wild-type (WT) bacterium in bubonic and pneumonic animal models (mouse and rat) of plague. These data correlated with greatly reduced survivability of the aforementioned mutants in murine macrophages. Furthermore, the Δlpp ΔmsbB double mutant was grossly compromised in its ability to disseminate to distal organs in mice and in evoking cytokines/chemokines in infected animal tissues. Importantly, mice that survived challenge with the Δlpp ΔmsbB double mutant, but not the Δlpp or ΔmsbB single mutant, in a pneumonic plague model were significantly protected against a subsequent lethal WT CO92 rechallenge. These data were substantiated by the fact that the Δlpp ΔmsbB double mutant maintained an immunogenicity comparable to that of the WT strain and induced long-lasting T-cell responses against heat-killed WT CO92 antigens. Taken together, the data indicate that deletion of the msbB gene augmented the attenuation of the Δlpp mutant by crippling the spread of the double mutant to the peripheral organs of animals and by inducing cytokine/chemokine responses. Thus, the Δlpp ΔmsbB double mutant could provide a new live-attenuated background

  17. 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

  18. 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

  19. 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

  20. Graphs and Matroids Weighted in a Bounded Incline Algebra

    PubMed Central

    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

  1. 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

  2. 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

  3. Segmental lichen planus pigmentosus: An unusual presentation

    PubMed Central

    Kumar, Y Hari Kishan; Babu, Anagha Ramesh

    2014-01-01

    Lichen planus pigmentosus (LPP) is a distinct clinical entity commonly encountered in the Indian population. It is considered a variant of lichen planus (LP). A 40-year-old male presented with asymptomatic hyperpigmented macules in a segmental distribution since 10 years that were clinically and histopathologically suggestive of LPP. We propose the terminology “segmental lichen planus pigmentosus” and report this unusual presentation. PMID:24860750

  4. 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.

  5. 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

  6. The intention to conceal activates the right prefrontal cortex: an event-related potential study.

    PubMed

    Matsuda, Izumi; Nittono, Hiroshi

    2015-03-01

    Recent studies on deception have shown that a late positive potential (LPP), a component of event-related brain potentials, is elicited when a participant wishes to conceal recognition of the eliciting stimulus. The LPP occurs about 500 ms after stimulus onset and has an occipital scalp distribution with concurrent negativity at frontal sites. The present study investigated the cortical sources of the LPP associated with the intention to conceal. Standardized low-resolution electromagnetic tomography analysis was applied on previously published concealment-related LPP data (Matsuda, Nittono, and Ogawa, 2013, N=30). The cortical sources of the LPP were estimated in the right middle frontal gyrus and the right inferior frontal gyrus, which fits well with the findings of fMRI studies. Previous research suggests that activities in the middle frontal gyrus and the right inferior frontal gyrus are associated with cognitive control and that greater relative right than left frontal activities are associated with withdrawal motivation. On the basis of these findings, it is concluded that the LPP may reflect cognitive control with withdrawal motivation that is recruited by the participants' goal of concealing their recognition and avoiding disclosure. A positive potential at occipital sites can be a sign of the activation in the prefrontal cortex.

  7. 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

  8. 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.

  9. 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

  10. 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

  11. Comparison of a new parallel-flow, plate dialyser and a hollow fibre dialyser.

    PubMed

    Sølling, J; Hansen, H E

    1979-01-01

    A new, low-price, parallel-flow, plate dialyser--the LPP dialyser--has been compared with a hollow fibre dialyser--the C-DAK dialyser. At dialysate flows of 510-680 ml/min and blood flows 140-200 ml/min the clearances of urea, creatinine and uric acid were 30-40 ml/min greater in the C-DAK dialyser. In the patients the mean creatinine at end of dialysis increased 1.7 mg% during treatment with the LPP dialyser. The ultrafiltration rate was found to be greater in the LPP dialyser than in the C-DAK dialyser. No membrane ruptures were observed in 200 LPP dialysers compared to 2 of 1200 C-DAK dialysers. The mean residual blood volume was 6.4 ml in the LPP dialyser + blood lines and 5.3 ml in the C-DAK dialyser + blood lines. The difference is insignificant. The LPP dialyser may be useful when dialysis is carried out frequency and when overhydration is a major problem.

  12. 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

  13. The electrocortical modulation effects of different emotion regulation strategies.

    PubMed

    Gan, Shuzhen; Yang, Jianfeng; Chen, Xuhai; Yang, Yufang

    2015-08-01

    The current event-related potential study investigated the modulation effects of different emotion regulation strategies on electrocortical responses. When watching negative or neutral pictures, participants were instructed to perform three tasks: cognitive reappraisal, expressive suppression and passive viewing. We found that negative pictures elicited a larger late positive potential (LPP) than neutral pictures. Moreover, processes involved in strategy also had an effect on LPP amplitude, which was indicated by a larger LPP in reappraisal compared with suppression and viewing tasks when neutral pictures were presented. After the influence of processes on LPP was excluded, results showed that reappraisal effectively decreased the emotion-enhanced LPP than suppression and viewing. The difference in regulatory effect may be determined by the underlying processing mechanism. A larger frontal-central component, N2, was observed in suppression than reappraisal and viewing, which suggested that it involved the processes focusing on behavioral response. While the larger LPP found in reappraisal implicated that it recruited cognitive processes focusing on the picture meaning.

  14. 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.

  15. 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.

  16. Analgesic, anticonvulsant and antioxidant activities of 3-[4-(3-trifluoromethyl-phenyl)-piperazin-1-yl]-dihydrofuran-2-one dihydrochloride in mice.

    PubMed

    Salat, Kinga; Moniczewski, Andrzej; Salat, Robert; Janaszek, Monika; Filipek, Barbara; Malawska, Barbara; Wieckowski, Krzysztof

    2012-03-01

    Recently we have shown that 3-[4-(3-trifluoromethyl-phenyl)-piperazin-1-yl]-dihydrofuran-2-one dihydrochloride (LPP1) is an antinociceptive and local anesthetic agent in rodents. Below an extended study of the pharmacological activity of LPP1 is described. In vitro LPP1 has no affinity for GABA(A), opioidergic μ and serotonergic 5-HT(1A) receptors. The total antioxidant capacity of LPP1 (1-10mM) measured as ABTS radical cation-scavenging activity showed that LPP1 has dose-dependent antioxidant properties in vitro. Low plasma concentration of this compound detected by means of HPLC method 30min after its intraperitoneal administration suggests a rapid conversion to metabolite(s) which may be responsible for its analgesic and anticonvulsant activities in vivo. In vivo the compound's influence on the electroconvulsive threshold and its activity in the maximal electroshock seizure test (MES) were evaluated. The results demonstrated that LPP1 had an anticonvulsant activity in the MES model (ED(50)=112mg/kg) and at a dose of 50mg/kg was able to elevate the electroconvulsive threshold for 8mA as compared to the vehicle-treated mice. The analgesic activity of LPP1 was investigated in the acetic acid-induced writhing test in two groups of mice: animals with sensory C-fibers ablated, and mice with C-fibers unimpaired. It proved the potent activity of this compound in both groups (approximately 85% as compared to the vehicle-treated mice). The adverse effects of LPP1 were evaluated as acute toxicity (LD(50)=747.8mg/kg) and motor coordination impairments in the rotarod and chimney tests. The results from these tests show that LPP1 at doses higher than 100mg/kg is likely to impair the motor performance of experimental animals. Concluding, LPP1 is an analgesic and anticonvulsant compound which has antioxidant properties in vitro. Further studies are necessary to assess whether the antioxidant activity and the receptor profiling demonstrated in vitro can be confirmed for its

  17. 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.

  18. Treatment of keratoacanthoma: Is intralesional methotrexate an option?

    PubMed Central

    Patel, Nima P; Cervino, A Lawrence

    2011-01-01

    BACKGROUND: Keratoacanthomas (KAs) are a variant of squamous cell carcinomas. Some KAs have shown aggressive behaviour, leading to metastasis and death. Surgical excision is the treatment of choice for most KA patients. Intralesional methotrexate (MTX) may also be a potential treatment option for KAs. OBJECTIVE: To evaluate intralesional MTX as a treatment modality for KA. METHODS: A retrospective chart review of nine patients with KAs treated with intralesional MTX was performed. Each patient had biopsy-proven KA. The lesion was initially debulked, and MTX was injected at the base. Patients were seen weekly in the office, and reinjected with intralesional MTX depending on the response of the lesion. Each patient was evaluated for their response to the intralesional MTX injections, the number of injections required and complications. RESULTS: Patients required approximately two to four intralesional injections (12.5 mg to 25 mg per injection) before KA resolution. Eight of nine (88.9%) patients experienced complete resolution of their tumours. One patient experienced treatment failure, and underwent surgical excision of the KA. The average follow-up period was 2.8 years, and there were no recurrences. CONCLUSION: The results from the present retrospective study show that intralesional MTX injection is an effective treatment option for KAs. The authors propose that intralesional MTX injection with initial debulking of the KA should be used as a first line of treatment when KAs present on the extremities, in cosmetically sensitive areas and in elderly patients with multiple comorbities. PMID:22654538

  19. 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

  20. 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.

  1. 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

  2. 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

  3. 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.

  4. 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

  5. Cylinder Pressure-Based Spark Advance Control for SI Engines

    NASA Astrophysics Data System (ADS)

    Park, Seungbum; Yoon, Paljoo; Sunwoo, Myoungho

    The introduction of inexpensive cylinder pressure sensors provides new opportunities for precise engine control. This paper presents a spark advance control strategy based upon cylinder pressure in spark ignition engines. It is well known that the location of peak pressure(LPP) reflects combustion phasing and can be used for controlling the spark advance. The well-known problems of the LPP-based spark advance control method are that many samples of data are required and there is loss of combustion phasing detection capability due to hook-back at late burn conditions. To solve these problems, a multi-layer feedforward neural network is employed. The LPP and hook-back are estimated, using the neural network, which needs only five output voltage samples from the pressure sensor. The neural network plays an important role in mitigating the A/D conversion load of an electronic engine controller by increasing the sampling interval from 1° crank angle (CA) to 20° CA. A proposed control algorithm does not need a sensor calibration and pegging (bias calculation) procedure because the neural network estimates the LPP from the raw sensor output voltage. The estimated LPP can be regarded as a good index for combustion phasing, and can also be used as an MBT control parameter. The feasibility of this methodology is closely examined through steady and transient engine operations to control individual cylinder spark advances. The experimental results have revealed a favorable agreement of optimal combustion phasing in each cylinder.

  6. 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.

  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. 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.

  9. Deconstructing the Emotion Regulatory Properties of Mindfulness: An Electrophysiological Investigation.

    PubMed

    Lin, Yanli; Fisher, Megan E; Roberts, Sean M M; Moser, Jason S

    2016-01-01

    The present study sought to uncover the emotion regulatory properties of mindfulness by examining its effects-differentiated as a meditative practice, state of mind and dispositional trait-on the late positive potential (LPP), an event-related potentials (ERPs) indexing emotional processing. Results revealed that mindfulness as a meditative practice produced a reduction in the difference between the LPP response to negative high arousing and neutral stimuli across time. In contrast, a state mindfulness induction (i.e., instructions to attend to the stimuli mindfully) failed to modulate the LPP. Dispositional mindfulness, however, was related to modulation of the LPP as a function of meditation practice. Dispositional mindfulness was associated with a reduction of the LPP response to negative high arousal stimuli and the difference between negative high arousal and neutral stimuli in participants who listened to a control audio recording but not for those who engaged in the guided meditation practice. Together, these findings provide experimental evidence demonstrating that brief mindfulness meditation, but not deliberate engagement in state mindfulness, produces demonstrable changes in emotional processing indicative of reduced emotional reactivity. Importantly, these effects are akin to those observed in individuals with naturally high dispositional mindfulness, suggesting that the benefits of mindfulness can be cultivated through practice. PMID:27656139

  10. 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

  11. The Late Positive Potential Predicts Emotion Regulation Strategy Use in School-Aged Children Concurrently and Two Years Later

    PubMed Central

    Babkirk, Sarah; Rios, Victor; Dennis, Tracy A.

    2014-01-01

    The ability to use cognitive emotion regulation strategies such as reappraisal may be a core component of emotional competence across development, but due to methodological challenges in measuring such strategies, they are rarely studied in young children. One neurophysiological measure, the late positive potential (LPP) has been examined in response to reappraisal as a potential neurosignature for emotion regulatory capacity in adults. The association between the LPP and emotion regulatory capacity in children is unknown. The present study examined whether the LPP during reappraisal could predict greater observed adaptive emotion regulation strategy use in school-aged children over a two-year period. Thirty-two five- to seven- year- olds participated in two identical lab visits spaced two years apart. EEG was continuously recorded during a computerized reappraisal task in which children viewed unpleasant images paired with either reappraisal or negative stories. Next they completed a disappointing and a frustrating task during which emotion regulation strategies was observed. As predicted, children who showed reappraisal-induced reductions in the LPP at the first assessment used significantly more adaptive ER strategies concurrently and two years later. These findings provide observation-based evidence that the LPP may be a viable neurosignature for emotion regulatory capacity in children. PMID:25438825

  12. Deconstructing the Emotion Regulatory Properties of Mindfulness: An Electrophysiological Investigation

    PubMed Central

    Lin, Yanli; Fisher, Megan E.; Roberts, Sean M. M.; Moser, Jason S.

    2016-01-01

    The present study sought to uncover the emotion regulatory properties of mindfulness by examining its effects—differentiated as a meditative practice, state of mind and dispositional trait—on the late positive potential (LPP), an event-related potentials (ERPs) indexing emotional processing. Results revealed that mindfulness as a meditative practice produced a reduction in the difference between the LPP response to negative high arousing and neutral stimuli across time. In contrast, a state mindfulness induction (i.e., instructions to attend to the stimuli mindfully) failed to modulate the LPP. Dispositional mindfulness, however, was related to modulation of the LPP as a function of meditation practice. Dispositional mindfulness was associated with a reduction of the LPP response to negative high arousal stimuli and the difference between negative high arousal and neutral stimuli in participants who listened to a control audio recording but not for those who engaged in the guided meditation practice. Together, these findings provide experimental evidence demonstrating that brief mindfulness meditation, but not deliberate engagement in state mindfulness, produces demonstrable changes in emotional processing indicative of reduced emotional reactivity. Importantly, these effects are akin to those observed in individuals with naturally high dispositional mindfulness, suggesting that the benefits of mindfulness can be cultivated through practice. PMID:27656139

  13. Molecular mechanisms underpinning laser printer and photocopier induced symptoms, including chronic fatigue syndrome and respiratory tract hyperresponsiveness: pharmacological treatment with cinnamon and hydrogen.

    PubMed

    Lucas, Kurt; Maes, Michael

    2013-01-01

    Emissions of laser printers and photocopiers (LP&P) may be associated with health problems. The aim of this review is to describe the clinical picture that is triggered by exposure to LP&P and the molecular mechanisms underpinning the symptoms. Exposure to LP&P to vulnerable subjects may cause a symptom complex consisting of 1) irritation and hyperresponsiveness of the upper and lower respiratory tract; and 2) chronic fatigue (syndrome, CFS). Symptoms occur within hours after L&P exposure and may last for some days or become chronic with exacerbations following LP&P exposure. Substances that can be found in toners or are generated during the printing process are Silica nanoparticles, Titanium Dioxide nanoparticles, Carbon Black, metals, ozone, volatile organic compounds (VOC), etc. The latter may generate oxidative and nitrosative stress (O&NS), damage-associated molecular patterns molecules, pulmonary and systemic inflammation, and modulate Toll Like Receptor 4 (TRL4)‑related mechanisms. It is concluded that LP&P emissions may cause activation of the TLR4 Radical Cycle and thus be associated with the onset of chronic inflammatory and O&NS illnesses, such as CFS, in some vulnerable individuals. Cinnamon, an antagonist of the TLR4 complex, and Hydrogen, a potent antiinflammatory and oxygen radical scavenger, may have efficacy treating LP&P-induced illness.

  14. Deconstructing the Emotion Regulatory Properties of Mindfulness: An Electrophysiological Investigation

    PubMed Central

    Lin, Yanli; Fisher, Megan E.; Roberts, Sean M. M.; Moser, Jason S.

    2016-01-01

    The present study sought to uncover the emotion regulatory properties of mindfulness by examining its effects—differentiated as a meditative practice, state of mind and dispositional trait—on the late positive potential (LPP), an event-related potentials (ERPs) indexing emotional processing. Results revealed that mindfulness as a meditative practice produced a reduction in the difference between the LPP response to negative high arousing and neutral stimuli across time. In contrast, a state mindfulness induction (i.e., instructions to attend to the stimuli mindfully) failed to modulate the LPP. Dispositional mindfulness, however, was related to modulation of the LPP as a function of meditation practice. Dispositional mindfulness was associated with a reduction of the LPP response to negative high arousal stimuli and the difference between negative high arousal and neutral stimuli in participants who listened to a control audio recording but not for those who engaged in the guided meditation practice. Together, these findings provide experimental evidence demonstrating that brief mindfulness meditation, but not deliberate engagement in state mindfulness, produces demonstrable changes in emotional processing indicative of reduced emotional reactivity. Importantly, these effects are akin to those observed in individuals with naturally high dispositional mindfulness, suggesting that the benefits of mindfulness can be cultivated through practice.

  15. Serotonin modulates the excitatory synaptic transmission in the dentate granule cells.

    PubMed

    Nozaki, Kanako; Kubo, Reika; Furukawa, Yasuo

    2016-06-01

    Serotonergic fibers from the raphe nuclei project to the hippocampal formation, the activity of which is known to modulate the inhibitory interneurons in the dentate gyrus. On the other hand, serotonergic modulation of the excitatory synapses in the dentate gyrus is not well examined. In the present study, we examined the effects of 5-HT on the excitatory postsynaptic potentials (EPSPs) in the dentate granule cells evoked by the selective stimulation of the lateral perforant path (LPP), the medial perforant path (MPP), or the mossy cell fibers (MCF). 5-HT depressed the amplitude of unitary EPSPs (uEPSPs) evoked by the stimulation of LPP or MPP, whereas uEPSPs evoked by MCF stimulation were little affected. The effect was partly explained by the decrease of the resting membrane resistance following the activation of 5-HT1A receptors, which was confirmed by computer simulations. We also found that the probability of evoking uEPSP by LPP stimulation but not MPP or MCF stimulation was reduced by 5-HT and that the paired-pulse ratio of LPP-evoked EPSP but not that of MPP- or MCF-evoked ones was increased by 5-HT. These effects were blocked by 5-HT2 antagonist, suggesting that the transmitter release in the LPP-granule cell synapse is inhibited by the activation of 5-HT2 receptors. The present results suggest that 5-HT can modulate the EPSPs in the dentate granule cells by at least two distinct mechanisms. PMID:26961099

  16. The effectiveness of solution-focused therapy and short- and long-term psychodynamic psychotherapy on self-concept during a 3-year follow-up.

    PubMed

    Lindfors, Olavi; Knekt, Paul; Virtala, Esa; Laaksonen, Maarit A

    2012-11-01

    This study compares the effectiveness of solution-focused therapy (SFT) and short- and long-term psychodynamic psychotherapy (SPP and LPP) on self-concept during a 3-year follow-up. Altogether, 326 patients with mood or anxiety disorder were randomized to SFT, SPP, and LPP in the Helsinki Psychotherapy Study. Outcome was assessed using the Structural Analysis of Social Behavior questionnaire at baseline and 7, 12, 24, and 36 months after. Overall, during the first year of follow-up, self-concept improved more in both SFT and SPP than in LPP, indicated by the primary outcome indicators self-directed affiliation (AF) and self-directed autonomy, as well as by most of the eight secondary cluster scores. After the 3-year follow-up, LPP was more effective than SFT in AF and in the cluster scores self-affirm, self-blame, and self-neglect, whereas no difference was noted between LPP and SPP. Long duration and psychodynamic orientation of therapy may be beneficial for self-concept improvement.

  17. Keto amphetamine toxicity-focus on the redox reactivity of the cathinone designer drug mephedrone.

    PubMed

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

    2014-09-01

    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.

  18. 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

  19. Keto amphetamine toxicity-focus on the redox reactivity of the cathinone designer drug mephedrone.

    PubMed

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

    2014-09-01

    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

  20. 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.

  1. Locality Preserving Projection Based on Endmember Extraction for Hyperspectral Image Dimensionality Reduction and Target Detection.

    PubMed

    Wang, Yiting; Huang, Shiqi; Liu, Zhigang; Wang, Hongxia; Liu, Daizhi

    2016-09-01

    In order to reduce the effect of spectral variability on calculation precision for the weighted matrix in the locality preserving projection (LPP) algorithm, an improved dimensionality reduction method named endmember extraction-based locality preserving projection (EE-LPP) is proposed in this paper. The method primarily uses the vertex component analysis (VCA) method to extract endmember spectra from hyperspectral imagery. It then calculates the similarity between pixel spectra and the endmember spectra by using the spectral angle distance, and uses it as the basis for selecting neighboring pixels in the image and constructs a weighted matrix between pixels. Finally, based on the weighted matrix, the idea of the LPP algorithm is applied to reduce the dimensions of hyperspectral image data. Experimental results of real hyperspectral data demonstrate that the low-dimensional features acquired by the proposed methods can fully reflect the characteristics of the original image and further improve target detection accuracy. PMID:27566254

  2. Processing of unattended, simple negative pictures resists perceptual load.

    PubMed

    Sand, Anders; Wiens, Stefan

    2011-05-11

    As researchers debate whether emotional pictures can be processed irrespective of spatial attention and perceptual load, negative and neutral pictures of simple figure-ground composition were shown at fixation and were surrounded by one, two, or three letters. When participants performed a picture discrimination task, there was evidence for motivated attention; that is, an early posterior negativity (EPN) and late positive potential (LPP) to negative versus neutral pictures. When participants performed a letter discrimination task, the EPN was unaffected whereas the LPP was reduced. Although performance decreased substantially with the number of letters (one to three), the LPP did not decrease further. Therefore, attention to simple, negative pictures at fixation seems to resist manipulations of perceptual load.

  3. 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.

  4. 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.

  5. Negative attention bias and processing deficits during the cognitive reappraisal of unpleasant emotions in HIV+ women.

    PubMed

    McIntosh, Roger C; Tartar, Jaime L; Widmayer, Susan; Rosselli, Monica

    2015-01-01

    Deficits in emotional processing may be attributed to HIV disease or comorbid psychiatric disorders. Electrocortical markers of emotional attention, i.e., amplitude of the P2 and late positive potential (LPP), were compared between 26 HIV+ women and 25 healthy controls during an emotional regulation paradigm. HIV+ women showed early attention bias to negative stimuli indexed by greater P2 amplitude. In contrast, compared with the passive viewing of unpleasant images, HIV+ women demonstrated attenuation of the early and late LPP during positive reappraisal. This interaction remained significant after adjusting for individual differences in apathy, anxiety, and depression. Post hoc analyses implicated time since HIV diagnosis with LPP attenuation during positive reappraisal. Advancing HIV disease may disrupt neural generators associated with the cognitive reappraisal of emotions independent of psychiatric function. PMID:25541865

  6. 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

  7. 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

  8. Lichen Planus Pigmentosus: The Controversial Consensus.

    PubMed

    Ghosh, Aparajita; Coondoo, Arijit

    2016-01-01

    A pigmented variant of lichen planus (LP) was first reported from India in 1974 by Bhutani et al. who coined the term LP pigmentosus (LPP) to give a descriptive nomenclature to it. LP has a number of variants, one of which is LPP. This disease has also later been reported from the Middle East, Latin America, Korea, and Japan, especially in people with darker skin. It has an insidious onset. Initially, small, black or brown macules appear on sun-exposed areas. They later merge to form large hyperpigmented patches. The disease principally affects the sun-exposed areas of the body such as the face, trunk, and upper extremities. The oral mucosa may rarely be involved. However, the palms, soles, and nails are not affected. Histologically, the epidermis is atrophic along with vacuolar degeneration of basal cell layer. The dermis exhibits incontinence of pigment with scattered melanophages and a sparse follicular or perivascular infiltrate. There is a considerable similarity in histopathological findings between LPP and erythema dyschromicum perstans. However, there are immunologic and clinical differences between the two. These observations have led to a controversy regarding the identity of the two entities. While some dermatologists consider them to be the same, others have opined that the two should be considered as distinctly different diseases. A number of associations such as hepatitis C virus infection, frontal fibrosing alopecia, acrokeratosis of Bazex and nephrotic syndrome have been reported with LPP. A rare variant, LPP inversus, with similar clinical and histopathological findings was reported in 2001. As opposed to LPP, this variant occurs in covered intertriginous locations such as groins and axillae and mostly affects white-skinned persons. PMID:27688435

  9. Lichen Planus Pigmentosus: The Controversial Consensus

    PubMed Central

    Ghosh, Aparajita; Coondoo, Arijit

    2016-01-01

    A pigmented variant of lichen planus (LP) was first reported from India in 1974 by Bhutani et al. who coined the term LP pigmentosus (LPP) to give a descriptive nomenclature to it. LP has a number of variants, one of which is LPP. This disease has also later been reported from the Middle East, Latin America, Korea, and Japan, especially in people with darker skin. It has an insidious onset. Initially, small, black or brown macules appear on sun-exposed areas. They later merge to form large hyperpigmented patches. The disease principally affects the sun-exposed areas of the body such as the face, trunk, and upper extremities. The oral mucosa may rarely be involved. However, the palms, soles, and nails are not affected. Histologically, the epidermis is atrophic along with vacuolar degeneration of basal cell layer. The dermis exhibits incontinence of pigment with scattered melanophages and a sparse follicular or perivascular infiltrate. There is a considerable similarity in histopathological findings between LPP and erythema dyschromicum perstans. However, there are immunologic and clinical differences between the two. These observations have led to a controversy regarding the identity of the two entities. While some dermatologists consider them to be the same, others have opined that the two should be considered as distinctly different diseases. A number of associations such as hepatitis C virus infection, frontal fibrosing alopecia, acrokeratosis of Bazex and nephrotic syndrome have been reported with LPP. A rare variant, LPP inversus, with similar clinical and histopathological findings was reported in 2001. As opposed to LPP, this variant occurs in covered intertriginous locations such as groins and axillae and mostly affects white-skinned persons. PMID:27688435

  10. Lichen Planus Pigmentosus: The Controversial Consensus

    PubMed Central

    Ghosh, Aparajita; Coondoo, Arijit

    2016-01-01

    A pigmented variant of lichen planus (LP) was first reported from India in 1974 by Bhutani et al. who coined the term LP pigmentosus (LPP) to give a descriptive nomenclature to it. LP has a number of variants, one of which is LPP. This disease has also later been reported from the Middle East, Latin America, Korea, and Japan, especially in people with darker skin. It has an insidious onset. Initially, small, black or brown macules appear on sun-exposed areas. They later merge to form large hyperpigmented patches. The disease principally affects the sun-exposed areas of the body such as the face, trunk, and upper extremities. The oral mucosa may rarely be involved. However, the palms, soles, and nails are not affected. Histologically, the epidermis is atrophic along with vacuolar degeneration of basal cell layer. The dermis exhibits incontinence of pigment with scattered melanophages and a sparse follicular or perivascular infiltrate. There is a considerable similarity in histopathological findings between LPP and erythema dyschromicum perstans. However, there are immunologic and clinical differences between the two. These observations have led to a controversy regarding the identity of the two entities. While some dermatologists consider them to be the same, others have opined that the two should be considered as distinctly different diseases. A number of associations such as hepatitis C virus infection, frontal fibrosing alopecia, acrokeratosis of Bazex and nephrotic syndrome have been reported with LPP. A rare variant, LPP inversus, with similar clinical and histopathological findings was reported in 2001. As opposed to LPP, this variant occurs in covered intertriginous locations such as groins and axillae and mostly affects white-skinned persons.

  11. Comparative effects of extremely high power microwave pulses and a brief CW irradiation on pacemaker function in isolated frog heart slices.

    PubMed

    Pakhomov, A G; Mathur, S P; Doyle, J; Stuck, B E; Kiel, J L; Murphy, M R

    2000-05-01

    The existence of specific bioeffects due to high peak power microwaves and their potential health hazards are among the most debated but least explored problems in microwave biology. The present study attempted to reveal such effects by comparing the bioeffects of short trains of extremely high power microwave pulses (EHPP, 1 micros width, 250-350 kW/g, 9.2 GHz) with those of relatively low power pulses (LPP, 0.5-10 s width, 3-30 W/g, 9.2 GHz). EHPP train duration and average power were made equal to those of an LPP; therefore both exposure modalities produced the same temperature rise. Bioeffects were studied in isolated, spontaneously beating slices of the frog heart. In most cases, a single EHPP train or LPP immediately decreased the inter-beat interval (IBI). The effect was proportional to microwave heating, fully reversible, and easily reproducible. The magnitude and time course of EHPP- and LPP-induced changes always were the same. No delayed or irreversible effects of irradiation were observed. The same effect could be repeated in a single preparation numerous times with no signs of adaptation, sensitization, lasting functional alteration, or damage. A qualitatively different effect, namely, a temporary arrest of preparation beats, could be observed when microwave heating exceeded physiologically tolerable limits. This effect also did not depend on whether the critical temperature rise was produced by LPP or EHPP exposure. Within the studied limits, we found no indications of EHPP-specific bioeffects. EHPP- and LPP-induced changes in the pacemaker rhythm of isolated frog heart preparation were identical and could be entirely attributed to microwave heating.

  12. 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.

  13. Lipid phosphate phosphatase-1 regulates lysophosphatidic acid-induced calcium release, NF-κB activation and interleukin-8 secretion in human bronchial epithelial cells

    PubMed Central

    2004-01-01

    LPA (lysophosphatidic acid), a potent bioactive phospholipid, elicits diverse cellular responses through activation of the G-protein-coupled receptors LPA1–LPA4. LPA-mediated signalling is partially regulated by LPPs (lipid phosphate phosphatases; LPP-1, -2 and -3) that belong to the phosphatase superfamily. This study addresses the role of LPPs in regulating LPA-mediated cell signalling and IL-8 (interleukin-8) secretion in HBEpCs (human bronchial epithelial cells). Reverse transcription–PCR and Western blotting revealed the presence and expression of LPP-1–3 in HBEpCs. Exogenous [3H]oleoyl LPA was hydrolysed to [3H]-mono-oleoylglycerol. Infection of HBEpCs with an adenoviral construct of human LPP-1 for 48 h enhanced the dephosphorylation of exogenous LPA by 2–3-fold compared with vector controls. Furthermore, overexpression of LPP-1 partially attenuated LPA-induced increases in the intracellular Ca2+ concentration, phosphorylation of IκB (inhibitory κB) and translocation of NF-κB (nuclear factor-κB) to the nucleus, and almost completely prevented IL-8 secretion. Infection of cells with an adenoviral construct of the mouse LPP-1 (R217K) mutant partially attenuated LPA-induced IL-8 secretion without altering LPA-induced changes in intracellular Ca2+ concentration, phosphorylation of IκB, NF-κB activation or IL-8 gene expression. Our results identify LPP-1 as a key regulator of LPA signalling and IL-8 secretion in HBEpCs. Thus LPPs could represent potential targets in regulating leucocyte infiltration and airway inflammation. PMID:15461590

  14. 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

  15. 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.

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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.

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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.

  7. 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

  8. Emotional event-related potentials are reduced if negative pictures presented at fixation are unattended.

    PubMed

    Wiens, Stefan; Sand, Anders; Norberg, Joakim; Andersson, Per

    2011-05-20

    Viewing of emotional pictures elicits two event-related potentials (ERPs) to emotional versus neutral pictures: an early posterior negativity (EPN) and a late positive potential (LPP). Because it is unresolved whether these indexes of emotional processing are reduced to task-irrelevant pictures at fixation, negative and neutral pictures from the International Affective Picture Set (IAPS) were shown at fixation together with 6 letters that surrounded the pictures. In separate tasks, participants were instructed to attend either the pictures or the letters. When the pictures were task relevant, results showed an EPN and LPP. In contrast, when the pictures were task irrelevant, the EPN was eliminated and the LPP reduced. Performance was high in both tasks (hit rates>87%), but somewhat better when the pictures were relevant. However, analyses showed no relationship between this performance difference and the differences in EPN and LPP between tasks. These results suggest that emotional processing of strong, negative pictures is sensitive to manipulations of attention even if the pictures are shown at fixation.

  9. 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
    ...

  10. 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…

  11. The Late Positive Potential: A Neurophysiological Marker for Emotion Regulation in Children

    ERIC Educational Resources Information Center

    Dennis, Tracy A.; Hajcak, Greg

    2009-01-01

    Background: The ability to modulate emotional responses, or emotion regulation, is a key mechanism in the development of mood disruptions. Detection of a neural marker for emotion regulation thus has the potential to inform early detection and intervention for mood problems. One such neural marker may be the late positive potential (LPP), which is…

  12. Molecular Epidemiology of Mycoplasma conjunctivae in Caprinae: Transmission across Species in Natural Outbreaks

    PubMed Central

    Belloy, Luc; Janovsky, Martin; Vilei, Edy M.; Pilo, Paola; Giacometti, Marco; Frey, Joachim

    2003-01-01

    Mycoplasma conjunctivae is the etiological agent of infectious keratoconjunctivitis, a highly contagious ocular infection that affects both domestic and wild Caprinae species in the European Alps. In order to study the transmission and spread of M. conjunctivae across domestic and wild Caprinae populations, we developed a molecular method for subtyping and identifying strains of M. conjunctivae. This method is based on DNA sequence determination of a variable domain within the gene lppS, a gene that encodes an antigenic lipoprotein of M. conjunctivae. This domain of lppS shows variations among different strains but remains constant upon generations of individual strains on growth medium and thus allows identification of individual strains and estimation of their phylogenetic intercorrelations. The variable domain of lppS is amplified by PCR using primers that match conserved sequences of lppS flanking it. Sequence analysis of the amplified fragment enables fine subtyping of M. conjunctivae strains. The method is applicable both to isolated strains and to clinical samples directly without requiring the cultivation of the strain. Using this method, we show that M. conjunctivae was transmitted between domestic and wild animals that were grazing in proximate pastures. Certain animals also presented infections with two different strains simultaneously. PMID:12676664

  13. 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.

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

    PubMed

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

    2014-09-01

    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. PMID:25273714

  15. 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.

  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. Maternal recognition of pregnancy in swine. I. Minimal requirement for exogenous estradiol-17 beta to induce either short or long pseudopregnancy in cycling gilts.

    PubMed

    Pusateri, A E; Smith, J M; Smith, J W; Thomford, P J; Diekman, M A

    1996-09-01

    Five experiments were conducted to determine the minimal requirement for estradiol-17 beta (E2) injections to induce either short pseudopregnancy (SPP) or long pseudopregnancy (LPP) in cycling gilts. In experiments 1 through 5, E2 was injected i.m. on combinations of days between 11 and 25 days postestrus. Exogenous E2 on Days 12 and 13 or on Days 12 through 19 was optimal for induction of SPP or LPP, respectively. The duration of E2-induced diestrus was clearly demarcated between SPP (n = 73, duration 23-35 days) and LPP (n = 23, duration > 50 days). A sixth experiment was conducted to determine the minimum dose of intrauterine E2 required to induce SPP, and these gilts received intrauterine infusions of 0, 4, 40, or 400 micrograms E2 per 24 h on Days 12 and 13 postestrus. Pseudopregnancy was induced in 0 of 12, 1 of 4, 1 of 11, and 4 of 7 gilts in the treatment groups, respectively. These data suggest that uterine exposure alone is not sufficient to induce SPP. The present results indicate that the optimal signal for inducing LPP in unmated cycling gilts, and perhaps also for maternal recognition of pregnancy in mated gilts, may occur in two phases with continuous exposure to E2 being required from Day 12 to Days 17-19.

  18. 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

  19. 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…

  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. 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.

  2. 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

  3. 78 FR 13692 - Clarks River National Wildlife Refuge, KY; Final Comprehensive Conservation Plan/Land Protection...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-28

    ..., we describe how we will manage this refuge for the next 15 years. ADDRESSES: You may obtain a copy of... administering Clarks River NWR for the next 15 years. The LPP will expand the current acquisition boundary of... is to provide refuge managers with a 15-year plan for achieving refuge purposes and...

  4. Can older adults resist the positivity effect in neural responding? The impact of verbal framing on event-related brain potentials elicited by emotional images.

    PubMed

    Rehmert, Andrea E; Kisley, Michael A

    2013-10-01

    Older adults have demonstrated an avoidance of negative information, presumably with a goal of greater emotional satisfaction. Understanding whether avoidance of negative information is a voluntary, motivated choice or an involuntary, automatic response will be important to differentiate, as decision making often involves emotional factors. With the use of an emotional framing event-related potential (ERP) paradigm, the present study investigated whether older adults could alter neural responses to negative stimuli through verbal reframing of evaluative response options. The late positive potential (LPP) response of 50 older adults and 50 younger adults was recorded while participants categorized emotional images in one of two framing conditions: positive ("more or less positive") or negative ("more or less negative"). It was hypothesized that older adults would be able to overcome a presumed tendency to down-regulate neural responding to negative stimuli in the negative framing condition, thus leading to larger LPP wave amplitudes to negative images. A similar effect was predicted for younger adults, but for positively valenced images, such that LPP responses would be increased in the positive framing condition compared with the negative framing condition. Overall, younger adults' LPP wave amplitudes were modulated by framing condition, including a reduction in the negativity bias in the positive frame. Older adults' neural responses were not significantly modulated, even though task-related behavior supported the notion that older adults were able to successfully adopt the negative framing condition.

  5. 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…

  6. 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…

  7. 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...

  8. 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…

  9. Language Policy and Planning: Challenges for Latin American Universities

    ERIC Educational Resources Information Center

    Hamel, Rainer Enrique; Álvarez López, Elisa; Carvalhal, Tatiana Pereira

    2016-01-01

    This article starts with an overview of the sociolinguistic situation in Latin America as a context for language policy and planning (LPP) decisions in the academic field. Then it gives a brief overview of the language policy challenges faced by universities to cope with neoliberal internationalisation. A conceptualisation of the domain as a…

  10. 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,…

  11. 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.

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

    PubMed

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

    2014-09-01

    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.

  13. Changes in attention to an emotional task after sleep deprivation: neurophysiological and behavioral findings.

    PubMed

    Alfarra, Ramey; Fins, Ana I; Chayo, Isaac; Tartar, Jaime L

    2015-01-01

    While sleep loss is shown to have widespread effects on cognitive processes, little is known about the impact of sleep loss on emotion processes. In order to expand on previous behavioral and physiological findings on how sleep loss influences emotion processing, we administered positive, negative, and neutral affective visual stimuli to individuals after one night of sleep deprivation while simultaneously acquiring EEG event related potential (ERP) data and recording affective behavioral responses. We compared these responses to a baseline testing session. We specifically looked at the late positive potential (LPP) component of the visual ERP as an established sensitive measure of attention to emotionally-charged visual stimuli. Our results show that after sleep deprivation, the LPP no longer discriminates between emotional and non-emotional pictures; after sleep deprivation the LPP amplitude was of similar amplitude for neutral, positive, and negative pictures. This effect was driven by an increase in the LPP to neutral pictures. Our behavioral measures show that, relative to baseline testing, emotional pictures are rated as less emotional following sleep deprivation with a concomitant reduction in emotional picture-induced anxiety. We did not observe any change in cortisol concentrations after sleep deprivation before or after emotional picture exposure, suggesting that the observed changes in emotion processing are independent of potential stress effects of sleep deprivation. Combined, our findings suggest that sleep loss interferes with proper allocation of attention resources during an emotional task.

  14. Targeting Reading Fluency through Brief Experimental Analysis and Parental Intervention over the Summer

    ERIC Educational Resources Information Center

    Schreder, Sara J.; Hupp, Stephen D. A.; Everett, Gregory E.; Krohn, Emily

    2012-01-01

    Although past research has examined repeated reading (RR) and listening passage preview (LPP) in great detail, several issues related to their applied usage with individual students remain. Questions including the number of times students are required to engage with the instructional materials during treatment and tracking fluency gains on…

  15. 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

  16. Combinational deletion of three membrane protein-encoding genes highly attenuates yersinia pestis while retaining immunogenicity in a mouse model of pneumonic plague.

    PubMed

    Tiner, Bethany L; Sha, Jian; Kirtley, Michelle L; Erova, Tatiana E; Popov, Vsevolod L; Baze, Wallace B; van Lier, Christina J; Ponnusamy, Duraisamy; Andersson, Jourdan A; Motin, Vladimir L; Chauhan, Sadhana; Chopra, Ashok K

    2015-04-01

    Previously, we showed that deletion of genes encoding Braun lipoprotein (Lpp) and MsbB attenuated Yersinia pestis CO92 in mouse and rat models of bubonic and pneumonic plague. While Lpp activates Toll-like receptor 2, the MsbB acyltransferase modifies lipopolysaccharide. Here, we deleted the ail gene (encoding the attachment-invasion locus) from wild-type (WT) strain CO92 or its lpp single and Δlpp ΔmsbB double mutants. While the Δail single mutant was minimally attenuated compared to the WT bacterium in a mouse model of pneumonic plague, the Δlpp Δail double mutant and the Δlpp ΔmsbB Δail triple mutant were increasingly attenuated, with the latter being unable to kill mice at a 50% lethal dose (LD50) equivalent to 6,800 LD50s of WT CO92. The mutant-infected animals developed balanced TH1- and TH2-based immune responses based on antibody isotyping. The triple mutant was cleared from mouse organs rapidly, with concurrent decreases in the production of various cytokines and histopathological lesions. When surviving animals infected with increasing doses of the triple mutant were subsequently challenged on day 24 with the bioluminescent WT CO92 strain (20 to 28 LD50s), 40 to 70% of the mice survived, with efficient clearing of the invading pathogen, as visualized in real time by in vivo imaging. The rapid clearance of the triple mutant, compared to that of WT CO92, from animals was related to the decreased adherence and invasion of human-derived HeLa and A549 alveolar epithelial cells and to its inability to survive intracellularly in these cells as well as in MH-S murine alveolar and primary human macrophages. An early burst of cytokine production in macrophages elicited by the triple mutant compared to WT CO92 and the mutant's sensitivity to the bactericidal effect of human serum would further augment bacterial clearance. Together, deletion of the ail gene from the Δlpp ΔmsbB double mutant severely attenuated Y. pestis CO92 to evoke pneumonic plague in a

  17. Combinational Deletion of Three Membrane Protein-Encoding Genes Highly Attenuates Yersinia pestis while Retaining Immunogenicity in a Mouse Model of Pneumonic Plague

    PubMed Central

    Tiner, Bethany L.; Kirtley, Michelle L.; Erova, Tatiana E.; Popov, Vsevolod L.; Baze, Wallace B.; van Lier, Christina J.; Ponnusamy, Duraisamy; Andersson, Jourdan A.; Motin, Vladimir L.; Chauhan, Sadhana

    2015-01-01

    Previously, we showed that deletion of genes encoding Braun lipoprotein (Lpp) and MsbB attenuated Yersinia pestis CO92 in mouse and rat models of bubonic and pneumonic plague. While Lpp activates Toll-like receptor 2, the MsbB acyltransferase modifies lipopolysaccharide. Here, we deleted the ail gene (encoding the attachment-invasion locus) from wild-type (WT) strain CO92 or its lpp single and Δlpp ΔmsbB double mutants. While the Δail single mutant was minimally attenuated compared to the WT bacterium in a mouse model of pneumonic plague, the Δlpp Δail double mutant and the Δlpp ΔmsbB Δail triple mutant were increasingly attenuated, with the latter being unable to kill mice at a 50% lethal dose (LD50) equivalent to 6,800 LD50s of WT CO92. The mutant-infected animals developed balanced TH1- and TH2-based immune responses based on antibody isotyping. The triple mutant was cleared from mouse organs rapidly, with concurrent decreases in the production of various cytokines and histopathological lesions. When surviving animals infected with increasing doses of the triple mutant were subsequently challenged on day 24 with the bioluminescent WT CO92 strain (20 to 28 LD50s), 40 to 70% of the mice survived, with efficient clearing of the invading pathogen, as visualized in real time by in vivo imaging. The rapid clearance of the triple mutant, compared to that of WT CO92, from animals was related to the decreased adherence and invasion of human-derived HeLa and A549 alveolar epithelial cells and to its inability to survive intracellularly in these cells as well as in MH-S murine alveolar and primary human macrophages. An early burst of cytokine production in macrophages elicited by the triple mutant compared to WT CO92 and the mutant's sensitivity to the bactericidal effect of human serum would further augment bacterial clearance. Together, deletion of the ail gene from the Δlpp ΔmsbB double mutant severely attenuated Y. pestis CO92 to evoke pneumonic plague in a

  18. 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

  19. 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.

  20. A Type IV Translocated Legionella Cysteine Phytase Counteracts Intracellular Growth Restriction by Phytate

    PubMed Central

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

    2014-01-01

    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 (Cys231) and arginine (Arg237) 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

  1. Salutary effect of gastric pentadecapeptide BPC 157 in two different stress urinary incontinence models in female rats

    PubMed Central

    Jandric, Ivan; Vrcic, Hrvoje; Balen, Marica Jandric; Kolenc, Danijela; Brcic, Luka; Radic, Bozo; Drmic, Domagoj; Seiwerth, Sven; Sikiric, Predrag

    2013-01-01

    Background Since an originally anti-ulcer stable gastric pentadecapeptide BPC 157 (PL 14736) was shown to promote healing of injured striated muscle and smooth muscle in the gastrointestinal tract, we explored its therapeutic potentials for leak point pressure (LPP) recovery in rat stress urinary incontinence (SUI) after transabdominal urethrolysis (TU) and prolonged vaginal dilatation (VD). Material/Methods During a 7-day period, TU-rats and VD-rats (or healthy rats) received BPC 157, either (i) intraperitoneally, 10 μg/kg or 10 ng/kg, once daily (first administration 30 min after surgery, last 24 h before LPP-testing and sacrifice), or (ii) per-orally, 10 μg/kg in drinking water (0.16 μg/mL, 12 mL/rat/day). Vesicourethral segments were harvested for immunohistochemical evaluation. Results All BPC 157 regimens counteracted decrease of LPP values in TU-rats and VD-rats. Additionally, BPC 157-TU rats (μg-intraperitoneally or per-orally) and BPC 157-VD rats (μg intraperitoneally) reached LPP values originally noted in healthy rats. Conversely, in healthy rats, BPC 157 did not alter LPP. Immunohistochemical studies revealed higher desmin (delineates striated organization of skeletal muscle), smooth muscle actin, and CD34 (angiogenic marker) positivity within the urethral wall in BPC 157-treated rats vs. controls, as well as overall preserved muscle/connective tissue ratio assessed with Mallory’s trichrome staining. Conclusions Pentadecapeptide BPC 157, applied parenterally or per-orally, appears to ameliorate the SUI in rat models, improving the otherwise detrimental course of healing after VD and TU, which may be analogous to human injury. These beneficial effects may possibly be selectively used in future strategies for treatment of SUI. PMID:23478678

  2. Too bad: Bias for angry faces in social anxiety interferes with identity processing.

    PubMed

    Hagemann, Julian; Straube, Thomas; Schulz, Claudia

    2016-04-01

    The recognition of faces across incidences is a complex function of the human brain and a crucial ability for communication and daily interactions. This first study on ERP correlates of emotional face learning in social anxiety disorder (SAD) investigates whether the known attentional bias for threatening faces leads to a corresponding memory bias. Therefore, 21 patients with SAD and 21 healthy controls (HCs) learned faces with emotional facial expressions (neutral, happy, and angry) and were later asked to recognize these out of novel identities all presented with a neutral facial expression. EEG was recorded throughout. Behaviorally, the faces' emotional expression modulated later recognition in terms of accuracy, response times, signal detection parameters and ratings of valence, but with better performance for happy than angry faces in HC as well as in SAD. In the learning phase, attention- and memory-associated event-related potentials (ERPs) P100, N170, P200, N250/EPN, and LPP indicated enhanced processing of angry faces, which was restricted to patients with SAD in N250/EPN and LPP. In the test phase, familiarity effects emerged in N250, FN400 and LPP. While N250 was affected by learned-angry faces, FN400 and LPP reflected image learning of neutral faces, which was restricted to SAD in LPP. We replicated the attentional bias to threatening faces, which was not restricted to early ERP components, but was prolonged to later stages of conscious processing, especially in SAD. In contrast to what had been expected, sustained hypervigilance to the emotional content seems to have impaired the processing of the facial identity, resulting in a happy face advantage at the behavioral level. This could be explained by prominent models assuming separate processing of facial emotion and identity. Hypervigilance in SAD might be a disadvantage in those studies focusing on other aspects of face processing than emotion.

  3. Current Filament Merging Driven by Cross-Field Plasma Flows

    NASA Astrophysics Data System (ADS)

    Vincena, S.; Gekelman, W.; Collette, A.; Cooper, C.

    2007-05-01

    The study of the penetration and mixing of plasmas with differing density, temperature, and species composition has wide-ranging applicability to space plasma systems such as coronal mass ejections, magnetic clouds, galactic jets, and super novae. In these laboratory experiments, two high-beta plasmas are created using a pair of 1.5J, 8ns lasers which strike facing solid carbon targets at right angles to the background magnetic field. The targets are immersed within a low-beta, helium plasma and the lasers are aimed to produce head-on, or glancing collisions. The cylindrical background plasma is 17 m long (10 parallel Alfven wavelengths) by 60 cm wide (300 ρi or 175 c/ωpe). The laser-produced plasmas (LPPs) expand as diamagnetic cavities, become polarized, and then E× B drift at speeds of Mach 10 (v/cs) across the field. As they do so, the ambient plasma facilitates charge separation between energetic LPP electrons and relatively unmagnetized 1keV LPP ions. One of the many resulting dynamic features is the release of a continuous stream of electrons from each LPP. Downstream from the LPP merging, the fast electron current filaments come together with reconnection-like X-line field patterns and eventually merge with a broadband spectrum of electromagnetic (whistler wave) fluctuations. Near-miss LPP collisions result in elongated current sheet formations and the shedding of magnetic field eddies. Current sheet thicknesses are a few electron inertial lengths and the width is approximately one ion inertial length. These results will be presented along with 3D measurements of the magnetic fields and the underlying current systems. These experiments are conducted at the Basic Plasma Science Facility, in the upgraded Large Plasma Device (LAPD) located at the University of California, Los Angeles, USA. This work is funded by the United States Department of Energy and the National Science Foundation.

  4. Does cigarette smoking relieve stress? Evidence from the event-related potential (ERP).

    PubMed

    Choi, Damee; Ota, Shotaro; Watanuki, Shigeki

    2015-12-01

    Previous studies have reported a paradox that cigarette smoking reduces stress psychologically; however, it increases the arousal level physiologically. To examine this issue, our study aimed to investigate whether cigarette smoking relieves stress by measuring the late positive potential (LPP), a component of the event-related potential (ERP). In Experiment 1, participants first watched emotionally neutral images; second, they received a break; and finally, they watched emotionally neutral images again. In the break, they smoked a cigarette (smoking condition) or simply rested without smoking (non-smoking condition). The procedure of Experiment 2 was the same as that of Experiment 1, except that the participants watched unpleasant images as stress stimuli before the break. In Experiment 1, the LPP decreased from before to after the break in the smoking condition, but not in the non-smoking condition, suggesting that smoking cigarettes in the neutral state reduces the arousal level. In Experiment 2, the LPP for 400-600 ms decreased from before to after the break, both in the smoking and non-smoking conditions; however, the LPP for 200-400 ms decreased from before to after the break only in the smoking condition. This suggests the possibility that cigarette smoking in the unpleasant state may facilitate a decrease in the arousal level faster than with non-smoking. In both Experiments 1 and 2, the subjective rating results also suggested that cigarette smoking decreased anxiety. Taken together, both the physiological (LPP) and the psychological responses from our study suggest that cigarette smoking perhaps relieves stress.

  5. Protein restriction in early life is associated with changes in insulin sensitivity and pancreatic β-cell function during pregnancy.

    PubMed

    Ignácio-Souza, Letícia Martins; Reis, Sílvia Regina; Arantes, Vanessa Cristina; Botosso, Bárbara Laet; Veloso, Roberto Vilela; Ferreira, Fabiano; Boschero, Antonio Carlos; Carneiro, Everardo Magalhães; Reis, Marise Auxiliadora de Barros; Latorraca, Márcia Queiroz

    2013-01-28

    Malnutrition in early life impairs glucose-stimulated insulin secretion in adulthood. Conversely, pregnancy is associated with a significant increase in glucose-stimulated insulin secretion under conditions of normoglycaemia. A failure in β-cell adaptive changes may contribute to the onset of diabetes. Thus, glucose homeostasis and β-cell function were evaluated in control-fed pregnant (CP) and non-pregnant (CNP) or protein-restricted pregnant (LPP) and non-pregnant (LPNP) rats, from fetal to adult life, and in protein-restricted rats that were recovered after weaning (RP and RNP). The typical insulin resistance of pregnancy was not observed in the RP rats, nor did pregnancy increase the insulin content/islet in the LPP group. The glucose dose-response curves from pregnant rats were shifted to the left in relation to the non-pregnant rats, except in the recovered group. Glucose utilisation but not oxidation in islets from the RP and LPP groups was reduced at a concentration of 8.3 mm-glucose compared with islets from the CP group. Cyclic AMP content and the potentiation of glucose-stimulated insulin secretion by isobutylmethylxanthine at a concentration of 2.8 mm-glucose indicated increased adenylyl cyclase 3 activity but reduced protein kinase A-α activity in islets from the RP and LPP rats. Protein kinase C (PKC)-α but not phospholipase C (PLC)-β1 expression was reduced in islets from the RP group. Phorbol-12-myristate 13-acetate produced a less potent stimulation of glucose-stimulated insulin secretion in the RP group. Thus, the alterations exhibited by islets from the LPP group appeared to be due to reduced islet mass and/or insulin biosynthesis. In the RP group the loss of the adaptive capacity apparently resulted from uncoupling between glucose metabolism and the amplifying signals of the secretory process, as well as a severe attenuation of the PLC/PKC pathway. PMID:22475371

  6. 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.

  7. Maternal recognition of pregnancy in swine. II. Plasma concentrations of progesterone and 13,14-dihydro-15-keto-prostaglandin F2 alpha during the estrous cycle and during short and long pseudopregnancy in gilts.

    PubMed

    Pusateri, A E; Wilson, M E; Diekman, M A

    1996-09-01

    Two experiments were conducted to determine plasma progesterone (P4) and 13,14-dihydro-15-keto-prostaglandin F2 alpha (PGFM) concentrations in unmated gilts induced to have either short pseudopregnancy (SPP) or long pseudopregnancy (LPP). In experiment 1, estradiol-17 beta (E2) was injected on different combinations of days between Days 11 and 16 of the estrous cycle. For gilts induced to exhibit SPP, the interestrous interval averaged 27.0 +/- 0.4 days compared to the control interval of 20.0 +/- 0.4 days. In experiment 2, E2 injections were given on Days 12 and 13 or on Days 12 through 25. Interestrous intervals in SPP and nonpseudopregnant gilts were 25.6 +/- 0.2 and 19.9 +/- 0.6 days, respectively. Four of six gilts treated with E2 on Days 12-25 were induced to have LPP lasting more than 100 days. In both experiments, plasma P4 declined to baseline approximately 3 days before posttreatment estrus, regardless of type of pseudopregnancy induced. Plasma PGFM peaked 4-6 days before posttreatment estrus in gilts displaying each type of response. In gilts exhibiting LPP, plasma PGFM concentrations tended to increase steadily during pseudopregnancy. These data suggest that the mechanisms of luteolysis during the estrous cycle of unmated gilts and during estrogen-induced SPP and LPP may be similar. The present results suggest that luteal persistence during SPP and LPP may be due to delayed peak release of prostaglandin F2 alpha by the uterus.

  8. Deletion of Braun lipoprotein and plasminogen-activating protease-encoding genes attenuates Yersinia pestis in mouse models of bubonic and pneumonic plague.

    PubMed

    van Lier, Christina J; Sha, Jian; Kirtley, Michelle L; Cao, Anthony; Tiner, Bethany L; Erova, Tatiana E; Cong, Yingzi; Kozlova, Elena V; Popov, Vsevolod L; Baze, Wallace B; Chopra, Ashok K

    2014-06-01

    Currently, there is no FDA-approved vaccine against Yersinia pestis, the causative agent of bubonic and pneumonic plague. Since both humoral immunity and cell-mediated immunity are essential in providing the host with protection against plague, we developed a live-attenuated vaccine strain by deleting the Braun lipoprotein (lpp) and plasminogen-activating protease (pla) genes from Y. pestis CO92. The Δlpp Δpla double isogenic mutant was highly attenuated in evoking both bubonic and pneumonic plague in a mouse model. Further, animals immunized with the mutant by either the intranasal or the subcutaneous route were significantly protected from developing subsequent pneumonic plague. In mice, the mutant poorly disseminated to peripheral organs and the production of proinflammatory cytokines concurrently decreased. Histopathologically, reduced damage to the lungs and livers of mice infected with the Δlpp Δpla double mutant compared to the level of damage in wild-type (WT) CO92-challenged animals was observed. The Δlpp Δpla mutant-immunized mice elicited a humoral immune response to the WT bacterium, as well as to CO92-specific antigens. Moreover, T cells from mutant-immunized animals exhibited significantly higher proliferative responses, when stimulated ex vivo with heat-killed WT CO92 antigens, than mice immunized with the same sublethal dose of WT CO92. Likewise, T cells from the mutant-immunized mice produced more gamma interferon (IFN-γ) and interleukin-4. These animals had an increasing number of tumor necrosis factor alpha (TNF-α)-producing CD4(+) and CD8(+) T cells than WT CO92-infected mice. These data emphasize the role of TNF-α and IFN-γ in protecting mice against pneumonic plague. Overall, our studies provide evidence that deletion of the lpp and pla genes acts synergistically in protecting animals against pneumonic plague, and we have demonstrated an immunological basis for this protection.

  9. Too bad: Bias for angry faces in social anxiety interferes with identity processing.

    PubMed

    Hagemann, Julian; Straube, Thomas; Schulz, Claudia

    2016-04-01

    The recognition of faces across incidences is a complex function of the human brain and a crucial ability for communication and daily interactions. This first study on ERP correlates of emotional face learning in social anxiety disorder (SAD) investigates whether the known attentional bias for threatening faces leads to a corresponding memory bias. Therefore, 21 patients with SAD and 21 healthy controls (HCs) learned faces with emotional facial expressions (neutral, happy, and angry) and were later asked to recognize these out of novel identities all presented with a neutral facial expression. EEG was recorded throughout. Behaviorally, the faces' emotional expression modulated later recognition in terms of accuracy, response times, signal detection parameters and ratings of valence, but with better performance for happy than angry faces in HC as well as in SAD. In the learning phase, attention- and memory-associated event-related potentials (ERPs) P100, N170, P200, N250/EPN, and LPP indicated enhanced processing of angry faces, which was restricted to patients with SAD in N250/EPN and LPP. In the test phase, familiarity effects emerged in N250, FN400 and LPP. While N250 was affected by learned-angry faces, FN400 and LPP reflected image learning of neutral faces, which was restricted to SAD in LPP. We replicated the attentional bias to threatening faces, which was not restricted to early ERP components, but was prolonged to later stages of conscious processing, especially in SAD. In contrast to what had been expected, sustained hypervigilance to the emotional content seems to have impaired the processing of the facial identity, resulting in a happy face advantage at the behavioral level. This could be explained by prominent models assuming separate processing of facial emotion and identity. Hypervigilance in SAD might be a disadvantage in those studies focusing on other aspects of face processing than emotion. PMID:26878979

  10. 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.

  11. Protein restriction in early life is associated with changes in insulin sensitivity and pancreatic β-cell function during pregnancy.

    PubMed

    Ignácio-Souza, Letícia Martins; Reis, Sílvia Regina; Arantes, Vanessa Cristina; Botosso, Bárbara Laet; Veloso, Roberto Vilela; Ferreira, Fabiano; Boschero, Antonio Carlos; Carneiro, Everardo Magalhães; Reis, Marise Auxiliadora de Barros; Latorraca, Márcia Queiroz

    2013-01-28

    Malnutrition in early life impairs glucose-stimulated insulin secretion in adulthood. Conversely, pregnancy is associated with a significant increase in glucose-stimulated insulin secretion under conditions of normoglycaemia. A failure in β-cell adaptive changes may contribute to the onset of diabetes. Thus, glucose homeostasis and β-cell function were evaluated in control-fed pregnant (CP) and non-pregnant (CNP) or protein-restricted pregnant (LPP) and non-pregnant (LPNP) rats, from fetal to adult life, and in protein-restricted rats that were recovered after weaning (RP and RNP). The typical insulin resistance of pregnancy was not observed in the RP rats, nor did pregnancy increase the insulin content/islet in the LPP group. The glucose dose-response curves from pregnant rats were shifted to the left in relation to the non-pregnant rats, except in the recovered group. Glucose utilisation but not oxidation in islets from the RP and LPP groups was reduced at a concentration of 8.3 mm-glucose compared with islets from the CP group. Cyclic AMP content and the potentiation of glucose-stimulated insulin secretion by isobutylmethylxanthine at a concentration of 2.8 mm-glucose indicated increased adenylyl cyclase 3 activity but reduced protein kinase A-α activity in islets from the RP and LPP rats. Protein kinase C (PKC)-α but not phospholipase C (PLC)-β1 expression was reduced in islets from the RP group. Phorbol-12-myristate 13-acetate produced a less potent stimulation of glucose-stimulated insulin secretion in the RP group. Thus, the alterations exhibited by islets from the LPP group appeared to be due to reduced islet mass and/or insulin biosynthesis. In the RP group the loss of the adaptive capacity apparently resulted from uncoupling between glucose metabolism and the amplifying signals of the secretory process, as well as a severe attenuation of the PLC/PKC pathway.

  12. 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

  13. Implementation and success of nurse telephone counseling in linguistically isolated Korean American patients with high blood pressure

    PubMed Central

    Han, Hae-Ra; Kim, Jiyun; Kim, Kim B.; Jeong, Seonghee; Levine, David; Li, Chunyu; Song, Heejung; Kim, Miyong T.

    2015-01-01

    Objective Nurse telephone counseling can improve the management of chronic conditions, but the effectiveness of this approach in underserved populations is unclear. This study evaluated the use of bilingual nurse-delivered telephone counseling in Korean Americans (KAs) participating in a community-based intervention trial to improve management of hypertension. Methods KAs were randomized to receive 12 months of hypertension-related telephone counseling that was more intensive (bi-weekly) or less intensive (monthly). Counseling logs were kept for 360 KAs who completed the pre- and post-intervention evaluations. Results The overall success rate for the intervention was 80.3%. The level of success was significantly influenced by the dose of counseling, employment status, and years of US residence. Over the 12-month counseling period, both groups showed improvement with regard to medication-taking, alcohol consumption, and exercise but not smoking, with no significant group differences. Conclusion Bilingual telephone counseling could reach monolingual KAs and improve their hypertension management behavior. Practice implications Bilingual nurse telephone counseling may have wide applicability, serving as an effective means of disseminating evidence-based chronic disease management guidelines to a linguistically isolated community with limited health resources and information. PMID:19945816

  14. Estimation of the acid dissociation constant of perfluoroalkyl carboxylic acids through an experimental investigation of their water-to-air transport.

    PubMed

    Vierke, Lena; Berger, Urs; Cousins, Ian T

    2013-10-01

    The acid dissociation constants (pKas) of perfluoroalkyl carboxylic acids (PFCAs) have been the subject of discussion in the literature; for example, values from -0.2 to 3.8 have been suggested for perfluorooctanoic acid (PFOA). The dissociated anionic conjugate bases of PFCAs have negligible air-water partition coefficients (KAWs) and do not volatilize from water. The neutral acids, however, have relatively high KAWs and volatilization from water has been demonstrated. The extent of volatilization of PFCAs in the environment will depend on the water pH and their pKa. Knowledge of the pKas of PFCAs is therefore vital for understanding their environmental transport and fate. We investigated the water-to-air transfer of PFCAs in a novel experimental setup. We used ∼1 μg L(-1) of PFCAs in water (above environmental background concentrations but below the concentration at which self-association occurs) at different water pH (pH 0.3 to pH 6.9) and sampled the PFCAs volatilized from water during a 2-day experiment. Our results suggest that the pKas of C4-11 PFCAs are <1.6. For PFOA, we derived a pKa of 0.5 from fitting the experimental measurements with a volatilization model. Perfluoroalkane sulfonic acids were not volatilized, suggesting that their pKas are below the investigated pH range (pKa <0.3).

  15. Knowledge and abilities catalog for nuclear power plant operators: Boiling water reactors, Revision 1

    SciTech Connect

    1995-08-01

    The Knowledge and Abilities Catalog for Nuclear Power Plant Operators: Boiling-Water Reactors (BWRs) (NUREG-1123, Revision 1) provides the basis for the development of content-valid licensing examinations for reactor operators (ROs) and senior reactor operators (SROs). The examinations developed using the BWR Catalog along with the Operator Licensing Examiner Standards (NUREG-1021) and the Examiner`s Handbook for Developing Operator Licensing Written Examinations (NUREG/BR-0122), will cover the topics listed under Title 10, Code of Federal Regulations, Part 55 (10 CFR 55). The BWR Catalog contains approximately 7,000 knowledge and ability (K/A) statements for ROs and SROs at BWRs. The catalog is organized into six major sections: Organization of the Catalog, Generic Knowledge and Ability Statements, Plant Systems grouped by Safety Functions, Emergency and Abnormal Plant Evolutions, Components, and Theory. Revision 1 to the BWR Catalog represents a modification in form and content of the original catalog. The K/As were linked to their applicable 10 CFR 55 item numbers. SRO level K/As were identified by 10 CFR 55.43 item numbers. The plant-wide generic and system generic K/As were combined in one section with approximately one hundred new K/As. Component Cooling Water and Instrument Air Systems were added to the Systems Section. Finally, High Containment Hydrogen Concentration and Plant Fire On Site evolutions added to the Emergency and Abnormal Plant Evolutions section.

  16. Purification and characterization of novel whey glycoprotein WGP-88 which binds to a monoclonal antibody to PAS-4 glycoprotein in the bovine milk fat globule membrane.

    PubMed

    Hwangbo, S; Azuma, N; Kurisaki, J; Kanno, C

    1997-09-01

    A monoclonal antibody to the PAS-4 glycoprotein (78 kDa) of the bovine milk fat globule membrane (MFGM) specifically recognized PAS-4, and was named KAS4. A component recognized by KAS4 was found in whey protein, this being a glycoprotein of 88 kDa by SDS-PAGE and named WGP-88. WGP-88 was purified and characterized in comparison with PAS-4. WGP-88 had apparent pI values of 6.45 and 6.39, while those of PAS-4 were 7.39 and 7.35. Neuraminidase digestion shifted the pI values of WGP-88 to 6.57 and of PAS-4 to 7.52. WGP-88 was rich in polar amino residues (44.9 mol%), while PAS-4 was abundant in nonpolar amino acid residues (48.7 mol%). WGP-88 contained 17.1% of carbohydrate and PAS-4 had 7.2%. The results of reductive hydrolysis, N-glycanase digestion, and a lectin blot analysis suggested that N- and O-linked sugar chains were contained in both glycoproteins. WGP-88 and PAS-4 had a different N-terminal amino acid sequence. WGP-88 and PAS-4 respectively inhibited competitively the binding of KAS4 to PAS-4 and WGP-88. Our studies revealed WGP-88 recognized by KAS4 mAb to be a novel whey protein and to have different biochemical properties from those of PAS-4.

  17. Colorado State University Program for developing, testing, evaluating and optimizing solar heating and cooling systems. Project status report, August--September 1994

    SciTech Connect

    Hittle, D.C.

    1994-11-01

    The current work has been to validate Florida Solar Energy Center`s models of the Solahart 302K and 302K-AS systems to prepare a rating for the Sacramento Municipal Utility District`s rebate program for solar domestic hot water heaters.

  18. 10 CFR 26.29 - Training.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... KAs in paragraph (a) of this section. The examination must include a comprehensive random sampling of... COMMISSION FITNESS FOR DUTY PROGRAMS Program Elements § 26.29 Training. (a) Training content. Licensees and other entities shall ensure that the individuals who are subject to this subpart have the following...

  19. 10 CFR 26.29 - Training.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... KAs in paragraph (a) of this section. The examination must include a comprehensive random sampling of... COMMISSION FITNESS FOR DUTY PROGRAMS Program Elements § 26.29 Training. (a) Training content. Licensees and other entities shall ensure that the individuals who are subject to this subpart have the following...

  20. Electrostatics of cysteine residues in proteins: Parameterization and validation of a simple model

    PubMed Central

    Salsbury, Freddie R.; Poole, Leslie B.; Fetrow, Jacquelyn S.

    2013-01-01

    One of the most popular and simple models for the calculation of pKas from a protein structure is the semi-macroscopic electrostatic model MEAD. This model requires empirical parameters for each residue to calculate pKas. Analysis of current, widely used empirical parameters for cysteine residues showed that they did not reproduce expected cysteine pKas; thus, we set out to identify parameters consistent with the CHARMM27 force field that capture both the behavior of typical cysteines in proteins and the behavior of cysteines which have perturbed pKas. The new parameters were validated in three ways: (1) calculation across a large set of typical cysteines in proteins (where the calculations are expected to reproduce expected ensemble behavior); (2) calculation across a set of perturbed cysteines in proteins (where the calculations are expected to reproduce the shifted ensemble behavior); and (3) comparison to experimentally determined pKa values (where the calculation should reproduce the pKa within experimental error). Both the general behavior of cysteines in proteins and the perturbed pKa in some proteins can be predicted reasonably well using the newly determined empirical parameters within the MEAD model for protein electrostatics. This study provides the first general analysis of the electrostatics of cysteines in proteins, with specific attention paid to capturing both the behavior of typical cysteines in a protein and the behavior of cysteines whose pKa should be shifted, and validation of force field parameters for cysteine residues. PMID:22777874

  1. Reactive γ-ketoaldehydes promote protein misfolding and preamyloid oligomer formation in rapidly-activated atrial cells.

    PubMed

    Sidorova, Tatiana N; Yermalitskaya, Liudmila V; Mace, Lisa C; Wells, K Sam; Boutaud, Olivier; Prinsen, Joseph K; Davies, Sean S; Roberts, L Jackson; Dikalov, Sergey I; Glabe, Charles G; Amarnath, Venkataraman; Barnett, Joey V; Murray, Katherine T

    2015-02-01

    Rapid activation causes remodeling of atrial myocytes resembling that which occurs in experimental and human atrial fibrillation (AF). Using this cellular model, we previously observed transcriptional upregulation of proteins implicated in protein misfolding and amyloidosis. For organ-specific amyloidoses such as Alzheimer's disease, preamyloid oligomers (PAOs) are now recognized to be the primary cytotoxic species. In the setting of oxidative stress, highly-reactive lipid-derived mediators known as γ-ketoaldehydes (γ-KAs) have been identified that rapidly adduct proteins and cause PAO formation for amyloid β1-42 implicated in Alzheimer's. We hypothesized that rapid activation of atrial cells triggers oxidative stress with lipid peroxidation and formation of γ-KAs, which then rapidly crosslink proteins to generate PAOs. To investigate this hypothesis, rapidly-paced and control, spontaneously-beating atrial HL-1 cells were probed with a conformation-specific antibody recognizing PAOs. Rapid stimulation of atrial cells caused the generation of cytosolic PAOs along with a myocyte stress response (e.g., transcriptional upregulation of Nppa and Hspa1a), both of which were absent in control, unpaced cells. Rapid activation also caused the formation of superoxide and γ-KA adducts in atriomyocytes, while direct exposure of cells to γ-KAs resulted in PAO production. Increased cytosolic atrial natriuretic peptide (ANP), and the generation of ANP oligomers with exposure to γ-KAs and rapid atrial HL-1 cell stimulation, strongly suggest a role for ANP in PAO formation. Salicylamine (SA) is a small molecule scavenger of γ-KAs that can protect proteins from modification by these reactive compounds. PAO formation and transcriptional remodeling were inhibited when cells were stimulated in the presence of SA, but not with the antioxidant curcumin, which is incapable of scavenging γ-KAs. These results demonstrate that γ-KAs promote protein misfolding and PAO formation as a

  2. A novel interaction linking the FAS-II and phthiocerol dimycocerosate (PDIM) biosynthetic pathways.

    PubMed

    Kruh, Nicole A; Borgaro, Janine G; Ruzsicska, Béla P; Xu, Hua; Tonge, Peter J

    2008-11-14

    The fatty acid biosynthesis (FAS-II) pathway in Mycobacterium tuberculosis generates long chain fatty acids that serve as the precursors to mycolic acids, essential components of the mycobacterial cell wall. Enzymes in the FAS-II pathway are thought to form one or more noncovalent multi-enzyme complexes within the cell, and a bacterial two-hybrid screen was used to search for missing components of the pathway and to furnish additional data on interactions involving these enzymes in vivo. Using the FAS-II beta-ketoacyl synthase, KasA, as bait, an extensive bacterial two-hybrid screen of a M. tuberculosis genome fragment library unexpectedly revealed a novel interaction between KasA and PpsB as well as PpsD, two polyketide modules involved in the biosynthesis of the virulence lipid phthiocerol dimycocerosate (PDIM). Sequence analysis revealed that KasA interacts with PpsB and PpsD in the region of the acyl carrier domain of each protein, raising the possibility that lipids could be transferred between the FAS-II and PDIM biosynthetic pathways. Subsequent studies utilizing purified proteins and radiolabeled lipids revealed that fatty acids loaded onto PpsB were transferred to KasA and also incorporated into long chain fatty acids synthesized using a Mycobacterium smegmatis lysate. These data suggest that in addition to producing PDIMs, the growing phthiocerol product can also be shuttled into the FAS-II pathway via KasA as an entry point for further elongation. Interactions between these biosynthetic pathways may exist as a simple means to increase mycobacterial lipid diversity, enhancing functionality and the overall complexity of the cell wall. PMID:18703500

  3. Nightside plasmapause positions observed by DE-1 as a function of geomagnetic indices - Comparison with whistler observations and model calculations

    NASA Technical Reports Server (NTRS)

    Decreau, P. M. E.; Lemaire, J.; Chappell, C. R.; Waite, J. H., Jr.

    1986-01-01

    The paper analyzes 28 plasmapause crossings made by the DE1 satellite in the night local time sector (from January to March 1982). Different signatures obtained by the Retarding Ion Mass Spectrometer instrument have been used for this analysis. The observed plasmapause positions (Lpp) have been organized as a function of geomagnetic indices. They are compared with the empirical relationship deduced by Carpenter and Parks (1973) from whistler observations. Moreover, the dependence of Lpp versus Kp has been inferred from model calculations using Kp dependent electric and magnetic fields derived from McIlwain's (1974) E3H electric field model and M2 magnetic field model respectively. Stationary models as well as time dependent ones, have been used to determine the positions of the plasmapause. The results of the model calculations are compared to the observations.

  4. Fairness influences early signatures of reward-related neural processing.

    PubMed

    Massi, Bart; Luhmann, Christian C

    2015-12-01

    Many humans exhibit a strong preference for fairness during decision-making. Although there is evidence that social factors influence reward-related and affective neural processing, it is unclear if this effect is mediated by compulsory outcome evaluation processes or results from slower deliberate cognition. Here we show that the feedback-related negativity (FRN) and late positive potential (LPP), two signatures of early hedonic processing, are modulated by the fairness of rewards during a passive rating task. We find that unfair payouts elicit larger FRNs than fair payouts, whereas fair payouts elicit larger LPPs than unfair payouts. This is true both in the time-domain, where the FRN and LPP are related, and in the time-frequency domain, where the two signals are largely independent. Ultimately, this work demonstrates that fairness affects the early stages of reward and affective processing, suggesting a common biological mechanism for social and personal reward evaluation.

  5. A simulation study of Large Area Crop Inventory Experiment (LACIE) technology

    NASA Technical Reports Server (NTRS)

    Ziegler, L. (Principal Investigator); Potter, J.

    1979-01-01

    The author has identified the following significant results. The LACIE performance predictor (LPP) was used to replicate LACIE phase 2 for a 15 year period, using accuracy assessment results for phase 2 error components. Results indicated that the (LPP) simulated the LACIE phase 2 procedures reasonably well. For the 15 year simulation, only 7 of the 15 production estimates were within 10 percent of the true production. The simulations indicated that the acreage estimator, based on CAMS phase 2 procedures, has a negative bias. This bias was too large to support the 90/90 criterion with the CV observed and simulated for the phase 2 production estimator. Results of this simulation study validate the theory that the acreage variance estimator in LACIE was conservative.

  6. 'I love Rock 'n' Roll'--music genre preference modulates brain responses to music.

    PubMed

    Istók, Eva; Brattico, Elvira; Jacobsen, Thomas; Ritter, Aileen; Tervaniemi, M

    2013-02-01

    The present study examined the effect of participants' music genre preference on the neural processes underlying evaluative and cognitive judgements of music using the event-related potential technique. To this aim, two participant groups differing in their preference for Latin American and Heavy Metal music performed a liking judgement and a genre classification task on a variety of excerpts of either music genre. A late positive potential (LPP) was elicited in all conditions between 600 and 900 ms after stimulus onset. During the genre classification task, an early negativity was elicited by the preferred compared to the non-preferred music at around 230-370 ms whereas the non-preferred genre was characterized by a larger LPP. The findings suggest that evaluative and cognitive judgements of music are accompanied by affective responses and that the valence of music may spontaneously modulate early processes of music categorization even when no overt liking judgement is required. PMID:23201033

  7. Implicit emotion regulation in the context of viewing artworks: ERP evidence in response to pleasant and unpleasant pictures.

    PubMed

    Van Dongen, Noah N N; Van Strien, Jan W; Dijkstra, Katinka

    2016-08-01

    Presenting affective pictures as a work of art could change perceivers' judgment and strength in emotional reactions. Aesthetic theory states that perceivers of art emotionally distance themselves, allowing them to appreciate works of art depicting gruesome events. To examine whether implicit emotion regulation is induced by an art context, we assessed whether presenting pleasant and unpleasant IAPS pictures as either "works of art comprising paintings, digital renderings, and photographs of staged scenes" or "photographs depicting real events" modulated perceivers' Late Positive Potentials (LPP) and likability ratings. In line with previous research and aesthetic theory, participants evaluated the IAPS pictures as more likable when they were presented as works of art than when they were presented as photographs. Moreover, participants' late LPP amplitudes (600-900ms post picture onset) in response to the pictures were attenuated in the art context condition. These results provide evidence for an implicit emotion regulation induced by the art context. PMID:27367861

  8. Differentiating Event-Related Potential Components Sensitive to Emotion in Middle Childhood: Evidence from Temporal-Spatial PCA

    PubMed Central

    Kujawa, Autumn; Weinberg, Anna; Hajcak, Greg; Klein, Daniel N.

    2012-01-01

    Event-related potentials (ERPs) may be particularly useful for examining emotional processing across development. Though a number of ERP components are sensitive to emotional content in adults, previous studies have yet to systematically examine the components sensitive to emotion in children. The current study used temporal-spatial principal components analysis (PCA) to identify ERP components in response to complex emotional images in nine-year-old children. Three components were modulated by emotional content and were similar to those previously observed in adults, including: the early posterior negativity, the P300, and a sustained relative positivity similar to the late positive potential (LPP). Compared to those previously observed in adults, the components sensitive to emotion in children were maximal over more occipital regions and the LPP component appeared to be less protracted in time, perhaps indicative of less elaborative processing of emotional stimuli. PMID:22692816

  9. Modulation of late positive potentials by sexual images in problem users and controls inconsistent with "porn addiction".

    PubMed

    Prause, Nicole; Steele, Vaughn R; Staley, Cameron; Sabatinelli, Dean; Hajcak, Greg

    2015-07-01

    "Excessive" viewing of visual sexual stimuli (VSS) is the most commonly reported hypersexual behavior problem and is especially amenable to laboratory study. A pattern of enhanced sexual cue responsiveness is expected in this sample if hypersexuality shares features of other addiction models. Participants (N=122) who either reported or denied problematic VSS use were presented with emotional, including explicit sexual, images while their evoked response potentials were recorded. An interaction of hypersexual problem group and the level of desire for sex with a partner predicted LPP amplitude. Specifically, those reporting problems regulating their VSS use who also reported higher sexual desire had lower LPP in response to VSS. This pattern appears different from substance addiction models. These are the first functional physiological data of persons reporting VSS regulation problems. PMID:26095441

  10. Fission product transport and behavior during two postulated loss of flow transients in the air

    SciTech Connect

    Adams, J.P.; Carboneau, M.L.

    1991-12-31

    This document discusses fission product behavior during two postulated loss-of-flow accidents (leading to high- and low-pressure core degradation, respectively) in the Advanced Test Reactor (ATR). These transients are designated ATR Transient LCPI5 (high-pressure) and LPP9 (low-pressure). Normally, transients of this nature would be easily mitigated using existing safety systems and procedures. In these analyses, failure of these safety systems was assumed so that core degradation and fission product release could be analyzed. A probabilistic risk assessment indicated that the probability of occurrence for these two transients is of the order of 10{sup {minus}5 }and 10{sup {minus}7} per reactor year for LCP15 and LPP9, respectively.

  11. Fission product transport and behavior during two postulated loss of flow transients in the air

    SciTech Connect

    Adams, J.P.; Carboneau, M.L.

    1991-01-01

    This document discusses fission product behavior during two postulated loss-of-flow accidents (leading to high- and low-pressure core degradation, respectively) in the Advanced Test Reactor (ATR). These transients are designated ATR Transient LCPI5 (high-pressure) and LPP9 (low-pressure). Normally, transients of this nature would be easily mitigated using existing safety systems and procedures. In these analyses, failure of these safety systems was assumed so that core degradation and fission product release could be analyzed. A probabilistic risk assessment indicated that the probability of occurrence for these two transients is of the order of 10{sup {minus}5 }and 10{sup {minus}7} per reactor year for LCP15 and LPP9, respectively.

  12. Pump-probe imaging of nanosecond laser-induced bubbles in distilled water solutions: Observations of laser-produced-plasma

    SciTech Connect

    Evans, R.; Camacho-Lopez, S.

    2010-11-15

    This article presents the analysis of the laser-produced-plasma (LPP) formed by the focusing of a 9 ns laser pulse, {lambda}=532 nm, with a NA=0.6 aspherical lens using energies between 100-1500 {mu}J, into distilled water with varying solutions of table salt. Observations of the filamentation plasma were made, which are explained by self-focusing of the laser pulse by the LPP through ponderomotive cavitation of the electron plasma in the center of the beam. The filamentation of the beam through a low density plasma wave guide explains why the transmission of the pump laser through the interaction region was notably higher on previous experiments that we performed [R. Evans et al., Opt. Express 16, 7481 (2008)], than a very similar set of experiments performed by Noack and Vogel [IEEE J. Quantum Electron. 35, 1156 (1999)].

  13. Judging emotional congruency: Explicit attention to situational context modulates processing of facial expressions of emotion.

    PubMed

    Diéguez-Risco, Teresa; Aguado, Luis; Albert, Jacobo; Hinojosa, José Antonio

    2015-12-01

    The influence of explicit evaluative processes on the contextual integration of facial expressions of emotion was studied in a procedure that required the participants to judge the congruency of happy and angry faces with preceding sentences describing emotion-inducing situations. Judgments were faster on congruent trials in the case of happy faces and on incongruent trials in the case of angry faces. At the electrophysiological level, a congruency effect was observed in the face-sensitive N170 component that showed larger amplitudes on incongruent trials. An interactive effect of congruency and emotion appeared on the LPP (late positive potential), with larger amplitudes in response to happy faces that followed anger-inducing situations. These results show that the deliberate intention to judge the contextual congruency of facial expressions influences not only processes involved in affective evaluation such as those indexed by the LPP but also earlier processing stages that are involved in face perception.

  14. Use of statistical design of experiments in the optimization of Ar-O2 low-pressure plasma treatment conditions of polydimethylsiloxane (PDMS) for increasing polarity and adhesion, and inhibiting hydrophobic recovery

    NASA Astrophysics Data System (ADS)

    Butrón-García, María Isabel; Jofre-Reche, José Antonio; Martín-Martínez, José Miguel

    2015-03-01

    Polydimethylsiloxane (PDMS) film was treated with RF low-pressure plasmas (LPPs) made of mixtures of oxygen and argon for increasing surface polarity, minimizing hydrophobic recovery (i.e. retard ageing) and increasing adhesion to acrylic adhesive tape for medical use. Statistical design of experiments has been used for determining the most influencing experimental parameters of the LPP treatment of PDMS. Water contact angle values (measured 24 h after treatment) and the O/C ratio obtained from XPS experiments were used as response variables. Working pressure was the most influencing parameter in LPP treatment of PDMS, and the duration of the treatment, the power and the oxygen-argon mixture composition determined noticeably its effectiveness. The optimal surface properties in PDMS and inhibited hydrophobic recovery were achieved by treatment with 93 vol% oxygen + 7 vol% argon LLP at low working pressure (300 mTorr), low power (25 W) and long duration of treatment (120 s).

  15. Growth mechanism, electronic spectral investigation and molecular orbital studies of L-prolinium phosphate.

    PubMed

    Liu, Xiaojing; Sun, Xin; Xu, Xijin; Sun, Ping

    2015-01-01

    By using atomic force microscopy, birth and spread has proved to be the primary growth mechanism for L-prolinium phosphate (LPP). The phenomenon of newly formed islands expanding to the edge of the preceding terrace was observed. The optimized molecular structure and the molecular properties were calculated by density functional theory method. Natural bond orbital analysis was carried out to demonstrate the various inter and intramolecular interactions that are responsible for the stabilization of LPP leading to high NLO activity. Molecular electrostatic potential, frontier molecular orbital analysis and thermodynamic properties were investigated to get a better insight of the molecular properties. Global and local reactivity descriptors were computed to predict the reactivity and reactive sites on the molecules. Non-linear optical (NLO) properties such as the total dipole moment (μ) and first order hyperopolarizability (β) were also calculated to predict NLO behavior.

  16. Modulation of late positive potentials by sexual images in problem users and controls inconsistent with "porn addiction".

    PubMed

    Prause, Nicole; Steele, Vaughn R; Staley, Cameron; Sabatinelli, Dean; Hajcak, Greg

    2015-07-01

    "Excessive" viewing of visual sexual stimuli (VSS) is the most commonly reported hypersexual behavior problem and is especially amenable to laboratory study. A pattern of enhanced sexual cue responsiveness is expected in this sample if hypersexuality shares features of other addiction models. Participants (N=122) who either reported or denied problematic VSS use were presented with emotional, including explicit sexual, images while their evoked response potentials were recorded. An interaction of hypersexual problem group and the level of desire for sex with a partner predicted LPP amplitude. Specifically, those reporting problems regulating their VSS use who also reported higher sexual desire had lower LPP in response to VSS. This pattern appears different from substance addiction models. These are the first functional physiological data of persons reporting VSS regulation problems.

  17. Spectral characteristics of quantum-cascade laser operating at 10.6 μm wavelength for a seed application in laser-produced-plasma extreme UV source.

    PubMed

    Nowak, Krzysztof M; Ohta, Takeshi; Suganuma, Takashi; Yokotsuka, Toshio; Fujimoto, Junichi; Mizoguchi, Hakaru; Endo, Akira

    2012-11-15

    In this Letter, we investigate, for the first time to our knowledge, the spectral properties of a quantum-cascade laser (QCL) from a point of view of a new application as a laser seeder for a nanosecond-pulse high-repetition frequency CO(2) laser operating at 10.6 μm wavelength. The motivation for this work is a renewed interest in such a pulse format and wavelength driven by a development of extreme UV (EUV) laser-produced-plasma (LPP) sources. These sources use pulsed multikilowatt CO(2) lasers to drive the EUV-emitting plasmas. Basic spectral performance characteristics of a custom-made QCL chip are measured, such as tuning range and chirp rate. The QCL is shown to have all essential qualities of a robust seed source for a high-repetition nanosecond-pulsed CO(2) laser required by EUV LPP sources.

  18. Spectral characteristics of quantum-cascade laser operating at 10.6 μm wavelength for a seed application in laser-produced-plasma extreme UV source.

    PubMed

    Nowak, Krzysztof M; Ohta, Takeshi; Suganuma, Takashi; Yokotsuka, Toshio; Fujimoto, Junichi; Mizoguchi, Hakaru; Endo, Akira

    2012-11-15

    In this Letter, we investigate, for the first time to our knowledge, the spectral properties of a quantum-cascade laser (QCL) from a point of view of a new application as a laser seeder for a nanosecond-pulse high-repetition frequency CO(2) laser operating at 10.6 μm wavelength. The motivation for this work is a renewed interest in such a pulse format and wavelength driven by a development of extreme UV (EUV) laser-produced-plasma (LPP) sources. These sources use pulsed multikilowatt CO(2) lasers to drive the EUV-emitting plasmas. Basic spectral performance characteristics of a custom-made QCL chip are measured, such as tuning range and chirp rate. The QCL is shown to have all essential qualities of a robust seed source for a high-repetition nanosecond-pulsed CO(2) laser required by EUV LPP sources. PMID:23164906

  19. Lead acetate induced cytotoxicity in male germinal cells of Swiss mice.

    PubMed

    Acharya, U R; Acharya, S; Mishra, M

    2003-07-01

    Single intraperitoneal injection of lead acetate (200 mg/kg b.w) to Swiss mice stimulated testicular weight loss with a constant increase in the incidence of abnormal sperm population and decrease in the total sperm count. Testicular ascorbic acid also declined significantly during the post-treatment phase with significant rise in Lipid Peroxidation Potential (LPP) of the tissue. Elevated LPP is indicative of oxidative stress in treated mice testes. The possible role of lead-induced oxidative stress in culminating increased sperm abnormality and decreased sperm count have been discussed. Further, possible antioxidative role of testicular ascorbic acid in minimizing oxidative stress in lead-treated mice has been demonstrated. PMID:12916762

  20. 'I love Rock 'n' Roll'--music genre preference modulates brain responses to music.

    PubMed

    Istók, Eva; Brattico, Elvira; Jacobsen, Thomas; Ritter, Aileen; Tervaniemi, M

    2013-02-01

    The present study examined the effect of participants' music genre preference on the neural processes underlying evaluative and cognitive judgements of music using the event-related potential technique. To this aim, two participant groups differing in their preference for Latin American and Heavy Metal music performed a liking judgement and a genre classification task on a variety of excerpts of either music genre. A late positive potential (LPP) was elicited in all conditions between 600 and 900 ms after stimulus onset. During the genre classification task, an early negativity was elicited by the preferred compared to the non-preferred music at around 230-370 ms whereas the non-preferred genre was characterized by a larger LPP. The findings suggest that evaluative and cognitive judgements of music are accompanied by affective responses and that the valence of music may spontaneously modulate early processes of music categorization even when no overt liking judgement is required.

  1. Insect endosymbiont proliferation is limited by lipid availability

    PubMed Central

    Herren, Jeremy K; Paredes, Juan C; Schüpfer, Fanny; Arafah, Karim; Bulet, Philippe; Lemaitre, Bruno

    2014-01-01

    Spiroplasma poulsonii is a maternally transmitted bacterial endosymbiont that is naturally associated with Drosophila melanogaster. S. poulsonii resides extracellularly in the hemolymph, where it must acquire metabolites to sustain proliferation. In this study, we find that Spiroplasma proliferation specifically depletes host hemolymph diacylglyceride, the major lipid class transported by the lipoprotein, Lpp. RNAi-mediated knockdown of Lpp expression, which reduces the amount of circulating lipids, inhibits Spiroplasma proliferation demonstrating that bacterial proliferation requires hemolymph-lipids. Altogether, our study shows that an insect endosymbiont acquires specific lipidic metabolites from the transport lipoproteins in the hemolymph of its host. In addition, we show that the proliferation of this endosymbiont is limited by the availability of hemolymph lipids. This feature could limit endosymbiont over-proliferation under conditions of host nutrient limitation as lipid availability is strongly influenced by the nutritional state. DOI: http://dx.doi.org/10.7554/eLife.02964.001 PMID:25027439

  2. Insect endosymbiont proliferation is limited by lipid availability.

    PubMed

    Herren, Jeremy K; Paredes, Juan C; Schüpfer, Fanny; Arafah, Karim; Bulet, Philippe; Lemaitre, Bruno

    2014-01-01

    Spiroplasma poulsonii is a maternally transmitted bacterial endosymbiont that is naturally associated with Drosophila melanogaster. S. poulsonii resides extracellularly in the hemolymph, where it must acquire metabolites to sustain proliferation. In this study, we find that Spiroplasma proliferation specifically depletes host hemolymph diacylglyceride, the major lipid class transported by the lipoprotein, Lpp. RNAi-mediated knockdown of Lpp expression, which reduces the amount of circulating lipids, inhibits Spiroplasma proliferation demonstrating that bacterial proliferation requires hemolymph-lipids. Altogether, our study shows that an insect endosymbiont acquires specific lipidic metabolites from the transport lipoproteins in the hemolymph of its host. In addition, we show that the proliferation of this endosymbiont is limited by the availability of hemolymph lipids. This feature could limit endosymbiont over-proliferation under conditions of host nutrient limitation as lipid availability is strongly influenced by the nutritional state. PMID:25027439

  3. Lichen Planus Pemphigoides Presenting Preferentially Over Preexisting Scars: A Rare Instance of Isotopic Phenomenon

    PubMed Central

    Kumar, Piyush; Savant, Sushil S; Das, Anupam; Hassan, Shahid; Barman, Panchami Deb

    2015-01-01

    An 18-year-old girl presented with multiple itchy hyperpigmented papules and plaques, along with tense blisters over the lower limbs and buttocks for last 3 months. These papules, plaques, and bullae were mostly localized to preexisting scars. The histopathological findings from papule and bulla were consistent with lichen planus (LP) and bullous pemphigoid, respectively. Direct immunofluorescence (DIF) of perilesional skin around bulla showed linear deposition of IgG and C3. Considering clinical, histopathological and DIF findings, diagnosis of LP pemphigoides (LPP) was made. The preferential localization of LPP lesions over preexisting scars was a very interesting finding in our case an extremely rare instance of the isotopic phenomenon. PMID:26677275

  4. LACIE performance predictor FOC users manual

    NASA Technical Reports Server (NTRS)

    1976-01-01

    The LACIE Performance Predictor (LPP) is a computer simulation of the LACIE process for predicting worldwide wheat production. The simulation provides for the introduction of various errors into the system and provides estimates based on these errors, thus allowing the user to determine the impact of selected error sources. The FOC LPP simulates the acquisition of the sample segment data by the LANDSAT Satellite (DAPTS), the classification of the agricultural area within the sample segment (CAMS), the estimation of the wheat yield (YES), and the production estimation and aggregation (CAS). These elements include data acquisition characteristics, environmental conditions, classification algorithms, the LACIE aggregation and data adjustment procedures. The operational structure for simulating these elements consists of the following key programs: (1) LACIE Utility Maintenance Process, (2) System Error Executive, (3) Ephemeris Generator, (4) Access Generator, (5) Acquisition Selector, (6) LACIE Error Model (LEM), and (7) Post Processor.

  5. Up-regulation of emotional responses to reward-predicting stimuli: an ERP study.

    PubMed

    Langeslag, Sandra J E; van Strien, Jan W

    2013-09-01

    Altered reward processing is a hallmark symptom of many psychiatric disorders. It has recently been shown that people are capable of down-regulating reward processing. Here, we examined whether people are capable of up-regulating emotional responses to reward-predicting stimuli. Participants passively viewed colored squares that predicted a reward or no reward, and up- or down-regulated their emotional responses to these reward-predicting stimuli by focusing on the reward meaning or the color of the squares respectively. The amplitude of the late positive potential (LPP) was taken as an objective index of regulation success. The LPP in response to reward-predicting squares was enhanced by up-regulation, suggesting that up-regulation of emotional responses to reward-predicting stimuli using a cognitive strategy is feasible. These results are highly relevant for the treatment of disorders characterized by diminished motivation, and for reward-based decision making in daily life. PMID:23770414

  6. Substrate recognition by β-ketoacyl-ACP synthases.

    PubMed

    Borgaro, Janine G; Chang, Andrew; Machutta, Carl A; Zhang, Xujie; Tonge, Peter J

    2011-12-13

    β-Ketoacyl-ACP synthase (KAS) enzymes catalyze Claisen condensation reactions in the fatty acid biosynthesis pathway. These reactions follow a ping-pong mechanism in which a donor substrate acylates the active site cysteine residue after which the acyl group is condensed with the malonyl-ACP acceptor substrate to form a β-ketoacyl-ACP. In the priming KASIII enzymes the donor substrate is an acyl-CoA while in the elongating KASI and KASII enzymes the donor is an acyl-ACP. Although the KASIII enzyme in Escherichia coli (ecFabH) is essential, the corresponding enzyme in Mycobacterium tuberculosis (mtFabH) is not, suggesting that the KASI or II enzyme in M. tuberculosis (KasA or KasB, respectively) must be able to accept a CoA donor substrate. Since KasA is essential, the substrate specificity of this KASI enzyme has been explored using substrates based on phosphopantetheine, CoA, ACP, and AcpM peptide mimics. This analysis has been extended to the KASI and KASII enzymes from E. coli (ecFabB and ecFabF) where we show that a 14-residue malonyl-phosphopantetheine peptide can efficiently replace malonyl-ecACP as the acceptor substrate in the ecFabF reaction. While ecFabF is able to catalyze the condensation reaction when CoA is the carrier for both substrates, the KASI enzymes ecFabB and KasA have an absolute requirement for an ACP substrate as the acyl donor. Provided that this requirement is met, variation in the acceptor carrier substrate has little impact on the k(cat)/K(m) for the KASI reaction. For the KASI enzymes we propose that the binding of ecACP (AcpM) results in a conformational change that leads to an open form of the enzyme to which the malonyl acceptor substrate binds. Finally, the substrate inhibition observed when palmitoyl-CoA is the donor substrate for the KasA reaction has implications for the importance of mtFabH in the mycobacterial FASII pathway. PMID:22017312

  7. Regulation of Romantic Love Feelings: Preconceptions, Strategies, and Feasibility

    PubMed Central

    Langeslag, Sandra J. E.; van Strien, Jan W.

    2016-01-01

    Love feelings can be more intense than desired (e.g., after a break-up) or less intense than desired (e.g., in long-term relationships). If only we could control our love feelings! We present the concept of explicit love regulation, which we define as the use of behavioral and cognitive strategies to change the intensity of current feelings of romantic love. We present the first two studies on preconceptions about, strategies for, and the feasibility of love regulation. Questionnaire responses showed that people perceive love feelings as somewhat uncontrollable. Still, in four open questions people reported to use strategies such as cognitive reappraisal, distraction, avoidance, and undertaking (new) activities to cope with break-ups, to maintain long-term relationships, and to regulate love feelings. Instructed up-regulation of love using reappraisal increased subjective feelings of attachment, while love down-regulation decreased subjective feelings of infatuation and attachment. We used the late positive potential (LPP) amplitude as an objective index of regulation success. Instructed love up-regulation enhanced the LPP between 300–400 ms in participants who were involved in a relationship and in participants who had recently experienced a romantic break-up, while love down-regulation reduced the LPP between 700–3000 ms in participants who were involved in a relationship. These findings corroborate the self-reported feasibility of love regulation, although they are complicated by the finding that love up-regulation also reduced the LPP between 700–3000 ms in participants who were involved in a relationship. To conclude, although people have the preconception that love feelings are uncontrollable, we show for the first time that intentional regulation of love feelings using reappraisal, and perhaps other strategies, is feasible. Love regulation will benefit individuals and society because it could enhance positive effects and reduce negative effects of

  8. Self-Referential Processing in Depressed Adolescents: A High-Density ERP Study

    PubMed Central

    Auerbach, Randy P.; Stanton, Colin H.; Proudfit, Greg Hajcak; Pizzagalli, Diego A.

    2015-01-01

    Despite the alarming increase in the prevalence of depression during adolescence, particularly among female adolescents, the pathophysiology of depression in adolescents remains largely unknown. Event-related potentials (ERPs) provide an ideal approach to investigate cognitive-affective processes associated with depression in adolescents, especially in the context of negative self-referential processing biases. In this study, healthy (n = 30) and depressed (n = 22) female adolescents completed a self-referential encoding task while ERP data were recorded. To examine cognitive-affective processes associated with self-referential processing, P1, P2, and late positive potential (LPP) responses to negative and positive words were investigated, and intracortical sources of scalp effects were probed using Low Resolution Electromagnetic Tomography (LORETA). Additionally, we tested whether key cognitive processes (e.g., maladaptive self-view, self-criticism) previously implicated in depression related to ERP components. Relative to healthy female subjects, depressed females endorsed more negative and fewer positive words, and free recalled and recognized fewer positive words. With respect to ERPs, compared to healthy female adolescents, depressed adolescents exhibited greater P1 amplitudes following negative words, which was associated with a more maladaptive self-view and self-criticism. In both early and late LPP responses, depressed females showed greater activity following negative versus positive words, whereas healthy females demonstrated the opposite pattern. For both P1 and LPP, LORETA revealed reduced inferior frontal gyrus activity in response to negative words in depressed versus healthy female adolescents. Collectively, these findings suggest that the P1 and LPP reflect biased self-referential processing in female adolescents with depression. Potential treatment implications are discussed. PMID:25643205

  9. Insights on the structure and stability of Licanantase: a trimeric acid-stable coiled-coil lipoprotein from Acidithiobacillus thiooxidans.

    PubMed

    Abarca, Fernando; Gutierrez-Maldonado, Sebastian E; Parada, Pilar; Martinez, Patricio; Maass, Alejandro; Perez-Acle, Tomas

    2014-01-01

    Licanantase (Lic) is the major component of the secretome of Acidithiobacillus thiooxidans when grown in elemental sulphur. When used as an additive, Lic improves copper recovery from bioleaching processes. However, this recovery enhancement is not fully understood. In this context, our aim is to predict the 3D structure of Lic, to shed light on its structure-function relationships. Bioinformatics analyses on the amino acid sequence of Lic showed a great similarity with Lpp, an Escherichia coli Lipoprotein that can form stable trimers in solution. Lic and Lpp share the secretion motif, intracellular processing and alpha helix structure, as well as the distribution of hydrophobic residues in heptads forming a hydrophobic core, typical of coiled-coil structures. Cross-linking experiments showed the presence of Lic trimers, supporting our predictions. Taking the in vitro and in silico evidence as a whole, we propose that the most probable structure for Lic is a trimeric coiled-coil. According to this prediction, a suitable model for Lic was produced using the de novo algorithm "Rosetta Fold-and-Dock". To assess the structural stability of our model, Molecular Dynamics (MD) and Replica Exchange MD simulations were performed using the structure of Lpp and a 14-alanine Lpp mutant as controls, at both acidic and neutral pH. Our results suggest that Lic was the most stable structure among the studied proteins in both pH conditions. This increased stability can be explained by a higher number of both intermonomer hydrophobic contacts and hydrogen bonds, key elements for the stability of Lic's secondary and tertiary structure.

  10. Insights on the structure and stability of Licanantase: a trimeric acid-stable coiled-coil lipoprotein from Acidithiobacillus thiooxidans

    PubMed Central

    Abarca, Fernando; Gutierrez-Maldonado, Sebastian E.; Parada, Pilar; Martinez, Patricio; Maass, Alejandro

    2014-01-01

    Licanantase (Lic) is the major component of the secretome of Acidithiobacillus thiooxidans when grown in elemental sulphur. When used as an additive, Lic improves copper recovery from bioleaching processes. However, this recovery enhancement is not fully understood. In this context, our aim is to predict the 3D structure of Lic, to shed light on its structure-function relationships. Bioinformatics analyses on the amino acid sequence of Lic showed a great similarity with Lpp, an Escherichia coli Lipoprotein that can form stable trimers in solution. Lic and Lpp share the secretion motif, intracellular processing and alpha helix structure, as well as the distribution of hydrophobic residues in heptads forming a hydrophobic core, typical of coiled-coil structures. Cross-linking experiments showed the presence of Lic trimers, supporting our predictions. Taking the in vitro and in silico evidence as a whole, we propose that the most probable structure for Lic is a trimeric coiled-coil. According to this prediction, a suitable model for Lic was produced using the de novo algorithm “Rosetta Fold-and-Dock”. To assess the structural stability of our model, Molecular Dynamics (MD) and Replica Exchange MD simulations were performed using the structure of Lpp and a 14-alanine Lpp mutant as controls, at both acidic and neutral pH. Our results suggest that Lic was the most stable structure among the studied proteins in both pH conditions. This increased stability can be explained by a higher number of both intermonomer hydrophobic contacts and hydrogen bonds, key elements for the stability of Lic’s secondary and tertiary structure. PMID:25165619

  11. Inhibition of lipid phosphate phosphatase activity by VPC32183 suppresses the ability of diacylglycerol pyrophosphate to activate ERK(1/2) MAP kinases.

    PubMed

    Violet, Pierre-Christian; Billon-Denis, Emmanuelle; Robin, Philippe

    2012-11-01

    The lipidic metabolite, diacylglycerol pyrophosphate (DGPP), in its dioctanoyl form (DGPP 8:0), has been described as an antagonist for mammalian lysophosphatidic acid (LPA) receptors LPA1 and LPA3. In this study we show that DGPP 8:0 does not antagonize LPA dependent activation of ERK(1/2) MAP kinases but strongly stimulated them in various mammalian cell lines. LPA and DGPP 8:0 stimulation of ERK(1/2) occurred through different pathways. The DGPP 8:0 effect appeared to be dependent on PKC, Raf and MEK but was insensitive to pertussis toxin and did not involve G protein activation. Finally we showed that DGPP 8:0 effect on ERK(1/2) was dependent on its dephosphorylation by a phosphatase activity sharing lipid phosphate phosphatase properties. The inhibition of this phosphatase activity by VPC32183, a previously characterized LPA receptor antagonist, blocked the DGPP 8:0 effect on ERK(1/2) activation. Moreover, down-regulation of lipid phosphate phosphatase 1 (LPP1) expression by RNA interference technique also reduced DGPP 8:0-induced ERK(1/2) activation. Consistently, over expression of LPP1 in HEK293 cells increases DGPP 8:0 hydrolysis and this increased activity was inhibited by VPC32183. In conclusion, DGPP 8:0 does not exert its effect by acting on a G protein coupled receptor, but through its dephosphorylation by LPP1, generating dioctanoyl phosphatidic acid which in turn activates PKC. These results suggest that LPP1 could have a positive regulatory function on cellular signaling processes such as ERK(1/2) activation.

  12. Regulation of Romantic Love Feelings: Preconceptions, Strategies, and Feasibility.

    PubMed

    Langeslag, Sandra J E; van Strien, Jan W

    2016-01-01

    Love feelings can be more intense than desired (e.g., after a break-up) or less intense than desired (e.g., in long-term relationships). If only we could control our love feelings! We present the concept of explicit love regulation, which we define as the use of behavioral and cognitive strategies to change the intensity of current feelings of romantic love. We present the first two studies on preconceptions about, strategies for, and the feasibility of love regulation. Questionnaire responses showed that people perceive love feelings as somewhat uncontrollable. Still, in four open questions people reported to use strategies such as cognitive reappraisal, distraction, avoidance, and undertaking (new) activities to cope with break-ups, to maintain long-term relationships, and to regulate love feelings. Instructed up-regulation of love using reappraisal increased subjective feelings of attachment, while love down-regulation decreased subjective feelings of infatuation and attachment. We used the late positive potential (LPP) amplitude as an objective index of regulation success. Instructed love up-regulation enhanced the LPP between 300-400 ms in participants who were involved in a relationship and in participants who had recently experienced a romantic break-up, while love down-regulation reduced the LPP between 700-3000 ms in participants who were involved in a relationship. These findings corroborate the self-reported feasibility of love regulation, although they are complicated by the finding that love up-regulation also reduced the LPP between 700-3000 ms in participants who were involved in a relationship. To conclude, although people have the preconception that love feelings are uncontrollable, we show for the first time that intentional regulation of love feelings using reappraisal, and perhaps other strategies, is feasible. Love regulation will benefit individuals and society because it could enhance positive effects and reduce negative effects of romantic

  13. Los Alamos experiments on the few nucleon systems

    SciTech Connect

    Spinka, H.

    1986-01-01

    A summary of recently studied proton-, pion-, and neutron-induced reactions on nuclei up to /sup 4/He at LAMPF is given. Upgrades to the LAMPF experimental facilities for these studies are described. Some new proton-proton total cross sections in pure helicity states (..delta..sigma/sub L/(pp)) from the ZGS near 3 GeV/c are also presented. 46 refs., 4 figs.

  14. The cost-effectiveness of short-term and long-term psychotherapy in the treatment of depressive and anxiety disorders during a 5-year follow-up.

    PubMed

    Maljanen, Timo; Knekt, Paul; Lindfors, Olavi; Virtala, Esa; Tillman, Päivi; Härkänen, Tommi

    2016-01-15

    Both short-term and long-term psychotherapies are used extensively in treating different mental disorders, but there have been practically no attempts to compare their cost-effectiveness. The aim of this study, which is part of the Helsinki Psychotherapy Study, is to assess the cost-effectiveness of two short-term therapies compared to that of a long-term therapy. In this study 326 outpatients suffering from mood or anxiety disorder were randomized to solution-focused therapy (SFT), short-term psychodynamic psychotherapy (SPP) or to long-term psychodynamic psychotherapy (LPP). Psychiatric symptoms and working ability were assessed at baseline and then 4-9 times during a 5-year follow-up using eight widely used measures including e.g. Beck Depression Inventory (BDI), Hamilton Depression Rating Scale (HDRS), Symptom Check List, anxiety scale (SCL-90-Anx), Hamilton Anxiety Rating Scale (HARS), Symptom Check List, Global Severity Index (SCL-90-GSI), and the Work-subscale (SAS-Work) of the Social Adjustment Scale (SAS-SR). Both direct and indirect costs were measured. During the 5-year follow-up period statistically significant improvements were observed in all health indicators in all therapy groups. At first the recovery was faster in the short-term therapy groups than in the LPP group, but taking the whole follow-up period into account, the effectiveness of the LPP was somewhat greater than that of the short-term therapies. Especially the direct costs were, however, much higher in the LPP group than in the short-term therapy groups. Thus the long-term therapy can hardly be regarded as cost-effective compared to short-term therapies when patients are randomized to the therapy groups. PMID:26540079

  15. A low-protein diet during pregnancy alters glucose metabolism and insulin secretion.

    PubMed

    Souza, Denise de Fátima I; Ignácio-Souza, Letícia M; Reis, Sílvia Regina de L; Reis, Marise Auxiliadora de B; Stoppiglia, Luiz Fabrizio; Carneiro, Everardo Magalhães; Boschero, Antonio Carlos; Arantes, Vanessa Cristina; Latorraca, Márcia Queiroz

    2012-03-01

    In pancreatic islets, glucose metabolism is a key process for insulin secretion, and pregnancy requires an increase in insulin secretion to compensate for the typical insulin resistance at the end of this period. Because a low-protein diet decreases insulin secretion, this type of diet could impair glucose homeostasis, leading to gestational diabetes. In pancreatic islets, we investigated GLUT2, glucokinase and hexokinase expression patterns as well as glucose uptake, utilization and oxidation rates. Adult control non-pregnant (CNP) and control pregnant (CP) rats were fed a normal protein diet (17%), whereas low-protein non-pregnant (LPNP) and low-protein pregnant (LPP) rats were fed a low-protein diet (6%) from days 1 to 15 of pregnancy. The insulin secretion in 2.8 mmol l(-1) of glucose was higher in islets from LPP rats than that in islets from CP, CNP and LPNP rats. Maximal insulin release was obtained at 8.3 and 16.7 mmol l(-1) of glucose in LPP and CP groups, respectively. The glucose dose-response curve from LPNP group was shifted to the right in relation to the CNP group. In the CP group, the concentration-response curve to glucose was shifted to the left compared with the CNP group. The LPP groups exhibited an "inverted U-shape" dose-response curve. The alterations in the GLUT2, glucokinase and hexokinase expression patterns neither impaired glucose metabolism nor correlated with glucose islet sensitivity, suggesting that β-cell sensitivity to glucose requires secondary events other than the observed metabolic/molecular events. PMID:22034157

  16. Real-time measurement of materials properties at high temperatures by laser produced plasmas

    NASA Technical Reports Server (NTRS)

    Kim, Yong W.

    1990-01-01

    Determination of elemental composition and thermophysical properties of materials at high temperatures, as visualized in the context of containerless materials processing in a microgravity environment, presents a variety of unusual requirements owing to the thermal hazards and interferences from electromagnetic control fields. In addition, such information is intended for process control applications and thus the measurements must be real time in nature. A new technique is described which was developed for real time, in-situ determination of the elemental composition of molten metallic alloys such as specialty steel. The technique is based on time-resolved spectroscopy of a laser produced plasma (LPP) plume resulting from the interaction of a giant laser pulse with a material target. The sensitivity and precision were demonstrated to be comparable to, or better than, the conventional methods of analysis which are applicable only to post-mortem specimens sampled from a molten metal pool. The LPP technique can be applied widely to other materials composition analysis applications. The LPP technique is extremely information rich and therefore provides opportunities for extracting other physical properties in addition to the materials composition. The case in point is that it is possible to determine thermophysical properties of the target materials at high temperatures by monitoring generation and transport of acoustic pulses as well as a number of other fluid-dynamic processes triggered by the LPP event. By manipulation of the scaling properties of the laser-matter interaction, many different kinds of flow events, ranging from shock waves to surface waves to flow induced instabilities, can be generated in a controllable manner. Time-resolved detection of these events can lead to such thermophysical quantities as volume and shear viscosities, thermal conductivity, specific heat, mass density, and others.

  17. Feedback-Related Negativity in Children with Two Subtypes of Attention Deficit Hyperactivity Disorder

    PubMed Central

    Gong, Jingbo; Yuan, Jiajin; Wang, Suhong; Shi, Lijuan; Cui, Xilong; Luo, Xuerong

    2014-01-01

    Objective The current model of ADHD suggests abnormal reward and punishment sensitivity, although differences in ADHD subgroups are unclear. This study aimed to investigate the effect of feedback valence (reward or punishment) and punishment magnitude (small or large) on Feedback-Related Negativity (FRN) and Late Positive Potential (LPP) in two subtypes of ADHD (ADHD-C and ADHD-I) compared to typically developing children (TD) during a children's gambling task. Methods Children with ADHD-C (n = 16), children with ADHD-I (n = 15) and typically developing children (n = 15) performed a children's gambling task under three feedback conditions: large losses, small losses and gains. FRN and LPP components in brain potentials were recorded and analyzed. Results In TD children and children with ADHD-C, large loss feedback evoked more negative FRN amplitudes than small loss feedback, suggesting that brain sensitivity to the punishment and its magnitude is not impaired in children with ADHD-C. In contrast to these two groups, the FRN effect was absent in children with ADHD-I. The LPP amplitudes were larger in children with ADHD-C in comparison with those with ADHD-I, regardless of feedback valence and magnitude. Conclusion Children with ADHD-C exhibit intact brain sensitivity to punishment similar to TD children. In contrast, children with ADHD-I are significantly impaired in neural sensitivity to the feedback stimuli and in particular, to punishment, compared to TD and ADHD-C children. Thus, FRN, rather than LPP, is a reliable index of the difference in reward and punishment sensitivity across different ADHD-subcategories. PMID:24932610

  18. Regulation of Romantic Love Feelings: Preconceptions, Strategies, and Feasibility.

    PubMed

    Langeslag, Sandra J E; van Strien, Jan W

    2016-01-01

    Love feelings can be more intense than desired (e.g., after a break-up) or less intense than desired (e.g., in long-term relationships). If only we could control our love feelings! We present the concept of explicit love regulation, which we define as the use of behavioral and cognitive strategies to change the intensity of current feelings of romantic love. We present the first two studies on preconceptions about, strategies for, and the feasibility of love regulation. Questionnaire responses showed that people perceive love feelings as somewhat uncontrollable. Still, in four open questions people reported to use strategies such as cognitive reappraisal, distraction, avoidance, and undertaking (new) activities to cope with break-ups, to maintain long-term relationships, and to regulate love feelings. Instructed up-regulation of love using reappraisal increased subjective feelings of attachment, while love down-regulation decreased subjective feelings of infatuation and attachment. We used the late positive potential (LPP) amplitude as an objective index of regulation success. Instructed love up-regulation enhanced the LPP between 300-400 ms in participants who were involved in a relationship and in participants who had recently experienced a romantic break-up, while love down-regulation reduced the LPP between 700-3000 ms in participants who were involved in a relationship. These findings corroborate the self-reported feasibility of love regulation, although they are complicated by the finding that love up-regulation also reduced the LPP between 700-3000 ms in participants who were involved in a relationship. To conclude, although people have the preconception that love feelings are uncontrollable, we show for the first time that intentional regulation of love feelings using reappraisal, and perhaps other strategies, is feasible. Love regulation will benefit individuals and society because it could enhance positive effects and reduce negative effects of romantic

  19. Experiments with Fermilab polarized proton and polarized antiproton beams

    SciTech Connect

    Yokosawa, A.

    1990-01-01

    We summarize activities concerning the Fermilab polarized beams. They include a brief description of the polarized-beam facility, measurements of beam polarization by polarimeters, asymmetry measurements in the {pi}{degree} production at high p{sub {perpendicular}} and in the {Lambda} ({Sigma}{degree}), {pi}{sup {plus minus}}, {pi}{degree} production at large x{sub F}, and {Delta}{sigma}{sub L}(pp, {bar p}p) measurements. 18 refs.

  20. Experiments with Fermilab polarized proton and antiproton beams

    SciTech Connect

    Yokosawa, A.

    1990-01-01

    We summarize activities concerning the Fermilab polarized beams. They include a brief description of the polarized-beam facility, measurements of beam polarization by polarimeters, asymmetry measurements in the {pi}{degree} production at high p{sub {perpendicular}} and in the {Lambda} ({Sigma}{degree}), {pi}{sup {plus minus}}, {pi}{degree} production at large x{sub F}, and {Delta}{sigma}{sub L}(pp, {bar p}p) measurements. 20 refs., 5 figs.

  1. Insights on the structure and stability of Licanantase: a trimeric acid-stable coiled-coil lipoprotein from Acidithiobacillus thiooxidans.

    PubMed

    Abarca, Fernando; Gutierrez-Maldonado, Sebastian E; Parada, Pilar; Martinez, Patricio; Maass, Alejandro; Perez-Acle, Tomas

    2014-01-01

    Licanantase (Lic) is the major component of the secretome of Acidithiobacillus thiooxidans when grown in elemental sulphur. When used as an additive, Lic improves copper recovery from bioleaching processes. However, this recovery enhancement is not fully understood. In this context, our aim is to predict the 3D structure of Lic, to shed light on its structure-function relationships. Bioinformatics analyses on the amino acid sequence of Lic showed a great similarity with Lpp, an Escherichia coli Lipoprotein that can form stable trimers in solution. Lic and Lpp share the secretion motif, intracellular processing and alpha helix structure, as well as the distribution of hydrophobic residues in heptads forming a hydrophobic core, typical of coiled-coil structures. Cross-linking experiments showed the presence of Lic trimers, supporting our predictions. Taking the in vitro and in silico evidence as a whole, we propose that the most probable structure for Lic is a trimeric coiled-coil. According to this prediction, a suitable model for Lic was produced using the de novo algorithm "Rosetta Fold-and-Dock". To assess the structural stability of our model, Molecular Dynamics (MD) and Replica Exchange MD simulations were performed using the structure of Lpp and a 14-alanine Lpp mutant as controls, at both acidic and neutral pH. Our results suggest that Lic was the most stable structure among the studied proteins in both pH conditions. This increased stability can be explained by a higher number of both intermonomer hydrophobic contacts and hydrogen bonds, key elements for the stability of Lic's secondary and tertiary structure. PMID:25165619

  2. The cost-effectiveness of short-term and long-term psychotherapy in the treatment of depressive and anxiety disorders during a 5-year follow-up.

    PubMed

    Maljanen, Timo; Knekt, Paul; Lindfors, Olavi; Virtala, Esa; Tillman, Päivi; Härkänen, Tommi

    2016-01-15

    Both short-term and long-term psychotherapies are used extensively in treating different mental disorders, but there have been practically no attempts to compare their cost-effectiveness. The aim of this study, which is part of the Helsinki Psychotherapy Study, is to assess the cost-effectiveness of two short-term therapies compared to that of a long-term therapy. In this study 326 outpatients suffering from mood or anxiety disorder were randomized to solution-focused therapy (SFT), short-term psychodynamic psychotherapy (SPP) or to long-term psychodynamic psychotherapy (LPP). Psychiatric symptoms and working ability were assessed at baseline and then 4-9 times during a 5-year follow-up using eight widely used measures including e.g. Beck Depression Inventory (BDI), Hamilton Depression Rating Scale (HDRS), Symptom Check List, anxiety scale (SCL-90-Anx), Hamilton Anxiety Rating Scale (HARS), Symptom Check List, Global Severity Index (SCL-90-GSI), and the Work-subscale (SAS-Work) of the Social Adjustment Scale (SAS-SR). Both direct and indirect costs were measured. During the 5-year follow-up period statistically significant improvements were observed in all health indicators in all therapy groups. At first the recovery was faster in the short-term therapy groups than in the LPP group, but taking the whole follow-up period into account, the effectiveness of the LPP was somewhat greater than that of the short-term therapies. Especially the direct costs were, however, much higher in the LPP group than in the short-term therapy groups. Thus the long-term therapy can hardly be regarded as cost-effective compared to short-term therapies when patients are randomized to the therapy groups.

  3. Effects of Uncertainty on ERPs to Emotional Pictures Depend on Emotional Valence.

    PubMed

    Lin, Huiyan; Jin, Hua; Liang, Jiafeng; Yin, Ruru; Liu, Ting; Wang, Yiwen

    2015-01-01

    Uncertainty about the emotional content of an upcoming event has found to modulate neural activity to the event before its occurrence. However, it is still under debate whether the uncertainty effects occur after the occurrence of the event. To address this issue, participants were asked to view emotional pictures that were shortly after a cue, which either indicated a certain emotion of the picture or not. Both certain and uncertain cues were used by neutral symbols. The anticipatory phase (i.e., inter-trial interval, ITI) between the cue and the picture was short to enhance the effects of uncertainty. In addition, we used positive and negative pictures that differed only in valence but not in arousal to investigate whether the uncertainty effect was dependent on emotional valence. Electroencephalography (EEG) was recorded during the presentation of the pictures. Event-related potential (ERP) results showed that negative pictures evoked smaller P2 and late LPP but larger N2 in the uncertain as compared to the certain condition; whereas we did not find the uncertainty effect in early LPP. For positive pictures, the early LPP was larger in the uncertain as compared to the certain condition; however, there were no uncertainty effects in some other ERP components (e.g., P2, N2, and late LPP). The findings suggest that uncertainty modulates neural activity to emotional pictures and this modulation is altered by the valence of the pictures, indicating that individuals alter the allocation of attentional resources toward uncertain emotional pictures dependently on the valence of the pictures. PMID:26733916

  4. Effects of Uncertainty on ERPs to Emotional Pictures Depend on Emotional Valence

    PubMed Central

    Lin, Huiyan; Jin, Hua; Liang, Jiafeng; Yin, Ruru; Liu, Ting; Wang, Yiwen

    2015-01-01

    Uncertainty about the emotional content of an upcoming event has found to modulate neural activity to the event before its occurrence. However, it is still under debate whether the uncertainty effects occur after the occurrence of the event. To address this issue, participants were asked to view emotional pictures that were shortly after a cue, which either indicated a certain emotion of the picture or not. Both certain and uncertain cues were used by neutral symbols. The anticipatory phase (i.e., inter-trial interval, ITI) between the cue and the picture was short to enhance the effects of uncertainty. In addition, we used positive and negative pictures that differed only in valence but not in arousal to investigate whether the uncertainty effect was dependent on emotional valence. Electroencephalography (EEG) was recorded during the presentation of the pictures. Event-related potential (ERP) results showed that negative pictures evoked smaller P2 and late LPP but larger N2 in the uncertain as compared to the certain condition; whereas we did not find the uncertainty effect in early LPP. For positive pictures, the early LPP was larger in the uncertain as compared to the certain condition; however, there were no uncertainty effects in some other ERP components (e.g., P2, N2, and late LPP). The findings suggest that uncertainty modulates neural activity to emotional pictures and this modulation is altered by the valence of the pictures, indicating that individuals alter the allocation of attentional resources toward uncertain emotional pictures dependently on the valence of the pictures. PMID:26733916

  5. Laser-produced plasma measurement of thermal diffusivity of molten metals

    SciTech Connect

    Kim, Yong W.; Park, C.S.

    1995-12-01

    We have shown that a laser-produced plasma plume which is representative in composition of the condensed phase target can be reproducibly generated if the movement of the surface due to evaporation is kept in pace with the thermal diffusion front propagating into the bulk. The resulting mass loss is then strongly controlled by the thermal diffusivity of the target matter, and this relationship has been exploited to measure the thermal diffusivity of metallic alloys. We have developed a novel RF levitator-heater as a contamination-free molten metal source to be used as a target for LPP plume generation. In order to determine the mass loss due to LPP excitation, a new high sensitivity transducer has been constructed for measurement of the resulting impulse imparted on the specimen. The impulse transducer is built onto the specimen holder within the levitation-assisted molten metal source. The LPP method has been fully excercised for measurement of the thermal diffusivity of a molten specimen relative to the value for its room temperature solid. The results for SS304 and SS316 are presented together with a critique of the results. A numerical modeling of specimen heating in the molten metal source and the physical basis of the new hod are also presented.

  6. Fuel-Air Mixing Effect on Nox Emissions for a Lean Premixed-Prevaporized Combustion System

    NASA Technical Reports Server (NTRS)

    Lee, Chi-Ming; Chun, Kue S.; Locke, Randy J.

    1995-01-01

    The lean premixed-prevaporized (LPP) concept effectively meets low nitrogen oxides (NOx) emission requirements for combustors with the high inlet temperature and pressure typical of the High-Speed Civil Transport (HSCT). For the LPP system fuel-air mixture uniformity is probably the most important factor for low NOx emissions. Previous studies have suggested that the fuel-air mixture uniformity can be severely affected by changing the number and configuration of fuel injection points. Therefore, an experimental study was performed to determine how the number of fuel injection points and their arrangement affect NOx emissions from an LPP system. The NOx emissions were measured by a gas-sampling probe in a flame-tube rig at the following conditions: inlet temperature of 810 K (1000 F), rig pressure of 10 atm, reference velocity of 150 ft/s, and residence time near 0.005 s. Additionally, a focused Schlieren diagnostic technique coupled with a high speed camera was used to provide a qualitative description of the spatial flow field.

  7. Binge drinking, depression, and electrocortical responses to emotional images.

    PubMed

    Connell, Arin M; Patton, Emily; McKillop, Hannah

    2015-09-01

    Binge drinking and depression are highly prevalent, associated with cognitive and affective impairments, and frequently co-occur. Yet little research has examined their joint relations with such processing impairment. The current study examines the relation between symptoms of depression, binge drinking, and the magnitude of early (early posterior negativity, EPN) and later (P3 and late positive potential, LPP) visual processing components of affectively negative, positive, and neutral visual stimuli. Participants included 42 undergraduate students recruited on the basis of depressive symptoms. Results of repeated measures analyses of variance (ANOVAs; Depression × Binge × Emotion × Laterality) showed that binge drinkers exhibited lower LPP amplitudes for negative images, compared with nonbinge drinkers, regardless of depression, consistent with motivational models of alcohol abuse. Otherwise, differences across depressed and nondepressed groups were largest among binge drinkers, including a pattern of stronger early attentional engagement (EPN) to negative and neutral images, but decreased later processing (P3 and LPP) across all emotional categories, consistent with a vigilance-avoidance response pattern. PMID:25915691

  8. Rumination and Rebound from Failure as a Function of Gender and Time on Task.

    PubMed

    Whiteman, Ronald C; Mangels, Jennifer A

    2016-01-01

    Rumination is a trait response to blocked goals that can have positive or negative outcomes for goal resolution depending on where attention is focused. Whereas "moody brooding" on affective states may be maladaptive, especially for females, "reflective pondering" on concrete strategies for problem solving may be more adaptive. In the context of a challenging general knowledge test, we examined how Brooding and Reflection rumination styles predicted students' subjective and event-related responses (ERPs) to negative feedback, as well as use of this feedback to rebound from failure on a later surprise retest. For females only, Brooding predicted unpleasant feelings after failure as the task progressed. It also predicted enhanced attention to errors through both bottom-up and top-down processes, as indexed by increased early (400-600 ms) and later (600-1000 ms) late positive potentials (LPP), respectively. Reflection, despite increasing females' initial attention to negative feedback (i.e., early LPP), as well as both genders' recurring negative thoughts, did not result in sustained top-down attention (i.e., late LPP) or enhanced negative feelings toward errors. Reflection also facilitated rebound from failure in both genders, although Brooding did not hinder it. Implications of these gender and time-related rumination effects for learning in challenging academic situations are discussed. PMID:26901231

  9. Aging and emotional memory: the co-occurrence of neurophysiological and behavioral positivity effects.

    PubMed

    Langeslag, Sandra J E; van Strien, Jan W

    2009-06-01

    The positivity effect is a trend for adults to increasingly process positive and/or decreasingly process negative information compared with other information with advancing age. The positivity effect has been observed with behavioral measures, such as in attention and memory tests, and with measures of neurophysiological activity, such as in amygdala activation and the late positive potential (LPP). In this study, it was investigated whether these behavioral and neurophysiological positivity effects co-occur. The electroencephalogram of younger (19-26 years) and older (65-82 years) adults was recorded while they encoded unpleasant, neutral, and pleasant pictures for retrieval in free and cued recall tests. Positivity effects occurred in the late LPP amplitude (700-1,000 ms) and in the free recall test, with negativity biases in younger adults and no biases in older adults. The occurrence of a valence bias in the LPP was substantially but nonsignificantly correlated with the occurrence of a similar valence bias in memory in the older adults. In conclusion, neurophysiological and behavioral positivity effects appear to co-occur, a finding that awaits expansion using different neurophysiological and behavioral measures. PMID:19485614

  10. Ion flux enhancements and oscillations in spatially confined laser produced aluminum plasmas

    SciTech Connect

    Singh, S. C. Fallon, C.; Hayden, P.; Yeates, P.; Costello, J. T.; Mujawar, M.

    2014-09-15

    Ion signals from laser produced plasmas (LPPs) generated inside aluminum rectangular cavities at a fixed depth d = 2 mm and varying width, x = 1.0, 1.6, and 2.75 mm were obtained by spatially varying the position of a negatively biased Langmuir probe. Damped oscillatory features superimposed on Maxwellian distributed ion signals were observed. Depending on the distance of the probe from the target surface, three to twelve fold enhancements in peak ion density were observed via confinement of the LPP, generated within rectangular cavities of varying width which constrained the plasma plume to near one dimensional expansion in the vertical plane. The effects of lateral spatial confinement on the expansion velocity of the LPP plume front, the temperature, density and expansion velocity of ions, enhancement of ion flux, and ion energy distribution were recorded. The periodic behavior of ion signals was analyzed and found to be related to the electron plasma frequency and electron-ion collision frequency. The effects of confinement and enhancement of various ion parameters and expansion velocities of the LPP ion plume are explained on the basis of shock wave theory.

  11. Novelty and emotion: Pupillary and cortical responses during viewing of natural scenes.

    PubMed

    Ferrari, Vera; De Cesarei, Andrea; Mastria, Serena; Lugli, Luisa; Baroni, Giulia; Nicoletti, Roberto; Codispoti, Maurizio

    2016-01-01

    Given the remarkable similarities in the antecedent conditions-stimulus motivational relevance and novelty (i.e., probability of occurrence)-that elicit amplitude modulation of the late positive potential (LPP) and the pupillary dilation response, the present study examines whether these two indexes of orienting response reflect common processes that are responsible for modulatory patterns in motivationally relevant contexts. In the present study, the LPP and the pupillary dilation response were co-registered in a free-picture viewing context in which stimulus novelty was manipulated through repeated presentation of the same picture exemplar. More specifically, pictures depicting both emotional and neutral contents could be novel, that is never seen before in the course of the study, or repeated 4-8 times in a row (i.e., massed repetition). Results showed that, despite massed repetitions, the late positive potential amplitude continued to be highly modulated by picture content, whereas affective modulation of pupil dilation decreased with picture repetition. These findings indicate that, although the LPP and pupil dilation are similarly affected by motivational relevance during the viewing of novel pictures, they differ when pictures are highly familiar, possibly reflecting different functional meanings in the context of the orienting response. PMID:26631353

  12. The role of plasma evolution and photon transport in optimizing future advanced lithography sources

    SciTech Connect

    Sizyuk, Tatyana; Hassanein, Ahmed

    2013-08-28

    Laser produced plasma (LPP) sources for extreme ultraviolet (EUV) photons are currently based on using small liquid tin droplets as target that has many advantages including generation of stable continuous targets at high repetition rate, larger photons collection angle, and reduced contamination and damage to the optical mirror collection system from plasma debris and energetic particles. The ideal target is to generate a source of maximum EUV radiation output and collection in the 13.5 nm range with minimum atomic debris. Based on recent experimental results and our modeling predictions, the smallest efficient droplets are of diameters in the range of 20–30 μm in LPP devices with dual-beam technique. Such devices can produce EUV sources with conversion efficiency around 3% and with collected EUV power of 190 W or more that can satisfy current requirements for high volume manufacturing. One of the most important characteristics of these devices is in the low amount of atomic debris produced due to the small initial mass of droplets and the significant vaporization rate during the pre-pulse stage. In this study, we analyzed in detail plasma evolution processes in LPP systems using small spherical tin targets to predict the optimum droplet size yielding maximum EUV output. We identified several important processes during laser-plasma interaction that can affect conditions for optimum EUV photons generation and collection. The importance and accurate description of modeling these physical processes increase with the decrease in target size and its simulation domain.

  13. A fusion feature and its improvement based on locality preserving projections for rolling element bearing fault classification

    NASA Astrophysics Data System (ADS)

    Ding, Xiaoxi; He, Qingbo; Luo, Nianwu

    2015-01-01

    The sensitive feature extraction from vibration signals is still a great challenge for effective fault classification of rolling element bearing. Current fault classification generally depends on feature pattern difference of different fault classes. This paper explores the active role of healthy pattern in fault classification and proposes a new fusion feature extraction method based on locality preserving projections (LPP). This study intends to discover the local feature pattern difference between each bearing status and the healthy condition to characterize and discriminate different bearing statuses. Specifically, the proposed fusion feature is achieved by two main steps. In the first step, a two-class model is firstly constructed for each class by using this class of signals and healthy condition signals. Then a fusion mapping is generated by mathematically combing the mappings of the LPP or its improvement for all two-class models. In the second step, the LPP is further applied to reduce the fusion mapping dimension, which is to find more sensitive low-dimensional information hidden in the high-dimensional fusion feature structure. The final achieved fusion feature can enhance the discrimination between all classes by improving the between-class scatter and within-class scatter for fault classification. Experimental results using different bearing fault types and severities under different loads show that the proposed method is well-suited and effective for bearing fault classification.

  14. Tissue engineered bulking agent with adipose-derived stem cells and silk fibroin microspheres for the treatment of intrinsic urethral sphincter deficiency.

    PubMed

    Shi, Li Bing; Cai, Hong Xia; Chen, Long Kun; Wu, Yan; Zhu, Shou An; Gong, Xiao Nan; Xia, Ya Xian; Ouyang, Hong Wei; Zou, Xiao Hui

    2014-02-01

    In this study we developed a tissue engineered bulking agent that consisted of adipose-derived stem cells (ADSCs) and silk fibroin microspheres to treat stress urinary incontinence caused by severe intrinsic sphincter deficiency (ISD). ISD models were established by completely transection of the bilateral pudendal nerve (PNT) and confirmed by the decreased leak-point pressure (LPP) and increased lumen area of urethra. Injection of silk fibroin microspheres could recover LPP and lumen area at 4 weeks but its efficacy disappears at 8, 12 weeks. Moreover, it was exciting to find that tissue engineered bulking agent brought long-term efficacy (at 4, 8, 12 weeks post-injection) on the recovery of LPP and lumen area. Concomitantly with the function, tissue engineered bulking agent treated group also improved the urethral sphincter structure as exhibited by better tissue regeneration. The findings showed that silk fibroin microspheres alone could work effectively in short-term, while tissue engineered bulking agent that combined silk fibroin microspheres with ADSCs exhibited promising long-term efficacy. This study developed a new strategy of tissue engineered bulking agent for future ISD therapy.

  15. An Evaluation of the Efficacy of Selective Alpha-Blockers in the Treatment of Children with Neurogenic Bladder Dysfunction—Preliminary Findings

    PubMed Central

    Kroll, Paweł; Gajewska, Ewa; Zachwieja, Jacek; Sobieska, Magdalena; Mańkowski, Przemysław

    2016-01-01

    The aim of this study was to assess the usefulness of selective α1-blockers in children with neurogenic urinary tract dysfunctions and increased leak point pressure (LPP). 14 children from age 6 to 16 years with neurogenic urinary tract dysfunctions (neurogenic bladder) and LPP > 40 cm H2O were enrolled in the study. All patients received a selective α1-blocker (doxazosin) for 6–8 weeks with an initial dosage of 0.03 mg/kg. During the observation period the continuation of oral anticholinergics, Clean Intermittent Catheterization (CIC), observation of “urinary dryness” and urinary incontinence periods were recommended. Patients were scheduled for a follow-up visit and urodynamic investigation after 6–8 weeks after the doxazosin therapy was started. In 4 patients, urine leakage occurred at lower pressures; in 9 patients, no significant changes in urine leak point pressures were detected; in 3 patients, there was a significant increase in the bladder capacity; in one patient, deterioration in continence was noted. The differences both in LPP and LPV before and after the treatment were not statistically significant. Our observations are consistent with the conclusions from other studies and showed no evident efficacy of doxazosin in children with neurogenic bladder. PMID:26999168

  16. Leak path passivation by in situ Al-N for InGaN solar cells operating at wavelengths up to 570 nm

    NASA Astrophysics Data System (ADS)

    Wang, Ke; Imai, Daichi; Kusakabe, Kazuhide; Yoshikawa, Akihiko

    2016-02-01

    A leak path passivation (LPP) technology for InGaN solar cells with photo-response up to 570 nm was developed by inserting in situ monolayers of Al-N into active layers. The InGaN layer in the passivated sample is partially relaxed and incorporates more than 23.5% In. By adopting in situ Al-N LPP, the open circuit voltage increases from 0.96 V to 1.35 V under one sun illumination (1.45-1.68 V under 72 suns), and the dark shunt resistance increases from 3.6 kΩ cm2 to 12.6 kΩ cm2, leading to an increase in power conversion efficiency by a factor of 2.0-2.26 (1-72 suns). This in situ Al-N LPP approach paves a way to exploit the full potential of InGaN for high efficiency solar cell application, accepting the reality of defective high-In-content thick and relaxed InGaN.

  17. Rumination and Rebound from Failure as a Function of Gender and Time on Task

    PubMed Central

    Whiteman, Ronald C.; Mangels, Jennifer A.

    2016-01-01

    Rumination is a trait response to blocked goals that can have positive or negative outcomes for goal resolution depending on where attention is focused. Whereas “moody brooding” on affective states may be maladaptive, especially for females, “reflective pondering” on concrete strategies for problem solving may be more adaptive. In the context of a challenging general knowledge test, we examined how Brooding and Reflection rumination styles predicted students’ subjective and event-related responses (ERPs) to negative feedback, as well as use of this feedback to rebound from failure on a later surprise retest. For females only, Brooding predicted unpleasant feelings after failure as the task progressed. It also predicted enhanced attention to errors through both bottom-up and top-down processes, as indexed by increased early (400–600 ms) and later (600–1000 ms) late positive potentials (LPP), respectively. Reflection, despite increasing females’ initial attention to negative feedback (i.e., early LPP), as well as both genders’ recurring negative thoughts, did not result in sustained top-down attention (i.e., late LPP) or enhanced negative feelings toward errors. Reflection also facilitated rebound from failure in both genders, although Brooding did not hinder it. Implications of these gender and time-related rumination effects for learning in challenging academic situations are discussed. PMID:26901231

  18. Thermophysical property measurement at high temperatures by laser-produced plasmas

    SciTech Connect

    Kim, Y.W.

    1993-05-01

    Excitation by a high-power laser pulse of a material surface generates a sequence of plasma, fluid flow, and acoustic events. These are well separated in time, and their detection and analysis can lead to determination of material properties of the condensed phase target. We have developed a new methodology for real-time determination of molten metal composition by time-resolved spectroscopy of laser-produced plasmas (LPP). If the laser pulse is shaped in such a way that the movement of the bulk surface due to evaporation is kept in pace with the thermal diffusion front advancing into the interior of the target, the LPP plume becomes representative of the bulk in elemental composition. In addition, the mass loss due to LPP ablation is very well correlated with the thermal diffusivity of the target matter. For several elemental solid specimens, we show that the product of the ablation thickness and heat of formation is proportional to the thermal diffusivity per unit molecular weight. Such measurements can be extended to molten metal specimens if the mass loss by ablation, density, heat of formation, and molecular weight can be determined simultaneously. The results from the solid specimen and the progress with a levitation-assisted molten metal experiment are presented.

  19. Laser-produced plasma measurement of thermal diffusivity of molten metals

    NASA Astrophysics Data System (ADS)

    Kim, Y. W.; Park, C. S.

    1996-09-01

    We have shown that a laser-produced plasma plume which is representative in elemental composition of the condensed phase target can be reproducibly generated if the movement of the surface due to evaporation is kept in pace with the thermal diffusion front propagating into the bulk. The resulting mass loss is then strongly controlled by the thermal diffusivity of the target matter, and this relationship has been exploited to measure the thermal diffusivity of metallic alloys. We have developed a novel RF Ievitator-heater as a contamination-free molten metal source to be used as a target for LPP plume generation. In order to determine the mass loss due to LPP excitation, a new high-sensitivity transducer has been constructed for measurement of the resulting impulse imparted on the specimen. The impulse transducer is built onto the specimen holder within the levitation-assisted molten metal source. The LPP method has been fully exercised for measurement of the thermal diffusivity of a molten specimen relative to the value for its room temperature solid. The results for SS304 and SS316 are presented, together with a critique of the results. A numerical modeling of the specimen heating in the molten metal source and the physical basis of the new method are also presented.

  20. Tetracyclines increase lipid phosphate phosphatase expression on plasma membranes and turnover of plasma lysophosphatidate.

    PubMed

    Tang, Xiaoyun; Zhao, Yuan Y; Dewald, Jay; Curtis, Jonathan M; Brindley, David N

    2016-04-01

    Extracellular lysophosphatidate and sphingosine 1-phosphate (S1P) are important bioactive lipids, which signal through G-protein-coupled receptors to stimulate cell growth and survival. The lysophosphatidate and S1P signals are terminated partly by degradation through three broad-specificity lipid phosphate phosphatases (LPPs) on the cell surface. Significantly, the expression of LPP1 and LPP3 is decreased in many cancers, and this increases the impact of lysophosphatidate and S1P signaling. However, relatively little is known about the physiological or pharmacological regulation of the expression of the different LPPs. We now show that treating several malignant and nonmalignant cell lines with 1 μg/ml tetracycline, doxycycline, or minocycline significantly increased the extracellular degradation of lysophosphatidate. S1P degradation was also increased in cells that expressed high LPP3 activity. These results depended on an increase in the stabilities of the three LPPs and increased expression on the plasma membrane. We tested the physiological significance of these results and showed that treating rats with doxycycline accelerated the clearance of lysophosphatidate, but not S1P, from the circulation. However, administering 100 mg/kg/day doxycycline to mice decreased plasma concentrations of lysophosphatidate and S1P. This study demonstrates a completely new property of tetracyclines in increasing the plasma membrane expression of the LPPs.

  1. Brain and personality bases of insensitivity to infant cues in neglectful mothers: an event-related potential study.

    PubMed

    Rodrigo, María José; León, Inmaculada; Quiñones, Ileana; Lage, Agustín; Byrne, Sonia; Bobes, María Antonieta

    2011-02-01

    This investigation examined the neural and personality correlates of processing infant facial expressions in mothers with substantiated neglect of a child under 5 years old. Event-related potentials (ERPs) were recorded from 14 neglectful and 14 control mothers as they viewed and categorized pictures of infant cries, laughs, and neutral faces. Maternal self-reports of anhedonia and empathy were also completed. Early (negative occipitotemporal component peaking at around 170 ms on the scalp [N170] and positive electrical potential peaking at about 200 ms [P200]) and late positive potential (LPP) components were selected. Both groups of mothers showed behavioral discrimination between the different facial expressions via reaction time and accuracy measures. Neglectful mothers did not exhibit increased N170 amplitude at temporal leads in response to viewing crying versus laughing and neutral expressions compared to control mothers. Both groups had greater P200 and LPP amplitudes at centroparietal leads in response to viewing crying versus neutral facial expressions. However, neglectful mothers displayed an overall attenuated brain response in LPP that was related to their higher scores in social anhedonia but not to their empathy scores. The ERP data suggest that the brain's failures in the early differentiation of cry stimuli and in the sustained processing of infant expressions related to social anhedonia may underlie the insensitive responding in neglectful mothers. The implications of these results for the design and evaluation of preventive interventions are discussed.

  2. The impact of oxytocin administration and maternal love withdrawal on event-related potential (ERP) responses to emotional faces with performance feedback.

    PubMed

    Huffmeijer, Renske; Alink, Lenneke R A; Tops, Mattie; Grewen, Karen M; Light, Kathleen C; Bakermans-Kranenburg, Marian J; van Ijzendoorn, Marinus H

    2013-03-01

    This is the first experimental study on the effect of oxytocin administration on the neural processing of facial stimuli conducted with female participants that uses event-related potentials (ERPs). Using a double-blind, placebo-controlled within-subjects design, we studied the effects of 16 IU of intranasal oxytocin on ERPs to pictures combining performance feedback with emotional facial expressions in 48 female undergraduate students. Participants also reported on the amount of love withdrawal they experienced from their mothers. Vertex positive potential (VPP) and late positive potential (LPP) amplitudes were more positive after oxytocin compared to placebo administration. This suggests that oxytocin increased attention to the feedback stimuli (LPP) and enhanced the processing of emotional faces (VPP). Oxytocin heightened processing of the happy and disgusted faces primarily for those reporting less love withdrawal. Significant associations with LPP amplitude suggest that more maternal love withdrawal relates to the allocation of attention toward the motivationally relevant combination of negative feedback with a disgusted face.

  3. An EEG/ERP investigation of the development of empathy in early and middle childhood.

    PubMed

    Cheng, Yawei; Chen, Chenyi; Decety, Jean

    2014-10-01

    Empathic arousal is the first ontogenetic building block of empathy to appear during infancy and early childhood. As development progresses, empathic arousal becomes associated with an increasing ability to differentiate between self and other, which is a critical aspect of mature empathetic ability (Decety and Jackson, 2004). This allows for better regulation of contagious distress and understanding others mental states. In the current study, we recorded electroencephalographic event-related potentials and mu suppression induced by short visual animations that depicted painful situations in 57 typically developing children aged between 3 and 9 years as well as 15 young adults. Results indicate that the difference wave of an early automatic component (N200), indexing empathic arousal, showed an age-related decrease in amplitude. In contrast, the difference wave of late-positive potentials (LPP), associated with cognitive appraisal, showed an age-related gain. Only early LPP was detected in children, whereas both early and late LPP were observed in adults. Furthermore, as compared with adults, children showed stronger mu suppression when viewing both painful and non-painful stimuli. These findings provide neurophysiological support for the development of empathy during childhood, as indicated by a gradual decrease in emotional arousal and an increase in cognitive appraisal with age. PMID:25261920

  4. Integration of moral values during L2 sentence processing.

    PubMed

    Foucart, Alice; Moreno, Eva; Martin, Clara D; Costa, Albert

    2015-11-01

    This study reports an event-related potential (ERP) experiment examining whether valuation (i.e., one's own values) is integrated incrementally and whether it affects L2 speakers' online interpretation of the sentence. We presented Spanish native speakers and French-Spanish mid-proficiency late L2 speakers with visual sentences containing value-consistent and value-inconsistent statements (e.g., 'Nowadays, paedophilia should be prohibited/tolerated across the world.'). Participants' brain activity was recorded as they were reading the sentences and indicating whether they agreed with the statements or not. Behaviourally, the two groups revealed identical valuation. The ERP analyses showed both a semantic (N400) and an affect-related response (LPP) to value-inconsistent statements in the native group, but only an LPP in the non-native group. These results suggest that valuation is integrated online (presence of LPP) during L2 sentence comprehension but that it does not interfere with semantic processing (absence of N400).

  5. The motivational salience of cigarette-related stimuli among former, never, and current smokers

    PubMed Central

    Robinson, Jason D.; Versace, Francesco; Engelmann, Jeffery M.; Cui, Yong; Slapin, Aurelija; Oum, Robert; Cinciripini, Paul M.

    2014-01-01

    While smokers are known to find smoking-related stimuli to be motivationally salient, the extent to which former smokers do so is largely unknown. In this study, we collected event-related potential (ERP) data from former and never smokers and compared them to a sample of current smokers interested in quitting who completed the same ERP paradigm prior to smoking cessation treatment. All participants (n = 180) attended one laboratory session where we recorded dense-array ERPs in response to cigarette-related, pleasant, unpleasant, and neutral pictures, and where we collected valence and arousal ratings of the pictures. We identified three spatial and temporal regions of interest, corresponding to the P1 (120-132 ms), early posterior negativity (EPN; 244-316 ms), and late positive potential (LPP; 384-800 ms) ERP components. We found that all participants produced larger P1 responses to cigarette-related pictures compared to the other picture categories. With the EPN component, we found that, similar to pleasant and unpleasant pictures, cigarette-related pictures attracted early attentional resources, regardless of smoking status. Both former and never smokers produced reduced LPP responses to cigarette-related and pleasant pictures compared to current smokers. Current smokers rated the cigarette-related pictures as being more pleasant and arousing than the former and never smokers. The LPP and picture rating results suggest that former smokers, like never smokers, do not find cigarette-related stimuli to be as motivationally salient as current smokers. PMID:25436840

  6. Ion flux enhancements and oscillations in spatially confined laser produced aluminum plasmas

    NASA Astrophysics Data System (ADS)

    Singh, S. C.; Fallon, C.; Hayden, P.; Mujawar, M.; Yeates, P.; Costello, J. T.

    2014-09-01

    Ion signals from laser produced plasmas (LPPs) generated inside aluminum rectangular cavities at a fixed depth d = 2 mm and varying width, x = 1.0, 1.6, and 2.75 mm were obtained by spatially varying the position of a negatively biased Langmuir probe. Damped oscillatory features superimposed on Maxwellian distributed ion signals were observed. Depending on the distance of the probe from the target surface, three to twelve fold enhancements in peak ion density were observed via confinement of the LPP, generated within rectangular cavities of varying width which constrained the plasma plume to near one dimensional expansion in the vertical plane. The effects of lateral spatial confinement on the expansion velocity of the LPP plume front, the temperature, density and expansion velocity of ions, enhancement of ion flux, and ion energy distribution were recorded. The periodic behavior of ion signals was analyzed and found to be related to the electron plasma frequency and electron-ion collision frequency. The effects of confinement and enhancement of various ion parameters and expansion velocities of the LPP ion plume are explained on the basis of shock wave theory.

  7. Chirality-Induced Dynamic Kohn Anomalies in Graphene

    NASA Astrophysics Data System (ADS)

    Tse, Wang-Kong; Hu, Ben Yu-Kuang; Das Sarma, S.

    2008-08-01

    We develop a theory for the renormalization of the phonon energy dispersion in graphene due to the combined effects of both Coulomb and electron-phonon (e-ph) interactions. We obtain the renormalized phonon energy spectrum by an exact analytic derivation of the phonon self-energy, finding three distinct Kohn anomalies (KAs) at the phonon wave vector q=ω/v, 2kF±ω/v for LO phonons and one at q=ω/v for TO phonons. The presence of these new KAs in graphene, in contrast to the usual KA q=2kF in ordinary metals, originates from the dynamical screening of e-ph interaction (with a concomitant breakdown of the Born-Oppenheimer approximation) and the peculiar chirality of the graphene e-ph coupling.

  8. Nonisothermal Thermogravimetric Analysis of Thai Lignite with High CaO Content

    PubMed Central

    Pintana, Pakamon

    2013-01-01

    Thermal behaviors and combustion kinetics of Thai lignite with different SO3-free CaO contents were investigated. Nonisothermal thermogravimetric method was carried out under oxygen environment at heating rates of 10, 30, and 50°C min−1 from ambient up to 1300°C. Flynn-Wall-Ozawa (FWO) and Kissinger-Akahira-Sunose (KAS) methods were adopted to estimate the apparent activation energy (E) for the thermal decomposition of these coals. Different thermal degradation behaviors were observed in lignites with low (14%) and high (42%) CaO content. Activation energy of the lignite combustion was found to vary with the conversion fraction. In comparison with the KAS method, higher E values were obtained by the FWO method for all conversions considered. High CaO lignite was observed to have higher activation energy than the low CaO coal. PMID:24250259

  9. Regulation of lipid biosynthesis, sliding motility, and biofilm formation by a membrane-anchored nucleoid-associated protein of Mycobacterium tuberculosis.

    PubMed

    Ghosh, Soumitra; Indi, Shantinath S; Nagaraja, Valakunja

    2013-04-01

    Bacteria use a number of small basic proteins for organization and compaction of their genomes. By their interaction with DNA, these nucleoid-associated proteins (NAPs) also influence gene expression. Rv3852, a NAP of Mycobacterium tuberculosis, is conserved among the pathogenic and slow-growing species of mycobacteria. Here, we show that the protein predominantly localizes in the cell membrane and that the carboxy-terminal region with the propensity to form a transmembrane helix is necessary for its membrane localization. The protein is involved in genome organization, and its ectopic expression in Mycobacterium smegmatis resulted in altered nucleoid morphology, defects in biofilm formation, sliding motility, and change in apolar lipid profile. We demonstrate its crucial role in regulating the expression of KasA, KasB, and GroEL1 proteins, which are in turn involved in controlling the surface phenotypes in mycobacteria. PMID:23396914

  10. Rv3080c regulates the rate of inhibition of mycobacteria by isoniazid through FabD.

    PubMed

    Kumari, Ruma; Saxena, Richa; Tiwari, Sameer; Tripathi, Dinesh K; Srivastava, Kishore K

    2013-02-01

    The mycobacterial FASII multi-enzyme complex has been identified to be a target of Ser/Thr protein kinases (STPKs) of Mycobacterium tuberculosis (MTB), with substrates, including the malonyl-CoA:ACP transacylase (FabD) and the β-ketoacyl-ACP synthases KasA and KasB. These proteins are phosphorylated by various kinases in vitro. The present study links the correlation of FASII pathway with serine threonine protein kinase of MTB. In the preliminary finding, we have shown that mycobacterial protein Rv3080c (PknK) phosphorylates FabD and the knockdown of PknK protein in mycobacteria down regulates FabD expression. This event leads to the differential inhibition of mycobacteria in the presence of isoniazid (INH), as the inhibition of growth of mycobacteria in the presence of INH is enhanced in PknK deficient mycobacteria. PMID:23180244

  11. 2-Aminothiazole derivatives as antimycobacterial agents: Synthesis, characterization, in vitro and in silico studies.

    PubMed

    Makam, Parameshwar; Kannan, Tharanikkarasu

    2014-11-24

    A series of 2-aminothiazole derivatives with a wide range of substitutions at 2-, 4- and 5-positions were designed and synthesized using Hantzsch thiazole synthesis. These compounds were evaluated for their inhibitory potential against Mycobacterium tuberculosis (Mtb), H37Rv. The compound, 7n showed high antimycobacterial activity with MIC value of 6.25 μM and the succeeding compounds, 7b, 7e and 7f also exhibited antimycobacterial activity with MIC value of 12.50 μM. Docking studies of these molecules with β-Ketoacyl-ACP Synthase (KasA) protein of Mtb have been carried out to understand the mechanism of antimycobacterial action. The compound, 7n showed good interaction with KasA protein with the Ki value of 0.44 μM. PMID:25305331

  12. Physiological function of mycobacterial mtFabD, an essential malonyl-CoA:AcpM transacylase of type 2 fatty acid synthase FASII, in yeast mct1Delta cells.

    PubMed

    Gurvitz, Aner

    2009-01-01

    Mycobacterium tuberculosis mtFabD is an essential malonyl-CoA:AcpM transacylase and is important for vital protein-protein interactions within type 2 fatty acid synthase FASII. mtFabD contacts KasA, KasB, FabH, InhA, and possibly also HadAB, HadBC, and FabG1/MabA. Disruption of mtFabD's interactions during FASII has been proposed for drug development. Here, the gene for a mitochondrially targeted mtFabD was ectopically expressed in Saccharomyces cerevisiae mct1Delta mutant cells lacking the corresponding mitochondrial malonyl-CoA transferase Mct1p, allowing the mutants to recover their abilities to respire on glycerol and synthesize lipoic acid. Hence, mtFabD could physiologically function in an environment lacking holo-AcpM or other native interaction partners. PMID:19859569

  13. Inhibition of a Mycobacterium tuberculosis beta-ketoacyl ACP synthase by isoniazid.

    PubMed

    Mdluli, K; Slayden, R A; Zhu, Y; Ramaswamy, S; Pan, X; Mead, D; Crane, D D; Musser, J M; Barry, C E

    1998-06-01

    Although isoniazid (isonicotinic acid hydrazide, INH) is widely used for the treatment of tuberculosis, its molecular target has remained elusive. In response to INH treatment, saturated hexacosanoic acid (C26:0) accumulated on a 12-kilodalton acyl carrier protein (AcpM) that normally carried mycolic acid precursors as long as C50. A protein species purified from INH-treated Mycobacterium tuberculosis was shown to consist of a covalent complex of INH, AcpM, and a beta-ketoacyl acyl carrier protein synthase, KasA. Amino acid-altering mutations in the KasA protein were identified in INH-resistant patient isolates that lacked other mutations associated with resistance to this drug. PMID:9616124

  14. p Ka calculation of poliprotic acid: histamine

    NASA Astrophysics Data System (ADS)

    De Abreu, Heitor A.; De Almeida, Wagner B.; Duarte, Hélio A.

    2004-01-01

    Various theoretical studies have been reported addressing the performance of solvation models available to estimate p Ka values. However, no attention has been paid so far to the role played by the electronic, thermal and solvation energy individual contributions to the Gibbs free energy of the deprotonation process. In this work, we decompose the total Gibbs free energy into three distinct terms and then evaluate the dependence of each contribution on the level of theory employed for its determination using different levels of theory. The three possible p Kas of histamine have been estimated and compared with available experimental data. We found that the electronic energy term is sensitive to the level of theory and basis set, and, therefore, could be also a source of error in the theoretical calculation of p Kas.

  15. Pectin enhances rice (Oryza sativa) root phosphorus remobilization.

    PubMed

    Zhu, Xiao Fang; Wang, Zhi Wei; Wan, Jiang Xue; Sun, Ying; Wu, Yun Rong; Li, Gui Xin; Shen, Ren Fang; Zheng, Shao Jian

    2015-02-01

    Plants growing in phosphorus (P)-deficient conditions can either increase their exploration of the environment (hence increasing P uptake) or can solubilize and reutilize P from established tissue sources. However, it is currently unclear if P stored in root cell wall can be reutilized. The present study shows that culture of the rice cultivars 'Nipponbare' (Nip) and 'Kasalath' (Kas) in P-deficient conditions results in progressive reductions in root soluble inorganic phosphate (Pi). However, Nip consistently maintains a higher level of soluble Pi and lower relative cell wall P content than does Kas, indicating that more cell wall P is released in Nip than in Kas. P-deficient Nip has a greater pectin and hemicellulose 1 (HC1) content than does P-deficient Kas, consistent with the significant positive relationship between pectin and root-soluble Pi levels amongst multiple rice cultivars. These observations suggest that increased soluble Pi might result from increased pectin content during P starvation. In vitro experiments showed that pectin releases Pi from insoluble FePO4. Furthermore, an Arabidopsis thaliana mutant with reduced pectin levels (qua1-2), has less root soluble Pi and is more sensitive to P deficiency than the wild type (WT) Col-0, whereas NaCl-treated WT plants exhibit both an increased root pectin content and an elevated soluble Pi content during P-starvation. These observations indicate that pectin can facilitate the remobilization of P deposited in the cell wall. This is a previously unknown mechanism for the reutilization of P in P-starved plants.

  16. Acidity of edge surface sites of montmorillonite and kaolinite

    NASA Astrophysics Data System (ADS)

    Liu, Xiandong; Lu, Xiancai; Sprik, Michiel; Cheng, Jun; Meijer, Evert Jan; Wang, Rucheng

    2013-09-01

    Acid-base chemistry of clay minerals is central to their interfacial properties, but up to now a quantitative understanding on the surface acidity is still lacking. In this study, with first principles molecular dynamics (FPMD) based vertical energy gap technique, we calculate the acidity constants of surface groups on (0 1 0)-type edges of montmorillonite and kaolinite, which are representatives of 2:1 and 1:1-type clay minerals, respectively. It shows that tbnd Si-OH and tbnd Al-OH2OH groups of kaolinite have pKas of 6.9 and 5.7 and those of montmorillonite have pKas of 7.0 and 8.3, respectively. For each mineral, the calculated pKas are consistent with the experimental ranges derived from fittings of titration curves, indicating that tbnd Si-OH and tbnd Al-OH2OH groups are the major acidic sites responsible to pH-dependent experimental observations. The effect of Mg substitution in montmorillonite is investigated and it is found that Mg substitution increases the pKas of the neighboring tbnd Si-OH and tbnd Si-OH2 groups by 2-3 pKa units. Furthermore, our calculation shows that the pKa of edge tbnd Mg-(OH2)2 is as high as 13.2, indicating the protonated state dominates under common pH. Together with previous adsorption experiments, our derived acidity constants suggest that tbnd Si-O- and tbnd Al-(OH)2 groups are the most probable edge sites for complexing heavy metal cations.

  17. Spike-timing-dependent plasticity at resting and conditioned lateral perforant path synapses on granule cells in the dentate gyrus: different roles of N-methyl-D-aspartate and group I metabotropic glutamate receptors.

    PubMed

    Lin, Yi-Wen; Yang, Hsiu-Wen; Wang, Hui-Ju; Gong, Chi-Li; Chiu, Tsai-Hsien; Min, Ming-Yuan

    2006-05-01

    We examined the mechanisms underlying spike-timing-dependent plasticity induction at resting and conditioned lateral perforant pathway (LPP) synapses in the rat dentate gyrus. Two stimulating electrodes were placed in the outer third of the molecular layer and in the granule cell layer in hippocampal slices to evoke field excitatory postsynaptic potentials (fEPSPs) and antidromic field somatic spikes (afSSs), respectively. Long-term potentiation (LTP) of LPP synapses was induced by paired stimulation with fEPSP preceding afSS. Reversal of the temporal order of fEPSP and afSS stimulation resulted in long-term depression (LTD). Induction of LTP or LTD was blocked by D,L-2-amino-5-phosphonopentanoic acid (AP5), showing that both effects were N-methyl-D-aspartate receptor (NMDAR)-dependent. Induction of LTP was also blocked by inhibitors of calcium-calmodulin kinase II, protein kinase C or mitogen-activated/extracellular-signal regulated kinase, suggesting that these are downstream effectors of NMDAR activation, whereas induction of LTD was blocked by inhibitors of protein kinase C and protein phosphatase 2B. At LPP synapses previously potentiated by high-frequency stimulation or depressed by low-frequency stimulation, paired fEPSP-afSS stimulation resulted in 'de-depression' at depressed LPP synapses but had no effect on potentiated synapses, whereas reversal of the temporal order of fEPSP-afSS stimulation resulted in 'de-potentiation' at potentiated synapses but had no effect on depressed synapses. Induction of de-depression and de-potentiation was unaffected by ap5 but was blocked by 2-methyl-6-(phenylethynyl) pyridine hydrochloride, a group I metabotropic glutamate receptor blocker, showing that both were NMDAR-independent but group I metabotropic glutamate receptor-dependent. In conclusion, our results show that spike-timing-dependent plasticity can occur at both resting and conditioned LPP synapses, its induction in the former case being NMDAR-dependent and, in

  18. Simulation of Stratospheric Ozone in the KIAPSGM NWP model using linear photochemistry parameterization

    NASA Astrophysics Data System (ADS)

    Jeong, G. R.; Monge-Sanz, B.; Cariolle, D.; Lee, E. H.; Jin, E. K.

    2014-12-01

    Stratospheric ozone plays important roles in the Earth's weather and climate systems due to its physiochemical properties and a wide range of spectral absorption. Because of complicated chemical equations and expensive computational cost, NWP community has introduced a linear photochemistry parameterization (LPP) that Cariolle and Déqué suggested in 1986 with an insight of ozone-temperature relationships, to weather forecasting system. In this study, we simulated stratospheric ozone using recent LPP coefficients in a numerical weather prediction (NWP) model, the KIAPS-GM (Korea Institute of Atmospheric Prediction Systems - Global Model), and evaluated model results with observations. The KIAPS-GM uses three dimensional hydrostatic dynamical core based on the High-Order Method Modeling Environment (HOMME) in cubed sphere with a horizontal resolution of ne30np4 and 70 vertical layers up to 85km. LPP scheme was fully implemented into the KIAPS-GM including the ozone tracer advection. Prognostic ozone was estimated through interaction with local ozone field, temperature field, and radiation field as those physics fields were updated while climatological ozone (Fortuin and Kelder, 1998) was constantly fed into radiation fields in every month. ERA-interim ozone and meteorological data (Dee et al., 2011) were used as initial data. Simulation period was year 2008 when larger ozone hole events occurred than usual. We compared interactive ozone case with climatological ozone case. For the sensitivity studies to initial ozone fields and LPP coefficients, ERA-interim hourly and monthly ozone data were used; and LPP coefficients such as Cariolle and Teyssadre (2007) and Monge-Sanz et al. (2011) were interpolated into instantaneous pressure levels, respectively. Preliminary results show that the ozone concentration in interactive ozone case is higher than climatological one in the lower stratosphere and troposphere while the former is lower than the latter in the upper

  19. Surface acidity of quartz: understanding the crystallographic control.

    PubMed

    Liu, Xiandong; Cheng, Jun; Lu, Xiancai; Wang, Rucheng

    2014-12-28

    We report a first principles molecular dynamics (FPMD) study of surface acid chemistry of the two growth surfaces of quartz, (101̄0) (including Alpha and Beta terminations) and (101̄1) facets. The interfacial hydration structures are characterized in detail and the intrinsic pKas of surface silanols are evaluated using the FPMD based vertical energy gap method. The calculated acidity constants reveal that every surface termination shows a bimodal acid-base behavior. It is found that all doubly-protonated forms (i.e. SiOH2) on the three terminations have pKas lower than -2.5, implying that the silanols hardly get protonated in a common pH range. The pKas of surface silanols can be divided into 3 groups. The most acidic silanol is the donor SiOH on the (101̄0)-beta surface (pKa = 4.8), the medium includes the germinal silanol on (101̄0)-alpha and the outer silanol on (101̄1) (pKa = 8.5-9.3) and the least acidic are inner silanols on the (101̄1)-facet, acceptor SiOH on (101̄0)-beta, and the secondly-deprotonated OH (i.e. Si(O-)(OH)) on (101̄0)-alpha (pKa > 11.0). With the pKa values, we discuss the implication for understanding metal cations complexing on quartz surfaces.

  20. Korean-Americans' Knowledge about Depression and Attitudes about Treatment Options.

    PubMed

    Kim, Eunjung; Im, Eun-Ok

    2015-06-01

    The purpose of this pilot study was to explore first-generation Korean-Americans' knowledge about depression and attitudes about depression treatment options. Self-report survey data were gathered from 73 first-generation Korean-Americans (KAs) using instruments developed for this study. The data were analyzed using descriptive and inferential statistics including t-tests. Data indicated participants lacked knowledge about depression. Among all depression treatment options, exercise was the option that first-generation KAs were most willing to try and was rated as having the least shame attached to it. Taking an antidepressant was the option KAs reported being most unwilling to try and had the highest shame attached to it. No significant differences in knowledge about depression and attitudes about depression treatment options were found between low and high acculturation groups, with the exception that the high acculturation group demonstrated more agreement than the low acculturation group with the item that emotional symptoms, such as mood changes, can be depression symptoms. These results suggest that initiating depression treatment with exercise may be the most acceptable starting point in treating depression in first-generation KA immigrants. PMID:26241572

  1. Korean American women's perceptions about physical examinations and cancer screening services offered in Korea: the influences of medical tourism on Korean Americans.

    PubMed

    Oh, Kyeung Mi; Jun, Jungmi; Zhou, Qiuping; Kreps, Gary

    2014-04-01

    Cancer is the leading cause of death for Korean-Americans (KAs), while cancer screening rates among KAs have been consistently low. Seven semi-structured focus group interviews with 34 KA women aged 40 or older in the Washington, DC metropolitan area were conducted to explore the perceptions of KA women about seeking physical examinations and cancer screening services in Korea. Data were analyzed using a framework approach. Informants positively perceived the use of health screening services in Korea in comparison to seeking such services in the US. Decision-making factors included cost benefits, high quality services, and more convenient screening procedures in Korea. These benefits outweighed the risks of delaying health care and travelling a vast distance with incurring additional travel costs. Motivations to seek these services in Korea included opportunities to visit their homeland and to enjoy comfortable communication with their native language. The increase of available information about Korean medical services due to the industry's aggressive marketing/PR was identified as a facilitator. Most informants did not recognize possible negative health outcomes of obtaining services in Korea such as inappropriate follow up care if having abnormal findings. Educational programs are needed to educate KAs about the benefits and risks of getting the services in Korea and proper follow up care in the US. Health care providers need to know the different cancer risks and screening needs for this population.

  2. Metagenomic Analysis of the Sponge Discodermia Reveals the Production of the Cyanobacterial Natural Product Kasumigamide by ‘Entotheonella’

    PubMed Central

    Nakashima, Yu; Egami, Yoko; Kimura, Miki; Wakimoto, Toshiyuki; Abe, Ikuro

    2016-01-01

    Sponge metagenomes are a useful platform to mine cryptic biosynthetic gene clusters responsible for production of natural products involved in the sponge-microbe association. Since numerous sponge-derived bioactive metabolites are biosynthesized by the symbiotic bacteria, this strategy may concurrently reveal sponge-symbiont produced compounds. Accordingly, a metagenomic analysis of the Japanese marine sponge Discodermia calyx has resulted in the identification of a hybrid type I polyketide synthase-nonribosomal peptide synthetase gene (kas). Bioinformatic analysis of the gene product suggested its involvement in the biosynthesis of kasumigamide, a tetrapeptide originally isolated from freshwater free-living cyanobacterium Microcystis aeruginosa NIES-87. Subsequent investigation of the sponge metabolic profile revealed the presence of kasumigamide in the sponge extract. The kasumigamide producing bacterium was identified as an ‘Entotheonella’ sp. Moreover, an in silico analysis of kas gene homologs uncovered the presence of kas family genes in two additional bacteria from different phyla. The production of kasumigamide by distantly related multiple bacterial strains implicates horizontal gene transfer and raises the potential for a wider distribution across other bacterial groups. PMID:27732651

  3. Korean American women's perceptions about physical examinations and cancer screening services offered in Korea: the influences of medical tourism on Korean Americans.

    PubMed

    Oh, Kyeung Mi; Jun, Jungmi; Zhou, Qiuping; Kreps, Gary

    2014-04-01

    Cancer is the leading cause of death for Korean-Americans (KAs), while cancer screening rates among KAs have been consistently low. Seven semi-structured focus group interviews with 34 KA women aged 40 or older in the Washington, DC metropolitan area were conducted to explore the perceptions of KA women about seeking physical examinations and cancer screening services in Korea. Data were analyzed using a framework approach. Informants positively perceived the use of health screening services in Korea in comparison to seeking such services in the US. Decision-making factors included cost benefits, high quality services, and more convenient screening procedures in Korea. These benefits outweighed the risks of delaying health care and travelling a vast distance with incurring additional travel costs. Motivations to seek these services in Korea included opportunities to visit their homeland and to enjoy comfortable communication with their native language. The increase of available information about Korean medical services due to the industry's aggressive marketing/PR was identified as a facilitator. Most informants did not recognize possible negative health outcomes of obtaining services in Korea such as inappropriate follow up care if having abnormal findings. Educational programs are needed to educate KAs about the benefits and risks of getting the services in Korea and proper follow up care in the US. Health care providers need to know the different cancer risks and screening needs for this population. PMID:24322599

  4. Lewis pair polymerization by classical and frustrated Lewis pairs: acid, base and monomer scope and polymerization mechanism.

    PubMed

    Zhang, Yuetao; Miyake, Garret M; John, Mallory G; Falivene, Laura; Caporaso, Lucia; Cavallo, Luigi; Chen, Eugene Y-X

    2012-08-14

    Classical and frustrated Lewis pairs (LPs) of the strong Lewis acid (LA) Al(C(6)F(5))(3) with several Lewis base (LB) classes have been found to exhibit exceptional activity in the Lewis pair polymerization (LPP) of conjugated polar alkenes such as methyl methacrylate (MMA) as well as renewable α-methylene-γ-butyrolactone (MBL) and γ-methyl-α-methylene-γ-butyrolactone (γ-MMBL), leading to high molecular weight polymers, often with narrow molecular weight distributions. This study has investigated a large number of LPs, consisting of 11 LAs as well as 10 achiral and 4 chiral LBs, for LPP of 12 monomers of several different types. Although some more common LAs can also be utilized for LPP, Al(C(6)F(5))(3)-based LPs are far more active and effective than other LA-based LPs. On the other hand, several classes of LBs, when paired with Al(C(6)F(5))(3), can render highly active and effective LPP of MMA and γ-MMBL; such LBs include phosphines (e.g., P(t)Bu(3)), chiral chelating diphosphines, N-heterocyclic carbenes (NHCs), and phosphazene superbases (e.g., P(4)-(t)Bu). The P(4)-(t)Bu/Al(C(6)F(5))(3) pair exhibits the highest activity of the LP series, with a remarkably high turn-over frequency of 9.6 × 10(4) h(-1) (0.125 mol% catalyst, 100% MMA conversion in 30 s, M(n) = 2.12 × 10(5) g mol(-1), PDI = 1.34). The polymers produced by LPs at RT are typically atactic (P(γ)MMBL with ∼47% mr) or syndio-rich (PMMA with ∼70-75% rr), but highly syndiotactic PMMA with rr ∼91% can be produced by chiral or achiral LPs at -78 °C. Mechanistic studies have identified and structurally characterized zwitterionic phosphonium and imidazolium enolaluminates as the active species of the current LPP system, which are formed by the reaction of the monomer·Al(C(6)F(5))(3) adduct with P(t)Bu(3) and NHC bases, respectively. Kinetic studies have revealed that the MMA polymerization by the (t)Bu(3)P/Al(C(6)F(5))(3) pair is zero-order in monomer concentration after an initial

  5. Lewis pair polymerization by classical and frustrated Lewis pairs: acid, base and monomer scope and polymerization mechanism.

    PubMed

    Zhang, Yuetao; Miyake, Garret M; John, Mallory G; Falivene, Laura; Caporaso, Lucia; Cavallo, Luigi; Chen, Eugene Y-X

    2012-08-14

    Classical and frustrated Lewis pairs (LPs) of the strong Lewis acid (LA) Al(C(6)F(5))(3) with several Lewis base (LB) classes have been found to exhibit exceptional activity in the Lewis pair polymerization (LPP) of conjugated polar alkenes such as methyl methacrylate (MMA) as well as renewable α-methylene-γ-butyrolactone (MBL) and γ-methyl-α-methylene-γ-butyrolactone (γ-MMBL), leading to high molecular weight polymers, often with narrow molecular weight distributions. This study has investigated a large number of LPs, consisting of 11 LAs as well as 10 achiral and 4 chiral LBs, for LPP of 12 monomers of several different types. Although some more common LAs can also be utilized for LPP, Al(C(6)F(5))(3)-based LPs are far more active and effective than other LA-based LPs. On the other hand, several classes of LBs, when paired with Al(C(6)F(5))(3), can render highly active and effective LPP of MMA and γ-MMBL; such LBs include phosphines (e.g., P(t)Bu(3)), chiral chelating diphosphines, N-heterocyclic carbenes (NHCs), and phosphazene superbases (e.g., P(4)-(t)Bu). The P(4)-(t)Bu/Al(C(6)F(5))(3) pair exhibits the highest activity of the LP series, with a remarkably high turn-over frequency of 9.6 × 10(4) h(-1) (0.125 mol% catalyst, 100% MMA conversion in 30 s, M(n) = 2.12 × 10(5) g mol(-1), PDI = 1.34). The polymers produced by LPs at RT are typically atactic (P(γ)MMBL with ∼47% mr) or syndio-rich (PMMA with ∼70-75% rr), but highly syndiotactic PMMA with rr ∼91% can be produced by chiral or achiral LPs at -78 °C. Mechanistic studies have identified and structurally characterized zwitterionic phosphonium and imidazolium enolaluminates as the active species of the current LPP system, which are formed by the reaction of the monomer·Al(C(6)F(5))(3) adduct with P(t)Bu(3) and NHC bases, respectively. Kinetic studies have revealed that the MMA polymerization by the (t)Bu(3)P/Al(C(6)F(5))(3) pair is zero-order in monomer concentration after an initial

  6. Poly(ethylene glycol)-block-poly(ε-caprolactone)–and phospholipid-based stealth nanoparticles with enhanced therapeutic efficacy on murine breast cancer by improved intracellular drug delivery

    PubMed Central

    He, Xiaodan; Li, Li; Su, Hong; Zhou, Dinglun; Song, Hongmei; Wang, Ling; Jiang, Xuehua

    2015-01-01

    Background Effective anticancer drug delivery to the tumor site without rapid body clearance is a prerequisite for successful chemotherapy. 1,2-distearoyl-sn-glycero-3-phospho-ethanolamine-N-(methoxy[polyethyleneglycol]-2000) (DSPE-PEG2000) has been widely used in the preparation of stealth liposomes. Although PEG chains can efficiently preserve liposomes from rapid clearance by the reticuloendothelial system (RES), its application has been hindered by poor cellular uptake and unsatisfactory therapeutic effect. Methods To address the dilemma, we presented a facile approach to fabricate novel stealth nanoparticles generated by poly(ethylene glycol)-block-poly(ε-caprolactone) (PEG-b-PCL), soybean phosphatidylcholine (SPC), and cholesterol, namely LPPs (L represented lipid and PP represented PEG-b-PCL), for the delivery of anticancer drug paclitaxel (PTX). LPPs were prepared using the thin film hydration method. Two PEG-b-PCL polymers with different molecular weights (MW; PEG2000-b-PCL2000, MW: 4,000 Da and PEG5000-b-PCL5000, MW: 10,000 Da) were used to fabricate stealth nanoparticles. Conventional PEGylated liposome (LDP2000, L represented lipid and DP2000 represented DSPE-PEG2000) composed of SPC, cholesterol, and DSPE-PEG2000 was used as the control. The physical properties, cellular uptake, endocytosis pathway, cytotoxicity, pharmacokinetics, tumor accumulation, and anticancer efficacy of free PTX, PTX-loaded LPPs, and LDP2000 were systemically investigated after injection into 4T1 breast tumor–bearing mice. Results LPPs were vesicles around 100 nm in size with negative zeta potential. With enhanced stability, LPPs achieved sustainable release of cancer therapeutics. The cellular uptake level was closely related to the PEG chain length of PEG-b-PCL; a shorter PEG chain resulted in higher cellular uptake. Moreover, the cellular internalization of LPP2000 modified by PEG2000-b-PCL2000 on 4T1 cells was 2.1-fold higher than LDP2000 due to the improved stability of

  7. Neurophysiological processing of emotion and parenting interact to predict inhibited behavior: an affective-motivational framework

    PubMed Central

    Kessel, Ellen M.; Huselid, Rebecca F.; DeCicco, Jennifer M.; Dennis, Tracy A.

    2013-01-01

    Although inhibited behavior problems are prevalent in childhood, relatively little is known about the intrinsic and extrinsic factors that predict a child's ability to regulate inhibited behavior during fear- and anxiety-provoking tasks. Inhibited behavior may be linked to both disruptions in avoidance-related processing of aversive stimuli and in approach-related processing of appetitive stimuli, but previous findings are contradictory and rarely integrate consideration of the socialization context. The current exploratory study used a novel combination of neurophysiological and observation-based methods to examine whether a neurophysiological measure sensitive to approach- and avoidance-oriented emotional processing, the late positive potential (LPP), interacted with observed approach- (promotion) and avoidance- (prevention) oriented parenting practices to predict children's observed inhibited behavior. Participants were 5- to 7-year-old (N = 32) typically-developing children (M = 75.72 months, SD = 6.01). Electroencephalography was continuously recorded while children viewed aversive, appetitive, or neutral images, and the LPP was generated to each picture type separately. Promotion and prevention parenting were observed during an emotional challenge with the child. Child inhibited behavior was observed during a fear and a social evaluation task. As predicted, larger LPPs to aversive images predicted more inhibited behavior during both tasks, but only when parents demonstrated low promotion. In contrast, larger LPPs to appetitive images predicted less inhibited behavior during the social evaluative task, but only when parents demonstrated high promotion; children of high promotion parents showing smaller LPPs to appetitive images showed the greatest inhibition. Parent-child goodness-of-fit and the LPP as a neural biomarker for emotional processes related to inhibited behavior are discussed. PMID:23847499

  8. The presence of a culturally similar or dissimilar social partner affects neural responses to emotional stimuli

    PubMed Central

    Woodcock, Kate A.; Yu, Dian; Liu, Yi; Han, Shihui

    2013-01-01

    Background Emotional responding is sensitive to social context; however, little emphasis has been placed on the mechanisms by which social context effects changes in emotional responding. Objective We aimed to investigate the effects of social context on neural responses to emotional stimuli to inform on the mechanisms underpinning context-linked changes in emotional responding. Design We measured event-related potential (ERP) components known to index specific emotion processes and self-reports of explicit emotion regulation strategies and emotional arousal. Female Chinese university students observed positive, negative, and neutral photographs, whilst alone or accompanied by a culturally similar (Chinese) or dissimilar researcher (British). Results There was a reduction in the positive versus neutral differential N1 amplitude (indexing attentional capture by positive stimuli) in the dissimilar relative to alone context. In this context, there was also a corresponding increase in amplitude of a frontal late positive potential (LPP) component (indexing engagement of cognitive control resources). In the similar relative to alone context, these effects on differential N1 and frontal LPP amplitudes were less pronounced, but there was an additional decrease in the amplitude of a parietal LPP component (indexing motivational relevance) in response to positive stimuli. In response to negative stimuli, the differential N1 component was increased in the similar relative to dissimilar and alone (trend) context. Conclusion These data suggest that neural processes engaged in response to emotional stimuli are modulated by social context. Possible mechanisms for the social-context-linked changes in attentional capture by emotional stimuli include a context-directed modulation of the focus of attention, or an altered interpretation of the emotional stimuli based on additional information proportioned by the context. PMID:24693352

  9. Brain dynamics of visual attention during anticipation and encoding of threat- and safe-cues in spider-phobic individuals.

    PubMed

    Michalowski, Jaroslaw M; Pané-Farré, Christiane A; Löw, Andreas; Hamm, Alfons O

    2015-09-01

    This study systematically investigated the sensitivity of the phobic attention system by measuring event-related potentials (ERPs) in spider-phobic and non-phobic volunteers in a context where spider and neutral pictures were presented (phobic threat condition) and in contexts where no phobic but unpleasant and neutral or only neutral pictures were displayed (phobia-irrelevant conditions). In a between-group study, participants were assigned to phobia-irrelevant conditions either before or after the exposure to spider pictures (pre-exposure vs post-exposure participants). Additionally, each picture was preceded by a fixation cross presented in one of three different colors that were informative about the category of an upcoming picture. In the phobic threat condition, spider-phobic participants showed a larger P1 than controls for all pictures and signal cues. Moreover, individuals with spider phobia who were sensitized by the exposure to phobic stimuli (i.e. post-exposure participants) responded with an increased P1 also in phobia-irrelevant conditions. In contrast, no group differences between spider-phobic and non-phobic individuals were observed in the P1-amplitudes during viewing of phobia-irrelevant stimuli in the pre-exposure group. In addition, cues signaling neutral pictures elicited decreased stimulus-preceding negativity (SPN) compared with cues signaling emotional pictures. Moreover, emotional pictures and cues signaling emotional pictures evoked larger early posterior negativity (EPN) and late positive potential (LPP) than neutral stimuli. Spider phobics showed greater selective attention effects than controls for phobia-relevant pictures (increased EPN and LPP) and cues (increased LPP and SPN). Increased sensitization of the attention system observed in spider-phobic individuals might facilitate fear conditioning and promote generalization of fear playing an important role in the maintenance of anxiety disorders.

  10. Entomopathogenic nematodes in insect cadaver formulations for the control of Rhipicephalus microplus (Acari: Ixodidae).

    PubMed

    Monteiro, Caio Márcio de Oliveira; Matos, Renata da Silva; Araújo, Laryssa Xavier; Campos, Roberson; Bittencourt, Vânia Rita Elias Pinheiro; Dolinski, Claudia; Furlong, John; Prata, Márcia Cristina de Azevedo

    2014-07-14

    This study evaluated the efficacy of four entomopathogenic nematode (EPN) strains in insect cadaver formulations against Rhipicephalus microplus and compared the efficacy of the most virulent EPNs applied in cadavers of Galleria mellonella and Tenebrio molitor. In the first experiment, infected G. mellonela larvae were used as the source of EPNs. Engorged females of R. microplus were placed in pots filled with soil and different numbers of G. mellonella larvae infected with one of four species of nematodes. All treatments with EPNs of the genus Heterorhabditis caused significant reduction (p<0.05) in the egg mass weight and hatching percentage of larvae. The EPNs of the genus Steinernema, except for the group exposed to Steinernema carpocapsae ALL, whose source nematodes included six larvae of G. mellonella, caused a significant reduction (p<0.05) in the egg mass weight produced per female. Steinernema feltiae SN applied with two, four, and six cadavers and S. carpocapsae ALL with two cadavers caused a reduction in hatching percentage of larvae of R. microplus (p<0.05). The percentage of control was above 95% in all groups treated with Heterorhabditis bacteriophora HP88 and Heterorhabditis indica LPP1 and in the treatment with four larvae infected with S. feltiae SN. The second experiment followed the same methodology, using G. mellonella and T. molitor larvae infected by the two most virulent EPNs. H. bacteriophora HP88 and H. indica LPP1 in different formulations caused reduction in the egg mass weight and hatching percentage of larvae. The percentage of control were 82.4 and 84.9% for H. bacteriophora HP88 and H. indica LPP1, respectively, formulated in T. molitor, and reaching 99.9% in groups formulated with G. mellonella. The EPNs tested in insect cadaver formulation showed pathogenicity to engorged females of R. microplus and EPNs of the genus Heterorhabditis formulated in G. mellonella larvae were more effective. PMID:24836639

  11. Smooth Muscle Precursor Cells Derived from Human Pluripotent Stem Cells for Treatment of Stress Urinary Incontinence

    PubMed Central

    Wang, Zhe; Li, Yan Hui; Wei, Yi; Green, Morgaine; Wani, Prachi; Zhang, Pengbo; Pera, Renee Reijo; Chen, Bertha

    2016-01-01

    There is great interest in using stem cells (SC) to regenerate a deficient urethral sphincter in patients with urinary incontinence. The smooth muscle component of the sphincter is a significant contributor to sphincter function. However, current translational efforts for sphincter muscle restoration focus only on skeletal muscle regeneration because they rely on adult mesenchymal SC as cell source. These adult SC do not yield sufficient smooth muscle cells (SMCs) for transplantation. We may be able to overcome this limitation by using pluripotent stem cell (PSC) to derive SMCs. Hence, we sought to investigate whether smooth muscle precursor cells (pSMCs) derived from human PSCs can restore urethral function in an animal model generated by surgical urethrolysis and ovariectomy. Rats were divided into four groups: control (no intervention), sham saline (surgery + saline injection), bladder SMC (surgery + human bladder SMC injection), and treatment (surgery + pSMC injection, which includes human embryonic stem cell (hESC) H9-derived pSMC, episomal reprogrammed induced pluripotent stem cells (iPSCs)-derived pSMC, or viral reprogrammed iPSC-derived pSMC). pSMCs (2 × 106 cells/rat) were injected periurethrally 3 weeks postsurgery. Leak point pressure (LPP) and baseline external urethral sphincter electromyography were measured 5 weeks postinjection. Both iPSC-derived pSMC treatment groups showed significantly higher LPP compared to the sham saline group, consistent with restoration of urethral sphincter function. While the difference between the H9-derived pSMC treatment and sham saline group was not significant, it did show a trend toward restoration of the LPP to the level of intact controls. Our data indicate that pSMCs derived from human PSCs (hESC and iPSC) can restore sphincter function. PMID:26785911

  12. Arousal, valence, and the uncanny valley: psychophysiological and self-report findings

    PubMed Central

    Cheetham, Marcus; Wu, Lingdan; Pauli, Paul; Jancke, Lutz

    2015-01-01

    The main prediction of the Uncanny Valley Hypothesis (UVH) is that observation of humanlike characters that are difficult to distinguish from the human counterpart will evoke a state of negative affect. Well-established electrophysiological [late positive potential (LPP) and facial electromyography (EMG)] and self-report [Self-Assessment Manikin (SAM)] indices of valence and arousal, i.e., the primary orthogonal dimensions of affective experience, were used to test this prediction by examining affective experience in response to categorically ambiguous compared with unambiguous avatar and human faces (N = 30). LPP and EMG provided direct psychophysiological indices of affective state during passive observation and the SAM provided self-reported indices of affective state during explicit cognitive evaluation of static facial stimuli. The faces were drawn from well-controlled morph continua representing the UVH’ dimension of human likeness (DHL). The results provide no support for the notion that category ambiguity along the DHL is specifically associated with enhanced experience of negative affect. On the contrary, the LPP and SAM-based measures of arousal and valence indicated a general increase in negative affective state (i.e., enhanced arousal and negative valence) with greater morph distance from the human end of the DHL. A second sample (N = 30) produced the same finding, using an ad hoc self-rating scale of feelings of familiarity, i.e., an oft-used measure of affective experience along the UVH’ familiarity dimension. In conclusion, this multi-method approach using well-validated psychophysiological and self-rating indices of arousal and valence rejects – for passive observation and for explicit affective evaluation of static faces – the main prediction of the UVH. PMID:26236260

  13. Attention modulations on the perception of social hierarchy at distinct temporal stages: an electrophysiological investigation.

    PubMed

    Feng, Chunliang; Tian, Tengxiang; Feng, Xue; Luo, Yue-Jia

    2015-04-01

    Recent behavioral and neuroscientific studies have revealed the preferential processing of superior-hierarchy cues. However, it remains poorly understood whether top-down controlled mechanisms modulate temporal dynamics of neurocognitive substrates underlying the preferential processing of these biologically and socially relevant cues. This was investigated in the current study by recording event-related potentials from participants who were presented with superior or inferior social hierarchy. Participants performed a hierarchy-judgment task that required attention to hierarchy cues or a gender-judgment task that withdrew their attention from these cues. Superior-hierarchy cues evoked stronger neural responses than inferior-hierarchy cues at both early (N170/N200) and late (late positive potential, LPP) temporal stages. Notably, the modulations of top-down attention were identified on the LPP component, such that superior-hierarchy cues evoked larger LPP amplitudes than inferior-hierarchy cues only in the attended condition; whereas the modulations of the N170/N200 component by hierarchy cues were evident in both attended and unattended conditions. These findings suggest that the preferential perception of superior-hierarchy cues involves both relatively automatic attentional bias at the early temporal stage as well as flexible and voluntary cognitive evaluation at the late temporal stage. Finally, these hierarchy-related effects were absent when participants were shown the same stimuli which, however, were not associated with social-hierarchy information in a non-hierarchy task (Experiment 2), suggesting that effects of social hierarchy at early and late temporal stages could not be accounted for by differences in physical attributes between these social cues. PMID:25681738

  14. Conditioned cortical reactivity to cues predicting cigarette-related or pleasant images.

    PubMed

    Deweese, Menton M; Robinson, Jason D; Cinciripini, Paul M; Versace, Francesco

    2016-03-01

    Through Pavlovian conditioning, reward-associated neutral stimuli can acquire incentive salience and motivate complex behaviors. In smokers, cigarette-associated cues may induce cravings and trigger smoking. Understanding the brain mechanisms underlying conditioned responses to cigarette-associated relative to other inherently pleasant stimuli might contribute to the development of more effective smoking cessation treatments that emphasize the rehabilitation of reward circuitry. Here we measured brain responses to geometric patterns (the conditioned stimuli, CSs) predicting cigarette-related, intrinsically pleasant and neutral images (the unconditioned stimuli, USs) using event-related potentials (ERPs) in 29 never-smokers, 20 nicotine-deprived smokers, and 19 non-deprived smokers. Results showed that during US presentation, cigarette-related and pleasant images prompted higher cortical positivity than neutral images over centro-parietal sensors between 400 and 800ms post-US onset (late positive potential, LPP). The LPP evoked by pleasant images was significantly larger than the LPP evoked by cigarette images. During CS presentation, ERPs evoked by geometric patterns predicting pleasant and cigarette-related images had significantly larger amplitude than ERPs evoked by CSs predicting neutral images. These effects were maximal over right parietal sites between 220 and 240ms post-CS onset and over occipital and frontal sites between 308 and 344ms post-CS onset. Smoking status did not modulate these effects. Our results show that stimuli with no intrinsic reward value (e.g., geometric patterns) may acquire rewarding properties through repeated pairings with established reward cues (i.e., cigarette-related, intrinsically pleasant).

  15. Experimental Demonstration of Collisionless Particle Acceleration Mechanisms and Entrainment of Ambient Plasma Ions by a Rapidly Expanding Diamagnetic Cavity.

    NASA Astrophysics Data System (ADS)

    Bonde, J.; Vincena, S. T.; Gekelman, W. N.

    2015-12-01

    The collisionless coupling of an expanding diamagnetic cavity to a magnetized, ambient plasma is studied in a laboratory environment using a laser-produced plasma (LPP). The seed LPP rapidly expands with velocities up to the background Alfvén speed, vexp ≤ vA. The boundary layer of the expansion is characterized with in situ diagnostics as a cylindrical version of the Ferraro-Rosenbluth current sheath. Maintenance of quasi-neutrality in this sheath forms an electric field opposing the cross-field expansion which simultaneously drives the electron current that forms the diamagnetic cavity, decelerates the LPP ions to stagnation, and accelerates ambient ions inward. The field topology across the background magnetic field is identical to that described by Bernhardt, et al. [1] for the AMPTE magnetotail barium releases. The boundary along the magnetic field, however, is shown to contain an electric field with E·B ≠ 0, which is absent in simple fluid models of diamagnetic cavities. The electric fields at this boundary help explain previous observations in the experiment of the ejection of suprathermal electrons and return currents that generated whistler- and Alfvén-wave radiation in the ambient plasma. Magnetic loops and an emissive probe measure the magnetic field and electrostatic potential along 3 dimensions while a laser-induced fluorescence scheme measures the cross-field flow of the ambient argon ions as they penetrate the diamagnetic cavity. Particle orbit solvers employing the measured fields corroborate the flow diagnostic and predict strong outflows of ambient ions with higher charge to mass ratios after diamagnetic cavity collapse. This experiment was conducted in the Large Plasma Device at the Basic Plasma Science Facility and funded by grants from the US Department of Energy and the National Science Foundation. [1] P.A. Bernhardt, R.A. Roussel-Dupre, M.B. Pongratz, J. Geophys. Res. 92, 57777 (1987).

  16. Clinical, Trichoscopic, and Histopathological Features of Primary Cicatricial Alopecias: A Retrospective Observational Study at a Tertiary Care Centre of North East India

    PubMed Central

    Thakur, Binod Kumar; Verma, Shikha; Raphael, Vandana

    2015-01-01

    Background: The primary cicatricial alopecias (PCAs) are a rare group of diseases where hair follicle is the primary target of destruction. There are a few studies on histopathological and trichoscopic features of PCA. Aims: To study the clinical, trichoscopic, and histopathological characteristics of PCAs of the scalp and to find out the concordance between trichoscopic and histopathological diagnosis. Materials and Methods: We retrospectively analyzed the clinical, trichoscopic, and histopathological features of 24 PCA patients. Fisher's Chi-square exact test was done to find the significant trichoscopic and histopathological features. Cohen's kappa coefficient was used to determine the agreement between histopathological and trichoscopic diagnosis. Results: A total of 24 patients of PCA were seen with a male: female ratio of 2:1. There were 10 (41.7%) patients of discoid lupus erythematosus (DLE), 5 (20.8%) of lichen planopilaris (LPP), 3 (12.5%) of dissecting cellulitis of scalp, and 2 (8.3%) each of pseudopelade of brocq, folliculitis decalvans, and frontal fibrosing alopecia. The important histopathological findings of DLE were follicular plugging, vacuolar changes in the basal layer, necrotic keratinocytes, and superficial and deep perifollicular and perivascular lymphocytic infiltrate. Histopathology of LPP showed vacuolar changes in the basal layer and lichenoid infiltrate involving the infundibulum and isthmus. Trichoscopy of DLE showed follicular plugging, yellow dots, and thick arborizing blood vessels. The peripilar cast was important finding in LPP. The characteristic yellow dot with three-dimensional structure was noted in dissecting cellulitis of the scalp. The Cohen's kappa agreement was 0.89 between histopathological and trichoscopic diagnosis. Conclusion: The diagnosis of PCA is challenging because of overlapping features clinically and histopathologically. Trichoscopy may provide quick and reliable diagnosis and obviate the necessity of scalp

  17. Event-Related Potentials Reveal Preserved Attention Allocation but Impaired Emotion Regulation in Patients with Epilepsy and Comorbid Negative Affect

    PubMed Central

    De Taeye, Leen; Pourtois, Gilles; Meurs, Alfred; Boon, Paul; Vonck, Kristl; Carrette, Evelien; Raedt, Robrecht

    2015-01-01

    Patients with epilepsy have a high prevalence of comorbid mood disorders. This study aims to evaluate whether negative affect in epilepsy is associated with dysfunction of emotion regulation. Event-related potentials (ERPs) are used in order to unravel the exact electrophysiological time course and investigate whether a possible dysfunction arises during early (attention) and/or late (regulation) stages of emotion control. Fifty epileptic patients with (n = 25) versus without (n = 25) comorbid negative affect plus twenty-five matched controls were recruited. ERPs were recorded while subjects performed a face- or house-matching task in which fearful, sad or neutral faces were presented either at attended or unattended spatial locations. Two ERP components were analyzed: the early vertex positive potential (VPP) which is normally enhanced for faces, and the late positive potential (LPP) that is typically larger for emotional stimuli. All participants had larger amplitude of the early face-sensitive VPP for attended faces compared to houses, regardless of their emotional content. By contrast, in patients with negative affect only, the amplitude of the LPP was significantly increased for unattended negative emotional expressions. These VPP results indicate that epilepsy with or without negative affect does not interfere with the early structural encoding and attention selection of faces. However, the LPP results suggest abnormal regulation processes during the processing of unattended emotional faces in patients with epilepsy and comorbid negative affect. In conclusion, this ERP study reveals that early object-based attention processes are not compromised by epilepsy, but instead, when combined with negative affect, this neurological disease is associated with dysfunction during the later stages of emotion regulation. As such, these new neurophysiological findings shed light on the complex interplay of epilepsy with negative affect during the processing of emotional

  18. Event-related potentials reveal task-dependence and inter-individual differences in negation processing during silent listening and explicit truth-value evaluation.

    PubMed

    Herbert, C; Kissler, J

    2014-09-26

    In sentences such as dogs cannot fly/bark, evaluation of the truth-value of the sentence is assumed to appear after the negation has been integrated into the sentence structure. Moreover negation processing and truth-value processing are considered effortful processes, whereas processing of the semantic relatedness of the words within sentences is thought to occur automatically. In the present study, modulation of event-related brain potentials (N400 and late positive potential, LPP) was investigated during an implicit task (silent listening) and active truth-value evaluation to test these theoretical assumptions and determine if truth-value evaluation will be modulated by the way participants processed the negated information implicitly prior to truth-value verification. Participants first listened to negated sentences and then evaluated these sentences for their truth-value in an active evaluation task. During passive listening, the LPP was generally more pronounced for targets in false negative (FN) than true negative (TN) sentences, indicating enhanced attention allocation to semantically-related but false targets. N400 modulation by truth-value (FN>TN) was observed in 11 out of 24 participants. However, during active evaluation, processing of semantically-unrelated but true targets (TN) elicited larger N400 and LPP amplitudes as well as a pronounced frontal negativity. This pattern was particularly prominent in those 11 individuals, whose N400 modulation during silent listening indicated that they were more sensitive to violations of the truth-value than to semantic priming effects. The results provide evidence for implicit truth-value processing during silent listening of negated sentences and for task dependence related to inter-individual differences in implicit negation processing.

  19. Reanalysis of Radiation Belt Electron Phase Space Density using the UCLA 1-D VERB code and Kalman filtering: Correlation between the inner edge of the outer radiation belt phase space density and the plasmapause location

    NASA Astrophysics Data System (ADS)

    Espy, P. J.; Daae, M.; Shprits, Y.

    2010-12-01

    The correlation between the inner edge of the outer radiation belt phase space density (PSD) and the plasmapause location (Lpp) using reanalysis is investigated. A large data set is applied for the statistical analysis, using data from 1990-1991 from the CRRES satellite, GEO 1989, GPS-ns18 and Akebono. These data are incorporated into reanalysis by means of a Kalman filter with the UCLA 1-D VERB code. The result is a continuous radial and temporal distribution of the PSD from L*=3 to L*=7. The innovation vector of the reconstructed PSD can give us information about regions where local loss or source processes are dominating. We analyze both the PSD and the innovation vector by binning them into slots of Dst and Kp values. This has been done by finding the time for when the Dst (Kp) is within each bin-size of 20 nT (1) from 10 nT to -130 nT (1 to 8). The PSD and innovation vector was then averaged over each of those times. The result shows a good correlation between the location of the inner edge of the outer radiation belt in the PSD and the location of the plasmapause, which is consistent with previous observations. The boundary between the inner edge of the radiation belt and the Lpp becomes sharper, and the radiation belt becomes thinner, during times of high geomagnetic activity. The innovation vector shows that the inner edge of the source region also lines up well with the Lpp, and further showing a battle between losses and sources during active times. This study also illustrates how data assimilation in the radiation belts can be used to understand the underlining processes of acceleration and loss in the inner magnetosphere.

  20. Inflammatory immune response by lipopolysaccharide-responsive nucleotide binding oligomerization domain (NOD)-like receptors in the Japanese pufferfish (Takifugu rubripes).

    PubMed

    Biswas, Gouranga; Bilen, Soner; Kono, Tomoya; Sakai, Masahiro; Hikima, Jun-ichi

    2016-02-01

    Some of NOD-like receptors (NLRs), the cytosolic pattern recognition receptors form a multi-protein complex, inflammasome consisting of one or more NLRs, the adaptor protein ASC and inflammatory caspase to generate mature inflammatory cytokines, interleukin (IL)-1β and IL-18. However, inflammasome-mediated inflammatory cascade involving any NLR member is unknown in a lower vertebrate like fish. Also, inflammatory cytokine induction pathway in response to a specific ligand, namely bacterial lipopolysaccharide (LPS) has not yet been clarified. Therefore, 13 predicted NLR sequences of the Japanese pufferfish, Fugu (Takifugu rubripes) were retrieved in silico and categorized as NLR-C1∼13. Expression analysis of these genes in Fugu head kidney (HK) cells stimulated with a heat-killed Lactobacillus paracasei spp. paracasei (Lpp), LPS, nigericin and a combination of nigericin + LPS showed consistent up-regulations of NLR-C1, 5, 7, 10 and 12 genes in both Lpp and LPS stimulations and NLR-C9 gene in LPS stimulation only. However, nigericin and nigericin + LPS caused an increased expression of NLR-C10 and 12 in HK cells and leukocytes. Fugu treated with Lpp and LPS (in vivo), and infected with Vibrio harveyi had an elevated expression of NLR-C10 and 12. Increased transcription of caspase-1, ASC, IL-1β and IL-18 was recorded in nigericin-stimulated HK cells and leukocytes. Results suggested activation of probable inflammasome-mediated inflammatory cytokine response in Fugu. Moreover, LPS may be a key ligand that induces some of the Fugu NLR-Cs (NLR-C9, 10 and 12). Further characterization and functional analysis of Fugu NLR-C10 and 12 for ligand sensing, and processing of pro-inflammatory cytokine, IL-1β would elucidate the inflammasome evolution in fish. PMID:26472618

  1. Characterization of the coherent structures in swirling flames stabilized in a two-staged multi-injection burner: Influence of the staging factor

    NASA Astrophysics Data System (ADS)

    Providakis, Theodore; Zimmer, Laurent; Scouflaire, Philippe; Ducruix, Sébastien

    2013-01-01

    Staged multi-injection combustors seem good candidates to face flame stabilization problems (combustion instabilities, flashback, flame extinction), encountered in lean premixed prevaporized (LPP) burners. Staging procedures enable fuel distribution control while multipoint injection can lead to a fast and efficient mixing. In the present study, a laboratory-scale staged multipoint combustor is characterized using High Speed Particle Image Velocimetry and Planar Laser Induced Fluorescence measurements. It is shown that the fuel distribution strongly affects the flame stabilization processes, modifying the thermo-acoustic coupling. Furthermore, results reveal the presence of a precessing vortex core (PVC), that can lead to a better flame stabilization in particular cases.

  2. Low-protein diets reduce PKAalpha expression in islets from pregnant rats.

    PubMed

    Milanski, Marciane; Arantes, Vanessa Cristina; Ferreira, Fabiano; de Barros Reis, Marise Auxiliadora; Carneiro, Everardo Magalhães; Boschero, Antonio Carlos; Collares-Buzato, Carla Beatriz; Latorraca, Márcia Queiroz

    2005-08-01

    We investigated the effect of protein restriction on insulin secretion and the expression of protein kinase (PK)Aalpha and PKCalpha in islets from control and pregnant rats. Adult control nonpregnant (CN) and control pregnant (CP) rats were fed a normal-protein diet (17%), whereas low-protein nonpregnant (LPN) and low-protein pregnant (LPP) rats were fed a low-protein diet (6%) for 15 d. In the presence of 2.8 and 8.3 mmol glucose/L, insulin secretion by islets of CP rats was higher than that by islets of CN rats. Compared with the CN groups, insulin secretion by islets of LPN rats was lower with 8.3 but not with 2.8 mmol glucose/L. The insulin secretion by islets of LPP rats was higher than by LPN rats at both glucose concentrations. IBMX (1 mmol/L), a phosphodiesterase inhibitor, increased insulin secretion by islets from pregnant rats, and this effect was greater in islets of CP rats than in LPP rats. Forskolin (0.01-100 micromol/L), a stimulator of adenylyl cyclase, increased insulin secretion only in islets of CN and CP rats, with a higher 50% effective concentration in islets of CP rats compared with CN rats. The insulin secretion induced by phorbol 12-myristate 13-acetate (a stimulator of PKC) was higher in islets of LPN and LPP rats than in the respective controls, especially at 8.3 mmol glucose/L. PKAalpha, but not PKCalpha, expression was lower in islets of rats fed low protein than in the controls, regardless of the physiological status of the rats. All endocrine cells of the islets, including beta-cells, expressed the PKAalpha isoform. The cytoplasmic distribution of this enzyme in beta-cells was not modified by pregnancy and/or protein restriction. In conclusion, our results indicate that the response of islets from rats fed low protein during pregnancy is similar to that of control rats, at least for physiologic glucose concentration. However, the decreased response to IBMX and forskolin indicates decreased production and/or sensitivity to cAMP; this

  3. [The spectra of a laser-produced plasma source with CO2, O2 and CF4 liquid aerosol spray target].

    PubMed

    Ni, Qi-Liang; Chen, Bo

    2008-11-01

    A laser-produced plasma (LPP) source with liquid aerosol spray target and nanosecond laser was developed, based on both soft X-ray radiation metrology and extreme ultraviolet projection lithography (EUVL). The LPP source is composed of a stainless steel solenoid valve whose temperature can be continuously controlled, a Nd : YAG laser with pulse width, working wavelength and pulse energy being 7 ns, 1.064 microm and 1J respectively, and a pulse generator which can synchronously control the valve and the laser. A standard General Valve Corporation series 99 stainless steel solenoid valve with copper gasket seals and a Kel-F poppet are used in order to minimize leakage and poppet deformation during high-pressure cryogenic operation. A close fitting copper cooling jacket surrounds the valve body. The jacket clamps a copper coolant carrying tube 3 mm in diameter, which is fed by an automatically pressurized liquid nitrogen-filled dewar. The valve temperature can be controlled between 77 and 473 K. For sufficiently high backing pressure and low temperature, the valve reservoir gas can undergo a gas-to-liquid phase transition. Upon valve pulsing, the liquid is ejected into a vacuum and breaks up into droplets, which is called liquid aerosol spray target. For the above-mentioned LPP source, firstly, by the use of Cowan program on the basis of non-relativistic quantum mechanics, the authors computed the radiative transition wavelengths and probabilities in soft X-ray region for O4+, O5+, O6+, O7+, F5+, F6+ and F7+ ions which were correspondingly produced from the interaction of the 10(11)-10(12) W x cm(-2) power laser with liquid O2, CO2 and CF4 aerosol spray targets. Secondly, the authors measured the spectra of liquid O2, CO2 and CF4 aerosol spray target LPP sources in the 6-20 nm band for the 8 x 10(11) W x cm(-2) laser irradiance. The measured results were compared with the Cowan calculated results ones, and the radiative transition wavelength and probability for the

  4. New Anabaena and Nostoc cyanophages from sewage settling ponds

    SciTech Connect

    Hu, N.; Thiel, T.; Giddings, T.H., Jr.; Wolk, C.P.

    1981-10-15

    We have isolated, from sewage settling ponds, 16 cyanophages for heterocyst forming, filamentous cyanobacteria of the genera Anabaena and Nostoc. These phages fall into three groups based on morphology, host range, one-step growth curves, and restriction digests. On the basis of these criteria they can be distinguished from cyanophages A-1(L), A-4(L), N-1, and AN-10 which we received from other laboratories. Certain of the newly described phages are similar in morphology to the short-tailed LPP cyanophages, and others to the long-tailed AS cyanophages.

  5. A Method for Recording Urethral Pressure Profiles in Female Rats

    PubMed Central

    Xu, Shengfei; Li, Xiaohui; Xu, Lei; Chen, Biao; Tan, Huibing; Du, Guanghui

    2015-01-01

    Aims Urethral pressure profile (UPP) and leak-point pressure (LPP) measurements as well as external urethral sphincter (EUS) electromyography (EMG) and videourodynamic analyses are the primary methods for evaluating urethral function in humans. However, UPP recording in female rats, a widely used animal model, is challenging due to their small body sizes. This study reports a novel method for recording UPP in female rats. Materials and Methods Seventeen anesthetized female rats were studied. LPP data for 14 rats were included. The other 3 rats were excluded because of death or abnormal urogenital organs. UPP curves were recorded using a modified water-perfusion catheter system, with the lateral hole facing the 3-, 6-, 9-, and 12-o’clock positions in a randomized sequence. LPP, functional urethral length (FUL) and maximum urethral closure pressure (MUCP) were analyzed. Results The mean LPP was 64.39 ± 20.29 cm H2O. The mean FUL and MUCP values at the 3-, 6-, 9-, and 12-o’clock positions were 12.90 ± 1.20, 16.70 ± 1.95, 13.90 ± 2.42, and 11.60 ± 0.97 mm, respectively, and 38.70 ± 11.85, 33.90 ± 11.82, 37.40 ± 11.95, and 71.90 ± 23.01 cm H2O, respectively. The FUL at the 6-o’clock position and MUCP at the 12-o’clock position were significantly greater than those at the other 3 positions. The FUL and MUCP of repeated UPP recordings were not significantly different than those of the first recordings. Conclusions UPP recording using a modified method based on a water-perfusion catheter system is feasible and replicable in female rats. It produces UPP curves that sensitively and appreciably reflect detailed pressure changes at different points within the urethra and thus provides opportunity to evaluate urethral structures, especially the urethral sphincter, in detail. These results may enhance the utility of female rat models in research of urinary sphincter mechanisms. PMID:26502072

  6. Atomic processes and equation of state of high Z plasmas for EUV sources and their effects on the spatial and temporal evolution of the plasmas

    NASA Astrophysics Data System (ADS)

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

    2016-03-01

    Laser-produced plasma (LPP) extreme ultraviolet (EUV) light sources have been intensively investigated due to potential application to next-generation semiconductor technology. Current studies focus on the atomic processes and hydrodynamics of plasmas to develop shorter wavelength sources at λ = 6.x nm as well as to improve the conversion efficiency (CE) of λ = 13.5 nm sources. This paper examines the atomic processes of mid-z elements, which are potential candidates for λ = 6.x nm source using n=3-3 transitions. Furthermore, a method to calculate the hydrodynamics of the plasmas in terms of the initial interaction between a relatively weak prepulse laser is presented.

  7. High-throughput, signature-tagged mutagenic approach to identify novel virulence factors of Yersinia pestis CO92 in a mouse model of infection.

    PubMed

    Ponnusamy, Duraisamy; Fitts, Eric C; Sha, Jian; Erova, Tatiana E; Kozlova, Elena V; Kirtley, Michelle L; Tiner, Bethany L; Andersson, Jourdan A; Chopra, Ashok K

    2015-05-01

    The identification of new virulence factors in Yersinia pestis and understanding their molecular mechanisms during an infection process are necessary in designing a better vaccine or to formulate an appropriate therapeutic intervention. By using a high-throughput, signature-tagged mutagenic approach, we created 5,088 mutants of Y. pestis strain CO92 and screened them in a mouse model of pneumonic plague at a dose equivalent to 5 50% lethal doses (LD50) of wild-type (WT) CO92. From this screen, we obtained 118 clones showing impairment in disseminating to the spleen, based on hybridization of input versus output DNA from mutant pools with 53 unique signature tags. In the subsequent screen, 20/118 mutants exhibited attenuation at 8 LD50 when tested in a mouse model of bubonic plague, with infection by 10/20 of the aforementioned mutants resulting in 40% or higher survival rates at an infectious dose of 40 LD50. Upon sequencing, six of the attenuated mutants were found to carry interruptions in genes encoding hypothetical proteins or proteins with putative functions. Mutants with in-frame deletion mutations of two of the genes identified from the screen, namely, rbsA, which codes for a putative sugar transport system ATP-binding protein, and vasK, a component of the type VI secretion system, were also found to exhibit some attenuation at 11 or 12 LD50 in a mouse model of pneumonic plague. Likewise, among the remaining 18 signature-tagged mutants, 9 were also attenuated (40 to 100%) at 12 LD50 in a pneumonic plague mouse model. Previously, we found that deleting genes encoding Braun lipoprotein (Lpp) and acyltransferase (MsbB), the latter of which modifies lipopolysaccharide function, reduced the virulence of Y. pestis CO92 in mouse models of bubonic and pneumonic plague. Deletion of rbsA and vasK genes from either the Δlpp single or the Δlpp ΔmsbB double mutant augmented the attenuation to provide 90 to 100% survivability to mice in a pneumonic plague model at 20

  8. Lichen Planopilaris Treated With a Peroxisome Proliferator—Activated Receptor γ Agonist

    PubMed Central

    Mirmirani, Paradi; Karnik, Pratima

    2010-01-01

    Primary cicatricial alopecias (PCAs), rare disorders that lead to permanent hair loss, have been poorly understood and are difficult to treat. Lichen planopilaris (LPP) is a prototypical PCA; patients often present with sudden onset of hair loss and clinically significant symptoms of itching, burning, and pain of the scalp. Examination reveals patchy alopecia or a more diffuse thinning of the scalp with characteristic perifollicular erythema and perifollicular scale at the margins of the areas of alopecia. Treatment typically includes use of anti-inflammatory medications; although symptomsmay improve, hair loss is often progressive. PMID:20026843

  9. Characterization of single-file flow through human retinal parafoveal capillaries using an adaptive optics scanning laser ophthalmoscope.

    PubMed

    Tam, Johnny; Tiruveedhula, Pavan; Roorda, Austin

    2011-03-02

    Adaptive Optics Scanning Laser Ophthalmoscopy was used to noninvasively acquire videos of single-file flow through live human retinal parafoveal capillaries. Videos were analyzed offline to investigate capillary flow dynamics. Certain capillaries accounted for a clear majority of leukocyte traffic (Leukocyte-Preferred-Paths, LPPs), while other capillaries primarily featured plasma gap flow (Plasma-Gap-Capillaries, PGCs). LPPs may serve as a protective mechanism to prevent inactivated leukocytes from entering exchange capillaries, and PGCs may serve as relief valves to minimize flow disruption due to the presence of a leukocyte in a neighboring LPP.

  10. High-Throughput, Signature-Tagged Mutagenic Approach To Identify Novel Virulence Factors of Yersinia pestis CO92 in a Mouse Model of Infection

    PubMed Central

    Ponnusamy, Duraisamy; Fitts, Eric C.; Erova, Tatiana E.; Kozlova, Elena V.; Kirtley, Michelle L.; Tiner, Bethany L.; Andersson, Jourdan A.

    2015-01-01

    The identification of new virulence factors in Yersinia pestis and understanding their molecular mechanisms during an infection process are necessary in designing a better vaccine or to formulate an appropriate therapeutic intervention. By using a high-throughput, signature-tagged mutagenic approach, we created 5,088 mutants of Y. pestis strain CO92 and screened them in a mouse model of pneumonic plague at a dose equivalent to 5 50% lethal doses (LD50) of wild-type (WT) CO92. From this screen, we obtained 118 clones showing impairment in disseminating to the spleen, based on hybridization of input versus output DNA from mutant pools with 53 unique signature tags. In the subsequent screen, 20/118 mutants exhibited attenuation at 8 LD50 when tested in a mouse model of bubonic plague, with infection by 10/20 of the aforementioned mutants resulting in 40% or higher survival rates at an infectious dose of 40 LD50. Upon sequencing, six of the attenuated mutants were found to carry interruptions in genes encoding hypothetical proteins or proteins with putative functions. Mutants with in-frame deletion mutations of two of the genes identified from the screen, namely, rbsA, which codes for a putative sugar transport system ATP-binding protein, and vasK, a component of the type VI secretion system, were also found to exhibit some attenuation at 11 or 12 LD50 in a mouse model of pneumonic plague. Likewise, among the remaining 18 signature-tagged mutants, 9 were also attenuated (40 to 100%) at 12 LD50 in a pneumonic plague mouse model. Previously, we found that deleting genes encoding Braun lipoprotein (Lpp) and acyltransferase (MsbB), the latter of which modifies lipopolysaccharide function, reduced the virulence of Y. pestis CO92 in mouse models of bubonic and pneumonic plague. Deletion of rbsA and vasK genes from either the Δlpp single or the Δlpp ΔmsbB double mutant augmented the attenuation to provide 90 to 100% survivability to mice in a pneumonic plague model at 20

  11. A step into the anarchist’s mind: examining political attitudes and ideology through event-related brain potentials

    PubMed Central

    Van Hiel, Alain; Pattyn, Sven; Onraet, Emma; Severens, Els

    2012-01-01

    The present study investigates patterns of event-related brain potentials following the presentation of attitudinal stimuli among political moderates (N = 12) and anarchists (N = 11). We used a modified oddball paradigm to investigate the evaluative inconsistency effect elicited by stimuli embedded in a sequence of contextual stimuli with an opposite valence. Increased late positive potentials (LPPs) of extreme political attitudes were observed. Moreover, this LPP enhancement was larger among anarchists than among moderates, indicating that an extreme political attitude of a moderate differs from an extreme political attitude of an anarchist. The discussion elaborates on the meaning of attitude extremity for moderates and extremists. PMID:21421734

  12. Recent results and future prospects for the polarized beam at Fermilab

    SciTech Connect

    Yokosawa, A.

    1990-01-01

    We summarize activities concerning the Fermilab polarized beams. They include a brief description of the polarized-beam facility, measurements of beam polarization by polarimeters, asymmetry measurements in the {pi}{degree} production at high p{sub {perpendicular}} and in the {Lambda} ({Sigma}{degree}), {pi}{sup {plus minus}}, {pi}{degree} production at large x{sub F}, and {Delta}{sigma}{sub L}(pp, {anti p}p) measurements (Fermilab E-704). In the future we plan to investigate the proton-spin crisis by determining the gluon spin distribution in inclusive production of direct gamma, {chi}2, and J/{psi}. 20 refs., 5 figs.

  13. Lichen planus pemphigoides associated with pregnancy mimicking pemphigoid gestationis.

    PubMed

    Rullán, Jennifer; Diaz, Nicole C; Vazquez-Botet, Miguel

    2016-06-01

    Lichen planus pemphigoides (LPP) is a rare condition characterized by tense blisters that arise on lesions of lichen planus (LP) and on unaffected skin. We present the case of a 25-year-old pregnant woman at 12 weeks' gestation who developed an acute bullous eruption after 5 months of worsening LP. Similarities to pemphigoid gestationis (PG) included lesions around the periumbilical area and multiple urticarial erythematous papules and plaques in addition to linear C3 and IgM deposition along the basement membrane zone (BMZ) on direct immunofluorescence (DIF). PMID:27416093

  14. [The spectra of a laser-produced plasma source with CO2, O2 and CF4 liquid aerosol spray target].

    PubMed

    Ni, Qi-Liang; Chen, Bo

    2008-11-01

    A laser-produced plasma (LPP) source with liquid aerosol spray target and nanosecond laser was developed, based on both soft X-ray radiation metrology and extreme ultraviolet projection lithography (EUVL). The LPP source is composed of a stainless steel solenoid valve whose temperature can be continuously controlled, a Nd : YAG laser with pulse width, working wavelength and pulse energy being 7 ns, 1.064 microm and 1J respectively, and a pulse generator which can synchronously control the valve and the laser. A standard General Valve Corporation series 99 stainless steel solenoid valve with copper gasket seals and a Kel-F poppet are used in order to minimize leakage and poppet deformation during high-pressure cryogenic operation. A close fitting copper cooling jacket surrounds the valve body. The jacket clamps a copper coolant carrying tube 3 mm in diameter, which is fed by an automatically pressurized liquid nitrogen-filled dewar. The valve temperature can be controlled between 77 and 473 K. For sufficiently high backing pressure and low temperature, the valve reservoir gas can undergo a gas-to-liquid phase transition. Upon valve pulsing, the liquid is ejected into a vacuum and breaks up into droplets, which is called liquid aerosol spray target. For the above-mentioned LPP source, firstly, by the use of Cowan program on the basis of non-relativistic quantum mechanics, the authors computed the radiative transition wavelengths and probabilities in soft X-ray region for O4+, O5+, O6+, O7+, F5+, F6+ and F7+ ions which were correspondingly produced from the interaction of the 10(11)-10(12) W x cm(-2) power laser with liquid O2, CO2 and CF4 aerosol spray targets. Secondly, the authors measured the spectra of liquid O2, CO2 and CF4 aerosol spray target LPP sources in the 6-20 nm band for the 8 x 10(11) W x cm(-2) laser irradiance. The measured results were compared with the Cowan calculated results ones, and the radiative transition wavelength and probability for the

  15. Sector Tests of a Low-NO(sub x), Lean, Direct- Injection, Multipoint Integrated Module Combustor Concept Conducted

    NASA Technical Reports Server (NTRS)

    Tacina, Robert R.; Wey, Chang-Lie; Laing, Peter; Mansour, Adel

    2002-01-01

    The low-emissions combustor development described 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) concepts. 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 possibility of autoignition or flashback precludes its use. LDI differs from LPP in that the fuel is injected directly into the flame zone, and thus, it does not have the potential for autoignition or flashback and should have greater stability. However, since it is not premixed and prevaporized, good atomization is necessary and the fuel must be mixed quickly and uniformly so that flame temperatures are low and NOx formation levels are comparable to those of LPP. The LDI concept described is a multipoint fuel injection/multiburning zone concept. Each of the multiple fuel injectors has an air swirler associated with it to provide quick mixing and a small recirculation zone for burning. The multipoint fuel injection provides quick, uniform mixing and the small multiburning zones provide for reduced burning residence time, resulting in low NOx formation. An integrated-module approach was used for the construction where chemically etched laminates, diffusion bonded together, combine the fuel injectors, air swirlers, and fuel manifold into a single element. The multipoint concept combustor was demonstrated in a 15 sector test. The configuration tested had 36

  16. Characterization of Sea Lettuce Surface Functional Groups by Potentiometric Titrations

    NASA Astrophysics Data System (ADS)

    Ebling, A. M.; Schijf, J.

    2008-12-01

    In pursuit of our ultimate goal to better understand the prodigious capacity of the marine macroalga Ulva lactuca (sea lettuce) for adsorbing a broad range of dissolved trace metals from seawater, we performed an initial characterization of its surface functional groups. Specifically, the number of distinct functional groups as well as their individual bulk concentrations and acid dissociation constants (pKas) were determined by potentiometric titrations in NaCl solutions of various ionic strengths (I = 0.01-5.0 M), under inert nitrogen atmosphere at 25°C. Depending on the ionic strength, Ulva samples were manually titrated down to pH 2 or 3 with 1 N HCl and then up to pH 10 with 1 N NaOH in steps of 0.1-0.2 units, continuously monitoring pH with a glass combination electrode. Titrations of a dehydrated Ulva standard reference material (BCR-279) were compared with fresh Ulva tissue cultured in our laboratory. A titration in filtered natural seawater was also compared with one in an NaCl solution of equal ionic strength. Equilibrium constants for the ionization of water in NaCl solutions as a function of ionic strength were obtained from the literature. Fits to the titration data ([H]T vs. pH) were performed with the FITEQL4.0 computer code using non-electrostatic 3-, 4-, and 5-site models, either by fixing ionic strength at its experimental value or by allowing it to be extrapolated to zero, while considering all functional group pKas and bulk concentrations as adjustable parameters. Since pKas and bulk concentrations were found to be strongly correlated, the latter were also fixed in some cases to further constrain the pKas. Whereas these calculations are currently ongoing, preliminary results point to three, possibly four, functional groups with pKas of about 4.1, 6.3, and 9.5 at I = 0. Bulk concentrations of the three groups are very similar, about 5-6×10-4 mol/g based on dry weight, which suggests that all are homogeneously distributed over the surface and

  17. Fatty acid biosynthesis in Pseudomonas aeruginosa is initiated by the FabY class of β-ketoacyl acyl carrier protein synthases.

    PubMed

    Yuan, Yanqiu; Sachdeva, Meena; Leeds, Jennifer A; Meredith, Timothy C

    2012-10-01

    The prototypical type II fatty acid synthesis (FAS) pathway in bacteria utilizes two distinct classes of β-ketoacyl synthase (KAS) domains to assemble long-chain fatty acids, the KASIII domain for initiation and the KASI/II domain for elongation. The central role of FAS in bacterial viability and virulence has stimulated significant effort toward developing KAS inhibitors, particularly against the KASIII domain of the β-acetoacetyl-acyl carrier protein (ACP) synthase FabH. Herein, we show that the opportunistic pathogen Pseudomonas aeruginosa does not utilize a FabH ortholog but rather a new class of divergent KAS I/II enzymes to initiate the FAS pathway. When a P. aeruginosa cosmid library was used to rescue growth in a fabH downregulated strain of Escherichia coli, a single unannotated open reading frame, PA5174, complemented fabH depletion. While deletion of all four KASIII domain-encoding genes in the same P. aeruginosa strain resulted in a wild-type growth phenotype, deletion of PA5174 alone specifically attenuated growth due to a defect in de novo FAS. Siderophore secretion and quorum-sensing signaling, particularly in the rhl and Pseudomonas quinolone signal (PQS) systems, was significantly muted in the absence of PA5174. The defect could be repaired by intergeneric complementation with E. coli fabH. Characterization of recombinant PA5174 confirmed a preference for short-chain acyl coenzyme A (acyl-CoA) substrates, supporting the identification of PA5174 as the predominant enzyme catalyzing the condensation of acetyl coenzyme A with malonyl-ACP in P. aeruginosa. The identification of the functional role for PA5174 in FAS defines the new FabY class of β-ketoacyl synthase KASI/II domain condensation enzymes.

  18. Population Genetics Study of Isoniazid Resistance Mutations and Evolution of Multidrug-Resistant Mycobacterium tuberculosis†

    PubMed Central

    Hazbón, Manzour Hernando; Brimacombe, Michael; Bobadilla del Valle, Miriam; Cavatore, Magali; Guerrero, Marta Inírida; Varma-Basil, Mandira; Billman-Jacobe, Helen; Lavender, Caroline; Fyfe, Janet; García-García, Lourdes; León, Clara Inés; Bose, Mridula; Chaves, Fernando; Murray, Megan; Eisenach, Kathleen D.; Sifuentes-Osornio, José; Cave, M. Donald; Ponce de León, Alfredo; Alland, David

    2006-01-01

    The molecular basis for isoniazid resistance in Mycobacterium tuberculosis is complex. Putative isoniazid resistance mutations have been identified in katG, ahpC, inhA, kasA, and ndh. However, small sample sizes and related potential biases in sample selection have precluded the development of statistically valid and significant population genetic analyses of clinical isoniazid resistance. We present the first large-scale analysis of 240 alleles previously associated with isoniazid resistance in a diverse set of 608 isoniazid-susceptible and 403 isoniazid-resistant clinical M. tuberculosis isolates. We detected 12 mutant alleles in isoniazid-susceptible isolates, suggesting that these alleles are not involved in isoniazid resistance. However, mutations in katG, ahpC, and inhA were strongly associated with isoniazid resistance, while kasA mutations were associated with isoniazid susceptibility. Remarkably, the distribution of isoniazid resistance-associated mutations was different in isoniazid-monoresistant isolates from that in multidrug-resistant isolates, with significantly fewer isoniazid resistance mutations in the isoniazid-monoresistant group. Mutations in katG315 were significantly more common in the multidrug-resistant isolates. Conversely, mutations in the inhA promoter were significantly more common in isoniazid-monoresistant isolates. We tested for interactions among mutations and resistance to different drugs. Mutations in katG, ahpC, and inhA were associated with rifampin resistance, but only katG315 mutations were associated with ethambutol resistance. There was also a significant inverse association between katG315 mutations and mutations in ahpC or inhA and between mutations in kasA and mutations in ahpC. Our results suggest that isoniazid resistance and the evolution of multidrug-resistant strains are complex dynamic processes that may be influenced by interactions between genes and drug-resistant phenotypes. PMID:16870753

  19. Psychometrics of shared decision making and communication as patient centered measures for two language groups.

    PubMed

    Alvarez, Kiara; Wang, Ye; Alegria, Margarita; Ault-Brutus, Andrea; Ramanayake, Natasha; Yeh, Yi-Hui; Jeffries, Julia R; Shrout, Patrick E

    2016-09-01

    Shared decision making (SDM) and effective patient-provider communication are key and interrelated elements of patient-centered care that impact health and behavioral health outcomes. Measurement of SDM and communication from the patient's perspective is necessary in order to ensure that health care systems and individual providers are responsive to patient views. However, there is a void of research addressing the psychometric properties of these measures with diverse patients, including non-English speakers, and in the context of behavioral health encounters. This study evaluated the psychometric properties of 2 patient-centered outcome measures, the Shared Decision-Making Questionnaire-9 (SDM-Q) and the Kim Alliance Scale-Communication subscale (KAS-CM), in a sample of 239 English and Spanish-speaking behavioral health patients. One dominant factor was found for each scale and this structure was used to examine whether there was measurement invariance across the 2 language groups. One SDM-Q item was inconsistent with the configural invariance comparison and was removed. The remaining SDM-Q items exhibited strong invariance, meaning that item loadings and item means were similar across the 2 groups. The KAS-CM items had limited variability, with most respondents indicating high communication levels, and the invariance analysis was done on binary versions of the items. These had metric invariance (loadings the same over groups) but several items violated the strong invariance test. In both groups, the SDM-Q had high internal consistency, whereas the KAS-CM was only adequate. These findings help interpret results for individual patients, taking into account cultural and linguistic differences in how patients perceive SDM and patient-provider communication. (PsycINFO Database Record PMID:27537002

  20. Gain of 11q/cyclin D1 overexpression is an essential early step in skin cancer development and causes abnormal tissue organization and differentiation.

    PubMed

    Burnworth, B; Popp, S; Stark, H-J; Steinkraus, V; Bröcker, E B; Hartschuh, W; Birek, C; Boukamp, P

    2006-07-27

    Non-melanoma skin cancers, in particular keratoacanthomas (KAs) and squamous cell carcinomas (SCCs), have become highly frequent tumor types especially in immune-suppressed transplant patients. Nevertheless, little is known about essential genetic changes. As a paradigm of 'early' changes, that is, changes still compatible with tumor regression, we studied KAs by comparative genomic hybridization and show that gain of chromosome 11q is not only one of the most frequent aberration (8/18), but in four tumors also the only aberration. Furthermore, 11q gain correlated with amplification of the cyclin D1 locus (10/14), as determined by fluorescence in situ hybridization, and overexpression of cyclin D1 protein (25/31), as detected by immunohistochemistry. For unraveling the functional consequence, we overexpressed cyclin D1 in HaCaT skin keratinocytes. These cells only gained little growth advantage in conventional and in organotypic co-cultures. However, although the control vector-transfected cells formed a well-stratified and orderly differentiated epidermis-like epithelium, they showed deregulation of tissue architecture with an altered localization of proliferation and impaired differentiation. The most severe phenotype was seen in a clone that additionally upregulated cdk4 and p21. These cells lacked terminal differentiation, exhibited a more autonomous growth in vitro and in vivo and even formed tumors in two injection sites with a growth pattern resembling that of human KAs. Thus, our results identify 11q13 gain/cyclin D1 overexpression as an important step in KA formation and point to a function that exceeds its known role in proliferation by disrupting tissue organization and thereby allowing abnormal growth.

  1. HBV-Related Health Behaviors in a Socio-Cultural Context: Perspectives from Khmers and Koreans

    PubMed Central

    Lee, Haeok; Kiang, Peter; Chea, Phala; Peou, Sonith; Tang, Shirley S.; Yang, JinHwang; Fawcett, Jacqueline; Hann, Hie-Won

    2014-01-01

    Purpose To explore factors influencing health and health care within the sociocultural context of Cambodian Americans (CAs or Khmers) and Korean Americans (KA) and to examine intergroup similarities and differences between CAs and KAs, focusing on hepatitis B virus (HBV) and liver cancer prevention behaviors. Methods The study used a qualitative design guided by the revised Network Episode Model (NEM) and informed by ethnographic analysis. Focus group interviews with key informants among CA community health leaders (CHLs, n=14) and individual interviews with key informants of KA CHLs (n=9) were audiotaped and transcribed. Results Three categories that influenced HBV and liver cancer prevention emerged from both CAs and KAs: the socio-cultural, individual, and behavioral. Four additional sub-categories (sub-themes) of sociocultural were identified as socio-history, socio-medicine, socio-linguistic, and socio-health resources. Both CAs and KAs, however, have low levels of knowledge and significant misunderstandings about HBV infection. Conclusions The study identifies and compares the social-cultural determinant for HBV and liver cancer and highlights the factors of education, intercultural communication, and interactions within socio-cultural contexts of CA and KA subgroups. In general, conceptual overlaps are apparent between Khmers (from now on, the terms, CA and Khmer, will be used interchangeably) and Koreans except for the sub-theme of socio-history. However, differences in concept-specific attributes point to the need to account for differing conceptualizations and implications of specific ethnic groups’ sociocultural contexts, and to design contextually-relevant outreach and educational interventions for targeted AAPI subgroups. PMID:24355416

  2. Immunohistochemical Evaluation of p53 and Ki67 Expression in Skin Epithelial Tumors

    PubMed Central

    Khodaeiani, Effat; Fakhrjou, Ashraf; Amirnia, Mehdi; Babaei-nezhad, Shahla; Taghvamanesh, Farshid; Razzagh-Karimi, Elham; Alikhah, Hossein

    2013-01-01

    Background and Aims: The cellular mechanisms responsible for initiating or limiting the tumors including skin types are of great importance. The p53 is a tumor-inhibiting gene which is believed to be defective in many malignant situations. Ki67 is a non-histonic protein which is mainly interfere with the proliferation and has many controlling effects during the cell cycle. Because of their importance in skin tumor cell growth, this study aimed at evaluating the p53 and Ki67 expression in skin epithelial tumors by immunohistochemical method. Materials and Methods: In a descriptive setting, 50 biopsy samples (30 basal cell carcinomas (BCCs), 10 squamous cell carcinomas (SCCs), 8 keratoacanthomas (KAs), and 2 trichoepitheliomas (TEs)) were immunohistochemically evaluated for p53 and Ki67 expression during a 14-month period. The incidence and expression rate of these two variables were separately reported in each group of samples. Results: The expression rate of p53 was 67.77% for the BCCs, 50.20% for the SCCs, and null for the KAs. For both TEs, it was 50%. The expression rate of Ki67 was 57.33% for the BCCs, 47.70% for the SCCs, 37.5% for the KAs, and 0.0% for TEs. The incidence of P53+ cells was 100% and 90% in the BCC and SCC samples, respectively. The both TEs were positive in this regard. The incidence of Ki67+ cells was 100% for the BCC, SCC, and KA samples. The both TEs were negative in this regard. Conclusion: This study showed that the incidence rate of p53- and Ki67-positive cells is very high in skin malignant epithelial tumors. The expression rate of these two variables is comparable with reports in the literature. Further studies with large sample size are recommended to be carried out for KA and TE samples. PMID:23723466

  3. Screening and characterization of mutations in isoniazid-resistant Mycobacterium tuberculosis isolates obtained in Brazil.

    PubMed

    Cardoso, Rosilene Fressatti; Cooksey, Robert C; Morlock, Glenn P; Barco, Patricia; Cecon, Leticia; Forestiero, Francisco; Leite, Clarice Q F; Sato, Daisy N; Shikama, Maria de Lourdes; Mamizuka, Elsa M; Hirata, Rosario D C; Hirata, Mario H

    2004-09-01

    We investigated mutations in the genes katG, inhA (regulatory and structural regions), and kasA and the oxyR-ahpC intergenic region of 97 isoniazid (INH)-resistant and 60 INH-susceptible Mycobacterium tuberculosis isolates obtained in two states in Brazil: São Paulo and Paraná. PCR-single-strand conformational polymorphism (PCR-SSCP) was evaluated for screening mutations in regions of prevalence, including codons 315 and 463 of katG, the regulatory region and codons 16 and 94 of inhA, kasA, and the oxyR-ahpC intergenic region. DNA sequencing of PCR amplicons was performed for all isolates with altered PCR-SSCP profiles. Mutations in katG were found in 83 (85.6%) of the 97 INH-resistant isolates, including mutations in codon 315 that occurred in 60 (61.9%) of the INH-resistant isolates and 23 previously unreported katG mutations. Mutations in the inhA promoter region occurred in 25 (25.8%) of the INH-resistant isolates; 6.2% of the isolates had inhA structural gene mutations, and 10.3% had mutations in the oxyR-ahpC intergenic region (one, nucleotide -48, previously unreported). Polymorphisms in the kasA gene occurred in both INH-resistant and INH-susceptible isolates. The most frequent polymorphism encoded a G(269)A substitution. Although KatG(315) substitutions are predominant, novel mutations also appear to be responsible for INH resistance in the two states in Brazil. Since ca. 90.7% of the INH-resistant isolates had mutations identified by SSCP electrophoresis, this method may be a useful genotypic screen for INH resistance. PMID:15328099

  4. Population genetics study of isoniazid resistance mutations and evolution of multidrug-resistant Mycobacterium tuberculosis.

    PubMed

    Hazbón, Manzour Hernando; Brimacombe, Michael; Bobadilla del Valle, Miriam; Cavatore, Magali; Guerrero, Marta Inírida; Varma-Basil, Mandira; Billman-Jacobe, Helen; Lavender, Caroline; Fyfe, Janet; García-García, Lourdes; León, Clara Inés; Bose, Mridula; Chaves, Fernando; Murray, Megan; Eisenach, Kathleen D; Sifuentes-Osornio, José; Cave, M Donald; Ponce de León, Alfredo; Alland, David

    2006-08-01

    The molecular basis for isoniazid resistance in Mycobacterium tuberculosis is complex. Putative isoniazid resistance mutations have been identified in katG, ahpC, inhA, kasA, and ndh. However, small sample sizes and related potential biases in sample selection have precluded the development of statistically valid and significant population genetic analyses of clinical isoniazid resistance. We present the first large-scale analysis of 240 alleles previously associated with isoniazid resistance in a diverse set of 608 isoniazid-susceptible and 403 isoniazid-resistant clinical M. tuberculosis isolates. We detected 12 mutant alleles in isoniazid-susceptible isolates, suggesting that these alleles are not involved in isoniazid resistance. However, mutations in katG, ahpC, and inhA were strongly associated with isoniazid resistance, while kasA mutations were associated with isoniazid susceptibility. Remarkably, the distribution of isoniazid resistance-associated mutations was different in isoniazid-monoresistant isolates from that in multidrug-resistant isolates, with significantly fewer isoniazid resistance mutations in the isoniazid-monoresistant group. Mutations in katG315 were significantly more common in the multidrug-resistant isolates. Conversely, mutations in the inhA promoter were significantly more common in isoniazid-monoresistant isolates. We tested for interactions among mutations and resistance to different drugs. Mutations in katG, ahpC, and inhA were associated with rifampin resistance, but only katG315 mutations were associated with ethambutol resistance. There was also a significant inverse association between katG315 mutations and mutations in ahpC or inhA and between mutations in kasA and mutations in ahpC. Our results suggest that isoniazid resistance and the evolution of multidrug-resistant strains are complex dynamic processes that may be influenced by interactions between genes and drug-resistant phenotypes. PMID:16870753

  5. Signature gene expression profiles discriminate between isoniazid-, thiolactomycin-, and triclosan-treated Mycobacterium tuberculosis.

    PubMed

    Betts, Joanna C; McLaren, Alistair; Lennon, Mark G; Kelly, Fiona M; Lukey, Pauline T; Blakemore, Steve J; Duncan, Ken

    2003-09-01

    Genomic technologies have the potential to greatly increase the efficiency of the drug development process. As part of our tuberculosis drug discovery program, we used DNA microarray technology to profile drug-induced effects in Mycobacterium tuberculosis. Expression profiles of M. tuberculosis treated with compounds that inhibit key metabolic pathways are required as references for the assessment of novel antimycobacterial agents. We have studied the response of M. tuberculosis to treatment with the mycolic acid biosynthesis inhibitors isoniazid, thiolactomycin, and triclosan. Thiolactomycin targets the beta-ketoacyl-acyl carrier protein (ACP) synthases KasA and KasB, while triclosan inhibits the enoyl-ACP reductase InhA. However, controversy surrounds the precise mode of action of isoniazid, with both InhA and KasA having been proposed as the primary target. We have shown that although the global response profiles of isoniazid and thiolactomycin are more closely related to each other than to that of triclosan, there are differences that distinguish the mode of action of these two drugs. In addition, we have identified two groups of genes, possibly forming efflux and detoxification systems, through which M. tuberculosis may limit the effects of triclosan. We have developed a mathematical model, based on the expression of 21 genes, which is able to perfectly discriminate between isoniazid-, thiolactomycin-, or triclosan-treated M. tuberculosis. This model is likely to prove invaluable as a tool to improve the efficiency of our drug development programs by providing a means to rapidly confirm the mode of action of thiolactomycin analogues or novel InhA inhibitors as well as helping to translate enzyme activity into whole-cell activity. PMID:12936993

  6. Analysis of a Plant Complex Resistance Gene Locus Underlying Immune-Related Hybrid Incompatibility and Its Occurrence in Nature

    PubMed Central

    Alcázar, Rubén; von Reth, Marcel; Bautor, Jaqueline; Chae, Eunyoung; Weigel, Detlef; Koornneef, Maarten; Parker, Jane E.

    2014-01-01

    Mechanisms underlying speciation in plants include detrimental (incompatible) genetic interactions between parental alleles that incur a fitness cost in hybrids. We reported on recessive hybrid incompatibility between an Arabidopsis thaliana strain from Poland, Landsberg erecta (Ler), and many Central Asian A. thaliana strains. The incompatible interaction is determined by a polymorphic cluster of Toll/interleukin-1 receptor-nucleotide binding-leucine rich repeat (TNL) RPP1 (Recognition of Peronospora parasitica1)-like genes in Ler and alleles of the receptor-like kinase Strubbelig Receptor Family 3 (SRF3) in Central Asian strains Kas-2 or Kond, causing temperature-dependent autoimmunity and loss of growth and reproductive fitness. Here, we genetically dissected the RPP1-like Ler locus to determine contributions of individual RPP1-like Ler (R1–R8) genes to the incompatibility. In a neutral background, expression of most RPP1-like Ler genes, except R3, has no effect on growth or pathogen resistance. Incompatibility involves increased R3 expression and engineered R3 overexpression in a neutral background induces dwarfism and sterility. However, no individual RPP1-like Ler gene is sufficient for incompatibility between Ler and Kas-2 or Kond, suggesting that co-action of at least two RPP1-like members underlies this epistatic interaction. We find that the RPP1-like Ler haplotype is frequent and occurs with other Ler RPP1-like alleles in a local population in Gorzów Wielkopolski (Poland). Only Gorzów individuals carrying the RPP1-like Ler haplotype are incompatible with Kas-2 and Kond, whereas other RPP1-like alleles in the population are compatible. Therefore, the RPP1-like Ler haplotype has been maintained in genetically different individuals at a single site, allowing exploration of forces shaping the evolution of RPP1-like genes at local and regional population scales. PMID:25503786

  7. Carbonic anhydrase activators: the first activation study of the human secretory isoform VI with amino acids and amines.

    PubMed

    Nishimori, Isao; Onishi, Saburo; Vullo, Daniela; Innocenti, Alessio; Scozzafava, Andrea; Supuran, Claudiu T

    2007-08-01

    The secretory isozyme of human carbonic anhydrase (hCA, EC 4.2.1.1), hCA VI, has been cloned, expressed, and purified in a bacterial expression system. The kinetic parameters for the CO(2) hydration reaction proved hCA VI to possess a k(cat) of 3.4 x 10(5)s(-1) and k(cat)/K(M) of 4.9 x 10(7)M(-1)s(-1) (at pH 7.5 and 20 degrees C). hCA VI has a significant catalytic activity for the physiological reaction, of the same order of magnitude as the ubiquitous isoform CA I or the transmembrane, tumor-associated isozyme CA IX. A series of amino acids and amines were shown to act as CA VI activators, with variable efficacies. l-His, l-Trp, and dopamine showed weak CA VI activating effects (K(A)s in the range of 21-42 microM), whereas d-His, d-Phe, l-DOPA, l-Trp, serotonin, and some pyridyl-alkylamines were better activators, with K(A)s in the range of 13-19 microM. The best CA VI activators were l-Phe, d-DOPA, l-Tyr, 4-amino-l-Phe, and histamine, with K(A)s in the range of 1.23-9.31 microM. All these activators enhance k(cat), having no effect on K(M), participating thus in the rate determining step in the catalytic cycle, the proton transfer reactions between the enzyme active site and the environment. PMID:17499996

  8. Translation and Validation of the Dietary Approaches to Stop Hypertension for Koreans Intervention

    PubMed Central

    Kim, Hyerang; Song, Hee-Jung; Han, Hae-Ra; Kim, Kim B.; Kim, Miyong T.

    2015-01-01

    Background Lifestyle modification strategies such as adoption of the Dietary Approaches to Stop Hypertension (DASH) diet are now recognized as an integral part of high blood pressure (HBP) management. Although the high prevalence of HBP among Korean Americans (KAs) is well documented, few dietary interventions have been implemented in this population, in part because of a lack of culturally relevant nutrition education guidelines. Translating and testing the efficacy of culturally relevant dietary recommendations using a well-established dietary guideline such as DASH are imperative for promoting better cardiovascular health for this high-risk cultural group. Objective The aims of this study were to systematically translate and validate a culturally modified DASH for Koreans (K-DASH) and obtain preliminary evidence of efficacy. Methods A 2-step approach of intervention translation and efficacy testing, together with close adherence to principles of community-based participatory research, was used to maximize community input. A 1-group pre-post design with 24-hour urine and 24-hour ambulatory blood pressure monitoring comparisons was used to test the initial feasibility and efficacy of the K-DASH intervention. Results A total of 28 KAs with HBP participated in a 10-week dietary intervention consisting of group education sessions and individual counseling. Both systolic blood pressure and diastolic blood pressure, as measured by ambulatory blood pressure monitoring, were significantly decreased at postintervention evaluation (systolic blood pressure, −4.5 mm Hg; diastolic blood pressure, −2.6 mm Hg; P < .05). Serum low-density lipoprotein cholesterol was significantly decreased (−7.3 mg/dL; P < .05). Serum potassium and ascorbic acid levels were also improved in the reference range. Urine potassium level was significantly increased, supporting increased fruit and vegetable consumption. Conclusion This pilot study has (a) demonstrated that a cultural adaptation

  9. Colorado State University program for developing, testing, evaluating and optimizing solar heating and cooling systems: Project status report for the months of October and November, 1994

    SciTech Connect

    Not Available

    1994-12-01

    This report describes a project to develop tools for evaluating solar heating and cooling systems. Current work on this project has been to validate the Florida Solar Energy Center`s (FSEC) models of the Solahart 302K and 302K-AS systems to prepare a rating for the Sacramento Municipal Utility District`s rebate program for solar domestic hot water heaters. A preliminary rating has been issued by FSEC and updated ratings will be released as necessary. Two of the problems that were mentioned in the August/September report are addressed and a tank heat loss test is discussed. Work continues on improving and validating the models.

  10. Evidence of Clonal Expansion in the Genome of a Multidrug-Resistant Mycobacterium tuberculosis Clinical Isolate from Peru.

    PubMed

    Galarza, M; Tarazona, D; Borda, V; Agapito, J C; Guio, H

    2014-01-01

    We report the genome sequence of Mycobacterium tuberculosis INS-MDR from Peru, a multidrug-resistant tuberculosis (MDR-TB) and Latin American-Mediterranean (LAM) lineage strain. Our analysis showed mutations related to drug resistance in the rpoB (D516V), katG (S315T), kasA (G269S), and pncA (Q10R) genes. Our evidence suggests that INS-MDR may be a clonal expansion related to the African strain KZN 1435. PMID:24578270

  11. Contribution of dfrA and inhA mutations to the detection of isoniazid-resistant Mycobacterium tuberculosis isolates.

    PubMed

    Ho, Yu Min; Sun, Yong-Jiang; Wong, Sin-Yew; Lee, Ann S G

    2009-09-01

    Screening of 127 isoniazid (INH)-resistant Mycobacterium tuberculosis isolates from Singapore for mutations within the dfrA and inhA genes revealed mutations in 0 and 5 (3.9%) isolates respectively, implying that mutations in dfrA do not contribute to the detection of INH-resistant M. tuberculosis and that mutations within inhA are rare. Thirty-seven (29%) of the 127 isolates had no mutations in any of the genes implicated in INH resistance (katG, kasA, and ndh; inhA and ahpC promoters), suggesting that there are new INH targets yet to be discovered. PMID:19581462

  12. [New technologies in the determination of drug susceptibility in Mycobacterium tuberculosis].

    PubMed

    Skotnikova, O I; Mikhaĭlovich, V M; Nosova, E Iu; Lapa, S A; Griadunov, D A; Donnikov, M Iu; Badleeva, M V; Galkina, K Iu; Dorozhkova, I R; Litvinov, V I; Zasedatelev, A S; Moroz, A M; Mirzabekov, A D

    2004-01-01

    A variety of mutations in the genes rpoB, katG, inhA, ahpC, kasA was studied by using different molecular biological methods (conformational polymorphism of single-chain fragments, heteroduplex analysis, biochips) in rifampicin- and isoniazid-resistant Mycobacterium tuberculosis (MBT) strains isolated from patients with pulmonary tuberculosis. Twenty-nine mutation combinations were identified in the MBT strains. The use of biochips is the most promising method for identifying the type of mutations responsible for the simultaneous resistance to rifampicin and isoniazid. Detection of several MBT strains in one patient requires the use a combination of molecular biological and microbiological studies. PMID:15315132

  13. Novel mutations in ndh in isoniazid-resistant Mycobacterium tuberculosis isolates.

    PubMed

    Lee, A S; Teo, A S; Wong, S Y

    2001-07-01

    Novel mutations in NADH dehydrogenase (ndh) were detected in 8 of 84 (9.5%) isoniazid (INH)-resistant isolates (T110A [n = 1], R268H [n = 7]), but not in 22 INH-susceptible isolates of Mycobacterium tuberculosis. Significantly, all eight isolates with mutations at ndh did not have mutations at katG, kasA, or the promoter regions of inhA or ahpC, except for one isolate. Mutations in ndh appear to be an additional molecular mechanism for isoniazid resistance in M. tuberculosis. PMID:11408244

  14. Evidence of Clonal Expansion in the Genome of a Multidrug-Resistant Mycobacterium tuberculosis Clinical Isolate from Peru

    PubMed Central

    Galarza, M.; Tarazona, D.; Borda, V.; Agapito, J. C.

    2014-01-01

    We report the genome sequence of Mycobacterium tuberculosis INS-MDR from Peru, a multidrug-resistant tuberculosis (MDR-TB) and Latin American-Mediterranean (LAM) lineage strain. Our analysis showed mutations related to drug resistance in the rpoB (D516V), katG (S315T), kasA (G269S), and pncA (Q10R) genes. Our evidence suggests that INS-MDR may be a clonal expansion related to the African strain KZN 1435. PMID:24578270

  15. IL12RB2 Gene Is Associated with the Age of Type 1 Diabetes Onset in Croatian Family Trios

    PubMed Central

    Pehlić, Marina; Vrkić, Dina; Škrabić, Veselin; Jerončić, Ana; Stipančić, Gordana; Urojić, Anita Špehar; Marjanac, Igor; Jakšić, Jasminka; Kačić, Zrinka; Boraska, Vesna; Zemunik, Tatijana

    2012-01-01

    Background Common complex diseases are influenced by both genetic and environmental factors. Many genetic factors overlap between various autoimmune diseases. The aim of the present study is to determine whether four genetic variants known to be risk variants for several autoimmune diseases could be associated with an increased susceptibility to type 1 diabetes mellitus. Methods and Findings We genotyped four genetic variants (rs2358817, rs1049550, rs6679356, rs9865818) within VTCN1, ANXA11, IL12RB2 and LPP genes respectively, in 265 T1DM family trios in Croatian population. We did not detect association of these polymorphisms with T1DM. However, quantitative transmission disequilibrium test (QTDT, orthogonal model) revealed a significant association between the age of onset of T1DM and IL12RB2 rs6679356 variant. An earlier onset of T1DM was associated with the rs6679356 minor dominant allele C (p = 0.005). The association remained significant even after the Bonferroni correction for multiple testing and permutation. Conclusions Variants originally associated with juvenile idiopathic arthritis (VTCN1 gene), sarcoidosis (ANXA11 gene), primary biliary cirrhosis (IL12RB2 gene) and celiac disease (LPP gene) were not associated with type 1 diabetes in our dataset. Nevertheless, association of IL12RB2 rs6679356 polymorphism with the age of T1DM onset suggests that this gene plays a role in defining the time of disease onset. PMID:23152861

  16. Heights integrated model as instrument for simulation of hydrodynamic, radiation transport, and heat conduction phenomena of laser-produced plasma in EUV applications.

    SciTech Connect

    Sizyuk, V.; Hassanein, A.; Morozov, V.; Sizyuk, T.; Mathematics and Computer Science

    2007-01-16

    The HEIGHTS integrated model has been developed as an instrument for simulation and optimization of laser-produced plasma (LPP) sources relevant to extreme ultraviolet (EUV) lithography. The model combines three general parts: hydrodynamics, radiation transport, and heat conduction. The first part employs a total variation diminishing scheme in the Lax-Friedrich formulation (TVD-LF); the second part, a Monte Carlo model; and the third part, implicit schemes with sparse matrix technology. All model parts consider physical processes in three-dimensional geometry. The influence of a generated magnetic field on laser plasma behavior was estimated, and it was found that this effect could be neglected for laser intensities relevant to EUV (up to {approx}10{sup 12} W/cm{sup 2}). All applied schemes were tested on analytical problems separately. Benchmark modeling of the full EUV source problem with a planar tin target showed good correspondence with experimental and theoretical data. Preliminary results are presented for tin droplet- and planar-target LPP devices. The influence of three-dimensional effects on EUV properties of source is discussed.

  17. Improved categorization of subtle facial expressions modulates Late Positive Potential.

    PubMed

    Pollux, P M J

    2016-05-13

    Biases in facial expression recognition can be reduced successfully using feedback-based training tasks. Here we investigate with event-related potentials (ERPs) at which stages of stimulus processing emotion-related modulations are influenced by training. Categorization of subtle facial expressions (morphed from neutral to happy, sad or surprise) was trained with correct-response feedback on each trial. ERPs were recorded before and after training while participants categorized facial expressions without response feedback. Behavioral data demonstrated large improvements in categorization of subtle facial expression which transferred to new face models not used during training. ERPs were modulated by training from 450 ms post-stimulus onward, characterized by a more gradual increase in P3b/Late Positive Potential (LPP) amplitude as expression intensity increased. This effect was indistinguishable for faces used for training and for new faces. It was proposed that training elicited a more fine-grained analysis of facial information for all subtle expressions, resulting in improved recognition and enhanced emotional motivational salience (reflected in P3b/LPP amplitude) of faces previously categorized as expressing no emotion. PMID:26912280

  18. Activation of the Rcs Signal Transduction System Is Responsible for the Thermosensitive Growth Defect of an Escherichia coli Mutant Lacking Phosphatidylglycerol and Cardiolipin

    PubMed Central

    Shiba, Yasuhiro; Yokoyama, Yasuko; Aono, Yoshiko; Kiuchi, Takashi; Kusaka, Jin; Matsumoto, Kouji; Hara, Hiroshi

    2004-01-01

    The lethal effect of an Escherichia coli pgsA null mutation, which causes a complete lack of the major acidic phospholipids, phosphatidylglycerol and cardiolipin, is alleviated by a lack of the major outer membrane lipoprotein encoded by the lpp gene, but an lpp pgsA strain shows a thermosensitive growth defect. Using transposon mutagenesis, we found that this thermosensitivity was suppressed by disruption of the rcsC, rcsF, and yojN genes, which code for a sensor kinase, accessory positive factor, and phosphotransmitter, respectively, of the Rcs phosphorelay signal transduction system initially identified as regulating the capsular polysaccharide synthesis (cps) genes. Disruption of the rcsB gene coding for the response regulator of the system also suppressed the thermosensitivity, whereas disruption of cpsE did not. By monitoring the expression of a cpsB′-lac fusion, we showed that the Rcs system is activated in the pgsA mutant and is reverted to a wild-type level by the rcs mutations. These results indicate that envelope stress due to an acidic phospholipid deficiency activates the Rcs phosphorelay system and thereby causes the thermosensitive growth defect independent of the activation of capsule synthesis. PMID:15375134

  19. Computer-mediated communication preferences predict biobehavioral measures of social-emotional functioning.

    PubMed

    Babkirk, Sarah; Luehring-Jones, Peter; Dennis-Tiwary, Tracy A

    2016-12-01

    The use of computer-mediated communication (CMC) as a form of social interaction has become increasingly prevalent, yet few studies examine individual differences that may shed light on implications of CMC for adjustment. The current study examined neurocognitive individual differences associated with preferences to use technology in relation to social-emotional outcomes. In Study 1 (N = 91), a self-report measure, the Social Media Communication Questionnaire (SMCQ), was evaluated as an assessment of preferences for communicating positive and negative emotions on a scale ranging from purely via CMC to purely face-to-face. In Study 2, SMCQ preferences were examined in relation to event-related potentials (ERPs) associated with early emotional attention capture and reactivity (the frontal N1) and later sustained emotional processing and regulation (the late positive potential (LPP)). Electroencephalography (EEG) was recorded while 22 participants passively viewed emotional and neutral pictures and completed an emotion regulation task with instructions to increase, decrease, or maintain their emotional responses. A greater preference for CMC was associated with reduced size of and satisfaction with social support, greater early (N1) attention capture by emotional stimuli, and reduced LPP amplitudes to unpleasant stimuli in the increase emotion regulatory task. These findings are discussed in the context of possible emotion- and social-regulatory functions of CMC.

  20. Different timing features in brain processing of core and moral disgust pictures: an event-related potentials study.

    PubMed

    Zhang, Xiangyi; Guo, Qi; Zhang, Youxue; Lou, Liandi; Ding, Daoqun

    2015-01-01

    Disgust, an emotion motivating withdrawal from offensive stimuli, protects us from the risk of biological pathogens and sociomoral violations. Homogeneity of its two types, namely, core and moral disgust has been under intensive debate. To examine the dynamic relationship between them, we recorded event-related potentials (ERPs) for core disgust, moral disgust and neutral pictures while participants performed a modified oddball task. ERP analysis revealed that N1 and P2 amplitudes were largest for the core disgust pictures, indicating automatic processing of the core disgust-evoking pictures. N2 amplitudes were higher for pictures evoking moral disgust relative to core disgust and neutral pictures, reflecting a violation of social norms. The core disgust pictures elicited larger P3 and late positive potential (LPP) amplitudes in comparison with the moral disgust pictures which, in turn, elicited larger P3 and LPP amplitudes when compared to the neutral pictures. Taken together, these findings indicated that core and moral disgust pictures elicited different neural activities at various stages of information processing, which provided supporting evidence for the heterogeneity of disgust.

  1. Snake pictures draw more early attention than spider pictures in non-phobic women: evidence from event-related brain potentials.

    PubMed

    Van Strien, J W; Eijlers, R; Franken, I H A; Huijding, J

    2014-02-01

    Snakes were probably the first predators of mammals and may have been important agents of evolutionary changes in the primate visual system allowing rapid visual detection of fearful stimuli (Isbell, 2006). By means of early and late attention-related brain potentials, we examined the hypothesis that more early visual attention is automatically allocated to snakes than to spiders. To measure the early posterior negativity (EPN), 24 healthy, non-phobic women watched the random rapid serial presentation of 600 snake pictures, 600 spider pictures, and 600 bird pictures (three pictures per second). To measure the late positive potential (LPP), they also watched similar pictures (30 pictures per stimulus category) in a non-speeded presentation. The EPN amplitude was largest for snake pictures, intermediate for spider pictures and smallest for bird pictures. The LPP was significantly larger for both snake and spider pictures when compared to bird pictures. Interestingly, spider fear (as measured by a questionnaire) was associated with EPN amplitude for spider pictures, whereas snake fear was not associated with EPN amplitude for snake pictures. The results suggest that ancestral priorities modulate the early capture of visual attention and that early attention to snakes is more innate and independent of reported fear.

  2. Description-based reappraisal regulate the emotion induced by erotic and neutral images in a Chinese population

    PubMed Central

    Peng, Jiaxin; Qu, Chen; Gu, Ruolei; Luo, Yue-Jia

    2013-01-01

    Previous emotion-regulation research has shown that the late positive potential (LPP) is sensitive to the down-regulation of emotion; however, whether LPP is also sensitive to the up-regulation of emotion remains unclear. The present study examined the description-based reappraisal effects on the up-regulation of positive emotions induced by erotic and neutral images in a Chinese population. Self-reported ratings and event-related potential (ERP) were recorded when subjects viewed pleasant and neutral images, which were shown after either a neutral or positive description. Self-reported results showed that images following positive descriptions were rated as more pleasant compared to images following neutral descriptions. ERP results revealed that the P2, P3, and slow wave (SW) components were larger for erotic pictures than for neutral pictures, while the positive description condition yielded attenuated erotic image-induced P2, P3 and SW and increased SW induced by neutral images. The results demonstrated that description-based reappraisal, as a method of reappraisal, significantly modulates the emotional experience and ERP responses to erotic and neutral images. PMID:23335894

  3. The temporal dynamics of reversal learning: P3 amplitude predicts valence-specific behavioral adjustment.

    PubMed

    Donaldson, Kayla R; Ait Oumeziane, Belel; Hélie, Sebastien; Foti, Dan

    2016-07-01

    Adapting behavior to dynamic stimulus-reward contingences is a core feature of reversal learning and a capacity thought to be critical to socio-emotional behavior. Impairment in reversal learning has been linked to multiple psychiatric outcomes, including depression, Parkinson's disorder, and substance abuse. A recent influential study introduced an innovative laboratory reversal-learning paradigm capable of disentangling the roles of feedback valence and expectancy. Here, we sought to use this paradigm in order to examine the time-course of reward and punishment learning using event-related potentials among a large, representative sample (N=101). Three distinct phases of processing were examined: initial feedback evaluation (reward positivity, or RewP), allocation of attention (P3), and sustained processing (late positive potential, or LPP). Results indicate a differential pattern of valence and expectancy across these processing stages: the RewP was uniquely related to valence (i.e., positive vs. negative feedback), the P3 was uniquely associated with expectancy (i.e., unexpected vs. expected feedback), and the LPP was sensitive to both valence and expectancy (i.e., main effects of each, but no interaction). The link between ERP amplitudes and behavioral performance was strongest for the P3, and this association was valence-specific. Overall, these findings highlight the potential utility of the P3 as a neural marker for feedback processing in reversal-based learning and establish a foundation for future research in clinical populations.

  4. Heritability of the neural response to emotional pictures: evidence from ERPs in an adult twin sample

    PubMed Central

    Venables, Noah C.; Proudfit, Greg Hajcak; Patrick, Christopher J.

    2015-01-01

    Affect-modulated event-related potentials (ERPs) are increasingly used to study psychopathology and individual differences in emotion processing. Many have suggested that variation in these neural responses reflects genetically mediated risk. However, to date, no studies have demonstrated genetic contributions to affect-modulated ERPs. The present study therefore sought to examine the heritability of a range of ERPs elicited during affective picture viewing. One hundred and thirty monozygotic and 124 dizygotic twin pairs passively viewed 30 pleasant, 30 neutral and 30 unpleasant images for 6 s each. The early posterior negativity was scored for each subject; in addition, the P300/late positive potential (LPP) was scored in multiple time windows and sites. Results indicate that the centro-parietal P300 (occurring between 300 and 600 ms) is subject to substantial genetic contributions. Furthermore, variance in the P300 elicited by affective stimuli was moderately heritable even after controlling for the P300 elicited by neutral stimuli. Later and more frontal activation (i.e. between 1000 and 3000 ms) also showed evidence of heritablity. Early parietal, and perhaps later frontal portions of the P300/LPP complex, may therefore represent promising neurobehavioral markers of genetically influenced processing of emotional information. PMID:24795435

  5. Additive effects of affective arousal and top-down attention on the event-related brain responses to human bodies.

    PubMed

    Hietanen, Jari K; Kirjavainen, Ilkka; Nummenmaa, Lauri

    2014-12-01

    The early visual event-related 'N170 response' is sensitive to human body configuration and it is enhanced to nude versus clothed bodies. We tested whether the N170 response as well as later EPN and P3/LPP responses to nude bodies reflect the effect of increased arousal elicited by these stimuli, or top-down allocation of object-based attention to the nude bodies. Participants saw pictures of clothed and nude bodies and faces. In each block, participants were asked to direct their attention towards stimuli from a specified target category while ignoring others. Object-based attention did not modulate the N170 amplitudes towards attended stimuli; instead N170 response was larger to nude bodies compared to stimuli from other categories. Top-down attention and affective arousal had additive effects on the EPN and P3/LPP responses reflecting later processing stages. We conclude that nude human bodies have a privileged status in the visual processing system due to the affective arousal they trigger. PMID:25224182

  6. The temporal dynamics of reversal learning: P3 amplitude predicts valence-specific behavioral adjustment.

    PubMed

    Donaldson, Kayla R; Ait Oumeziane, Belel; Hélie, Sebastien; Foti, Dan

    2016-07-01

    Adapting behavior to dynamic stimulus-reward contingences is a core feature of reversal learning and a capacity thought to be critical to socio-emotional behavior. Impairment in reversal learning has been linked to multiple psychiatric outcomes, including depression, Parkinson's disorder, and substance abuse. A recent influential study introduced an innovative laboratory reversal-learning paradigm capable of disentangling the roles of feedback valence and expectancy. Here, we sought to use this paradigm in order to examine the time-course of reward and punishment learning using event-related potentials among a large, representative sample (N=101). Three distinct phases of processing were examined: initial feedback evaluation (reward positivity, or RewP), allocation of attention (P3), and sustained processing (late positive potential, or LPP). Results indicate a differential pattern of valence and expectancy across these processing stages: the RewP was uniquely related to valence (i.e., positive vs. negative feedback), the P3 was uniquely associated with expectancy (i.e., unexpected vs. expected feedback), and the LPP was sensitive to both valence and expectancy (i.e., main effects of each, but no interaction). The link between ERP amplitudes and behavioral performance was strongest for the P3, and this association was valence-specific. Overall, these findings highlight the potential utility of the P3 as a neural marker for feedback processing in reversal-based learning and establish a foundation for future research in clinical populations. PMID:27059320

  7. Spatiotemporal neural dynamics of moral judgment: A high-density ERP study

    PubMed Central

    Yoder, Keith J.

    2014-01-01

    Morality is a pervasive aspect of human nature across all cultures, and neuroscience investigations are necessary for identifying what computational mechanisms underpin moral cognition. The current study used high-density ERPs to examine how moral evaluations are mediated by automatic and controlled processes as well as how quickly information and causal-intentional representations can be extracted when viewing morally laden behavior. The study also explored the extent to which individual dispositions in affective and cognitive empathy as well as justice sensitivity influence the encoding of moral valence when healthy participants make moral judgments about prosocial (interpersonal assistance) and antisocial (interpersonal harm) actions. Moral judgment differences were reflected in differential amplitudes for components associated with cognitive appraisal (LPP) as well as early components associated with emotional salience (N1 and N2). Moreover, source estimation was performed to indicate potential neural generators. A posterior-to-anterior shift was observed, with current density peaks first in right inferior parietal cortex (at the temporoparietal junction), then later in medial prefrontal cortex. Cognitive empathy scores predicted behavioral ratings of blame as well as differential amplitudes in LPP and component activity at posterior sites. Overall, this study offers important insights into the temporal unfolding of moral evaluations, including when in time individual differences in empathy influence neural encoding of moral valence. PMID:24905282

  8. Enhancements of extreme ultraviolet emission using prepulsed Sn laser-produced plasmas for advanced lithography applications

    SciTech Connect

    Freeman, J. R.; Harilal, S. S.; Hassanein, A.

    2011-10-15

    Laser-produced plasmas (LPP) from Sn targets are seriously considered to be the light source for extreme ultraviolet (EUV) next generation lithography, and optimization of such a source will lead to improved efficiency and reduced cost of ownership of the entire lithography system. We investigated the role of reheating a prepulsed plasma and its effect on EUV conversion efficiency (CE). A 6 ns, 1.06 {mu}m Nd:yttrium aluminum garnet laser was used to generate the initial plasma that was then reheated by a 40 ns, 10.6 {mu}m CO{sub 2} laser to generate enhanced EUV emission from a planar Sn target. The effects of prepulsed laser intensity and delay timings between the prepulsed and the pumping pulse were investigated to find the optimal pre-plasma conditions before the pumping pulse. The initial optimization of these parameters resulted in 25% increase in CE from the tin LPP. The cause of increased EUV emission was identified from EUV emission spectra and ion signal data.

  9. Persistent STAT5 activation in myeloid neoplasms recruits p53 into gene regulation.

    PubMed

    Girardot, M; Pecquet, C; Chachoua, I; Van Hees, J; Guibert, S; Ferrant, A; Knoops, L; Baxter, E J; Beer, P A; Giraudier, S; Moriggl, R; Vainchenker, W; Green, A R; Constantinescu, S N

    2015-03-01

    STAT (Signal Transducer and Activator of Transcription) transcription factors are constitutively activated in most hematopoietic cancers. We previously identified a target gene, LPP/miR-28 (LIM domain containing preferred translocation partner in lipoma), induced by constitutive activation of STAT5, but not by transient cytokine-activated STAT5. miR-28 exerts negative effects on thrombopoietin receptor signaling and platelet formation. Here, we demonstrate that, in transformed hematopoietic cells, STAT5 and p53 must be synergistically bound to chromatin for induction of LPP/miR-28 transcription. Genome-wide association studies show that both STAT5 and p53 are co-localized on the chromatin at 463 genomic positions in proximal promoters. Chromatin binding of p53 is dependent on persistent STAT5 activation at these proximal promoters. The transcriptional activity of selected promoters bound by STAT5 and p53 was significantly changed upon STAT5 or p53 inhibition. Abnormal expression of several STAT5-p53 target genes (LEP, ATP5J, GTF2A2, VEGFC, NPY1R and NPY5R) is frequently detected in platelets of myeloproliferative neoplasm (MPN) patients, but not in platelets from healthy controls. In conclusion, persistently active STAT5 can recruit normal p53, like in the case of MPN cells, but also p53 mutants, such as p53 M133K in human erythroleukemia cells, leading to pathologic gene expression that differs from canonical STAT5 or p53 transcriptional programs.

  10. Social provocation modulates decision making and feedback processing: Examining the trajectory of development in adolescent participants.

    PubMed

    Pincham, Hannah L; Wu, Claire; Killikelly, Clare; Vuillier, Laura; Fearon, R M Pasco

    2015-10-01

    Increasingly, research is turning to the ways in which social context impacts decision making and feedback processing in adolescents. The current study recorded electroencephalography to examine the trajectory of development across adolescence, with a focus on how social context impacts cognition and behaviour. To that end, younger (10-12 years) and older (14-16 years) adolescents played a modified Taylor Aggression Paradigm against two virtual opponents: a low-provoker and a high-provoker. During the task's decision phase (where participants select punishment for their opponent), we examined two event-related potentials: the N2 and the late positive potential (LPP). During the outcome phase (where participants experience win or loss feedback), we measured the feedback related negativity (FRN). Although N2 amplitudes did not vary with provocation, LPP amplitudes were enhanced under high provocation for the younger group, suggesting that emotional reactivity during the decision phase was heightened for early adolescents. During the outcome phase, the FRN was reduced following win outcomes under high provocation for both groups, suggesting that a highly provocative social opponent may influence the reward response. Collectively, the data argue that social context is an important factor modulating neural responses in adolescent behavioural and brain development.

  11. Perceived communicative context and emotional content amplify visual word processing in the fusiform gyrus.

    PubMed

    Schindler, Sebastian; Wegrzyn, Martin; Steppacher, Inga; Kissler, Johanna

    2015-04-15

    The personal significance of a language statement depends on its communicative context. However, this is rarely taken into account in neuroscience studies. Here, we investigate how the implied source of single word statements alters their cortical processing. Participants' brain event-related potentials were recorded in response to identical word streams consisting of positive, negative, and neutral trait adjectives stated to either represent personal trait feedback from a human or to be randomly generated by a computer. Results showed a strong impact of perceived sender. Regardless of content, the notion of receiving feedback from a human enhanced all components, starting with the P2 and encompassing early posterior negativity (EPN), P3, and the late positive potential (LPP). Moreover, negative feedback by the "human sender" elicited a larger EPN, whereas positive feedback generally induced a larger LPP. Source estimations revealed differences between "senders" in visual areas, particularly the bilateral fusiform gyri. Likewise, emotional content enhanced activity in these areas. These results specify how even implied sender identity changes the processing of single words in seemingly realistic communicative settings, amplifying their processing in the visual brain. This suggests that the concept of motivated attention extends from stimulus significance to simultaneous appraisal of contextual relevance. Finally, consistent with distinct stages of emotional processing, at least in contexts perceived as social, humans are initially alerted to negative content, but later process what is perceived as positive feedback more intensely. PMID:25878274

  12. Emotional processing and psychopathic traits in male college students: An event-related potential study.

    PubMed

    Medina, Amy L; Kirilko, Elvira; Grose-Fifer, Jillian

    2016-08-01

    Emotional processing deficits are often considered a hallmark of psychopathy. However, there are relatively few studies that have investigated how the late positive potential (LPP) elicited by both positive and negative emotional stimuli is modulated by psychopathic traits, especially in undergraduates. Attentional deficits have also been posited to be associated with emotional blunting in psychopathy, consequently, results from previous studies may have been influenced by task demands. Therefore, we investigated the relationship between the neural correlates of emotional processing and psychopathic traits by measuring event-related potentials (ERPs) during a task with a relatively low cognitive load. A group of male undergraduates were classified as having either high or low levels of psychopathic traits according to their total scores on the Psychopathic Personality Inventory - Revised (PPI-R). A subgroup of these participants then passively viewed complex emotional and neutral images from the International Affective Picture System (IAPS) while their EEGs were recorded. As hypothesized, in general the late LPP elicited by emotional pictures was found to be significantly reduced for participants with high Total PPI-R scores relative to those with low scores, especially for pictures that were rated as less emotionally arousing. Our data suggest that male undergraduates with high, but subclinical levels of psychopathic traits did not maintain continued higher-order processing of affective information, especially when it was perceived to be less arousing in nature. PMID:27302151

  13. Kr photoionized plasma induced by intense extreme ultraviolet pulses

    NASA Astrophysics Data System (ADS)

    Bartnik, A.; Wachulak, P.; Fiedorowicz, H.; Skrzeczanowski, W.

    2016-04-01

    Irradiation of any gas with an intense EUV (extreme ultraviolet) radiation beam can result in creation of photoionized plasmas. The parameters of such plasmas can be significantly different when compared with those of the laser produced plasmas (LPP) or discharge plasmas. In this work, the photoionized plasmas were created in a krypton gas irradiated using an LPP EUV source operating at a 10 Hz repetition rate. The Kr gas was injected into the vacuum chamber synchronously with the EUV radiation pulses. The EUV beam was focused onto a Kr gas stream using an axisymmetrical ellipsoidal collector. The resulting low temperature Kr plasmas emitted electromagnetic radiation in the wide spectral range. The emission spectra were measured either in the EUV or an optical range. The EUV spectrum was dominated by emission lines originating from Kr III and Kr IV ions, and the UV/VIS spectra were composed from Kr II and Kr I lines. The spectral lines recorded in EUV, UV, and VIS ranges were used for the construction of Boltzmann plots to be used for the estimation of the electron temperature. It was shown that for the lowest Kr III and Kr IV levels, the local thermodynamic equilibrium (LTE) conditions were not fulfilled. The electron temperature was thus estimated based on Kr II and Kr I species where the partial LTE conditions could be expected.

  14. Behavior of Dental/Implant Alloys in Commercial Mouthwash Solution Studied by Electrochemical Techniques

    NASA Astrophysics Data System (ADS)

    Mareci, Daniel; Strugaru, Sorin Iacob; Iacoban, Sorin; Bolat, Georgiana; Munteanu, Corneliu

    2013-03-01

    This study investigates the electrochemical behavior of the various dental materials: Paliag (Ag-Pd based), Wiron 99 (Ni-Cr based), Cp-Ti (commercial pure titanium), and experimental Ti12Mo5Ta alloy in commercial mouthwash solution with 500 ppm F- (Oral B®) and compares it with the behavior of the same dental materials in artificial saliva. Linear potentiodynamic polarization (LPP) and electrochemical impedance spectroscopy (EIS) are the electrochemical procedures of investigation. The passivation of all dental samples in artificial saliva and mouthwash solution occurred spontaneously at open circuit potential. The corrosion current density of all tested dental materials in mouthwash solution were low (1-2 μA/cm2). The results suggest a non-predominant fluoride effect on the passive layer formed on all samples at open circuit potential. No passivation could be established with Paliag alloy when polarized in mouthwash solution. The EIS results confirm that all dental sample exhibit passivity in mouthwash solution at open circuit potential (polarization resistance was around 5 × 105 Ω cm2). For Paliag alloy after LPP in mouthwash solution the protectiveness passive layer was no more present. The corrosion resistances of four dental materials in mouthwash solution are in the following order: Ti12Mo5Ta > Cp-Ti > Wiron 99 > Paliag.

  15. Emotion-modulated startle in psychopathy: Clarifying familiar effects

    PubMed Central

    Baskin-Sommers, Arielle R.; Curtin, John J.; Newman, Joseph P.

    2012-01-01

    The behavior of psychopathic individuals is thought to reflect a core fear deficit that prevents these individuals from appreciating the consequences of their choices and actions. However, growing evidence suggests that psychopathy-related emotion deficits are moderated by attention and, thus, may not reflect a reduced capacity for emotion responding. The present study attempts to reconcile this attention perspective with one of the most cited findings in psychopathy, which reports emotion-modulated startle deficits among psychopathic individuals during picture viewing. In this study, we evaluate the potential effects of a putative attention bottleneck on the emotion processing of psychopathic offenders during picture viewing by manipulating picture familiarity and examining emotion-modulated startle and late positive potential (LPP). As predicted, psychopathic individuals displayed the classic deficit in emotion-modulated startle during novel pictures, but they showed no deficit in emotion-modulated startle during familiar pictures. Conversely, results for LPP responses revealed psychopathy-related differences during familiar pictures and no psychopathy-related differences during novel pictures. Important differences related to the two Factors of psychopathy are also discussed. Overall, the results of this study not only highlight the differential importance of perceptual load on emotion processing in psychopathy, but also raise interesting questions about the varied effects of attention on psychopathy-related emotion deficits. PMID:23356218

  16. Neurophysiological evidence for remediation of reward processing deficits in chronic pain and opioid misuse following treatment with Mindfulness-Oriented Recovery Enhancement: exploratory ERP findings from a pilot RCT.

    PubMed

    Garland, Eric L; Froeliger, Brett; Howard, Matthew O

    2015-04-01

    Dysregulated processing of natural rewards may be a central pathogenic process in the etiology and maintenance of prescription opioid misuse and addiction among chronic pain patients. This study examined whether a Mindfulness-Oriented Recovery Enhancement (MORE) intervention could augment natural reward processing through training in savoring as indicated by event-related brain potentials (ERPs). Participants were chronic pain patients at risk for opioid misuse who were randomized to 8 weeks of MORE (n = 11) or a support group control condition (n = 18). ERPs to images representing naturally rewarding stimuli (e.g., beautiful landscapes, intimate couples) and neutral images were measured before and after 8 weeks of treatment. Analyses focused on the late positive potential (LPP)--an ERP response in the 400-1,000 ms time window thought to index allocation of attention to emotional information. Treatment with MORE was associated with significant increases in LPP response to natural reward stimuli relative to neutral stimuli which were correlated with enhanced positive affective cue-responses and reductions in opioid craving from pre- to post-treatment. Findings suggest that cognitive training regimens centered on strengthening attention to natural rewards may remediate reward processing deficits underpinning addictive behavior.

  17. Ameliorative effects of Bacopa monniera on lead-induced oxidative stress in different regions of rat brain.

    PubMed

    Velaga, Manoj Kumar; Basuri, Charan Kumar; Robinson Taylor, Kendra S; Yallapragada, Prabhakara Rao; Rajanna, Sharada; Rajanna, Bettaiya

    2014-07-01

    Bacopa monniera is a rejuvenating herb for brain cells enhancing learning and cognitive ability. In the present investigation, the ameliorative effects of Bacopa monniera were examined against lead-induced oxidative stress in different regions of rat brain. Male rats were divided into five groups: control (1000 ppm sodium acetate) and exposed (1000 ppm lead acetate) for 4 weeks; DMSA (Meso-2,3-Dimercaptosuccinic acid)-treated (90 mg/kg body weight/day); Bacopa monniera-treated (BM) (10 mg/kg body weight/day) and a combination of BM + DMSA for seven consecutive days after 4 weeks of lead exposure. After treatment, the whole brain was isolated by sacrificing rats and four regions were separated namely cerebellum, hippocampus, frontal cortex and brain stem. Results indicated a significant (p < 0.05) increase in reactive oxygen species (ROS), lipid peroxidation products (LPP) and total protein carbonyl content (TPCC) in association with tissue metal content in all the four regions of brain for exposed group compared with their respective controls. However, the lead-induced ROS, LPP, TPCC and tissue metal content were lowered on treatment with Bacopa monniera, almost reaching the control group values in all the above brain regions compared to DMSA and a combination therapy. Results suggest that Bacopa monniera can mitigate the lead induced-oxidative stress tissue specifically by pharmacologic interventions which encompass both chelation as well as antioxidant functions.

  18. Specific interaction between Mycobacterium tuberculosis lipoprotein-derived peptides and target cells inhibits mycobacterial entry in vitro

    PubMed Central

    Ocampo, Marisol; Curtidor, Hernando; Vanegas, Magnolia; Patarroyo, Manuel Alfonso; Patarroyo, Manuel Elkin

    2014-01-01

    Summary Tuberculosis (TB) continues being one of the diseases having the greatest mortality rates around the world, 8.7 million cases having been reported in 2011. An efficient vaccine against TB having a great impact on public health is an urgent need. Usually, selecting antigens for vaccines has been based on proteins having immunogenic properties for patients suffering TB and having had promising results in mice and non-human primates. Our approach has been based on a functional approach involving the pathogen–host interaction in the search for antigens to be included in designing an efficient, minimal, subunit-based anti-tuberculosis vaccine. This means that Mycobacterium tuberculosis has mainly been involved in studies and that lipoproteins represent an important kind of protein on the cell envelope which can also contribute towards this pathogen's virulence. This study has assessed the expression of four lipoproteins from M. tuberculosis H37Rv, i.e. Rv1411c (LprG), Rv1911c (LppC), Rv2270 (LppN) and Rv3763 (LpqH), and the possible biological activity of peptides derived from these. Five peptides were found for these proteins which had high specific binding to both alveolar A549 epithelial cells and U937 monocyte-derived macrophages which were able to significantly inhibit mycobacterial entry to these cells in vitro. PMID:25041568

  19. Steatosis-induced proteins adducts with lipid peroxidation products and nuclear electrophilic stress in hepatocytes

    PubMed Central

    Anavi, Sarit; Ni, Zhixu; Tirosh, Oren; Fedorova, Maria

    2014-01-01

    Accumulating evidence suggests that fatty livers are particularly more susceptible to several pathological conditions, including hepatic inflammation, cirrhosis and liver cancer. However the exact mechanism of such susceptibility is still largely obscure. The current study aimed to elucidate the effect of hepatocytes lipid accumulation on the nuclear electrophilic stress. Accumulation of intracellular lipids was significantly increased in HepG2 cells incubated with fatty acid (FA) complex (1 mM, 2:1 oleic and palmitic acids). In FA-treated cells, lipid droplets were localized around the nucleus and seemed to induce mechanical force, leading to the disruption of the nucleus morphology. Level of reactive oxygen species (ROS) was significantly increased in FA-loaded cells and was further augmented by treatment with moderate stressor (CoCl2). Increased ROS resulted in formation of reactive carbonyls (aldehydes and ketones, derived from lipid peroxidation) with a strong perinuclear accumulation. Mass-spectroscopy analysis indicated that lipid accumulation per-se can results in modification of nuclear protein by reactive lipid peroxidation products (oxoLPP). 235 Modified proteins involved in transcription regulation, splicing, protein synthesis and degradation, DNA repair and lipid metabolism were identified uniquely in FA-treated cells. These findings suggest that steatosis can affect nuclear redox state, and induce modifications of nuclear proteins by reactive oxoLPP accumulated in the perinuclear space upon FA-treatment. PMID:25560244

  20. Development of an autofluorescent whole-cell biocatalyst by displaying dual functional moieties on Escherichia coli cell surfaces and construction of a coculture with organophosphate-mineralizing activity .

    PubMed

    Yang, Chao; Zhu, Yaran; Yang, Jijian; Liu, Zheng; Qiao, Chuanling; Mulchandani, Ashok; Chen, Wilfred

    2008-12-01

    Surface display of the active proteins on living cells has enormous potential in the degradation of numerous toxic compounds. Here, we report the codisplay of organophosphorus hydrolase (OPH) and enhanced green fluorescent protein (GFP) on the cell surface of Escherichia coli by use of the truncated ice nucleation protein (INPNC) and Lpp-OmpA fusion systems. The surface localization of both INPNC-OPH and Lpp-OmpA-GFP was demonstrated by Western blot analysis, immunofluorescence microscopy, and a protease accessibility experiment. Anchorage of GFP and OPH on the outer membrane neither inhibits cell growth nor affects cell viability, as shown by growth kinetics of cells and stability of resting cultures. The engineered E. coli can be applied in the form of a whole-cell biocatalyst and can be tracked by fluorescence during bioremediation. This strategy of codisplay should open a new dimension for the display of multiple functional moieties on the surface of a bacterial cell. Furthermore, a coculture comprised of the engineered E. coli and a natural p-nitrophenol (PNP) degrader, Ochrobactrum sp. strain LL-1, was assembled for complete mineralization of organophosphates (OPs) with a PNP substitution. The coculture degraded OPs as well as PNP rapidly. Therefore, the coculture with autofluorescent and mineralizing activities can potentially be applied for bioremediation of OP-contaminated sites. PMID:18952884

  1. Effects of emotional intensity under perceptual load: An event-related potentials (ERPs) study.

    PubMed

    Müller-Bardorff, Miriam; Schulz, Claudia; Peterburs, Jutta; Bruchmann, Maximilian; Mothes-Lasch, Martin; Miltner, Wolfgang; Straube, Thomas

    2016-05-01

    Effects of emotional intensity and valence on visual event-related potentials (ERPs) are still poorly understood, in particular in the context of limited attentional resources. In the present EEG study, we investigated the effect of emotional intensity of different emotional facial expressions on P1, N170, early posterior negativity (EPN) and late positive potential (LPP) while varying the amount of available attentional resources. A new stimulus set comprising 90 full color pictures of neutral, happy (low, high intensity), and angry (low, high intensity) expressions was developed. These facial expressions were presented centrally, superimposed by two horizontal bars, and participants engaged in a focal bars task. Availability of attentional resources was varied in two conditions by manipulating the difficulty of the focal bars task (low vs. high perceptual load). Our findings demonstrate intensity and valence effects of task-irrelevant facial expressions on early (N170) and intermediate processing stages (EPN). In addition, task-related effects of perceptual load evolved at intermediate processing stages and were full blown in the time window of LPP. In line with limited resource accounts, valence effects on N170 and EPN were reduced under high perceptual load. Interestingly, apart from this valence by load interaction no further interactions between stimulus and task-driven factors were obtained: Effects of emotional intensity were not modulated by the perceptual load of the focal bars task, indicating that emotional intensity was processed even though attentional resources were heavily restricted. PMID:26995785

  2. Different Timing Features in Brain Processing of Core and Moral Disgust Pictures: An Event-Related Potentials Study

    PubMed Central

    Zhang, Youxue; Lou, Liandi; Ding, Daoqun

    2015-01-01

    Disgust, an emotion motivating withdrawal from offensive stimuli, protects us from the risk of biological pathogens and sociomoral violations. Homogeneity of its two types, namely, core and moral disgust has been under intensive debate. To examine the dynamic relationship between them, we recorded event-related potentials (ERPs) for core disgust, moral disgust and neutral pictures while participants performed a modified oddball task. ERP analysis revealed that N1 and P2 amplitudes were largest for the core disgust pictures, indicating automatic processing of the core disgust-evoking pictures. N2 amplitudes were higher for pictures evoking moral disgust relative to core disgust and neutral pictures, reflecting a violation of social norms. The core disgust pictures elicited larger P3 and late positive potential (LPP) amplitudes in comparison with the moral disgust pictures which, in turn, elicited larger P3 and LPP amplitudes when compared to the neutral pictures. Taken together, these findings indicated that core and moral disgust pictures elicited different neural activities at various stages of information processing, which provided supporting evidence for the heterogeneity of disgust. PMID:26011635

  3. Trait rejection sensitivity is associated with vigilance and defensive response rather than detection of social rejection cues

    PubMed Central

    Kawamoto, Taishi; Nittono, Hiroshi; Ura, Mitsuhiro

    2015-01-01

    Prior studies suggest that psychological difficulties arise from higher trait Rejection Sensitivity (RS)—heightened vigilance and differential detection of social rejection cues and defensive response to. On the other hand, from an evolutionary perspective, rapid and efficient detection of social rejection cues can be considered beneficial. We conducted a survey and an electrophysiological experiment to reconcile this seeming contradiction. We compared the effects of RS and Rejection Detection Capability (RDC) on perceived interpersonal experiences (Study 1) and on neurocognitive processes in response to cues of social rejection (disgusted faces; Study 2). We found that RS and RDC were not significantly related, although RS was positively related to perceived social rejection experiences and RDC was positively related to perceived social inclusion experiences. Event-related brain potentials (ERPs) revealed that higher RS was related to cognitive avoidance (i.e., P1) and heightened motivated attention (i.e., late positive potential: LPP), but not to facial expression encoding (i.e., N170) toward disgusted faces. On the other hand, higher RDC was related to heightened N170 amplitude, but not to P1 and LPP amplitudes. These findings imply that sensitivity to rejection is apparently distinct from the ability to detect social rejection cues and instead reflects intense vigilance and defensive response to those cues. We discussed an alternative explanation of the relationship between RS and RDC from a signal detection perspective. PMID:26483750

  4. Neurophysiological Evidence for Remediation of Reward Processing Deficits in Chronic Pain and Opioid Misuse Following Treatment with Mindfulness-Oriented Recovery Enhancement: Exploratory ERP Findings from a Pilot RCT

    PubMed Central

    Garland, Eric L.; Froeliger, Brett; Howard, Matthew O.

    2014-01-01

    Dysregulated processing of natural rewards may be a central pathogenic process in the etiology and maintenance of prescription opioid misuse and addiction among chronic pain patients. This study examined whether a Mindfulness-Oriented Recovery Enhancement (MORE) intervention could enhance natural reward processing through training in savoring as indicated by event-related brain potentials (ERPs). Participants were chronic pain patients at risk for opioid misuse who were randomized to eight weeks of MORE (n=11) or a support group control condition (n=18). ERPs to images representing naturally rewarding stimuli (e.g., beautiful landscapes, intimate couples) and neutral images were measured before and after 8 weeks of treatment. Analyses focused on the late positive potential (LPP) - an ERP response in the 400 – 1000 ms time window thought to index allocation of attention to emotional information. Treatment with MORE was associated with significant increases in LPP response to natural reward stimuli relative to neutral stimuli which were correlated with enhanced positive affective cue-responses and reductions in opioid craving from pre- to post-treatment. Findings suggest that cognitive training regimens centered on strengthening attention to natural rewards may remediate reward processing deficits underpinning addictive behavior. PMID:25385024

  5. AB101. Therapeutic effect of low intensity pulsed ultrasound in stress urinary incontinence

    PubMed Central

    Yang, Bicheng; Lei, Hongen; Guan, Ruili; Li, Huixi; Xin, Zhongcheng

    2016-01-01

    Objective Stress urinary incontinence, a major type of urinary incontinence, increases with age and is often developed after partum injury. Low intensity pulsed ultrasound (LIPUS) has been investigated in the treatment of many diseases showing its ability of restoring soft tissue injury. We investigated the therapeutic effect of low intensity pulsed ultrasound in stress urinary incontinence. Methods Thirty-two Sprague Dawley rats in SUI group underwent vaginal distension (VD) and bilateral ovariectomy mimicking partum injury. Eight rats served as mock operation control. Eight rats each in SUI group was treated with low-dosage LESW (0.03 mJ/mm2), medium-dosage LESW (0.06 mJ/mm2), or high-dosage LESW (0.09 mJ/mm2). The rest eight rats served as none-treatment group. For functional study, leak point pressure test (LPP) was performed 2 weeks after the last LESW. Masson trichrome staining was performed to validate the pathological changes. Results The LPP was restored in medium-dosage LESW and high-dosage LESW groups, but not in low-dosage LESW group. More robust striated muscle regeneration was found in these two groups comparing with the none-treatment group. Conclusions LIPUS ameliorate the symptom of SUI via activating striated muscle regeneration.

  6. Spatiotemporal neural dynamics of moral judgment: a high-density ERP study.

    PubMed

    Yoder, Keith J; Decety, Jean

    2014-07-01

    Morality is a pervasive aspect of human nature across all cultures, and neuroscience investigations are necessary for identifying what computational mechanisms underpin moral cognition. The current study used high-density ERPs to examine how moral evaluations are mediated by automatic and controlled processes as well as how quickly information and causal-intentional representations can be extracted when viewing morally laden behavior. The study also explored the extent to which individual dispositions in affective and cognitive empathy as well as justice sensitivity influence the encoding of moral valence when healthy participants make moral judgments about prosocial (interpersonal assistance) and antisocial (interpersonal harm) actions. Moral judgment differences were reflected in differential amplitudes for components associated with cognitive appraisal (LPP) as well as early components associated with emotional salience (N1 and N2). Moreover, source estimation was performed to indicate potential neural generators. A posterior-to-anterior shift was observed, with current density peaks first in right inferior parietal cortex (at the temporoparietal junction), then later in medial prefrontal cortex. Cognitive empathy scores predicted behavioral ratings of blame as well as differential amplitudes in LPP and component activity at posterior sites. Overall, this study offers important insights into the temporal unfolding of moral evaluations, including when in time individual differences in empathy influence neural encoding of moral valence.

  7. HSCT Sector Combustor Evaluations for Demonstration Engine

    NASA Technical Reports Server (NTRS)

    Greenfield, Stuart; Heberling, Paul; Kastl, John; Matulaitis, John; Huff, Cynthia

    2004-01-01

    In LET Task 10, critical development issues of the HSCT lean-burn low emissions combustor were addressed with a range of engineering tools. Laser diagnostics and CFD analysis were applied to develop a clearer understanding of the fuel-air premixing process and premixed combustion. Subcomponent tests evaluated the emissions and operability performance of the fuel-air premixers. Sector combustor tests evaluated the performance of the integrated combustor system. A 3-cup sector was designed and procured for laser diagnostics studies at NASA Glenn. The results of these efforts supported the earlier selection of the Cyclone Swirler as the pilot stage premixer and the IMFH (Integrated Mixer Flame Holder) tube as the main stage premixer of the LPP combustor. In the combustor system preliminary design subtask, initial efforts to transform the sector combustor design into a practical subscale engine combustor met with significant challenges. Concerns about the durability of a stepped combustor dome and the need for a removable fuel injection system resulted in the invention and refinement of the MRA (Multistage Radial Axial) combustor system in 1994. The MRA combustor was selected for the HSR Phase II LPP subscale combustor testing in the CPC Program.

  8. Spectral investigations of photoionized plasmas induced in atomic and molecular gases using nanosecond extreme ultraviolet (EUV) pulses

    SciTech Connect

    Bartnik, A.; Fiedorowicz, H.; Wachulak, P.

    2014-07-15

    In this paper, results of spectral investigations of low temperature photoionized plasmas, created by irradiation of gases with intense pulses of extreme ultraviolet (EUV) radiation from a laser-produced plasma (LPP) source, are presented. The LPP source was based on a double-stream KrXe/He gas-puff target irradiated with 4 ns/0.8 J/10 Hz Nd:YAG laser pulses. The most intense emission from the source spanned a relatively narrow spectral region λ ≈ 10–12 nm; however, spectrally integrated intensity at longer wavelengths was also significant. The EUV beam was focused on a gas stream, injected into a vacuum chamber synchronously with the EUV pulses. Irradiation of gases resulted in formation of photoionized plasmas emitting radiation in the EUV range. Radiation spectra, measured for plasmas produced in various gases, are dominated by emission lines, originating from single charged ions. Significant differences in spectral intensities and distributions between plasmas created in neon and molecular gases were observed.

  9. Effects of emotional intensity under perceptual load: An event-related potentials (ERPs) study.

    PubMed

    Müller-Bardorff, Miriam; Schulz, Claudia; Peterburs, Jutta; Bruchmann, Maximilian; Mothes-Lasch, Martin; Miltner, Wolfgang; Straube, Thomas

    2016-05-01

    Effects of emotional intensity and valence on visual event-related potentials (ERPs) are still poorly understood, in particular in the context of limited attentional resources. In the present EEG study, we investigated the effect of emotional intensity of different emotional facial expressions on P1, N170, early posterior negativity (EPN) and late positive potential (LPP) while varying the amount of available attentional resources. A new stimulus set comprising 90 full color pictures of neutral, happy (low, high intensity), and angry (low, high intensity) expressions was developed. These facial expressions were presented centrally, superimposed by two horizontal bars, and participants engaged in a focal bars task. Availability of attentional resources was varied in two conditions by manipulating the difficulty of the focal bars task (low vs. high perceptual load). Our findings demonstrate intensity and valence effects of task-irrelevant facial expressions on early (N170) and intermediate processing stages (EPN). In addition, task-related effects of perceptual load evolved at intermediate processing stages and were full blown in the time window of LPP. In line with limited resource accounts, valence effects on N170 and EPN were reduced under high perceptual load. Interestingly, apart from this valence by load interaction no further interactions between stimulus and task-driven factors were obtained: Effects of emotional intensity were not modulated by the perceptual load of the focal bars task, indicating that emotional intensity was processed even though attentional resources were heavily restricted.

  10. Late positive potential to explicit sexual images associated with the number of sexual intercourse partners.

    PubMed

    Prause, Nicole; Steele, Vaughn R; Staley, Cameron; Sabatinelli, Dean

    2015-01-01

    Risky sexual behaviors typically occur when a person is sexually motivated by potent, sexual reward cues. Yet, individual differences in sensitivity to sexual cues have not been examined with respect to sexual risk behaviors. A greater responsiveness to sexual cues might provide greater motivation for a person to act sexually; a lower responsiveness to sexual cues might lead a person to seek more intense, novel, possibly risky, sexual acts. In this study, event-related potentials were recorded in 64 men and women while they viewed a series of emotional, including explicit sexual, photographs. The motivational salience of the sexual cues was varied by including more and less explicit sexual images. Indeed, the more explicit sexual stimuli resulted in enhanced late positive potentials (LPP) relative to the less explicit sexual images. Participants with fewer sexual intercourse partners in the last year had reduced LPP amplitude to the less explicit sexual images than the more explicit sexual images, whereas participants with more partners responded similarly to the more and less explicit sexual images. This pattern of results is consistent with a greater responsivity model. Those who engage in more sexual behaviors consistent with risk are also more responsive to less explicit sexual cues.

  11. Effects of recent word exposure on emotion-word Stroop interference: an ERP study.

    PubMed

    Gootjes, Liselotte; Coppens, Leonora C; Zwaan, Rolf A; Franken, Ingmar H A; Van Strien, Jan W

    2011-03-01

    Attentional bias towards emotional linguistic material has been examined extensively with the emotion-word Stroop task. Although findings in clinical groups show an interference effect of emotional words that relate to the specific concern of the group, findings concerning healthy groups are less clear. In the present study, we investigated whether emotional Stroop interference in healthy individuals is affected by exposure of the words prior to the task. We used event-related potentials (ERPs) to examine the temporal aspects of Stroop interference. Participants took longer to indicate the colour of negative than of neutral words. Exposure of words prior to the Stroop task increased response latencies, but this effect was equal for neutral and negative words. At the neurophysiological level, we found more positive-going ERPs at later latencies (P290, N400 and LPP) in response to negative than in response to neutral Stroop words. The N400 was less negative for exposed than for new words, but this effect did not interact with the emotional valence of the words. For new (i.e., unexposed) words, the behavioural Stroop interference correlated with the P290, N400 and LPP emotion effects (negative minus neutral words). The successive ERP components suggest better prelexical, semantic, and sustained attentional processing of emotion words, even when the emotional content of the words is task-irrelevant.

  12. Improved categorization of subtle facial expressions modulates Late Positive Potential.

    PubMed

    Pollux, P M J

    2016-05-13

    Biases in facial expression recognition can be reduced successfully using feedback-based training tasks. Here we investigate with event-related potentials (ERPs) at which stages of stimulus processing emotion-related modulations are influenced by training. Categorization of subtle facial expressions (morphed from neutral to happy, sad or surprise) was trained with correct-response feedback on each trial. ERPs were recorded before and after training while participants categorized facial expressions without response feedback. Behavioral data demonstrated large improvements in categorization of subtle facial expression which transferred to new face models not used during training. ERPs were modulated by training from 450 ms post-stimulus onward, characterized by a more gradual increase in P3b/Late Positive Potential (LPP) amplitude as expression intensity increased. This effect was indistinguishable for faces used for training and for new faces. It was proposed that training elicited a more fine-grained analysis of facial information for all subtle expressions, resulting in improved recognition and enhanced emotional motivational salience (reflected in P3b/LPP amplitude) of faces previously categorized as expressing no emotion.

  13. Distinct Patterns of Dysfunctional Appetitive and Aversive Motivation in Bipolar Disorder Versus Schizophrenia: An Event Related Potential Study

    PubMed Central

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

    2016-01-01

    Schizophrenia and bipolar disorder are associated with different clinical profiles of disturbances in motivation, yet few studies have compared the neurophysiological correlates of such disturbances. Outpatients with schizophrenia (n = 34), or bipolar disorder I (n = 33), and healthy controls (n = 31) completed a task in which the Late Positive Potential (LPP), an index of motivated attention, was assessed along motivational gradients determined by apparent distance from potential rewards or punishments. Sequences of cues signaling possible monetary gains or losses appeared to loom progressively closer to the viewer; a reaction time (RT) task after the final cue determined the outcome. Controls showed the expected pattern with LPPs for appetitive and aversive cues that were initially elevated, smaller during intermediate positions, and escalated just prior to the RT task. The clinical groups showed different patterns in the final positions just prior to the RT task: the bipolar group’s LPPs to both types of cues peaked relatively early during looming sequences and subsequently decreased, whereas the schizophrenia group showed relatively small LPP escalations, particularly for aversive cues. These distinct patterns suggest that the temporal unfolding of attentional resource allocation for motivationally significant events may qualitatively differ between these disorders. PMID:26845261

  14. Emotional processing in Colombian ex-combatants and its relationship with empathy and executive functions.

    PubMed

    Tobón, Carlos; Ibañez, Agustín; Velilla, Lina; Duque, Jon; Ochoa, John; Trujillo, Natalia; Decety, Jean; Pineda, David

    2015-04-01

    In this work, the neural correlates of emotional processing in Colombian ex-combatants with different empathy profiles were compared to normal controls matched for age, gender and educational level. Forty ex-combatants and 20 non ex-combatants were recruited for this study. Empathy levels as well as executive functions were measured. Empathy level was used to create three groups. Group 1 (G1) included ex-combatants with normal empathy scores, and Group 2 included ex-combatants with low scores on at least one empathy sub-scales. In control group (Ctrl), participants with no antecedents of being combatants and with normal scores in empathy were included. Age, gender, educational and intelligence quotients level were controlled among groups. event-related potentials (ERPs) were recorded while individuals performed an affective picture processing task that included positive, neutral and negative emotional stimuli, which elicit an early modulation of emotion categorization (Early Posterior Negativity (EPN)) and late evaluative process (LPP). EPN differences were found among affective categories, but no group effects were observed at this component. LPP showed a main effect of category and group (higher amplitudes in ex-combatants). There was an inverse correlation between empathy and executive functions scores and ERPs. Results are discussed according to the impact of emotional processing on empathy profile.

  15. Rapid destruction of the rhodamine B using TiO2 photocatalyst in the liquid phase plasma

    PubMed Central

    2013-01-01

    Background Rhodamine B (RhB) is widely used as a colorant in textiles and food stuffs, and is also a well-known water tracer fluorescent. It is harmful to human beings and animals, and causes irritation of the skin, eyes and respiratory tract. The carcinogenicity, reproductive and developmental toxicity, neurotoxicity and chronic toxicity toward humans and animals have been experimentally proven. RhB cannot be effectively removed by biological treatment due to the slow kinetics. Therefore, RhB is chosen as a model pollutant for liquid phase plasma (LPP) treatment in the present investigation. Results This paper presents experimental results for the bleaching of RhB from aqueous solutions in the presence of TiO2 photocatalyst with LPP system. Properties of generated plasma were investigated by optical emission spectroscopy methods. The results of electrical-discharge degradation of RhB showed that the decomposition rate increased with the applied voltage, pulse width, and frequency. The oxygen gas addition to reactant solution increases the degradation rate by active oxygen species. The RhB decomposition rate was shown to increase with the TiO2 particle dosage. Conclusion This work presents the conclusions on the photocatalytic oxidation of RhB, as a function of plasma conditions, oxygen gas bubbling as well as TiO2 particle dosage. We knew that using the liquid phase plasma system with TiO2 photocatalyst at high speed we could remove the organic matter in the water. PMID:24041151

  16. Motivational processing of food cues in anorexia nervosa: a pilot study.

    PubMed

    Novosel, Anna; Lackner, Nina; Unterrainer, Human-Friedrich; Dunitz-Scheer, Marguerite; Scheer, Peter Jaron Zwi; Wallner-Liebmann, Sandra Johanna; Neuper, Christa

    2014-06-01

    Current literature suggests an increased attentional bias toward food stimuli in eating-disordered individuals compared to healthy controls. In line with these research efforts, the present study aims to investigate the processing of food stimuli (enriched by emotional stimuli) between patients diagnosed for anorexia nervosa (AN) and healthy controls by means of electroencephalography. Twenty-two female adolescents (eleven AN patients vs. eleven healthy controls) were investigated. Positive event-related potentials "P300" and "late positive potential" (LPP) reflecting attentional processing (caused by motivationally relevant stimuli) were investigated during passive viewing of the food cue picture stream. This method was used for the first time in a sample of individuals with AN. As a main result, AN patients exhibited a higher amount of attentional bias in P300 and LPP, while watching food stimuli. Moreover, AN patients rated food stimuli as less pleasant. For a conclusion, there is substantial evidence pointing to an abnormal attentional brain reactivity to food pictures in AN. Therefore, food stimuli seem to be more motivationally relevant for AN patients than for healthy controls. By broadening existing knowledge, these findings might bear some implications for the treatment for AN. However, further research is recommended in order to confirm the results coming from rather limited data.

  17. The Negativity Bias in Affective Picture Processing Depends on Top-Down and Bottom-Up Motivational Significance

    PubMed Central

    Hilgard, Joseph; Weinberg, Anna; Proudfit, Greg Hajcak; Bartholow, Bruce D.

    2014-01-01

    It is widely believed that negative information is psychologically more meaningful than positive information, a phenomenon known generally as the negativity bias. However, findings concerning the possibility of a negativity bias in emotional picture processing have been mixed, with recent studies indicating the lack of such a bias in event-related brain potentials (ERPs) when pleasant and unpleasant images are equated for motivational relevance. Here, we investigated two factors that could influence the detection of a negativity bias: picture presentation paradigm and specific picture content. Across two studies, participants viewed pleasant-affiliative, pleasant-thrilling, unpleasant-threatening and neutral images presented in the context of oddball, blocked and random viewing paradigms. Across paradigms, emotional images elicited larger responses in the late positive potential (LPP) than did neutral images. A negativity bias was detected in the oddball paradigm and when thrilling, rather than affiliative, pleasant stimuli were used. Findings are discussed in terms of factors known to influence LPP amplitude and their relevance to differential effects across picture viewing paradigms. PMID:24866528

  18. A Scent of Anxiety: Olfactory Context Conditioning and its Influence on Social Cues.

    PubMed

    Kastner, Anna K; Flohr, Elena L R; Pauli, Paul; Wieser, Matthias J

    2016-02-01

    Perception and evaluation of objects are highly dependent on surrounding contexts. Threatening contexts enhance processing of faces. Because odors are assumed to deliver strong contextual information, the present study aimed at demonstrating 1) that odors can constitute threat and safety contexts, and 2) consequently modulate the processing of faces presented in these contexts. Therefore, previously neutral odors were used as contextual stimuli in a context conditioning paradigm, resulting in an olfactory anxiety and a safety context. Then, faces showing angry, neutral, or fearful expressions were presented within both contexts during a test phase to investigate the effects of threat versus safety contexts on face perception. The late positive potential (LPP) from the EEG, skin conductance level, and subjective ratings were recorded. Results reveal successful olfactory context conditioning as reflected in enhanced processing of the anxiety context, indicated by enhanced LPP after conditioning, increased skin conductance level, and marginally respectively increased ratings. Moreover, faces presented within the threat context were rated as more unpleasant and marginally more arousing than faces presented in the safety context. Thus, olfactory stimuli can serve as context in fear conditioning, and a threatening olfactory context seems to enhance processing of stimuli perceived within this context.

  19. Simulation of particle velocity in a laser-produced tin plasma extreme ultraviolet source

    SciTech Connect

    Masnavi, Majid; Nakajima, Mitsuo; Horioka, Kazuhiko; Araghy, Homaira Parchamy; Endo, Akira

    2011-06-15

    In connection with fast heating in a laser produced plasma (LPP) extreme ultraviolet (EUV) source, the superheating behavior of bulk tin (Sn) at high heating rates is investigated. A constant temperature and pressure molecular dynamics simulation using modified Lennard-Jones and Coulomb potentials suitable for studying the liquid structure of Sn is employed in order to derive the caloric curves of the solid and liquid phases. The results have shown transient effects on the phase transitions. Superheating is observed during the melting and vaporizing processes. The velocity distribution of Sn particles against typical laser fluence in a LPP EUV light source has been numerically investigated using a simplified method including a one-dimensional, two-temperature, molecular dynamics, and steady-state ionization model. In the framework of our model, it was found that ejected Sn particles have a maximum velocity on the order of 10 to 40 km/s in plasma created using a nanosecond pre-pulse neodymium-doped yttrium aluminum garnet (Nd:YAG, 1.06 {mu}m) laser in EUV lithography experiments.

  20. Involvement of lysophosphatidic acid, sphingosine 1-phosphate and ceramide 1-phosphate in the metabolization of phosphatidic acid by lipid phosphate phosphatases in bovine rod outer segments.

    PubMed

    Pasquaré, Susana J; Salvador, Gabriela A; Giusto, Norma Maria

    2008-07-01

    The aim of the present research was to evaluate the generation of [2-3H]diacylglycerol ([2-3H]DAG) from [2-3H]-Phosphatidic acid ([2-3H]PA) by lipid phosphate phosphatases (LPPs) at different concentrations of lysophosphatidic acid (LPA), sphingosine 1-phosphate (S1P), and ceramide 1-phosphate (C1P) in purified ROS obtained from dark-adapted retinas (DROS) or light-adapted retinas (BLROS) as well as in ROS membrane preparations depleted of soluble and peripheral proteins. Western blot analysis revealed the presence of LPP3 exclusively in all membrane preparations. Immunoblots of entire ROS and depleted ROS did not show dark-light differences in LPP3 levels. LPPs activities were diminished by 53% in BLROS with respect to DROS. The major competitive effect on PA hydrolysis was exerted by LPA and S1P in DROS and by C1P in BLROS. LPPs activities in depleted ROS were similar to the activity observed in entire DROS and BLROS, respectively. LPA, S1P and C1P competed at different extent in depleted DROS and BLROS. Sphingosine and ceramide inhibited LPPs activities in entire and depleted DROS. Ceramide also inhibited LPPs activities in entire and in depleted BLROS. Our findings are indicative of a different degree of competition between PA and LPA, S1P and C1P by LPPs depending on the illumination state of the retina. PMID:18288612

  1. Spectral investigations of photoionized plasmas induced in atomic and molecular gases using nanosecond extreme ultraviolet (EUV) pulses

    NASA Astrophysics Data System (ADS)

    Bartnik, A.; Fiedorowicz, H.; Wachulak, P.

    2014-07-01

    In this paper, results of spectral investigations of low temperature photoionized plasmas, created by irradiation of gases with intense pulses of extreme ultraviolet (EUV) radiation from a laser-produced plasma (LPP) source, are presented. The LPP source was based on a double-stream KrXe/He gas-puff target irradiated with 4 ns/0.8 J/10 Hz Nd:YAG laser pulses. The most intense emission from the source spanned a relatively narrow spectral region λ ≈ 10-12 nm; however, spectrally integrated intensity at longer wavelengths was also significant. The EUV beam was focused on a gas stream, injected into a vacuum chamber synchronously with the EUV pulses. Irradiation of gases resulted in formation of photoionized plasmas emitting radiation in the EUV range. Radiation spectra, measured for plasmas produced in various gases, are dominated by emission lines, originating from single charged ions. Significant differences in spectral intensities and distributions between plasmas created in neon and molecular gases were observed.

  2. Emotion blocks the path to learning under stereotype threat.

    PubMed

    Mangels, Jennifer A; Good, Catherine; Whiteman, Ronald C; Maniscalco, Brian; Dweck, Carol S

    2012-02-01

    Gender-based stereotypes undermine females' performance on challenging math tests, but how do they influence their ability to learn from the errors they make? Females under stereotype threat or non-threat were presented with accuracy feedback after each problem on a GRE-like math test, followed by an optional interactive tutorial that provided step-wise problem-solving instruction. Event-related potentials tracked the initial detection of the negative feedback following errors [feedback related negativity (FRN), P3a], as well as any subsequent sustained attention/arousal to that information [late positive potential (LPP)]. Learning was defined as success in applying tutorial information to correction of initial test errors on a surprise retest 24-h later. Under non-threat conditions, emotional responses to negative feedback did not curtail exploration of the tutor, and the amount of tutor exploration predicted learning success. In the stereotype threat condition, however, greater initial salience of the failure (FRN) predicted less exploration of the tutor, and sustained attention to the negative feedback (LPP) predicted poor learning from what was explored. Thus, under stereotype threat, emotional responses to negative feedback predicted both disengagement from learning and interference with learning attempts. We discuss the importance of emotion regulation in successful rebound from failure for stigmatized groups in stereotype-salient environments.

  3. Inhibitory effect of plantaricin peptides (Pln E/F and J/K) against Escherichia coli.

    PubMed

    Pal, Gargi; Srivastava, Sheela

    2014-11-01

    Plantaricins are small bioactive peptides produced by Lactobacillus plantarum strains that exhibit significant antimicrobial activity against closely-related Gram-positive bacteria, including food spoilage organisms. In comparison, bacteriocins including plantaricins, are usually less effective against Gram-negative organisms. In this study, we demonstrate that heterologously expressed and purified plantaricins, Pln E, -F, -J, and -K when tested against Gram negative model organism Escherichia coli K-12 were highly effective under certain conditions. The apparent tolerance of Gram-negative members to these peptides has been explained on the basis of the presence of the outer membrane (OM) that acts as a protective barrier. We have shown that agents and/or conditions that destabilize OM of E. coli K-12, make it susceptible to plantaricin peptides. In order to further strengthen this conclusion, an OM lipoprotein-defective lpp mutant strain of E. coli K-12 was also studied and compared. A significant loss of cell viability both in terms of CFU/ml as well as with live-dead dual staining combined with flow cytometry, could be demonstrated with the lpp mutant in comparison to the wild type strain. The results indicate that plantaricins can inhibit Gram-negative bacteria if the outer-membrane is weakened and it can be used in preservation of food with the help of some food-grade chelating agents. PMID:25138074

  4. A Simple ERP Method for Quantitative Analysis of Cognitive Workload in Myoelectric Prosthesis Control and Human-Machine Interaction

    PubMed Central

    Deeny, Sean; Chicoine, Caitlin; Hargrove, Levi; Parrish, Todd; Jayaraman, Arun

    2014-01-01

    Common goals in the development of human-machine interface (HMI) technology are to reduce cognitive workload and increase function. However, objective and quantitative outcome measures assessing cognitive workload have not been standardized for HMI research. The present study examines the efficacy of a simple event-related potential (ERP) measure of cortical effort during myoelectric control of a virtual limb for use as an outcome tool. Participants trained and tested on two methods of control, direct control (DC) and pattern recognition control (PRC), while electroencephalographic (EEG) activity was recorded. Eighteen healthy participants with intact limbs were tested using DC and PRC under three conditions: passive viewing, easy, and hard. Novel auditory probes were presented at random intervals during testing, and significant task-difficulty effects were observed in the P200, P300, and a late positive potential (LPP), supporting the efficacy of ERPs as a cognitive workload measure in HMI tasks. LPP amplitude distinguished DC from PRC in the hard condition with higher amplitude in PRC, consistent with lower cognitive workload in PRC relative to DC for complex movements. Participants completed trials faster in the easy condition using DC relative to PRC, but completed trials more slowly using DC relative to PRC in the hard condition. The results provide promising support for ERPs as an outcome measure for cognitive workload in HMI research such as prosthetics, exoskeletons, and other assistive devices, and can be used to evaluate and guide new technologies for more intuitive HMI control. PMID:25402345

  5. The neuroscience of implicit moral evaluation and its relation to generosity in early childhood

    PubMed Central

    Cowell, Jason M.; Decety, Jean

    2014-01-01

    Summary Despite cultural and individual variation, humans are a judgmental bunch [1]. There is accumulating evidence for early social and moral evaluation as shown by research with infants and children documenting the notion that some behaviors are perceived as right and others are wrong [2]. Moreover, social interactions are governed by a concern for fairness and the others’ well-being [3, 4]. However, while generosity increases between infancy and late childhood, it is less clear what mechanisms guide this change [5]. Early predispositions towards prosociality are thought to arise in concert with the social and cultural environment, developing into adult morality, a complex incorporation of emotional, motivational, and cognitive processes [6, 7]. Using EEG combined with eye-tracking and behavioral sharing, we investigated, for the first time, the temporal neuro-dynamics of implicit moral evaluation in 3–5 year old children. Results show distinct early automatic attentional (EPN) and later cognitively controlled (N2, LPP) patterns of neural response while viewing characters engaging in helping and harming behaviors. Importantly, later (LPP), but not early (EPN) waveforms, predicted actual generosity. These results shed light on theories of moral development by documenting the respective contribution of automatic and cognitive neural processes underpinning social evaluation, and directly link these neural computations to prosocial behavior in children. PMID:25532892

  6. A Scent of Anxiety: Olfactory Context Conditioning and its Influence on Social Cues.

    PubMed

    Kastner, Anna K; Flohr, Elena L R; Pauli, Paul; Wieser, Matthias J

    2016-02-01

    Perception and evaluation of objects are highly dependent on surrounding contexts. Threatening contexts enhance processing of faces. Because odors are assumed to deliver strong contextual information, the present study aimed at demonstrating 1) that odors can constitute threat and safety contexts, and 2) consequently modulate the processing of faces presented in these contexts. Therefore, previously neutral odors were used as contextual stimuli in a context conditioning paradigm, resulting in an olfactory anxiety and a safety context. Then, faces showing angry, neutral, or fearful expressions were presented within both contexts during a test phase to investigate the effects of threat versus safety contexts on face perception. The late positive potential (LPP) from the EEG, skin conductance level, and subjective ratings were recorded. Results reveal successful olfactory context conditioning as reflected in enhanced processing of the anxiety context, indicated by enhanced LPP after conditioning, increased skin conductance level, and marginally respectively increased ratings. Moreover, faces presented within the threat context were rated as more unpleasant and marginally more arousing than faces presented in the safety context. Thus, olfactory stimuli can serve as context in fear conditioning, and a threatening olfactory context seems to enhance processing of stimuli perceived within this context. PMID:26547015

  7. Late positive potential to explicit sexual images associated with the number of sexual intercourse partners

    PubMed Central

    Steele, Vaughn R.; Staley, Cameron; Sabatinelli, Dean

    2015-01-01

    Risky sexual behaviors typically occur when a person is sexually motivated by potent, sexual reward cues. Yet, individual differences in sensitivity to sexual cues have not been examined with respect to sexual risk behaviors. A greater responsiveness to sexual cues might provide greater motivation for a person to act sexually; a lower responsiveness to sexual cues might lead a person to seek more intense, novel, possibly risky, sexual acts. In this study, event-related potentials were recorded in 64 men and women while they viewed a series of emotional, including explicit sexual, photographs. The motivational salience of the sexual cues was varied by including more and less explicit sexual images. Indeed, the more explicit sexual stimuli resulted in enhanced late positive potentials (LPP) relative to the less explicit sexual images. Participants with fewer sexual intercourse partners in the last year had reduced LPP amplitude to the less explicit sexual images than the more explicit sexual images, whereas participants with more partners responded similarly to the more and less explicit sexual images. This pattern of results is consistent with a greater responsivity model. Those who engage in more sexual behaviors consistent with risk are also more responsive to less explicit sexual cues. PMID:24526189

  8. Kinetics of petroleum coke/biomass blends during co-gasification

    NASA Astrophysics Data System (ADS)

    Zhang, Jian-liang; Guo, Jian; Wang, Guang-wei; Xu, Tao; Chai, Yi-fan; Zheng, Chang-le; Xu, Run-sheng

    2016-09-01

    The co-gasification behavior and synergistic effect of petroleum coke, biomass, and their blends were studied by thermogravimetric analysis under CO2 atmosphere at different heating rates. The isoconversional method was used to calculate the activation energy. The results showed that the gasification process occurred in two stages: pyrolysis and char gasification. A synergistic effect was observed in the char gasification stage. This effect was caused by alkali and alkaline earth metals in the biomass ash. Kinetics analysis showed that the activation energy in the pyrolysis stage was less than that in the char gasification stage. In the char gasification stage, the activation energy was 129.1-177.8 kJ/mol for petroleum coke, whereas it was 120.3-150.5 kJ/mol for biomass. We also observed that the activation energy calculated by the Flynn-Wall-Ozawa (FWO) method were larger than those calculated by the Kissinger-Akahira-Sunosen (KAS) method. When the conversion was 1.0, the activation energy was 106.2 kJ/mol when calculated by the KAS method, whereas it was 120.3 kJ/mol when calculated by the FWO method.

  9. Expression of fatty acid synthesis genes and fatty acid accumulation in haematococcus pluvialis under different stressors

    PubMed Central

    2012-01-01

    Background Biofuel has been the focus of intensive global research over the past few years. The development of 4th generation biofuel production (algae-to-biofuels) based on metabolic engineering of algae is still in its infancy, one of the main barriers is our lacking of understanding of microalgal growth, metabolism and biofuel production. Although fatty acid (FA) biosynthesis pathway genes have been all cloned and biosynthesis pathway was built up in some higher plants, the molecular mechanism for its regulation in microalgae is far away from elucidation. Results We cloned main key genes for FA biosynthesis in Haematococcus pluvialis, a green microalga as a potential biodiesel feedstock, and investigated the correlations between their expression alternation and FA composition and content detected by GC-MS under different stress treatments, such as nitrogen depletion, salinity, high or low temperature. Our results showed that high temperature, high salinity, and nitrogen depletion treatments played significant roles in promoting microalgal FA synthesis, while FA qualities were not changed much. Correlation analysis showed that acyl carrier protein (ACP), 3-ketoacyl-ACP-synthase (KAS), and acyl-ACP thioesterase (FATA) gene expression had significant correlations with monounsaturated FA (MUFA) synthesis and polyunsaturated FA (PUFA) synthesis. Conclusions We proposed that ACP, KAS, and FATA in H. pluvialis may play an important role in FA synthesis and may be rate limiting genes, which probably could be modified for the further study of metabolic engineering to improve microalgal biofuel quality and production. PMID:22448811

  10. Analysis of SARS-CoV E protein ion channel activity by tuning the protein and lipid charge.

    PubMed

    Verdiá-Báguena, Carmina; Nieto-Torres, Jose L; Alcaraz, Antonio; Dediego, Marta L; Enjuanes, Luis; Aguilella, Vicente M

    2013-09-01

    A partial characterization of the ion channels formed by the SARS coronavirus (CoV) envelope (E) protein was previously reported (C. Verdiá-Báguena et al., 2012 [12]). Here, we provide new significant insights on the involvement of lipids in the structure and function of the CoV E protein channel on the basis of three series of experiments. First, reversal potential measurements over a wide range of pH allow the dissection of the contributions to channel selectivity coming from ionizable residues of the protein transmembrane domain and also from the negatively charged groups of diphytanoyl phosphatidylserine (DPhPS) lipid. The corresponding effective pKas are consistent with the model pKas of the acidic residue candidates for titration. Second, the change of channel conductance with salt concentration reveals two distinct regimes (Donnan-controlled electrodiffusion and bulk-like electrodiffusion) fully compatible with the outcomes of selectivity experiments. Third, by measuring channel conductance in mixtures of neutral diphytanoyl phosphatidylcholine (DPhPC) lipids and negatively charged DPhPS lipids in low and high salt concentrations we conclude that the protein-lipid conformation in the channel is likely the same in charged and neutral lipids. Overall, the whole set of experiments supports the proteolipidic structure of SARS-CoV E channels and explains the large difference in channel conductance observed between neutral and charged membranes.

  11. Evaluation of the Uniform Field Distortions Produced by a Toroidal Dielectric Body / Novērtējums Viendabīga Elektriskā Lauka Izkropļojumiem, Kurus Rada Toroīda Formas Dielektrisks Ķermenis

    NASA Astrophysics Data System (ADS)

    Krasnitsky, Y. A.; Popov, A. E.; Kalnacs, A.

    2015-08-01

    Distortions of the structure of a uniform electric field when a dielectric body with a toroidal shape is placed in it are considered in the quasi-static approximation. The rate of distortion is proposed to estimate through the effective permittivity of toroid determined by solving the corresponding boundary value problem. Some numerical estimates obtained using specially developed software in the language of Matlab are given. Darbā apskatīts kvazi-statisks tuvinājums viendabīga elektriskā lauka izkropļojumiem gadījumos, kad tajā tiek ievietots dielektrisks toroīda formas ķermenis. Izkropļojumu apmēru tiek piedāvāts novērtēt ar toroīda efektīvo caurlaidību, kas tiek noteikta, atrisinot atbilstošo robežvērtību uzdevumu. Tiek doti skaitliski novērtējumi, kas iegūti, lietojot speciāli valodā Matlab izstrādātu programmatūru.

  12. Computational Tools for Interpreting Ion Channel pH-Dependence

    PubMed Central

    Sazanavets, Ivan; Warwicker, Jim

    2015-01-01

    Activity in many biological systems is mediated by pH, involving proton titratable groups with pKas in the relevant pH range. Experimental analysis of pH-dependence in proteins focusses on particular sidechains, often with mutagenesis of histidine, due to its pKa near to neutral pH. The key question for algorithms that predict pKas is whether they are sufficiently accurate to effectively narrow the search for molecular determinants of pH-dependence. Through analysis of inwardly rectifying potassium (Kir) channels and acid-sensing ion channels (ASICs), mutational effects on pH-dependence are probed, distinguishing between groups described as pH-coupled or pH-sensor. Whereas mutation can lead to a shift in transition pH between open and closed forms for either type of group, only for pH-sensor groups does mutation modulate the amplitude of the transition. It is shown that a hybrid Finite Difference Poisson-Boltzmann (FDPB) – Debye-Hückel continuum electrostatic model can filter mutation candidates, providing enrichment for key pH-coupled and pH-sensor residues in both ASICs and Kir channels, in comparison with application of FDPB alone. PMID:25915903

  13. Computational Tools for Interpreting Ion Channel pH-Dependence.

    PubMed

    Sazanavets, Ivan; Warwicker, Jim

    2015-01-01

    Activity in many biological systems is mediated by pH, involving proton titratable groups with pKas in the relevant pH range. Experimental analysis of pH-dependence in proteins focusses on particular sidechains, often with mutagenesis of histidine, due to its pKa near to neutral pH. The key question for algorithms that predict pKas is whether they are sufficiently accurate to effectively narrow the search for molecular determinants of pH-dependence. Through analysis of inwardly rectifying potassium (Kir) channels and acid-sensing ion channels (ASICs), mutational effects on pH-dependence are probed, distinguishing between groups described as pH-coupled or pH-sensor. Whereas mutation can lead to a shift in transition pH between open and closed forms for either type of group, only for pH-sensor groups does mutation modulate the amplitude of the transition. It is shown that a hybrid Finite Difference Poisson-Boltzmann (FDPB) - Debye-Hückel continuum electrostatic model can filter mutation candidates, providing enrichment for key pH-coupled and pH-sensor residues in both ASICs and Kir channels, in comparison with application of FDPB alone. PMID:25915903

  14. Carbonic anhydrase activators: Activation of the β-carbonic anhydrase from Malassezia globosa with amines and amino acids.

    PubMed

    Vullo, Daniela; Del Prete, Sonia; Capasso, Clemente; Supuran, Claudiu T

    2016-03-01

    The β-carbonic anhydrase (CA, EC 4.2.1.1) from the dandruff producing fungus Malassezia globosa, MgCA, was investigated for its activation with amines and amino acids. MgCA was weakly activated by amino acids such as L-/D-His, L-Phe, D-DOPA, D-Trp, L-/D-Tyr and by the amine serotonin (KAs of 12.5-29.3μM) but more effectively activated by d-Phe, l-DOPA, l-Trp, histamine, dopamine, pyridyl-alkylamines, and 4-(2-aminoethyl)-morpholine, with KAs of 5.82-10.9μM. The best activators were l-adrenaline and 1-(2-aminoethyl)piperazine, with activation constants of 0.72-0.81μM. This study may help a better understanding of the activation mechanisms of β-CAs from pathogenic fungi as well as the design of tighter binding ligands for this enzyme which is a drug target for novel types of anti-dandruff agents.

  15. Is it safe to place a tibial intramedullary nail through a traumatic knee arthrotomy?

    PubMed

    Bauer, Jennifer M; Bible, Jesse E; Mir, Hassan R

    2014-03-01

    We conducted a study to compare postoperative infection and nonunion rates in tibial intramedullary nails (IMNs) placed through either uninjured knees or traumatic knee arthrotomies (KAs). We reviewed all adult tibial diaphyseal fractures (n = 1378) treated with an IMN between 1998 and 2010. Fourteen of these nails were placed through a traumatic KA. Each patient in the study group was assigned 4 separate matched controls for comparison. Controls were matched on age, sex, diabetes, smoking, and fracture classification (closed or open with Gustilo-Anderson). There were no postoperative infections (knee or fracture site) in the traumatic KA group and 2 (3.5%) in the control group (P = .473). One nonunion (7.1%) was noted in the traumatic KA group, and 9 (16%) were noted in the control group (P = .6694). To our knowledge, this is the first study to report outcomes of placing tibial IMNs through traumatic KAs. In our sample, the practice presented no increased risk either for infection (at the knee or the fracture site) or for nonunion with appropriate surgical debridement. PMID:24660176

  16. The Role of p16, p21, p27, p53 and Ki-67 Expression in the Differential Diagnosis of Cutaneous Squamous Cell Carcinomas and Keratoacanthomas: An Immunohistochemical Study

    PubMed Central

    Bedir, Recep; Güçer, Hasan; Şehitoğlu, İbrahim; Yurdakul, Cüneyt; Bağcı, Pelin; Üstüner, Pelin

    2016-01-01

    Background: Distinguishing squamous cell carcinoma (SCC) from keratoacanthoma (KA) by histopathological features may not be sufficient for a differential diagnosis, as KAs may, in some cases, imitate well-differentiated SCCs. Aims: In this study, we investigated whether the expression of the p16, p21, p27, p53 genes and a Ki-67 proliferation index are useful in distinguishing between these two tumors. Study Design: Cross-sectional study. Methods: Immunohistochemistry was used to investigate the expression of the p16, p21, p27, p53 genes and the Ki-67 proliferation index was investigated in well-differentiated SCC with KA-like features (n=40) and KA (n=30). Results: The results of all of the examined markers, except for p27 (p16, p21, p53, and Ki-67) were found to be significantly different between the SCC and KA samples (p<0.05). Conclusion: In well-differentiated SCC with KA-like features and KA cases where the differential diagnosis is difficult from a histopathological perspective, the use of p16, p21, p53 expression and a Ki-67 proliferation index can be useful for the differential diagnosis of SCCs and KAs. PMID:27403379

  17. Shewanella oneidensis FabB: A β-ketoacyl-ACP Synthase That Works with C16:1-ACP

    PubMed Central

    Luo, Qixia; Li, Meng; Fu, Huihui; Meng, Qiu; Gao, Haichun

    2016-01-01

    It is established that Escherichia coli β-ketoacyl-ACP synthase (KAS) I (encoded by EcfabB) is the primary, if not exclusive, factor for elongation of the cis-3-decenoyl-ACP (C10:1-ACP) but not effective with C16:1- or longer-chain-ACPs. To test the extent to which these features apply to KAS I proteins in other species, in this study, we examined the physiological role of FabB in Shewanella oneidensis, an excellent model for researching type II fatty acid synthetic (FAS) system and its regulation. We showed that the loss of either FabA (the enzyme that introduces double bond) or FabB, in the absence of DesA which desaturizes C16 and C18 to generate respective C16:1 and C18:1, leads to a UFA auxotroph. However, fatty acid profiles of membrane phospholipid of the fabA and fabB mutants are significantly different, suggesting that FabB participates in steps beyond elongation of C10:1-ACP. Further analyses demonstrated that S. oneidensis FabB differs from EcFabB in that (i) it is not the only enzyme capable of catalyzing elongation of the cis-3-decenoyl-ACP produced by FabA, (ii) it plays a critical role in elongation of C16:1- and longer-chain-ACPs, and (iii) its overproduction is detrimental. PMID:27014246

  18. Carbonic anhydrase activators: Activation of the β-carbonic anhydrase from Malassezia globosa with amines and amino acids.

    PubMed

    Vullo, Daniela; Del Prete, Sonia; Capasso, Clemente; Supuran, Claudiu T

    2016-03-01

    The β-carbonic anhydrase (CA, EC 4.2.1.1) from the dandruff producing fungus Malassezia globosa, MgCA, was investigated for its activation with amines and amino acids. MgCA was weakly activated by amino acids such as L-/D-His, L-Phe, D-DOPA, D-Trp, L-/D-Tyr and by the amine serotonin (KAs of 12.5-29.3μM) but more effectively activated by d-Phe, l-DOPA, l-Trp, histamine, dopamine, pyridyl-alkylamines, and 4-(2-aminoethyl)-morpholine, with KAs of 5.82-10.9μM. The best activators were l-adrenaline and 1-(2-aminoethyl)piperazine, with activation constants of 0.72-0.81μM. This study may help a better understanding of the activation mechanisms of β-CAs from pathogenic fungi as well as the design of tighter binding ligands for this enzyme which is a drug target for novel types of anti-dandruff agents. PMID:26856923

  19. The Mycobacterium tuberculosis FAS-II condensing enzymes: their role in mycolic acid biosynthesis, acid-fastness, pathogenesis and in future drug development.

    PubMed

    Bhatt, Apoorva; Molle, Virginie; Besra, Gurdyal S; Jacobs, William R; Kremer, Laurent

    2007-06-01

    Mycolic acids are very long-chain fatty acids representing essential components of the mycobacterial cell wall. Considering their importance, characterization of key enzymes participating in mycolic acid biosynthesis not only allows an understanding of their role in the physiology of mycobacteria, but also might lead to the identification of new drug targets. Mycolates are synthesized by at least two discrete elongation systems, the type I and type II fatty acid synthases (FAS-I and FAS-II respectively). Among the FAS-II components, the condensing enzymes that catalyse the formation of carbon-carbon bonds have received considerable interest. Four condensases participate in initiation (mtFabH), elongation (KasA and KasB) and termination (Pks13) steps, leading to full-length mycolates. We present the recent biochemical and structural data for these important enzymes. Special emphasis is given to their role in growth, intracellular survival, biofilm formation, as well as in the physiopathology of tuberculosis. Recent studies demonstrated that phosphorylation of these enzymes by mycobacterial kinases affects their activities. We propose here a model in which kinases that sense environmental changes can phosphorylate the condensing enzymes, thus representing a novel mechanism of regulating mycolic acid biosynthesis. Finally, we discuss the attractiveness of these enzymes as valid targets for future antituberculosis drug development. PMID:17555433

  20. GroEL1: a dedicated chaperone involved in mycolic acid biosynthesis during biofilm formation in mycobacteria.

    PubMed

    Ojha, Anil; Anand, Mridula; Bhatt, Apoorva; Kremer, Laurent; Jacobs, William R; Hatfull, Graham F

    2005-12-01

    Mycobacteria are unusual in encoding two GroEL paralogs, GroEL1 and GroEL2. GroEL2 is essential--presumably providing the housekeeping chaperone functions--while groEL1 is nonessential, contains the attB site for phage Bxb1 integration, and encodes a putative chaperone with unusual structural features. Inactivation of the Mycobacterium smegmatis groEL1 gene by phage Bxb1 integration allows normal planktonic growth but prevents the formation of mature biofilms. GroEL1 modulates synthesis of mycolates--long-chain fatty acid components of the mycobacterial cell wall--specifically during biofilm formation and physically associates with KasA, a key component of the type II Fatty Acid Synthase involved in mycolic acid synthesis. Biofilm formation is associated with elevated synthesis of short-chain (C56-C68) fatty acids, and strains with altered mycolate profiles--including an InhA mutant resistant to the antituberculosis drug isoniazid and a strain overexpressing KasA--are defective in biofilm formation. PMID:16325580

  1. The β-ketoacyl-ACP synthase from Mycobacterium tuberculosis as potential drug targets.

    PubMed

    Singh, V; Mani, I; Chaudhary, D K; Somvanshi, P

    2011-01-01

    The continuous preventive measures and control of tuberculosis are often hampered by re-emergence of multi-drug-resistant (MDR) strains of Mycobacterium tuberculosis. A novel drug approach is desperately needed to combat the global threat posed by MDR strains. In spite of current advancement in biological techniques viz. microarray and proteomics data for tuberculosis, no such potent drug has been developed in the past decades yet. Therefore, mycolic acid is an essential constituent which is involved in the formation of cell wall of Mycobacterium species. The biosynthesis of mycolic acid is involved in two fatty acid synthase systems, the multifunctional polypeptide fatty acid synthase I (FASI) which performs de novo fatty acid synthesis and dissociate FASII system. FASII system consists of monofunctional enzymes and acyl carrier protein (ACP), elongating FASI products to long chain mycolic acid precursor. In this review, the β-ketoacyl-ACP synthases (fadH, kasA and kasB) are distinct and play a vital role in mycolic acid synthesis, cell wall synthesis, biofilm formation and also pathogenesis. On the basis of substantial observation we suggest that these enzymes may be used as promising and attractive targets for novel anti-TB drugs designing and discovery. PMID:21370994

  2. Molecular analysis of isoniazid-resistant clinical isolates of Mycobacterium tuberculosis from India.

    PubMed

    Nusrath Unissa, A; Selvakumar, N; Narayanan, Sujatha; Narayanan, P R

    2008-01-01

    The presence of mutations in specific regions of katG, inhA, oxyR-ahpC and kasA associated with isoniazid (INH)-resistant clinical isolates of Mycobacterium tuberculosis from India were analysed by DNA sequencing. Point mutations in the katG gene at codon 315 and a mutation at codon 138 were detected in 64.3% (45/70) and 4% (1/25) of isolates, respectively. Polymorphisms at codon 463 of the katG gene were found both in resistant and sensitive isolates. Mutation at the inhA and oxyR-ahpC promoter regions occurred in 11.4% (8/70) and 35.0% (14/40) of the isolates, respectively. No mutation was found to occur in kasA and inhA structural gene regions. Of the 70 resistant isolates studied, 55 (78.6%) showed mutation in the regions sequenced. This is the first comprehensive molecular analysis of INH resistance in India, which suggests that point mutation rather than deletion and insertion is the major cause of INH resistance. PMID:18006278

  3. Comparative metabolic profiling of mce1 operon mutant vs wild-type Mycobacterium tuberculosis strains.

    PubMed

    Queiroz, Adriano; Medina-Cleghorn, Daniel; Marjanovic, Olivera; Nomura, Daniel K; Riley, Lee W

    2015-11-01

    Mycobacterium tuberculosis disrupted in a 13-gene operon (mce1) accumulates free mycolic acids (FM) in its cell wall and causes accelerated death in mice. Here, to more comprehensively analyze differences in their cell wall lipid composition, we used an untargeted metabolomics approach to compare the lipid profiles of wild-type and mce1 operon mutant strains. By liquid chromatography-mass spectrometry, we identified >400 distinct lipids significantly altered in the mce1 mutant compared to wild type. These lipids included decreased levels of saccharolipids and glycerophospholipids, and increased levels of alpha-, methoxy- and keto mycolic acids (MA), and hydroxyphthioceranic acid. The mutant showed reduced expression of mmpL8, mmpL10, stf0, pks2 and papA2 genes involved in transport and metabolism of lipids recognized to induce proinflammatory response; these lipids were found to be decreased in the mutant. In contrast, the transcripts of mmpL3, fasI, kasA, kasB, acpM and RV3451 involved in MA transport and metabolism increased; MA inhibits inflammatory response in macrophages. Since the mce1 operon is known to be regulated in intracellular M. tuberculosis, we speculate that the differences we observed in cell wall lipid metabolism and composition may affect host response to M. tuberculosis infection and determine the clinical outcome of such an infection. PMID:26319139

  4. New approaches to target the mycolic acid biosynthesis pathway for the development of tuberculosis therapeutics.

    PubMed

    North, E Jeffrey; Jackson, Mary; Lee, Richard E

    2014-01-01

    Mycolic acids are the major lipid components of the unique mycobacterial cell wall responsible for the protection of the tuberculosis bacilli from many outside threats. Mycolic acids are synthesized in the cytoplasm and transported to the outer membrane as trehalose- containing glycolipids before being esterified to the arabinogalactan portion of the cell wall and outer membrane glycolipids. The large size of these unique fatty acids is a result of a huge metabolic investment that has been evolutionarily conserved, indicating the importance of these lipids to the mycobacterial cellular survival. There are many key enzymes involved in the mycolic acid biosynthetic pathway, including fatty acid synthesis (KasA, KasB, MabA, InhA, HadABC), mycolic acid modifying enzymes (SAM-dependent methyltransferases, aNAT), fatty acid activating and condensing enzymes (FadD32, Acc, Pks13), transporters (MmpL3) and tranferases (Antigen 85A-C) all of which are excellent potential drug targets. Not surprisingly, in recent years many new compounds have been reported to inhibit specific portions of this pathway, discovered through both phenotypic screening and target enzyme screening. In this review, we analyze the new and emerging inhibitors of this pathway discovered in the post-genomic era of tuberculosis drug discovery, several of which show great promise as selective tuberculosis therapeutics. PMID:24245756

  5. Mycobacterium tuberculosis SigM positively regulates Esx secreted protein and nonribosomal peptide synthetase genes and down regulates virulence-associated surface lipid synthesis.

    PubMed

    Raman, Sahadevan; Puyang, Xiaoling; Cheng, Tan-Yun; Young, David C; Moody, D Branch; Husson, Robert N

    2006-12-01

    The Mycobacterium tuberculosis genome encodes 12 alternative sigma factors, several of which regulate stress responses and are required for virulence in animal models of acute infection. In this work we investigated M. tuberculosis SigM, a member of the extracytoplasmic function subfamily of alternative sigma factors. This sigma factor is expressed at low levels in vitro and does not appear to function in stress response regulation. Instead, SigM positively regulates genes required for the synthesis of surface or secreted molecules. Among these are genes encoding two pairs of Esx secreted proteins, a multisubunit nonribosomal peptide synthetase operon, and genes encoding two members of the proline-proline-glutamate (PPE) family of proteins. Genes up regulated in a sigM mutant strain include a different PPE gene, as well as several genes involved in surface lipid synthesis. Among these are genes involved in synthesis of phthiocerol dimycocerosate (PDIM), a surface lipid critical for virulence during acute infection, and the kasA-kasB operon, which is required for mycolic acid synthesis. Analysis of surface lipids showed that PDIM synthesis is increased in a sigM-disrupted strain and is undetectable in a sigM overexpression strain. These findings demonstrate that SigM positively and negatively regulates cell surface and secreted molecules that are likely to function in host-pathogen interactions. PMID:17028284

  6. New Approaches to Target the Mycolic Acid Biosynthesis Pathway for the Development of Tuberculosis Therapeutics

    PubMed Central

    North, E. Jeffrey; Jackson, Mary; Lee, Richard E.

    2015-01-01

    Mycolic acids are the major lipid component of the unique mycobacterial cell wall responsible for the protection of the tuberculosis bacilli from many outside threats. Mycolic acids are synthesized in the cytoplasm and transported to the outer membrane as trehalose-containing glycolipids before being esterified to the arabinogalactan portion of the cell wall and outer membrane glycolipids. The large size of these unique fatty acids is a result of a huge metabolic investment that has been evolutionarily conserved, indicating the importance of these lipids to the mycobacterial cellular survival. There are many key enzymes involved in the mycolic acid biosynthetic pathway, including fatty acid synthesis (KasA, KasB, MabA, InhA, HadABC), mycolic acid modifying enzymes (SAM-dependent methyltransferases, aNAT), fatty acid activating and condensing enzymes (FadD32, Acc, Pks13), transporters (MmpL3) and tranferases (Antigen 85A-C) all of which are excellent potential drug targets. Not surprisingly, in recent years many new compounds have been reported to inhibit specific portions of this pathway, discovered through both phenotypic screening and target enzyme screening. In this review, we analyze the new and emerging inhibitors of this pathway discovered in the post-genomic era of tuberculosis drug discovery, several of which show great promise as selective tuberculosis therapeutics. PMID:24245756

  7. Carbonic anhydrase activators: an activation study of the human mitochondrial isoforms VA and VB with amino acids and amines.

    PubMed

    Vullo, Daniela; Nishimori, Isao; Innocenti, Alessio; Scozzafava, Andrea; Supuran, Claudiu T

    2007-03-01

    The mitochondrial isozymes of human carbonic anhydrase (hCA, EC 4.2.1.1), hCA VA and hCA VB, were investigated for activation with a series of amino acids and amines. D-His, L-DOPA, histamine, dopamine, and 4-(2-aminoethyl)morpholine were excellent hCA VA activators, with KAs in the range of 10-130 nM. Good hCA VB activating effects were identified for L-His, D-Phe, D-DOPA, L-Trp, L-Tyr, serotonin, and 2-(2-aminoethyl)-pyridine, with KAs in the range of 44-110 nM. All these activators enhanced kcat, having no effect on KM, favoring thus the rate-determining step in the catalytic cycle, the proton transfer reactions between the active site and environment. The activation pattern of the two mitochondrial isoforms is very different from each other and as compared to those of the cytosolic isoforms hCA I and II. PMID:17174092

  8. Computational Tools for Interpreting Ion Channel pH-Dependence.

    PubMed

    Sazanavets, Ivan; Warwicker, Jim

    2015-01-01

    Activity in many biological systems is mediated by pH, involving proton titratable groups with pKas in the relevant pH range. Experimental analysis of pH-dependence in proteins focusses on particular sidechains, often with mutagenesis of histidine, due to its pKa near to neutral pH. The key question for algorithms that predict pKas is whether they are sufficiently accurate to effectively narrow the search for molecular determinants of pH-dependence. Through analysis of inwardly rectifying potassium (Kir) channels and acid-sensing ion channels (ASICs), mutational effects on pH-dependence are probed, distinguishing between groups described as pH-coupled or pH-sensor. Whereas mutation can lead to a shift in transition pH between open and closed forms for either type of group, only for pH-sensor groups does mutation modulate the amplitude of the transition. It is shown that a hybrid Finite Difference Poisson-Boltzmann (FDPB) - Debye-Hückel continuum electrostatic model can filter mutation candidates, providing enrichment for key pH-coupled and pH-sensor residues in both ASICs and Kir channels, in comparison with application of FDPB alone.

  9. Cerebral Correlates of Automatic Associations Towards Performance Enhancing Substances

    PubMed Central

    Schindler, Sebastian; Wolff, Wanja

    2015-01-01

    The direct assessment of explicit attitudes toward performance enhancing substances, for example Neuroenhancement or doping in sports, can be affected by social desirability biases and cheating attempts. According to Dual Process Theories of cognition, indirect measures like the Implicit Association Test (IAT) measure automatic associations toward a topic (as opposed to explicit attitudes measured by self-report measures). Such automatic associations are thought to occur rapidly and to evade voluntary control. However, whether or not such indirect tests actually reflect automatic associations is difficult to validate. Electroencephalography (EEG) has a superior time resolution which can differentiate between highly automatic compared to more elaborate processing stages. We therefore used EEG to examine on which processing stages cortical differences between negative or positive attitudes to doping occur, and whether or not these differences can be related to BIAT scores. We tested 42 university students (31 females, 24.43 ± 3.17 years old), who were requested to complete a brief doping IAT (BIAT) on attitudes toward doping. Cerebral activity during doping BIAT completion was assessed using high-density EEG. Behaviorally, participants D-scores exhibited negative attitudes toward doping, represented by faster reaction times in the doping + dislike pairing task. Event-related potentials (ERPs) revealed earliest effects between 200 and 300 ms. Here, a relatively larger occipital positivity was found for the doping + dislike pairing task. Further, in the LPP time range between 400 and 600 ms a larger late positive potential was found for the doping + dislike pairing task over central regions. These LPP amplitude differences were successfully predicting participants' BIAT D-scores. Results indicate that event-related potentials differentiate between positive and negative doping attitudes at stages of mid-latency. However, it seems that IAT scores can be predicted only

  10. High Modulus and High T(sub g) Thermally Stable Polymers from p-Ethynyl-Terminated Rigid-Rod Monomers. Part 2

    NASA Technical Reports Server (NTRS)

    Melissaris, Anastasios P.; Sutter, James K.; Litt, Morton H.; Scheiman, Daniel A.; Schuerman, Marla A.

    1995-01-01

    Novel p-ethynyl-substituted rigid rod monomers were studied by pressure Differential Scanning Calorimetry (DSC), ThermoGravimetric Analysis (TGA), IsothermoGravimetric Analysis (IGA), and TGA-IR. These monomers, 4,4'-bis(((4-ethynylphenyl)carbonyl)oxy)biphenyl, designated 1, 1,5-bis-(((4-ethynylphenyl)carbonyl)oxy)naphthalene, designated 2, and bis(4-ethynylphenyl)pyromellitimide, designated 3, were polymerized in the solid state. Thermal polymerization in N2 or air produced highly cross-linked resins with polymerization exotherms centered between 212 and 276 C. The (delta)H's of polymerization of these resins in air were found to be double those in N2. When monomers 1 and 2 were heated in air from 23 to 750 C at 10 C/min, the main decomposition product was carbon dioxide, evolving at a maximum rate between 500 and 600 C; water was also detected as a decomposition product. Void-free neat resin moldings, designated lp to 3p, were made by compression molding the monomers and then heating them. The resulting polymers were highly cross-linked, and their glass transition temperatures (T(sub g)) were much higher than their polymerization temperatures. Using ThermoMechanical Analysis (TMA), we found that polymers lp to 3p had T(sub g)'s of 422, 329, and 380 C, respectively. The thermal and thermooxidative stabilities improved when lp to 3p were postcured in N2 (the postcured polymers were designated 1pp to 3pp). The Linear Thermal Expansions (LTE) for lp and 3p were 1% between 23 and 420 C. Using rheological analysis, we could not clearly detect the T(sub g)'s of lp to 3p because their moduli dropped only slightly between 23 and 490 C and the changes in tan beta were very low. Because of high cross-link density, their moduli changed little as the resins went from a glassy to a rubbery state. Their shear storage moduli in air ranged from 0.82 (3p, 3pp) to 1.6 GPa (lpp) at 23 C, from 0.16 (2p) to 0.7GPa(lpp) at 380 C, and from 0.18(lpp)to 0.6GPa(2p) at 490 C. Finally, these

  11. Pronounced differences in signal processing and synaptic plasticity between piriform-hippocampal network stages: a prominent role for adenosine

    PubMed Central

    Trieu, Brian H; Kramár, Enikö A; Cox, Conor D; Jia, Yousheng; Wang, Weisheng; Gall, Christine M; Lynch, Gary

    2015-01-01

    Key points Extended trains of theta rhythm afferent activity lead to a biphasic response facilitation in field CA1 but not in the lateral perforant path input to the dentate gyrus. Processes that reverse long-term potentiation in field CA1 are not operative in the lateral perforant path: multiple lines of evidence indicate that this reflects differences in adenosine signalling. Adenosine A1 receptors modulate baseline synaptic transmission in the lateral olfactory tract but not the associational afferents of the piriform cortex. Levels of ecto-5’-nucleotidase (CD73), an enzyme that converts extracellular ATP into adenosine, are markedly different between regions and correlate with adenosine signalling and the efficacy of theta pulse stimulation in reversing long-term potentiation. Variations in transmitter mobilization, CD73 levels, and afferent divergence result in multivariate differences in signal processing through nodes in the cortico-hippocampal network. Abstract The present study evaluated learning-related synaptic operations across the serial stages of the olfactory cortex-hippocampus network. Theta frequency stimulation produced very different time-varying responses in the Schaffer-commissural projections than in the lateral perforant path (LPP), an effect associated with distinctions in transmitter mobilization. Long-term potentiation (LTP) had a higher threshold in LPP field potential studies but not in voltage clamped neurons; coupled with input/output relationships, these results suggest that LTP threshold differences reflect the degree of input divergence. Theta pulse stimulation erased LTP in CA1 but not in the dentate gyrus (DG), although adenosine eliminated potentiation in both areas, suggesting that theta increases extracellular adenosine to a greater degree in CA1. Moreover, adenosine A1 receptor antagonism had larger effects on theta responses in CA1 than in the DG, and concentrations of ecto-5’-nucleotidase (CD73) were much higher in CA1

  12. Charge exchange spectroscopy of multiply charged ions for the development of the EUV light source for the next generation photo lithography

    NASA Astrophysics Data System (ADS)

    Tanuma, Hajime

    2015-09-01

    As a candidate of an extreme ultra-violet (EUV) light source for a next generation lithography, laser produced plasmas (LPP) of Xe and Sn have been investigated intensively in this decade because these plasmas have a strong emission around 13.5 nm which had been determined as the wavelength for the EUV lithography. This emission was considered to be due to multiply charged Xe and Sn ions in hot plasmas. However, the detail atomic spectroscopic data of these multiply charged heavy ions had not been reported yet. To provide atomic data for the understanding and development of the LPP as the EUV light source, we have observed the EUV emission spectra from individual charge states of Xe and Sn ions by means of a charge exchange spectroscopy method. Multiply charged Xeq+ (q = 7-23) and Snq+ (q = 5-21) ions were produced with a 14.25 GHz electron cyclotron resonance ion source, and a charge-selected ion beam was directed into a collision chamber, where the ion interact with a target gas of He and Xe. EUV emissions from the collision center were observed with a compact flat-field grazing-incident spectrometer equipped with a liquid nitrogen cooled CCD camera. In experiments using Xe ions, we have found only Xe XI has a strong UTA (unresolved transition array) around 13.5 nm. On the other hand, various charge states of Sn from VIII to XIV contribute to the 13.5 nm emission. Identification of the transition lines was carried out by calculations using the Hebrew university Livermore laboratory atomic physics code and the Cowan code. Most of the emissions in the EUV region are attributed to the 4p-4d and 4d- nl (nl = 4f, 5p, and 5f) transitions. However, the 4d-4f transitions have approximately constant differences of about 0.5 nm between the experimental and theoretical results. This can be explained by considering the strong configuration interactions in the n=4 subshells. Using the experimental transition wavelengths of multiply charged Sn ions, theoretical modeling of

  13. Small Hydropower in Latvia and Intellectualization of its Operating Systems / Par Mazo HIDROENERĢĒTIKU LATVIJĀ un TĀS Staciju VADĪBAS SISTĒMAS INTELEKTUALIZĀCIJU

    NASA Astrophysics Data System (ADS)

    Mahnitko, A.; Gerhards, J.; Linkevics, O.; Varfolomejeva, R.; Umbrasko, I.

    2013-12-01

    The authors estimate the potential for power generation from water resources of small and medium-sized rivers, which are abundant in Latvia. They propose the algorithm for optimal operation of a small-scale hydropower plant (SHPP) at the chosen optimality criterion in view of the plant's participation in the market. The choice of SHPP optimization algorithm is made based on two mathematical programming methods - dynamic and generalized reduced gradient ones. Approbation of the algorithm is illustrated by an example of optimized SHPP operation. Darbā analizētas tradicionālo un pieejamo vietējo atjaunojamo energoresursu - mazo un vidējo upju hidroresursa izmantošanas iespējas Latvijas enerģētikā. Tiek sniegts faktiskais materiāls šajā jautājumā, kas iegūts, balstoties uz oficiālos avotos publicētiem citu autoru iepriekš veiktajiem pētījumiem. Tiek atzīmēts, ka teritoriju, kas atrodas mazo upju tuvumā un nav ietvertas centralizētās elektroapgādes sistēmā, saimnieciskā apgūšana rada apstākļus patērētāju stimulēšanai izmantot autonomus vietējos energoresursus, ieskaitot hidroenerģiju, izmantojošas mazas jaudas energoiekārtas. Atjaunojamās enerģijas tehnoloģiju un iekārtu pastāvīga attīstība un pilnveidošanās veicinās mazo upju plūsmas izmantošanas elektroenerģijas ražošanas efektivitātes paaugstināšanos. Mūsdienu enerģētikas attīstības koncepcija, kas balstīta uz viedo tīklu (smart grids) izveidi, ļauj paaugstināt mazās hidroenerģētikas darbības efektivitāti, integrējot to elektroenerģētiskajā sistēmā. Mazo hidroelektrostaciju (MHES) darbības vadības sistēmas intelektualizācijas pamatā jābūt kompleksam algoritmam un programmām, kas ļauj tiešsaistes (online) režīmā nodrošināt izdevīgu MHES darbības grafiku (režīmu) maksimālā ienākuma gūšanai, balstoties uz zināmu elektroenerģijas cenas prognozi attiecīgajam laika periodam (diennaktij). MHES darbības optimiz

  14. Temporal Dynamics of the Interaction between Reward and Time Delay during Intertemporal Choice

    PubMed Central

    Gui, Dan-Yang; Li, Jin-Zhen; Li, Xiaoli; Luo, Yue-jia

    2016-01-01

    Intertemporal choice involves the processes of valuation and choice. Choice is often the result of subjective valuation, in which reward is integrated with time delay. Here, using event-related potential (ERP) signals as temporal hallmarks, we aim to investigate temporal dynamics of how reward interacts with time delay during a delayed discounting task. We found that participants preferred immediate rewards when delayed rewards were small or over long-term delays. Our ERP results suggested that the P200 component reflected an initial valuation of reward and time delay, while the frontal N2 component correlated with individual choices of immediate option of rewards. The LPP component was modulated by the N2 component. These findings demonstrate that the N2 component is the key component in temporal dynamics of the interaction between reward and time valuation. PMID:27785126

  15. High-Temperature Optical Window Design

    NASA Technical Reports Server (NTRS)

    Roeloffs, Norman; Taranto, Nick

    1995-01-01

    A high-temperature optical window is essential to the optical diagnostics of high-temperature combustion rigs. Laser Doppler velocimetry, schlieren photography, light sheet visualization, and laser-induced fluorescence spectroscopy are a few of the tests that require optically clear access to the combustor flow stream. A design was developed for a high-temperature window that could withstand the severe environment of the NASA Lewis 3200 F Lean Premixed Prevaporized (LPP) Flame Tube Test Rig. The development of this design was both time consuming and costly. This report documents the design process and the lessons learned, in an effort to reduce the cost of developing future designs for high-temperature optical windows.

  16. Developmental and Individual Differences in the Neural Processing of Dynamic Expressions of Pain and Anger

    PubMed Central

    Missana, Manuela; Grigutsch, Maren; Grossmann, Tobias

    2014-01-01

    We examined the processing of facial expressions of pain and anger in 8-month-old infants and adults by measuring event-related brain potentials (ERPs) and frontal EEG alpha asymmetry. The ERP results revealed that while adults showed a late positive potential (LPP) to emotional expressions that was enhanced to pain expressions, reflecting increased evaluation and emotional arousal to pain expressions, infants showed a negative component (Nc) to emotional expressions that was enhanced to angry expressions, reflecting increased allocation of attention to angry faces. Moreover, infants and adults showed opposite patterns in their frontal asymmetry responses to pain and anger, suggesting developmental differences in the motivational processes engendered by these facial expressions. These findings are discussed in the light of associated individual differences in infant temperament and adult dispositional empathy. PMID:24705497

  17. Molecular identification of green algae from the rafts based infrastructure of Porphyra yezoensis.

    PubMed

    Shen, Qi; Li, Hongye; Li, Yan; Wang, Zongling; Liu, Jiesheng; Yang, Weidong

    2012-10-01

    To provide more information on the origin of the Ulva prolifera bloom in Qingdao sea area in China from 2007 to 2011, the diversity of green algae growing on the rafts of Porphyra yezoensis on the coast in Jiangsu Province was investigated based on ITS, rbcL and 5S sequences. Eighty-four of green algal samples from various sites and cruises in 2010 and 2011 were collected. According to ITS and rbcL sequences, samples from the rafts of P. yezoensis fell into four clades: Ulva linza-procera-prolifera (LPP) complex, Ulva flexuosa, Blidingia sp. and Urospora spp. However, based on the 5S rDNA, a more resolved DNA marker, only one of the 84 samples belonged to U. prolifera. Combined with the previous reports, it is likely that U. prolifera bloom in Qingdao sea area might consist of more than one origin, and Porphyra cultivation rafts might be one of the causes. PMID:22858010

  18. Analysis of the low-pressure plasma pretreated polymer surface in terms of acid-base approach

    NASA Astrophysics Data System (ADS)

    Kraus, Eduard; Orf, Lukas; Baudrit, Benjamin; Heidemeyer, Peter; Bastian, Martin; Bonenberger, Ramona; Starostina, Irina; Stoyanov, Oleg

    2016-05-01

    We demonstrate the use of a modern wetting method for determining the acid-base properties of treated polymer surfaces for different plastics and adhesives. The effect of the surface treatment with low pressure plasma was evaluated from the viewpoint of acid-base approach with plastics polyoxymethylene (POM) and polyetheretherketone (PEEK). The correlations between the acid-base properties and the identified mechanical tensile strengths of adhesive bonded joints were evaluated and discussed. In the investigated range the determination coefficients for POM and PEEK were calculated to R2 = 0.93 and R2 = 0.97, respectively. These relatively high determination coefficients showed a good correlation between the mechanical strength and the acidity parameter ΔDshort for use in bonding technology for surface pretreatment of polymers with LPP.

  19. Extreme ultraviolet light sources for use in semiconductor lithography—state of the art and future development

    NASA Astrophysics Data System (ADS)

    Stamm, Uwe

    2004-12-01

    This paper gives an overview of the development status and plans of extreme ultraviolet (EUV) light sources at XTREME technologies, a joint venture of Lambda Physik AG, Göttingen and JENOPTIK LOS GmbH, Jena, Germany. Results for gas discharge-produced plasma (GDPP) and laser-produced plasma (LPP), the two major technologies in EUV sources, are presented. The GDPP EUV sources use the Z-pinch principle with efficient sliding-discharge pre-ionization. First prototypes of commercial gas discharge sources with an EUV power of 35 W in 2π sr have already been integrated into EUV microsteppers. These sources are equipped with a debris-filter which supports an optics lifetime exceeding 100 million pulses at 1 kHz repetition rate. The same lifetime was achieved for the components of the discharge system itself. The progress in the development of high-power discharge sources based on xenon resulted in an EUV power of 200 W into a 2π sr solid angle, in continuous operation, at 4.5 kHz repetition rate, by implementation of porous-metal cooling technology. The available intermediate focus (IF) power is 22 W taking into account experimentally verified losses in a 1.8 sr source collector module. The usable IF power depends on the etendue of the optical system of the EUV scanner. For the current size of the EUV emitting plasma the etendue acceptance factor may be below 0.5. The currently usable IF power with 1.8 sr collector mirror may therefore be about 10 W. Z-pinch discharge sources with Sn as the emitter have been developed as a more efficient alternative to xenon fuelled sources. Tin sources showed a conversion efficiency (CE) that was double that of xenon. EUV power of 400 W in 2π sr has been generated at only 4.5 kHz repetition rate. The available IF power is 44 W. Estimates evaluating the tin source performance reveal the potential for achieving high-volume manufacturing (HVM) power specification by using existing technology. Because of their small plasma size and the

  20. Spectral purification and infrared light recycling in extreme ultraviolet lithography sources.

    PubMed

    Bayraktar, Muharrem; van Goor, Fred A; Boller, Klaus J; Bijkerk, Fred

    2014-04-01

    We present the design of a novel collector mirror for laser produced plasma (LPP) light sources to be used in extreme ultraviolet (EUV) lithography. The design prevents undesired infrared (IR) drive laser light, reflected from the plasma, from reaching the exit of the light source. This results in a strong purification of the EUV light, while the reflected IR light becomes refocused into the plasma for enhancing the IR-to-EUV conversion. The dual advantage of EUV purification and conversion enhancement is achieved by incorporating an IR Fresnel zone plate pattern into the EUV reflective multilayer coating of the collector mirror. Calculations using Fresnel-Kirchhoff's diffraction theory for a typical collector design show that the IR light at the EUV exit is suppressed by four orders of magnitude. Simultaneously, 37% of the reflected IR light is refocused back the plasma. PMID:24718234

  1. Re-appraisal and extension of the Gratton-Vargas two-dimensional analytical snowplow model of plasma focus evolution in the context of contemporary research

    NASA Astrophysics Data System (ADS)

    Auluck, S. K. H.

    2013-11-01

    Recent resurgence of interest in applications of dense plasma focus and doubts about the conventional view of dense plasma focus as a purely irrotational compressive flow have re-opened questions concerning device optimization. In this context, this paper re-appraises and extends the analytical snowplow model of plasma focus sheath evolution developed by F. Gratton and J. M. Vargas [Energy Storage, Compression and Switching, edited by V. Nardi, H. Sahlin, and W. H. Bostick (Plenum, New York, 1983), Vol. 2, p. 353)] and shows its relevance to contemporary research. The Gratton-Vargas (GV) model enables construction of a special orthogonal coordinate system in which the plasma flow problem can be simplified and a model of sheath structure can be formulated. The Lawrenceville Plasma Physics (LPP) plasma focus facility, which reports neutron yield better than global scaling law, is shown to be operating closer to an optimum operating point of the GV model as compared with PF-1000.

  2. Applications of compact laser-driven EUV/XUV plasma sources

    NASA Astrophysics Data System (ADS)

    Barkusky, Frank; Bayer, Armin; Döring, Stefan; Flöter, Bernhard; Großmann, Peter; Peth, Christian; Reese, Michael; Mann, Klaus

    2009-05-01

    In recent years, technological developments in the area of extreme ultraviolet lithography (EUVL) have experienced great improvements. So far, intense light sources based on discharge or laser plasmas, beam steering and imaging optics as well as sensitive detectors are available. Currently, applications of EUV radiation apart from microlithography, such as metrology, high-resolution microscopy, or surface analysis come more and more into focus. In this contribution we present an overview on the EUV/XUV activities of the Laser-Laboratorium Göttingen based on table-top laser-produced plasma (LPP) sources. As target materials gaseous or liquid jets of noble gases or solid Gold are employed. Depending on the applications, the very clean but low intense gaseous targets are mainly used for metrology, whereas the targets for high brilliances (liquid, solid) are used for microscopy and direct structuring. For the determination of interaction mechanisms between EUV radiation and matter, currently the solid Gold target is used. In order to obtain a small focal spot resulting in high EUV fluence, a modified Schwarzschild objective consisting of two spherical mirrors with Mo/Si multilayer coatings is adapted to this source. By demagnified (10x) imaging of the Au plasma an EUV spot of 3 μm diameter with a maximum energy density of ~1.3 J/cm2 is generated (pulse duration 8.8 ns). First applications of this integrated source and optics system reveal its potential for high-resolution modification and direct structuring of solid surfaces. For chemical analysis of various samples a NEXAFS setup was developed. It consists of a LPP, using gaseous Krypton as a broadband emitter in the water-window range, as well as a flat field spectrograph. The laboratory system is set to the XUV spectral range around the carbon K-edge (4.4 nm). The table-top setup allows measurements with spectral accuracy comparable to synchrotron experiments. NEXAFS-experiments in transmission and reflection are

  3. Imaging of Combustion Species in a Radially-Staged Gas Turbine Combustor

    NASA Technical Reports Server (NTRS)

    Locke, Randy J.; Hicks, Yolanda R.; Anderson, Robert C.; Ockunzzi, Kelly A.; Schock, Harold J.

    1996-01-01

    Planar laser-induced fluorescence (PLIF) is used to characterize the complex flowfield of a unique fuel-lean, radially-staged, high pressure gas turbine combustor. PLIF images of OH are presented for two fuel injector configurations. PLIF images of NO, the first acquired at these conditions, are presented and compared with gas sample extraction probe measurements. Flow field imaging of nascent C2 chemiluminescence is also investigated. An examination is made of the interaction between adjoining lean premixed prevaporized (LPP) injectors. Fluorescence interferences at conditions approaching 2000 K and 15 atm are observed and attributed to polycyclic aromatic hydrocarbon (PAH) emissions. All images are acquired at a position immediately downstream of the fuel injectors with the combustor burning JP-5 fuel.

  4. Challenges for 1x-nm device fabrication using EUVL: scanner and mask

    NASA Astrophysics Data System (ADS)

    Arnold, William H.

    2011-11-01

    EUVL lithography using high resolution step and scan systems operating at 13.5nm is being inserted in leading edge production lines for memory and logic devices. These tools use mirror optics and either laser produced plasma (LPP) or discharge produced plasma (DPP) sources along with reflective reduction masks to image circuit features. These tools show their capability to meet the challenging device requirements for imaging and overlay. Next generation scanners with resolution and overlay capability to produce 1X nm (10 nm class) memory and logic devices are in preparation. Challenges remain for EUVL, the principal of which are increasing source power enabling high productivity, building a volume mask business encouraging rapid learning cycles, and improving resist performance so it is capable of sub 20nm resolution.

  5. EUV source power and lifetime: the most critical issues for EUV lithography

    NASA Astrophysics Data System (ADS)

    Stamm, Uwe; Kleinschmidt, Juergen; Gaebel, Kai; Birner, Henry; Ahmad, Imtiaz; Bolshukhin, Denis; Brudermann, Jesko; Chinh, Tran Duc; Flohrer, Frank; Goetze, Sven; Hergenhan, Guido; Kloepfel, Diethard; Korobotchko, Vladimir; Mader, Bjorn; Mueller, Rainer; Ringling, Jens; Schriever, Guido; Ziener, Christian

    2004-05-01

    Semiconductor chip manufacturers are expecting to use extreme ultraviolet (EUV) lithography for high volume manufacturing of DRAMs and ICs starting by the end of this decade. Among all the technologies and modules which have to be developed EUV sources at 13.5 nm are considered to be the most critical issue. Specifically the required output power of 115 W at the entrance of the illuminator system in combination with the required lifetimes of source components and collector optics make the source technology critical for EUV lithography. The present paper gives an update of the development status of EUV light sources at XTREME technologies, a joint venture of Lambda Physik AG, Goettingen, and Jenoptik LOS GmbH, Jena, Germany. Results on both laser produced plasma (LPP) and gas discharge produced plasma (GDPP), the two major technologies in EUV sources, are given. The LPP EUV sources use xenon-jet target systems and pulsed lasers with 500 W average power at up to 10 kHz developed at XTREME technologies. The maximum conversion efficiency from laser power into EUV in-band power is 1.0 % into 2p solid angle. 2.0 W EUV radiation is generated at 13.5 nm in 2p sr solid angle. The small source volume of < 0.3 mm diameter will allow large collection angles of 5 sr. The intermediate focus power is estimated to 1 W. Collector mirror lifetime tests showed 5 million pulses lifetime without debris mitigation. With debris mitigation in place lifetimes of more than 1 billion pulses are estimated. For the next generation of higher power EUV LPP sources a laser driver has been tested at 1.3 kW average laser power. This will lead to 5 W EUV power in intermediate focus. The GDPP EUV sources use the Z-pinch principle with efficient sliding discharge pre-ionization. Prototype commercial gas discharge sources with an EUV power of 35W in 2p sr were already delivered for integration into EUV microsteppers. These sources are equipped with a debris-filter which results in an optics lifetime

  6. Are Happy Faces Attractive? The Roles of Early vs. Late Processing

    PubMed Central

    Sun, Delin; Chan, Chetwyn C. H.; Fan, Jintu; Wu, Yi; Lee, Tatia M. C.

    2015-01-01

    Facial attractiveness is closely related to romantic love. To understand if the neural underpinnings of perceived facial attractiveness and facial expression are similar constructs, we recorded neural signals using an event-related potential (ERP) methodology for 20 participants who were viewing faces with varied attractiveness and expressions. We found that attractiveness and expression were reflected by two early components, P2-lateral (P2l) and P2-medial (P2m), respectively; their interaction effect was reflected by LPP, a late component. The findings suggested that facial attractiveness and expression are first processed in parallel for discrimination between stimuli. After the initial processing, more attentional resources are allocated to the faces with the most positive or most negative valence in both the attractiveness and expression dimensions. The findings contribute to the theoretical model of face perception. PMID:26648885

  7. Eat your troubles away: electrocortical and experiential correlates of food image processing are related to emotional eating style and emotional state.

    PubMed

    Blechert, Jens; Goltsche, Julia E; Herbert, Beate M; Wilhelm, Frank H

    2014-02-01

    Emotional eating, a trait-like style of food intake in response to negative emotion states, represents an important aspect of overeating and eating related psychopathology. The mechanisms of emotional eating both on experiential and neuronal levels are not well delineated. We recorded event related potentials (ERPs) while individuals with high or low emotional eating style (HEE, n=25; LEE, n=20) viewed and rated pictures of high-caloric food during neutral state vs. negative idiosyncratic emotion induction. Craving ratings increased in HEE and decreased in LEE during negative relative to neutral states. ERPs to food pictures showed an enhanced late positive potential (LPP) over parieto-occipital regions for HEE compared to LEE. Emotional state modulated food picture evoked ERPs over right frontal regions in HEE only. This suggests that appetitive food processing is susceptible to both concurrent emotion and habitual eating style which is of relevance for overeating in healthy and abnormal eating.

  8. Molecular identification of green algae from the rafts based infrastructure of Porphyra yezoensis.

    PubMed

    Shen, Qi; Li, Hongye; Li, Yan; Wang, Zongling; Liu, Jiesheng; Yang, Weidong

    2012-10-01

    To provide more information on the origin of the Ulva prolifera bloom in Qingdao sea area in China from 2007 to 2011, the diversity of green algae growing on the rafts of Porphyra yezoensis on the coast in Jiangsu Province was investigated based on ITS, rbcL and 5S sequences. Eighty-four of green algal samples from various sites and cruises in 2010 and 2011 were collected. According to ITS and rbcL sequences, samples from the rafts of P. yezoensis fell into four clades: Ulva linza-procera-prolifera (LPP) complex, Ulva flexuosa, Blidingia sp. and Urospora spp. However, based on the 5S rDNA, a more resolved DNA marker, only one of the 84 samples belonged to U. prolifera. Combined with the previous reports, it is likely that U. prolifera bloom in Qingdao sea area might consist of more than one origin, and Porphyra cultivation rafts might be one of the causes.

  9. Pay attention to me! Late ERPs reveal gender differences in attention allocated to romantic partners.

    PubMed

    Burdwood, Erin N; Simons, Robert F

    2016-04-01

    The present study employed late ERPs to examine differences in the association between neural responses to romantic partners and relationship quality factors across men and women. Participants passively viewed photos of their romantic partners, celebrities, and strangers during a computerized facial processing task. All participants demonstrated enhanced positivity to partner faces at late ERP components (P3 and LPP), furthering the notion that significant others elicit more motivated and sustained attention than do other familiar or unfamiliar individuals. Neural responses to romantic partner faces were influenced by factors including overall relationship quality, investment, and communication quality, with associations varying by gender. Results highlight the key role that relationship quality factors play in the immediate processing of romantic partners-a finding with implications for couples counseling and research. PMID:26632025

  10. A new screening method to identify inhibitors of the Lol (localization of lipoproteins) system, a novel antibacterial target.

    PubMed

    Ito, Hideaki; Ura, Atsushi; Oyamada, Yoshihiro; Yoshida, Hiroaki; Yamagishi, Jun-Ichi; Narita, Shin-Ichiro; Matsuyama, Shin-Ichi; Tokuda, Hajime

    2007-01-01

    As the Lol system, which is involved in localization of lipoproteins, is essential for Escherichia coli growth and widely conserved among gram-negative bacteria, it is considered to be a promising target for the development of anti-gram-negative bacterial agents. However, no high-throughput screening method has so far been developed to screen for Lol system inhibitors. By combining three assay systems (anucleate cell blue assay, Lpp assay, and LolA-dependent release inhibition assay) and a drug susceptibility test, we have successfully developed a new screening method for identification of compounds that inhibit the Lol system. Using this new screening method, we screened 23,600 in-house chemical compounds and found 2 Lol system inhibitors. We therefore conclude that our new screening method can efficiently identify new antibacterial agents that target the Lol system.

  11. Are Happy Faces Attractive? The Roles of Early vs. Late Processing.

    PubMed

    Sun, Delin; Chan, Chetwyn C H; Fan, Jintu; Wu, Yi; Lee, Tatia M C

    2015-01-01

    Facial attractiveness is closely related to romantic love. To understand if the neural underpinnings of perceived facial attractiveness and facial expression are similar constructs, we recorded neural signals using an event-related potential (ERP) methodology for 20 participants who were viewing faces with varied attractiveness and expressions. We found that attractiveness and expression were reflected by two early components, P2-lateral (P2l) and P2-medial (P2m), respectively; their interaction effect was reflected by LPP, a late component. The findings suggested that facial attractiveness and expression are first processed in parallel for discrimination between stimuli. After the initial processing, more attentional resources are allocated to the faces with the most positive or most negative valence in both the attractiveness and expression dimensions. The findings contribute to the theoretical model of face perception. PMID:26648885

  12. Toward Quantitatively Accurate Calculation of the Redox-Associated Acid–Base and Ligand Binding Equilibria of Aquacobalamin

    DOE PAGES

    Johnston, Ryne C.; Zhou, Jing; Smith, Jeremy C.; Parks, Jerry M.

    2016-07-08

    In redox processes in complex transition metal-containing species are often intimately associated with changes in ligand protonation states and metal coordination number. Moreover, a major challenge is therefore to develop consistent computational approaches for computing pH-dependent redox and ligand dissociation properties of organometallic species. Reduction of the Co center in the vitamin B12 derivative aquacobalamin can be accompanied by ligand dissociation, protonation, or both, making these properties difficult to compute accurately. We examine this challenge here by using density functional theory and continuum solvation to compute Co ligand binding equilibrium constants (Kon/off), pKas and reduction potentials for models of aquacobalaminmore » in aqueous solution. We consider two models for cobalamin ligand coordination: the first follows the hexa, penta, tetra coordination scheme for CoIII, CoII, and CoI species, respectively, and the second model features saturation of each vacant axial coordination site on CoII and CoI species with a single, explicit water molecule to maintain six directly interacting ligands or water molecules in each oxidation state. Comparing these two coordination schemes in combination with five dispersion-corrected density functionals, we find that the accuracy of the computed properties is largely independent of the scheme used, but including only a continuum representation of the solvent yields marginally better results than saturating the first solvation shell around Co throughout. PBE performs best, displaying balanced accuracy and superior performance overall, with RMS errors of 80 mV for seven reduction potentials, 2.0 log units for five pKas and 2.3 log units for two log Kon/off values for the aquacobalamin system. Furthermore, we find that the BP86 functional commonly used in corrinoid studies suffers from erratic behavior and inaccurate descriptions of Co axial ligand binding, leading to substantial errors in predicted

  13. Toward Quantitatively Accurate Calculation of the Redox-Associated Acid-Base and Ligand Binding Equilibria of Aquacobalamin.

    PubMed

    Johnston, Ryne C; Zhou, Jing; Smith, Jeremy C; Parks, Jerry M

    2016-08-01

    Redox processes in complex transition metal-containing species are often intimately associated with changes in ligand protonation states and metal coordination number. A major challenge is therefore to develop consistent computational approaches for computing pH-dependent redox and ligand dissociation properties of organometallic species. Reduction of the Co center in the vitamin B12 derivative aquacobalamin can be accompanied by ligand dissociation, protonation, or both, making these properties difficult to compute accurately. We examine this challenge here by using density functional theory and continuum solvation to compute Co-ligand binding equilibrium constants (Kon/off), pKas, and reduction potentials for models of aquacobalamin in aqueous solution. We consider two models for cobalamin ligand coordination: the first follows the hexa, penta, tetra coordination scheme for Co(III), Co(II), and Co(I) species, respectively, and the second model features saturation of each vacant axial coordination site on Co(II) and Co(I) species with a single, explicit water molecule to maintain six directly interacting ligands or water molecules in each oxidation state. Comparing these two coordination schemes in combination with five dispersion-corrected density functionals, we find that the accuracy of the computed properties is largely independent of the scheme used, but including only a continuum representation of the solvent yields marginally better results than saturating the first solvation shell around Co throughout. PBE performs best, displaying balanced accuracy and superior performance overall, with RMS errors of 80 mV for seven reduction potentials, 2.0 log units for five pKas and 2.3 log units for two log Kon/off values for the aquacobalamin system. Furthermore, we find that the BP86 functional commonly used in corrinoid studies suffers from erratic behavior and inaccurate descriptions of Co-axial ligand binding, leading to substantial errors in predicted pKas and

  14. Toward Quantitatively Accurate Calculation of the Redox-Associated Acid-Base and Ligand Binding Equilibria of Aquacobalamin.

    PubMed

    Johnston, Ryne C; Zhou, Jing; Smith, Jeremy C; Parks, Jerry M

    2016-08-01

    Redox processes in complex transition metal-containing species are often intimately associated with changes in ligand protonation states and metal coordination number. A major challenge is therefore to develop consistent computational approaches for computing pH-dependent redox and ligand dissociation properties of organometallic species. Reduction of the Co center in the vitamin B12 derivative aquacobalamin can be accompanied by ligand dissociation, protonation, or both, making these properties difficult to compute accurately. We examine this challenge here by using density functional theory and continuum solvation to compute Co-ligand binding equilibrium constants (Kon/off), pKas, and reduction potentials for models of aquacobalamin in aqueous solution. We consider two models for cobalamin ligand coordination: the first follows the hexa, penta, tetra coordination scheme for Co(III), Co(II), and Co(I) species, respectively, and the second model features saturation of each vacant axial coordination site on Co(II) and Co(I) species with a single, explicit water molecule to maintain six directly interacting ligands or water molecules in each oxidation state. Comparing these two coordination schemes in combination with five